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Sample records for human pharyngeal airway

  1. Pharyngeal airway changes following mandibular setback surgery

    Directory of Open Access Journals (Sweden)

    Babu Ramesh

    2005-01-01

    Full Text Available Treatment of dentofacial deformities with jaw osteotomies has an effect on airway anatomy and therefore mandibular setback surgery has the potential to diminish airway size. The purpose of this study was to evaluate the effect of mandibular setback surgery on airway size. 8 consecutive patients were examined prospectively. All patients underwent mandibular setback surgery. Cephalometric analysis was performed preoperatively and 3 months post operatively with particular attention to pharyngeal airway changes. Pharyngeal airway size decreased considerably in all, patients thus predisposing to development of obstructive sleep apnea. Therefore, large anteroposterior discrepancies should be corrected by combined maxillary and mandibular osteotomies.

  2. Risk factors for small pharyngeal airway dimensions in preorthodontic children

    DEFF Research Database (Denmark)

    Anandarajah, Seerone; Dudhia, Raahib; Sandham, Andrew

    2017-01-01

    Objective: To analyze which parameters, gathered from standard orthodontic diagnostic material, were most relevant for identifying small pharyngeal airway dimensions in preorthodontic children. Materials and Methods: The sample was composed of 105 cone beam computed tomography scans of healthy......, skeletal maturity and gender significant associations were found between pharyngeal airway dimensions and craniofacial morphology. Airway volume was positively associated with maxillary and mandibular width (P ... and sagittal jaw relationship were the most relevant factors for minimal cross-sectional area (r2 = 0.16). Conclusion: Pharyngeal airway dimensions were significantly associated with age, skeletal maturity, and craniofacial morphology in all three planes. Children with a reduced mandibular width and increased...

  3. Craniofacial and pharyngeal airway morphology in patients with acromegaly.

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    Balos Tuncer, Burcu; Canigur Bavbek, Nehir; Ozkan, Cigdem; Tuncer, Cumhur; Eroglu Altinova, Alev; Gungor, Kahraman; Akturk, Mujde; Balos Toruner, Fusun

    2015-08-01

    The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. With respect to controls, anterior (pacromegaly. Craniofacial changes were predominantly found in the frontal bone (pacromegaly exhibited diminished dimensions at nasal (pacromegaly. Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.

  4. Degrees of reality: airway anatomy of high-fidelity human patient simulators and airway trainers.

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    Schebesta, Karl; Hüpfl, Michael; Rössler, Bernhard; Ringl, Helmut; Müller, Michael P; Kimberger, Oliver

    2012-06-01

    Human patient simulators and airway training manikins are widely used to train airway management skills to medical professionals. Furthermore, these patient simulators are employed as standardized "patients" to evaluate airway devices. However, little is known about how realistic these patient simulators and airway-training manikins really are. This trial aimed to evaluate the upper airway anatomy of four high-fidelity patient simulators and two airway trainers in comparison with actual patients by means of radiographic measurements. The volume of the pharyngeal airspace was the primary outcome parameter. Computed tomography scans of 20 adult trauma patients without head or neck injuries were compared with computed tomography scans of four high-fidelity patient simulators and two airway trainers. By using 14 predefined distances, two cross-sectional areas and three volume parameters of the upper airway, the manikins' similarity to a human patient was assessed. The pharyngeal airspace of all manikins differed significantly from the patients' pharyngeal airspace. The HPS Human Patient Simulator (METI®, Sarasota, FL) was the most realistic high-fidelity patient simulator (6/19 [32%] of all parameters were within the 95% CI of human airway measurements). The airway anatomy of four high-fidelity patient simulators and two airway trainers does not reflect the upper airway anatomy of actual patients. This finding may impact airway training and confound comparative airway device studies.

  5. Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants.

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    Hasenstab, Kathryn A; Sitaram, Swetha; Lang, Ivan M; Shaker, Reza; Jadcherla, Sudarshan R

    2018-02-01

    Pharyngeal-provocation induced aerodigestive symptoms in infants remain an enigma. Sources of pharyngeal provocation can be anterograde as with feeding, and retrograde as in gastroesophageal reflux. We determined maturational and dose-response effects of targeted pharyngeal-stimulus on frequency, stability, and magnitude of pharyngeal and respiratory waveforms during multiple pharyngeal swallowing responses in preterm-born infants when they were of full-term postmenstrual age (PMA). Eighteen infants (11 male) were studied longitudinally at 39.8 ± 4.8 weeks PMA (time-1) and 44.1 ± 5.8 weeks PMA (time-2). Infants underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflow thermistor methods to test sensory-motor interactions between the pharynx, esophagus, and airway. Linear mixed models were used and data presented as mean ± SEM or %. Overall, responses to 250 stimuli were analyzed. Of the multiple pharyngeal swallowing responses (n = 160), with maturation (a) deglutition apnea duration decreases (p  0.05), and (c) respiratory changes were unaffected (p > 0.05). Initial and subsequent pharyngeal responses and respiratory rhythm interactions become more distinct with maturation. Interval oromotor experiences and volume-dependent increase in adaptive responses may be contributory. These mechanisms may be important in modulating and restoring respiratory rhythm normalcy.

  6. Pharyngeal airway changes associated with maxillary distraction osteogenesis in adult cleft lip and palate patients.

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    Aksu, Muge; Taner, Tülin; Sahin-Veske, Pınar; Kocadereli, Ilken; Konas, Ersoy; Mavili, Mehmet Emin

    2012-02-01

    To investigate 1) the changes in pharyngeal airway sizes associated with maxillary distraction osteogenesis and 2) the correlations between maxillary skeletal variables and the pharyngeal airway in adult patients with cleft lip and palate. The study was carried out in 14 adult subjects with cleft lip and palate. Predistraction records were taken at a mean age of 22.7 ± 4.6 years. All patients had placement of a rigid external distraction device (RED I; KLS Martin, Tuttlingen, Germany) after Le Fort I osteotomy. Lateral cephalograms were assessed before surgery and at short-term follow-up (8.0 ± 6.4 months). The cephalometric skeletal and pharyngeal airway variables were statistically evaluated by use of the Wilcoxon signed-rank test. Spearman ρ correlation was performed to check the correlations between maxillary skeletal and pharyngeal variables. The maxillary movement was 8.7 mm (P maxillary depth angle (+7.9°) and effective maxillary length (9.4 mm) increased significantly (P distraction, whereas the palatal plane angle remained unchanged. Anterior nasal spine (8.2 mm) and Posterior nasal spine (6.9 mm) moved anteriorly. The overjet increased (9.5 mm) significantly (P maxillary movement. PNS changes showed the highest correlation with posterior airway changes. The significant anterior movement of the maxilla resulted in significant increases in posterior, superoposterior, and middle airway spaces. The posterior airway space showed the highest significant positive correlation with the movement of PNS. The posterior and superoposterior airway spaces also showed significant positive correlations with the maxillary skeletal variables. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Effects of mandibular setback with or without maxillary advancement osteotomies on pharyngeal airways: An overview of systematic reviews.

    Directory of Open Access Journals (Sweden)

    Su Keng Tan

    Full Text Available Mandibular setback osteotomies potentially lead to narrowing of the pharyngeal airways, subsequently resulting in post-surgical obstructive sleep apnea (OSA.To summarize current evidence from systematic reviews that has evaluated pharyngeal airway changes after mandibular setback with or without concomitant upper jaw osteotomies.PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched with no restriction of language or date. Systematic reviews studying changes in pharyngeal airway dimensions and respiratory parameters after mandibular setback with or without concomitant upper jaw osteotomies have been identified, screened for eligibility, included and analyzed in this study.Six systematic reviews have been included. While isolated mandibular setback osteotomies result in reduced oropharyngeal airway dimensions, the reduction is lesser in cases with concomitant upper jaw osteotomies. Only scarce evidence exists currently to what happens to naso- and hypo-pharyngeal airways. There is no evidence for post-surgical OSA, even though some studies reported reduced respiratory parameters after single-jaw mandibular setback with or without concomitant upper jaw osteotomies.Although mandibular setback osteotomies reduce pharyngeal airway dimensions, evidence confirming post-surgical OSA was not found. Nevertheless, potential post-surgical OSA should be taken into serious consideration during the treatment planning of particular orthognathic cases. As moderate evidence exists that double-jaw surgeries lead to less compromised post-surgical pharyngeal airways, they should be considered as the method of choice especially in cases with severe dentoskeletal Class III deformity.PROSPERO (registration number: CRD42016046484.

  8. Three-dimensional evaluation of pharyngeal airway in individuals with varying growth patterns using cone beam computed tomography

    OpenAIRE

    Rohan Diwakar; Maninder Singh Sidhu; Mona Prabhakar; Seema Grover; Ritu Phogat

    2015-01-01

    Introduction: The purpose of this study was to evaluate the pharyngeal airway volume in individuals with different vertical growth patterns. Methods: Cone beam computed tomography scans were evaluated of 40 subjects with the age range from 14 to 25 years and were divided into three groups. Horizontal growers consisted of 13 subjects, normal growers consisted of 14 subjects, and the vertical growers consisted of 13 subjects. The pharyngeal airway volume was measured using In Vivo Dental 5.1 so...

  9. Three-dimensional evaluation of pharyngeal airway in individuals with varying growth patterns using cone beam computed tomography

    Directory of Open Access Journals (Sweden)

    Rohan Diwakar

    2015-01-01

    Full Text Available Introduction: The purpose of this study was to evaluate the pharyngeal airway volume in individuals with different vertical growth patterns. Methods: Cone beam computed tomography scans were evaluated of 40 subjects with the age range from 14 to 25 years and were divided into three groups. Horizontal growers consisted of 13 subjects, normal growers consisted of 14 subjects, and the vertical growers consisted of 13 subjects. The pharyngeal airway volume was measured using In Vivo Dental 5.1 software (Anatomage, Anatomy Imaging Software, San Jose, CA, USA. Results: The results obtained were analyzed statistically. The statistical test used for the analysis of the result was Student′s t-test. The independent t-test was done to compare the mean of the pharyngeal airway between the normal growers and horizontal growers and between the normal growers and the vertical growers. No statistically significant difference between the three groups was found in the volumetric measurements of the various sections of airway. Conclusions: Pharyngeal airway volume does not differ significantly in different vertical jaw relationships. It was possible to evaluate the pharyngeal airway volume three dimensionally.

  10. Pharyngeal Airway Space Changes After Condylar Replacement and Mandibular Advancement Surgery.

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    Yuen, Holly; Rossouw, P Emile; Wolford, Larry M; Wang, Hongyue

    2018-01-03

    The aim of this study was to examine the total volume and cross-sectional areas of the pharyngeal airway after bilateral condylar replacement and mandibular advancement surgery. A total of 137 patients (126 women and 11 men) underwent bilateral temporomandibular joint total joint replacement performed by 1 surgeon. A subsample of 30 patients who underwent condylar replacement and only mandibular advancement were evaluated for impact on the airway. Measurements were taken preoperatively, postoperatively, and at a follow-up 1 year after surgery on cone beam computed tomography scans. InVivoDental 3-dimensional imaging (Anatomage, San Jose, CA) was used to measure airway space regarding total volume (in cubic centimeters); minimum cross-sectional area (in square millimeters); minimum cross sections of the first, second, and third cervical vertebrae; and whether the patient had mandibular retrognathia before surgery. A second operator was used to test for interoperator error. Descriptive and bivariate statistics were computed, and the P value was set at .05. There was a significant increase in all measurements at the follow-up visit compared with the preoperative visit. There were no significant differences between groups based on simultaneous Le Fort I surgery, mandibular retrognathia, and gender. However, there were statistically significant differences in cross sections 1 and 2, as well as minimum cross-sectional area, regarding age. Condylar replacement and mandibular advancement have a significant association with an increase in airway space. The intraclass correlation coefficient showed excellent agreement between interoperator measurements. Patients undergoing bilateral temporomandibular joint replacement and mandibular advancement surgery showed an increase in pharyngeal airway space at a 1-year follow-up. In this study, age was significantly associated with the cross-sectional areas of the airway, with older patients having smaller values. Copyright © 2018

  11. Regional aerosol deposition in human upper airways

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1992-11-01

    Laboratory experimental studies were carried out to investigate the factors influencing the deposition of aerosols ranging in size from 1 nm to 10 [mu]m in the human nasal, oral, pharyngeal and laryngeal airways. These experimental studies were performed in replicate upper airway physical models and in human volunteer subjects. New replicate models of the oral passage of an infant, the oral passage of an adult at two openings and the combined nasal and oral airways of an adult were constructed during the period, adding to the existing models of adult, child and infant nasal and oral airways models. Deposition studies in the adult oral and adult nasal models were performed under simulated cyclic flow conditions with 1 nm particles to compare with previously measured constant flow studies. Similar studies with inertial particles (1--10 [mu]m diameter) were performed with the adult nasal model; in both instances, results with cyclic flow were similar to constant flow results using a simple average flow rate based on inspiratory volume and time of inspiration. Human subject studies were performed with particle sizes 5--20 nm for nasal inspiration; preliminary analysis shows good agreement with model studies at several representative flow rates. Nasal inspiratory inertial deposition of 1--4 [mu]m diameter particles was measured in several adults as a function of airway dimensions; dimensional changes of the valve area by decongestion did not produce concomitant deposition changes.

  12. Cephalometric evaluation of the pharyngeal airway space after orthognathic surgery and distraction osteogenesis of the jaw bones

    Directory of Open Access Journals (Sweden)

    S Ganapathy Sriram

    2014-01-01

    Full Text Available Objective: Orthognathic surgeries and distraction osteogenesis (DO of the jaw bones cause a change in the pharyngeal airway space (PAS. The aim of our study was to evaluate the magnitude of changes occurring in the pharyngeal airway after mandibular set-back surgeries and DO of maxilla/mandible. Materials and Methods: The study undertaken was a retrospective cephalometric study. Subjects included in our study had undergone mandibular set-back surgery or DO of maxilla/mandible. Lateral cephalograms of the subjects taken pre-operatively (T0, immediate post-operatively (T1 and after a minimum follow-up period of 6 months (T2 were studied. The cephalograms were traced manually and the following parameters were evaluated: Surface area of the PAS, pharyngeal airway width at the level of the base of the tongue, position of the hyoid bone and the tongue. Repeated measure ANOVA test was done to assess the presence of any significant changes in the proposed parameters at T0, T1 and T2. A correlation analysis was made between the mandibular/maxillary movements and the corresponding changes in the PAS. Results: Surgical movements of maxilla and mandible do have an effect on the pharyngeal airway. Conclusion: It was clearly evident that the effects of mandibular movements on the PAS and the hyoid bone is more significant than the maxillary movements.

  13. Changes in oro-pharyngeal airway dimension after treatment with function appliance in class II skeletal pattern

    International Nuclear Information System (INIS)

    Ali, B.; Shaikh, A.; Fida, M.

    2015-01-01

    Background: Functional appliances have been used since many decades for the correction of mandibular retrognathism. Similar oral appliances are a treatment modality for patients with Obstructive sleep apnea. Hence, interception at the right age with these growth modification appliances might benefit a child from developing long term respiratory insufficiency. Therefore, the purpose of our study was to assess the short term effects of Twin block appliance (CTB) on pharyngeal airway size in subjects with skeletal Class II pattern in a sample of Pakistani population. Methods: A retrospective study was conducted from orthodontic records of 62 children (31 males, 31 females) with retrognathic mandibles using lateral cephalograms obtained at initial visit and after CTB treatment. Paired t-test was used to compare the pre-functional and post-functional treatment airway size. Independent sample t-test was used for comparison between the genders and statistical significance was kept at =0.05. Results: The upper airway width (p<0.001), nasopharyngeal depth (p=0.03) and upper airway thickness (p=0.008) was substantially improved after CTB treatment. Males showed a greater increase in upper airway width (p= 0.03) and nasopharyngeal depth (p=0.01) in comparison to the females. Conclusion: Functional appliance therapy can improve the narrow pharyngeal airway of growing children presenting with deficient mandibles having Class II skeletal pattern. (author)

  14. Large Eddy Simulation and Reynolds-Averaged Navier-Stokes modeling of flow in a realistic pharyngeal airway model: an investigation of obstructive sleep apnea.

    Science.gov (United States)

    Mihaescu, Mihai; Murugappan, Shanmugam; Kalra, Maninder; Khosla, Sid; Gutmark, Ephraim

    2008-07-19

    Computational fluid dynamics techniques employing primarily steady Reynolds-Averaged Navier-Stokes (RANS) methodology have been recently used to characterize the transitional/turbulent flow field in human airways. The use of RANS implies that flow phenomena are averaged over time, the flow dynamics not being captured. Further, RANS uses two-equation turbulence models that are not adequate for predicting anisotropic flows, flows with high streamline curvature, or flows where separation occurs. A more accurate approach for such flow situations that occur in the human airway is Large Eddy Simulation (LES). The paper considers flow modeling in a pharyngeal airway model reconstructed from cross-sectional magnetic resonance scans of a patient with obstructive sleep apnea. The airway model is characterized by a maximum narrowing at the site of retropalatal pharynx. Two flow-modeling strategies are employed: steady RANS and the LES approach. In the RANS modeling framework both k-epsilon and k-omega turbulence models are used. The paper discusses the differences between the airflow characteristics obtained from the RANS and LES calculations. The largest discrepancies were found in the axial velocity distributions downstream of the minimum cross-sectional area. This region is characterized by flow separation and large radial velocity gradients across the developed shear layers. The largest difference in static pressure distributions on the airway walls was found between the LES and the k-epsilon data at the site of maximum narrowing in the retropalatal pharynx.

  15. THREE-DIMENSIONAL ASSESSMENT OF THE PHARYNGEAL AIRWAY AND MAXILLARY SINUS VOLUMES IN INDIVIDUALS WITH NON-SYNDROMIC CLEFT LIP AND PALATE

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    Ana NEMȚOI

    2015-09-01

    Full Text Available Introduction: Children with cleft lip and palate (CLP are known to have airway problems. Introduction of ConeBeam CT (CBCT and imaging software has facilitated generation of 3D images for assessing the volume of maxillary sinuses and pharyngeal airway. Consequently, the present study aimed at evaluating and comparing the maxillary sinus and pharyngeal airway volume of patients with cleft lip and palate in healthy patients, using cone beam computed tomography (CBCT images. Materials and method: The sample group included 27 individuals (15 with cleft lip and palate subjects and 12 healthy subjects. The pharyngeal airway and each maxillary sinus were three-dimensionally assessed, segmented and their volume was calculated. A comparison between the right and left sinus was performed by Student t-test, and the differences between the control and cleft groups were calculated using ANOVA. Results: No statistically significant differences were found when the maxillary sinuses volumes from each side were compared (p >0.05. The unilateral CLP patients presented the lowest sinus volume. Individuals with CLP did not exhibit a total airway volume smaller than the nonCLP controls. Conclusions: 3D imaging using CBCT and Romexis software is reliable for assessing maxillary sinus and pharyngeal airway volume. The present study showed that the pharyngeal airway is not compromised in CLP individuals. The unilateral CLP individuals present maxillary sinuses with smaller volumes, no differences being recorded between the cleft and non-cleft side.

  16. Three-dimensional evaluation of nasal and pharyngeal airway after Le Fort I maxillary distraction osteogenesis.

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    Gokce, S M; Gorgulu, S; Karacayli, U; Gokce, H S; Battal, B

    2015-04-01

    The aims of this study were to evaluate volumetric changes in the nasal cavity (NC) and pharyngeal airway space (PAS) after Le Fort I maxillary distraction osteogenesis (MDO) using a three-dimensional (3D) simulation program, and to determine the effects of MDO on respiratory function during sleep with polysomnography (PSG). 3D computed tomography images were obtained and analyzed before surgery (T0) and at a mean 8.2 ± 1.2 months postsurgery (T1) (SimPlant-OMS software) for 11 male patients (mean age 25.3 ± 5.9 years) with severe skeletal class III anomalies related to maxillary retrognathia. The simulation of osteotomies and placement of distractors were performed on stereolithographic 3D models. NC and PAS were segmented separately on these models for comparison of changes between T0 and T1. PSG including the apnoea-hypopnoea index (AHI), sleep efficiency, sleep stages (weakness, stages 1-4, and rapid eye movement (REM)), and mean lowest arterial O2 saturation were obtained at T0 and T1 to investigate changes in respiratory function during sleep. MDO was successful in all cases as planned on the models; the average forward movement at A point was 10.2mm. Increases in NC and PAS volume after MDO were statistically significant. These increases resulted in significant improvement in sleep quality. PSG parameters changed after MDO; AHI and sleep stages weakness, 1, and 2 decreased, whereas REM, stages 3 and 4, sleep efficiency, and mean O2 saturation increased. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  17. Regional aerosol deposition in human upper airways

    International Nuclear Information System (INIS)

    Swift, D.L.

    1989-01-01

    During the report period significant progress on the quantitative understanding of regional upper airway deposition of airborne particle has been realized. Replicate models of the human upper airways obtained from post-mortem casting of the nasal, oral, pharyngeal, laryngeal and upper tracheal regions and in vivo magnetic resonance imaging (MRI) of the same regions of adults and children have been employed to determine the overall and local deposition characteristics of aerosols in the ultrafine (1--100 μm diameter) and fine (0.8--12 μm diameter) region. Studies have been carried out for both nasal and oral breathing during inspiratory and expiratory flow at constant flow rates representative of rest and states of exercise. The results of these investigations indicate that particles in the size range of ''unattached'' radon progeny (1--3 nm) are deposited in both the nasal and oral passages with high efficiency (60--80%) for both inspiration and expiration, with the nasal deposition being somewhat greater (5--10%) than oral deposition. The effect of flow rate on upper airway deposition for both pathways is not great; data analysis indicates that the deposition for all flow rates from 4--50 liters/minute can be grouped by plotting deposition vs Q- 1/8 , where Q is flow rate, a far weaker dependency than observed for inertial deposition. Diffusional transport is the primary mechanism of deposition, and size dependence can be accounted for by plotting, deposition percent vs D n where D is particle diffusion coefficient and n ranges from 0.5--0.66. 2 refs

  18. Comparative Evaluation of the Pharyngeal Airway Space in Unilateral and Bilateral Cleft Lip and Palate Individuals With Noncleft Individuals: A Cone Beam Computed Tomography Study.

    Science.gov (United States)

    Gandedkar, Narayan H; Chng, Chai Kiat; Basheer, Mohammad Abdul; Chen, Por Yong; Yeow, Vincent Kok Leng

    2017-09-01

      To evaluate the pharyngeal airway space changes in complete unilateral cleft lip and palate (UCLP) and bilateral cleft lip and palate (BCLP) individuals, and compare with age and sex-matched noncleft (NC) control subjects.   Retrospective study.   Cleft and Craniofacial Centre, KK Women's and Children's Hospital, Singapore.   Twenty UCLP (mean age: 13.4 ± 0.5 years), 18 BCLP (mean age: 13.5 ± 0.5 years) and 20 skeletal Class I subjects (mean age: 13.4 ± 0.6 years) were included in the study. Cone beam computed tomography scans were assessed for pharyngeal airway space (PAS) (oropharyngeal, nasopharyngeal, total airway space volume), and compared with PAS of age and sex-matched skeletal Class I NC individuals.   Pharyngeal airway space showed statistically significant differences in the UCLP, BCLP, and NC control subjects. Oropharyngeal (9338 ± 1108 mm 3 , P space (12 250 ± 1185 mm 3 , P .05).   The pharyngeal airway space was significantly reduced in the BCLP group than were those in UCLP and control groups. This reduced PAS should be taken into account when planning treatment for these individuals.

  19. Comparative study of patients suffering sore throat after general anesthesia using laryngeal mask airway and cuffed pharyngeal tube in adults

    Directory of Open Access Journals (Sweden)

    Hassani V

    2001-09-01

    Full Text Available Post-operative sore throat is one of the most common complications and complaints of patients after general anesthesia especially in operations that need endotracheal intubations. Its causes are: size of endotracheal tube and type of its cuff, inadequate airway humidification, trauma during intubation and suctioning, high flow of inspiratory gases, surgical manipulation of airway and adjacent organs, ect. Use of instruments with less invasion to upper respiratory tract, for example, face mask and airway, LMA or CPT are methods, used for decreasing the rate of post-operative sore throat. This study was performed to compare the rate of sore throat after general anesthesia between Laryngeal Mask Airway (LMA and Cuffed Pharyngeal Tube (CPT. From the patients, 120 ASA: PS-I cases, were selected, who were candidates for elective surgery of Orthopedics, Urology, General surgery and Gynecology in Hazrat Rasool-Akram Hospital Complex in the year 2000. Their operation were performed in supine position and did not need muscle relaxation and the patients had spontaneous breathing. Duration of surgery was less than 2 hours. The patients were randomly allocated into two groups: LMA was used for one group and CPT for others. Immediately after operation, in the recovery room and at 6, 12, 18 and 24 hours after removing the tube, the patients were asked about sore throat and the results were recorded in the related sheets. The results was 31.7 percent of patients in group LMA and 0 percent of patients in group CPT, had sore throat. There were significant difference between groups (LMA and CPT in presentation of sore throat (P<0.001.

  20. The human airway epithelial basal cell transcriptome.

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    Neil R Hackett

    2011-05-01

    Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

  1. Pharyngeal airway dimensions in skeletal class II: A cephalometric growth study

    International Nuclear Information System (INIS)

    Uslu-Akcam, Ozge

    2017-01-01

    This retrospective study aimed to evaluate the nasopharyngeal and oropharyngeal dimensions of individuals with skeletal class II, division 1 and division 2 patterns during the pre-peak, peak, and post-peak growth periods for comparison with a skeletal class I control group. Totally 124 lateral cephalograms (47 for skeletal class I; 45 for skeletal class II, division 1; and 32 for skeletal class II, division 2) in pre-peak, peak, and post-peak growth periods were selected from the department archives. Thirteen landmarks, 4 angular and 4 linear measurements, and 4 proportional calculations were obtained. The ANOVA and Duncan test were applied to compare the differences among the study groups during the growth periods. Statistically significant differences were found between the skeletal class II, division 2 group and other groups for the gonion-gnathion/sella-nasion angle. The sella-nasion-B-point angle was different among the groups, while the A-point-nasion-B-point angle was significantly different for all 3 groups. The nasopharyngeal airway space showed a statistically significant difference among the groups throughout the growth periods. The interaction among the growth periods and study groups was statistically significant regarding the upper oropharyngeal airway space measurement. The lower oropharyngeal airway space measurement showed a statistically significant difference among the groups, with the smallest dimension observed in the skeletal class II, division 2 group. The naso-oropharyngeal airway dimensions showed a statistically significant difference among the class II, division 1; class II, division 2; and class I groups during different growth periods

  2. Pharyngeal airway dimensions in skeletal class II: A cephalometric growth study

    Energy Technology Data Exchange (ETDEWEB)

    Uslu-Akcam, Ozge [Clinic of Orthodontics, Ministry of Health, Tepebasi Oral and Dental Health Hospital, Ankara (Turkmenistan)

    2017-03-15

    This retrospective study aimed to evaluate the nasopharyngeal and oropharyngeal dimensions of individuals with skeletal class II, division 1 and division 2 patterns during the pre-peak, peak, and post-peak growth periods for comparison with a skeletal class I control group. Totally 124 lateral cephalograms (47 for skeletal class I; 45 for skeletal class II, division 1; and 32 for skeletal class II, division 2) in pre-peak, peak, and post-peak growth periods were selected from the department archives. Thirteen landmarks, 4 angular and 4 linear measurements, and 4 proportional calculations were obtained. The ANOVA and Duncan test were applied to compare the differences among the study groups during the growth periods. Statistically significant differences were found between the skeletal class II, division 2 group and other groups for the gonion-gnathion/sella-nasion angle. The sella-nasion-B-point angle was different among the groups, while the A-point-nasion-B-point angle was significantly different for all 3 groups. The nasopharyngeal airway space showed a statistically significant difference among the groups throughout the growth periods. The interaction among the growth periods and study groups was statistically significant regarding the upper oropharyngeal airway space measurement. The lower oropharyngeal airway space measurement showed a statistically significant difference among the groups, with the smallest dimension observed in the skeletal class II, division 2 group. The naso-oropharyngeal airway dimensions showed a statistically significant difference among the class II, division 1; class II, division 2; and class I groups during different growth periods.

  3. Regional aerosol deposition in human upper airways. Progress report, March 1, 1992--February 28, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1992-11-01

    Laboratory experimental studies were carried out to investigate the factors influencing the deposition of aerosols ranging in size from 1 nm to 10 {mu}m in the human nasal, oral, pharyngeal and laryngeal airways. These experimental studies were performed in replicate upper airway physical models and in human volunteer subjects. New replicate models of the oral passage of an infant, the oral passage of an adult at two openings and the combined nasal and oral airways of an adult were constructed during the period, adding to the existing models of adult, child and infant nasal and oral airways models. Deposition studies in the adult oral and adult nasal models were performed under simulated cyclic flow conditions with 1 nm particles to compare with previously measured constant flow studies. Similar studies with inertial particles (1--10 {mu}m diameter) were performed with the adult nasal model; in both instances, results with cyclic flow were similar to constant flow results using a simple average flow rate based on inspiratory volume and time of inspiration. Human subject studies were performed with particle sizes 5--20 nm for nasal inspiration; preliminary analysis shows good agreement with model studies at several representative flow rates. Nasal inspiratory inertial deposition of 1--4 {mu}m diameter particles was measured in several adults as a function of airway dimensions; dimensional changes of the valve area by decongestion did not produce concomitant deposition changes.

  4. Water permeability in human airway epithelium

    DEFF Research Database (Denmark)

    Pedersen, Peter Steen; Procida, Kristina; Larsen, Per Leganger

    2005-01-01

    Osmotic water permeability (P(f)) was studied in spheroid-shaped human airway epithelia explants derived from nasal polyps by the use of a new improved tissue collection and isolation procedure. The fluid-filled spheroids were lined with a single cell layer with the ciliated apical cell membrane ...

  5. Neuronal NOS localises to human airway cilia.

    Science.gov (United States)

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Test of the Starling resistor model in the human upper airway during sleep.

    Science.gov (United States)

    Wellman, Andrew; Genta, Pedro R; Owens, Robert L; Edwards, Bradley A; Sands, Scott A; Loring, Stephen H; White, David P; Jackson, Andrew C; Pedersen, Ole F; Butler, James P

    2014-12-15

    The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model--that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors. Resistance between the nose and the site of collapse (the upstream segment) was measured before and after the onset of flow limitation to determine whether the upstream dimensions remained fixed (as predicted by the Starling resistor model) or narrowed (a violation of the Starling resistor model). The upstream resistance from early to mid inspiration increased considerably during flow limitation (by 35 ± 41 cmH2O · liter(-1) · s(-1), P < 0.001). However, there was a wide range of variability between patients, and the increase in upstream resistance was strongly correlated with the amount of NED (r = 0.75, P < 0.001). Therefore, patients with little NED exhibited little upstream narrowing (consistent with the Starling model), and patients with large NED exhibited large upstream narrowing (inconsistent with the Starling model). These findings support the idea that there is not a single model of pharyngeal collapse, but rather that different mechanisms may dominate in different patients. These differences could potentially be exploited for treatment selection. Copyright © 2014 the American Physiological Society.

  7. Airway skills training using a human patient simulator

    African Journals Online (AJOL)

    Thesegan Moodley

    2016-04-11

    Apr 11, 2016 ... Airway management problems may be particularly challenging to junior doctors.1 ... They respond to real-time, real-life clinical ... Keywords: human patient simulator, simulation, airway management, psychomotor skills.

  8. A Comparative Study of Cuffed Pharyngeal Tube (CPR with Endotracheal Tube in Airway Management and Ventilation of Spontaneously Breathing Patients Undergoing General Anesthesia

    Directory of Open Access Journals (Sweden)

    F Mir Mohammad Sadeghi

    2002-09-01

    Full Text Available Background: Cuffed pharyngeal tube is a device designed for ventilation of anesthetized patients. CPT has advantages over face mask including: maintaining of face mask can be difficult and boring after several minutes and mobility of the practitioner is reduced due to involvement of hands. Mask pressure can cause soft tissue and nerve damage around the nose. Anesthetic gas leakage from the mask adds to the operation room pollution. In difficult intubation CPT can be life-saving. Materials and Methods: In our study CPT was compared with endotracheal tube (ET in anesthetized patients. A scoring system for evaluating ventilation of patients was designed using symmetric chest wall motion during ventilation with anesthesia bag and sensing lung compliance through it, auscultation of breathing sounds, oscilation of bag with breathing and peripheral oxygen saturation by pulse oxymetry. Respiratory complications (pulmonary aspiration, Iaryngospasm and bronchospasm, nausea and vomiting were looked for during anesthesia. Results: The results showed that CPT was successful as ET in ventilation of spontaneously breathing patients and incidence of respiratory complications with CPT was no more than ET. Airway resistance was significantly greater with CPT than ET (P<0.05. Patients with ET had significantly greater incidence of sore throat than with CPT (P<0.05. Conclusion: Thus we concluded that CPT can be used for ventilation of anesthetized patients not predisposed to pulmonary aspiration and whose peak airway pressure does not exceed 20-25 CmH2O.

  9. Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system.

    Science.gov (United States)

    Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen

    2012-08-01

    Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22-59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43±1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60-90 min post-iTBS (maximum 54±19%, P≤0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P=0.39) on either hemisphere. APB responses similarly did not change significantly (P=0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  10. Development of a realistic human airway model.

    Science.gov (United States)

    Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

    2012-03-01

    Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained.

  11. Comparative Evaluation of the Pharyngeal Airways and Related Soft Tissues of Unilateral and Bilateral Cleft Lip and Palate Patients With the Noncleft Individuals.

    Science.gov (United States)

    Aras, Isil; Dogan, Servet

    2017-01-01

      This study is a comparison of pharyngeal airways and associated soft tissues of unilateral and bilateral cleft lip and palate patients with the noncleft individuals.   Twenty-four unilateral cleft lip and palate patients (UCLP), 21 bilateral cleft lip and palate patients (BCLP), and 26 noncleft patients (NC) between ages 15 to 17 were included in the study. Eleven linear, 1 angular, and 1 proportional measurements were carried out on pretreatment lateral cephalometric head films of these individuals.   The nasopharyngeal depths were markedly reduced in BCLP when compared with the NC (P clefts, BCLP showed significant (P cleft groups compared to the controls. Similarly, the hyoid bone was positioned in a significantly (P cleft patients. Comparison of the mean ratio of velar length to nasopharyngeal depth of the three groups revealed significant (P cleft patients with significantly (P cleft patients show serious inadequacies compared to controls, with significant diversities among cleft types pertaining to some of the parameters investigated. It should be kept in mind that these variations can influence function in terms of respiration and phonation.

  12. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

    OpenAIRE

    Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S.; Pickles, Raymond J.

    2009-01-01

    Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human p...

  13. Mediators on human airway smooth muscle.

    Science.gov (United States)

    Armour, C; Johnson, P; Anticevich, S; Ammit, A; McKay, K; Hughes, M; Black, J

    1997-01-01

    1. Bronchial hyperresponsiveness in asthma may be due to several abnormalities, but must include alterations in the airway smooth muscle responsiveness and/or volume. 2. Increased responsiveness of airway smooth muscle in vitro can be induced by certain inflammatory cell products and by induction of sensitization (atopy). 3. Increased airway smooth muscle growth can also be induced by inflammatory cell products and atopic serum. 4. Mast cell numbers are increased in the airways of asthmatics and, in our studies, in airway smooth muscle that is sensitized and hyperresponsive. 5. We propose that there is a relationship between mast cells and airway smooth muscle cells which, once an allergic process has been initiated, results in the development of critical features in the lungs in asthma.

  14. Airway skills training using a human patient simulator | Moodley ...

    African Journals Online (AJOL)

    ... of airway management skills using the simulator. Participant satisfaction was much better in the simulator group. The importance of psychomotor reinforcement should be borne in mind when designing simulation courses. Keywords: human patient simulator, simulation, airway management, psychomotor skills ...

  15. Human airway xenograft models of epithelial cell regeneration

    Directory of Open Access Journals (Sweden)

    Puchelle Edith

    2000-10-01

    Full Text Available Abstract Regeneration and restoration of the airway epithelium after mechanical, viral or bacterial injury have a determinant role in the evolution of numerous respiratory diseases such as chronic bronchitis, asthma and cystic fibrosis. The study in vivo of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to restore a functional respiratory epithelium after several weeks. Recently, human tracheal xenografts have been developed in immunodeficient severe combined immunodeficiency (SCID and nude mice. In this review we recall that human airway cells implanted in such conditioned host grafts can regenerate a well-differentiated and functional human epithelium; we stress the interest in these humanized mice in assaying candidate progenitor and stem cells of the human airway mucosa.

  16. In vivo models of human airway epithelium repair and regeneration

    Directory of Open Access Journals (Sweden)

    C. Coraux

    2005-12-01

    Full Text Available Despite an efficient defence system, the airway surface epithelium, in permanent contact with the external milieu, is frequently injured by inhaled pollutants, microorganisms and viruses. The response of the airway surface epithelium to an acute injury includes a succession of cellular events varying from the loss of the surface epithelium integrity to partial shedding of the epithelium or even to complete denudation of the basement membrane. The epithelium has then to repair and regenerate to restore its functions. The in vivo study of epithelial regeneration in animal models has shown that airway epithelial cells are able to dedifferentiate, spread, migrate over the denuded basement membrane and progressively redifferentiate to reconstitute a functional respiratory epithelium after several weeks. Humanised tracheal xenograft models have been developed in immunodeficient nude and severe combined immunodeficient (SCID mice in order to mimic the natural regeneration process of the human airway epithelium and to analyse the cellular and molecular events involved during the different steps of airway epithelial reconstitution. These models represent very powerful tools for analysing the modulation of the biological functions of the epithelium during its regeneration. They are also very useful for identifying stem/progenitor cells of the human airway epithelium. A better knowledge of the mechanisms involved in airway epithelium regeneration, as well as the characterisation of the epithelial stem and progenitor cells, may pave the way to regenerative therapeutics, allowing the reconstitution of a functional airway epithelium in numerous respiratory diseases, such as asthma, chronic obstructive pulmonary diseases, cystic fibrosis and bronchiolitis.

  17. Recombinant human DNase in children with airway malacia and lower respiratory tract infection.

    NARCIS (Netherlands)

    Boogaard, R.; Jongste, J.C. de; Vaessen-Verberne, A.A.; Hop, W.C.J.; Merkus, P.J.F.M.

    2009-01-01

    BACKGROUND: Children with airway malacia often have protracted courses of airway infections, because dynamic airway collapse during coughing results in impaired mucociliary clearance. The aim of this study was to determine the effect of the mucolytic drug recombinant human deoxyribonuclease

  18. Mechanics of airflow in the human nasal airways.

    Science.gov (United States)

    Doorly, D J; Taylor, D J; Schroter, R C

    2008-11-30

    The mechanics of airflow in the human nasal airways is reviewed, drawing on the findings of experimental and computational model studies. Modelling inevitably requires simplifications and assumptions, particularly given the complexity of the nasal airways. The processes entailed in modelling the nasal airways (from defining the model, to its production and, finally, validating the results) is critically examined, both for physical models and for computational simulations. Uncertainty still surrounds the appropriateness of the various assumptions made in modelling, particularly with regard to the nature of flow. New results are presented in which high-speed particle image velocimetry (PIV) and direct numerical simulation are applied to investigate the development of flow instability in the nasal cavity. These illustrate some of the improved capabilities afforded by technological developments for future model studies. The need for further improvements in characterising airway geometry and flow together with promising new methods are briefly discussed.

  19. A human model of restricted upper esophageal sphincter opening and its pharyngeal and UES deglutitive pressure phenomena

    Science.gov (United States)

    Jiao, Hongmei; Mei, Ling; Sharma, Tarun; Kern, Mark; Sanvanson, Patrick

    2016-01-01

    Oropharyngeal dysphagia due to upper esophageal sphincter (UES) dysfunction is commonly encountered in the clinical setting. Selective experimental perturbation of various components of the deglutitive apparatus can provide an opportunity to improve our understanding of the swallowing physiology and pathophysiology. The aim is to characterize the pharyngeal and UES deglutitive pressure phenomena in an experimentally induced restriction of UES opening in humans. We studied 14 volunteers without any dysphagic symptoms (7 men, 66 ± 11 yr) but with various supraesophageal reflux symptoms. To induce UES restriction, we used a handmade device that with adjustment could selectively apply 0, 20, 30, or 40 mmHg pressure perpendicularly to the cricoid cartilage. Deglutitive pharyngeal and UES pressure phenomena were determined during dry and 5- and 10-ml water swallows × 3 for each of the UES perturbations. External cricoid pressure against the UES resulted in a significant increase in hypopharyngeal intrabolus pressure and UES nadir deglutitive relaxation pressure for all tested swallowed volumes (P < 0.05). Application of external cricoid pressure increased the length of the UES high pressure zone from 2.5 ± 0.2 to 3.1 ± 0.2, 3.5 ± 0.1, and 3.7 ± 0.1 cm for 20, 30, and 40 mmHg cricoid pressure, respectively (P < 0.05). External cricoid pressure had no significant effect on pharyngeal peristalsis. On the other hand, irrespective of external cricoid pressure deglutitive velopharyngeal contractile integral progressively increased with increased swallowed volumes (P < 0.05). In conclusion, acute experimental restriction of UES opening by external cricoid pressure manifests the pressure characteristics of increased resistance to UES transsphincteric flow observed clinically without affecting the pharyngeal peristaltic contractile function. PMID:27198193

  20. Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.

    Directory of Open Access Journals (Sweden)

    Mehrdad Arjomandi

    Full Text Available Osteopontin (OPN is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.To determine whether secreted OPN (sOPN is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects. All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.These results suggest that sOPN in human airways (1 undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2 is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3 may contribute to recruitment or survival of alveolar macrophages.

  1. Effect of Head and Tongue Posture on the Pharyngeal Airway Dimensions and Morphology in Three-Dimensional Imaging: a Systematic Review

    DEFF Research Database (Denmark)

    Gurani, Sirwan Fernandez; Di Carlo, Gabriele; Cattaneo, Paolo M

    2016-01-01

    OBJECTIVES: Natural head position is recommended to be optimal at cone-beam computed tomography acquisition. For standardization purposes in control of treatment outcome, it is clinically relevant to discuss, if a change of posture from natural head position may have an effect on the pharyngeal...

  2. Airway basement membrane perimeter in human airways is not a constant; potential implications for airway remodeling in asthma.

    Science.gov (United States)

    McParland, Brent E; Paré, Peter D; Johnson, Peter R A; Armour, Carol L; Black, Judith L

    2004-08-01

    Many studies that demonstrate an increase in airway smooth muscle in asthmatic patients rely on the assumption that bronchial internal perimeter (P(i)) or basement membrane perimeter (P(bm)) is a constant, i.e., not affected by fixation pressure or the degree of smooth muscle shortening. Because it is the basement membrane that has been purported to be the indistensible structure, this study examines the assumption that P(bm) is not affected by fixation pressure. P(bm) was determined for the same human airway segment (n = 12) fixed at distending pressures of 0 cmH(2)O and 21 cmH(2)O in the absence of smooth muscle tone. P(bm) for the segment fixed at 0 cmH(2)O was determined morphometrically, and the P(bm) for the same segment, had the segment been fixed at 21 cmH(2)O, was predicted from knowing the luminal volume and length of the airway when distended to 21 cmH(2)O (organ bath-derived P(i)). To ensure an accurate transformation of the organ bath-derived P(i) value to a morphometry-derived P(bm) value, had the segment been fixed at 21 cmH(2)O, the relationship between organ bath-derived P(i) and morphometry-derived P(bm) was determined for five different bronchial segments distended to 21 cmH(2)O and fixed at 21 cmH(2)O (r(2) = 0.99, P < 0.0001). Mean P(bm) for bronchial segments fixed at 0 cmH(2)O was 9.4 +/- 0.4 mm, whereas mean predicted P(bm), had the segments been fixed at 21 cmH(2)O, was 14.1 +/- 0.5 mm (P < 0.0001). This indicates that P(bm) is not a constant when isolated airway segments without smooth muscle tone are fixed distended to 21 cmH(2)O. The implication of these results is that the increase in smooth muscle mass in asthma may have been overestimated in some previous studies. Therefore, further studies are required to examine the potential artifact using whole lungs with and without abolition of airway smooth muscle tone and/or inflation.

  3. Characterizing adult human nasal airway dimensions

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Griffith, W.C.

    1994-01-01

    Respiratory tract models used in calculating radiation dose from exposure to inhaled radioactive aerosols have only recently focused attention on the importance of the nasal airways (NAs). Because the NAs are the first tissues of the respiratory tract available for aerosol deposition in normally nose-breathing people, any deposition of aerosol in this anatomical structure will reduce the amounts available to be deposited in the remainder of the respiratory tract. Thus, uncertainties in estimating the deposition fractions in the NAs will propagate throughout the remainder of the respiratory tract, creating errors in the calculated dose estimates. Additionally, there is evidence that the NAs are also at risk for induction of cancer from exposure to certain occupational aerosols such as wood dust, leather dust, chromium, and nickel. The purpose of this investigation was to conduct an anatomical study to assess the variabilities in NA dimensions

  4. Transport and deposition of cohesive pharmaceutical powders in human airway

    Directory of Open Access Journals (Sweden)

    Wang Yuan

    2017-01-01

    Full Text Available Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD and discrete element method (DEM. The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

  5. Transport and deposition of cohesive pharmaceutical powders in human airway

    Science.gov (United States)

    Wang, Yuan; Chu, Kaiwei; Yu, Aibing

    2017-06-01

    Pharmaceutical powders used in inhalation therapy are in the size range of 1-5 microns and are usually cohesive. Understanding the cohesive behaviour of pharmaceutical powders during their transportation in human airway is significant in optimising aerosol drug delivery and targeting. In this study, the transport and deposition of cohesive pharmaceutical powders in a human airway model is simulated by a well-established numerical model which combines computational fluid dynamics (CFD) and discrete element method (DEM). The van der Waals force, as the dominant cohesive force, is simulated and its influence on particle transport and deposition behaviour is discussed. It is observed that even for dilute particle flow, the local particle concentration in the oral to trachea region can be high and particle aggregation happens due to the van der Waals force of attraction. It is concluded that the deposition mechanism for cohesive pharmaceutical powders, on one hand, is dominated by particle inertial impaction, as proven by previous studies; on the other hand, is significantly affected by particle aggregation induced by van der Waals force. To maximum respiratory drug delivery efficiency, efforts should be made to avoid pharmaceutical powder aggregation in human oral-to-trachea airway.

  6. Airway surface irregularities promote particle diffusion in the human lung

    International Nuclear Information System (INIS)

    Martonen, T.; North Carolina Univ., Chapel Hill, NC; Zhang, Z.; Yang, Y.; Bottei, G.

    1995-01-01

    Current NCRP and ICRP particle deposition models employed in risk assessment analyses treat the airways of the human lung as smooth-walled tubes. However, the upper airways of the tracheobronchial (TB) tree are line with cartilaginous rings. Recent supercomputer simulations of in vivo conditions (cited herein), where cartilaginous ring morphologies were based upon fibre-optic bronchoscope examinations, have clearly demonstrated their profound effects upon fluid dynamics. A physiologically based analytical model of fluid dynamics is presented, focusing upon applications to particle diffusion within the TB tree. The new model is the first to describe particle motion while simultaneously simulating effects of wall irregularities, entrance conditions and tube curvatures. This study may explain the enhanced deposition by particle diffusion detected in replica case experiments and have salient implications for the clinically observed preferential distributions of bronchogenic carcinomas associated with inhaled radionuclides. (author)

  7. Human eosinophil–airway smooth muscle cell interactions

    Directory of Open Access Journals (Sweden)

    J. Margaret Hughes

    2000-01-01

    Full Text Available Eosinophils are present throughout the airway wall of asthmatics. The nature of the interaction between human airway smooth muscle cells (ASMC and eosinophils was investigated in this study. We demonstrated, using light microscopy, that freshly isolated eosinophils from healthy donors rapidly attach to ASMC in vitro. Numbers of attached eosinophils were highest at 2 h, falling to 50% of maximum by 20 h. Eosinophil attachment at 2 h was reduced to 72% of control by anti-VCAM-1, and to 74% at 20 h by anti-ICAM-1. Pre-treatment of ASMC for 24 h with TNF-α, 10 nM, significantly increased eosinophil adhesion to 149 and 157% of control after 2 and 20 h. These results provide evidence that eosinophil interactions with ASMC involve VCAM-1 and ICAM-1 and are modulated by TNF-α.

  8. Regional aerosol deposition in human upper airways

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1991-11-01

    During the current report experimental studies of upper respiratory deposition of radon progeny aerosols and stimulant aerosols were carried out in replicate casts of nasal and oral passages of adults and children. Additionally, preliminary studies of nasal passage deposition of unattached Po{sup 218} particles was carried out in four human subjects. Data on nasal inspiratory deposition in replicate models of adults and infants from three collaborating laboratories were compared and a best-fit curve of deposition efficiency for both attached and unattached particles was obtained, showing excellent inter-laboratory agreement. This curve demonstrates that nasal inspiratory deposition of radon progeny is weakly dependent upon flow rate over physiologically realistic ranges of flow, does not show a significant age effect, and is relatively independent of nasal passage dimensions for a given age range. Improved replicate models of the human adult oral passage extending to the mid-trachea were constructed for medium and higher flow mouth breathing states; these models were used to assess the deposition of unattached Po{sup 218} particles during oronasal breathing in the oral passage and demonstrated lower deposition efficiency than the nasal passage. Measurements of both Po{sup 218} particle and attached fraction particle size deposition were performed in replicate nasal passage of a four week old infant. 5 refs., 1 fig.

  9. Regional aerosol deposition in human upper airways

    International Nuclear Information System (INIS)

    Swift, D.L.

    1991-01-01

    During the current report experimental studies of upper respiratory deposition of radon progeny aerosols and stimulant aerosols were carried out in replicate casts of nasal and oral passages of adults and children. Additionally, preliminary studies of nasal passage deposition of unattached Po 218 particles was carried out in four human subjects. Data on nasal inspiratory deposition in replicate models of adults and infants from three collaborating laboratories were compared and a best-fit curve of deposition efficiency for both attached and unattached particles was obtained, showing excellent inter-laboratory agreement. This curve demonstrates that nasal inspiratory deposition of radon progeny is weakly dependent upon flow rate over physiologically realistic ranges of flow, does not show a significant age effect, and is relatively independent of nasal passage dimensions for a given age range. Improved replicate models of the human adult oral passage extending to the mid-trachea were constructed for medium and higher flow mouth breathing states; these models were used to assess the deposition of unattached Po 218 particles during oronasal breathing in the oral passage and demonstrated lower deposition efficiency than the nasal passage. Measurements of both Po 218 particle and attached fraction particle size deposition were performed in replicate nasal passage of a four week old infant. 5 refs., 1 fig

  10. Pre-pharyngeal swallow effects of recurrent laryngeal nerve lesion on bolus shape and airway protection in an infant pig model

    Science.gov (United States)

    Gould, Francois D. H.; Yglesias, B.; Ohlemacher, J.; German, R. Z.

    2016-01-01

    Recurrent laryngeal nerve (RLN) damage in infants leads to increased dysphagia and aspiration pneumonia. Recent work has shown that intra oral transport and swallow kinematics change following RLN lesion, suggesting potential changes in bolus formation prior to the swallow. In this study we used geometric morphometrics to understand the effect of bolus shape on penetration and aspiration in infants with and without RLN lesion. We hypothesized 1) that geometric bolus properties are related to airway protection outcomes and 2) that in infants with RLN lesion, the relationship between geometric bolus properties and dysphagia is changed. In five infant pigs, dysphagia in 188 swallows was assessed using the Infant Mammalian Penetration Aspiration Score (IMPAS). Using images from high-speed VFSS, bolus shape, bolus area, and tongue outline were quantified digitally. Bolus shape was analyzed using elliptical Fourier analysis, and tongue outline using polynomial curve fitting. Despite large inter-individual differences, significant within individual effects of bolus shape and bolus area on airway protection exist. The relationship between penetration-aspiration score and both bolus area and shape changed post lesion. Tongue shape differed between pre and post lesion swallows, and between swallows with different IMPAS scores. Bolus shape and area affect airway protection outcomes. RLN lesion changes that relationship, indicating that proper bolus formation and control by the tongue requires intact laryngeal sensation. The impact of RLN lesion on dysphagia is pervasive. PMID:27873091

  11. Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.

    Directory of Open Access Journals (Sweden)

    Margaret A Scull

    2009-05-01

    Full Text Available Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE, we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C, avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C. These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C, rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2 or A/PR/8/34 (H1N1 genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA and neuraminidase (NA from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and

  12. Dysphagia associated with presumed pharyngeal dysfunction in 16 neonatal foals.

    Science.gov (United States)

    Holcombe, S J; Hurcombe, S D; Barr, B S; Schott, H C

    2012-02-01

    Dysphagia due to pharyngeal dysfunction occurs in human neonates and is associated with prematurity and hypoxic episodes. This syndrome probably occurs in neonatal foals but has not been reported. The objectives of this study were to describe 1) a series of neonatal foals with dysphagia due to pharyngeal dysfunction; 2) the progression, treatment and resolution of the dysphagia; 3) the comorbidities; and 4) the prognosis for life and athleticism for affected foals. Records from 3 referral equine hospitals were reviewed from neonatal foals with dysphagia of pharyngeal origin. Inclusion criteria were a normal to strong suckle, dysphagia evidenced by milk at the nostrils after nursing the dam, and endoscopic examination of the airway. Foals with mechanical reasons for dysphagia, botulism or hyperkalaemic periodic paralysis were not included. Sixteen neonatal foals qualified for the study. Eight (50%) were premature and/or diagnosed with hypoxic ischaemic encephalopathy. Twelve (75%) had aspiration pneumonia. Fifteen foals were discharged alive from the hospital, nursing the mare with no evidence of dysphagia (n = 14), or mild dysphagia (n = 1), a mean +/- s.d. of 7 +/- 6 days (median = 6.3 days, range 0-22 days) after hospital admission. One foal was subjectedto euthanasia in hospital. Follow-up nformation was available for 14 animals. Thirteen of 16 (81%) were alive and included one yearling and 12 horses >2 years old. Seven of the 14 (50%) were racing, training or in work, and 6 horses were pets, breeding animals or had unknown athletic status. Two had laryngeal deficits. One foal was subjected to euthanasia within weeks of discharge from the hospital due to aspiration pneumonia. Dysphagia related to pharyngeal dysfunction occurs in equine neonates and can resolve, but may require days to weeks of supportive care. Prognosis for life is favourable and for athleticism fair.

  13. Unsteady flow characteristics through a human nasal airway.

    Science.gov (United States)

    Lee, Jong-Hoon; Na, Yang; Kim, Sung-Kyun; Chung, Seung-Kyu

    2010-07-31

    Time-dependent characteristics of the flow in a human nasal airway constructed from the CT image of a healthy volunteer were investigated using a computational fluid dynamics (CFD) technique. To capture the time-varying nature of the flow as well as pressure and temperature fields, the large eddy simulation (LES) technique instead of the RANS (Reynolds Averaged Navier-Stokes) approach was adopted. To make the present analysis more relevant to a real human breathing cycle, the flow was designed to be induced by the pressure difference and the time-varying pressure at the end of trachea was described to reproduce the flow rate data from the measurement. Comparison of the present results with those of typical steady simulations showed that the difference in flow characteristics is magnified in the expiration phase. This fact may suggest that the inertial effect associated with unsteady flow is more important during the expiration period. Also, the fact that the distribution of the flow rate in a given cross-section of the airway changes significantly with time implies the importance of unsteady data for clinical decision. The wall shear stress was found to have relatively high values at the locations near nasopharynx and larynx but the magnitude changes with time during the whole respiratory cycle. Analysis of the temperature field showed that most of the temperature change occurs in the nasal cavity when the air is incoming and thus, the nasal cavity acts as a very efficient heat exchanger during an inspiration period. Copyright 2010 Elsevier B.V. All rights reserved.

  14. Human apolipoprotein E genotypes differentially modify house dust mite-induced airway disease in mice

    DEFF Research Database (Denmark)

    Yao, Xianglan; Dai, Cuilian; Fredriksson, Karin

    2012-01-01

    Apolipoprotein E (apoE) is an endogenous negative regulator of airway hyperreactivity (AHR) and mucous cell metaplasia in experimental models of house dust mite (HDM)-induced airway disease. The gene encoding human apoE is polymorphic, with three common alleles (e2, e3, and e4) reflecting single ...

  15. Influence of horse stable environment on human airways.

    Science.gov (United States)

    Elfman, Lena; Riihimäki, Miia; Pringle, John; Wålinder, Robert

    2009-05-25

    Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. The horse stable environment and stable-workers (n = 13) in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-beta-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Biomarkers involved in the development of airway diseases have been studied in relation to environmental exposure levels in equine stables. Respirable dust and 1

  16. Influence of horse stable environment on human airways

    Directory of Open Access Journals (Sweden)

    Pringle John

    2009-05-01

    Full Text Available Abstract Background Many people spend considerable amount of time each day in equine stable environments either as employees in the care and training of horses or in leisure activity. However, there are few studies available on how the stable environment affects human airways. This study examined in one horse stable qualitative differences in indoor air during winter and late summer conditions and assessed whether air quality was associated with clinically detectable respiratory signs or alterations to selected biomarkers of inflammation and lung function in stable personnel. Methods The horse stable environment and stable-workers (n = 13 in one stable were investigated three times; first in the winter, second in the interjacent late summer and the third time in the following winter stabling period. The stable measurements included levels of ammonia, hydrogen sulphide, total and respirable dust, airborne horse allergen, microorganisms, endotoxin and glucan. The stable-workers completed a questionnaire on respiratory symptoms, underwent nasal lavage with subsequent analysis of inflammation markers, and performed repeated measurements of pulmonary function. Results Measurements in the horse stable showed low organic dust levels and high horse allergen levels. Increased viable level of fungi in the air indicated a growing source in the stable. Air particle load as well as 1,3-β-glucan was higher at the two winter time-points, whereas endotoxin levels were higher at the summer time-point. Two stable-workers showed signs of bronchial obstruction with increased PEF-variability, increased inflammation biomarkers relating to reported allergy, cold or smoking and reported partly work-related symptoms. Furthermore, two other stable-workers reported work-related airway symptoms, of which one had doctor's diagnosed asthma which was well treated. Conclusion Biomarkers involved in the development of airway diseases have been studied in relation to

  17. DEPOSITION DISTRICUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE.

    Science.gov (United States)

    DEPOSITION DISTRIBUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE. Chong S. Kim*, USEPA National Health and Environmental Effects Research Lab. RTP, NC 27711; Z. Zhang and C. Kleinstreuer, Department of Mechanical and Aerospace Engineering, North C...

  18. Detonation Nanodiamond Toxicity in Human Airway Epithelial Cells Is Modulated by Air Oxidation

    Science.gov (United States)

    Detonational nanodiamonds (DND), a nanomaterial with an increasing range of industrial and biomedical applications, have previously been shown to induce a pro-inflammatory response in cultured human airway epithelial cells (HAEC). We now show that surface modifications induced by...

  19. Expression and function of human hemokinin-1 in human and guinea pig airways.

    Science.gov (United States)

    Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Risse, Paul-André; Sage, Edouard; Advenier, Charles; Devillier, Philippe

    2010-10-07

    Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  20. Expression and function of human hemokinin-1 in human and guinea pig airways

    Directory of Open Access Journals (Sweden)

    Sage Edouard

    2010-10-01

    Full Text Available Abstract Background Human hemokinin-1 (hHK-1 and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. Methods RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. Results In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. Conclusions We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  1. Morphology and Three-Dimensional Inhalation Flow in Human Airways in Healthy and Diseased Subjects

    Science.gov (United States)

    Van de Moortele, Tristan

    We investigate experimentally the relation between anatomical structure and respiratory function in healthy and diseased airways. Computed Tomography (CT) scans of human lungs are analyzed from the data base of a large multi-institution clinical study on Chronic Obstructive Pulmonary Disease (COPD). Through segmentation, the 3D volumes of the airways are determined at total lung capacity. A geometric analysis provides data on the morphometry of the airways, including the length and diameter of branches, the child-to-parent diameter ratio, and branching angles. While several geometric parameters are confirmed to match past studies for healthy subjects, previously unreported trends are reported on the length of branches. Specifically, in most dichotomous airway bifurcation, the branch of smaller diameter tends to be significantly longer than the one of larger diameter. Additionally, the branch diameter tends to be smaller in diseased airways than in healthy airways up to the 7th generation of bronchial branching. 3D fractal analysis is also performed on the airway volume. Fractal dimensions of 1.89 and 1.83 are found for healthy non-smokers and declining COPD subjects, respectively, furthering the belief that COPD (and lung disease in general) significantly affects the morphometry of the airways already in early stages of the disease. To investigate the inspiratory flow, 3D flow models of the airways are generated using Computer Aided Design (CAD) software and 3D printed. Using Magnetic Resonance Velocimetry (MRV), 3-component 3D flow fields are acquired for steady inhalation at Reynolds number Re 2000 defined at the trachea. Analysis of the flow data reveals that diseased subjects may experience greater secondary flow strength in their conducting airways, especially in deeper generations.

  2. Patient-specific three-dimensional explant spheroids derived from human nasal airway epithelium

    DEFF Research Database (Denmark)

    Marthin, June Kehlet; Stevens, Elizabeth Munkebjerg; Larsen, Lars Allan

    2017-01-01

    BACKGROUND: Three-dimensional explant spheroid formation is an ex vivo technique previously used in studies of airway epithelial ion and water transport. Explanted cells and sheets of nasal epithelium form fully differentiated spheroids enclosing a partly fluid-filled lumen with the ciliated apical...... surface facing the outside and accessible for analysis of ciliary function. METHODS: We performed a two-group comparison study of ciliary beat pattern and ciliary beat frequency in spheroids derived from nasal airway epithelium in patients with primary ciliary dyskinesia (PCD) and in healthy controls...... in the investigation of pathophysiological aspects and drug effects in human nasal airway epithelium....

  3. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

  4. Anti-inflammatory effects of embelin in A549 cells and human asthmatic airway epithelial tissues.

    Science.gov (United States)

    Lee, In-Seung; Cho, Dong-Hyuk; Kim, Ki-Suk; Kim, Kang-Hoon; Park, Jiyoung; Kim, Yumi; Jung, Ji Hoon; Kim, Kwanil; Jung, Hee-Jae; Jang, Hyeung-Jin

    2018-02-01

    Allergic asthma is the most common type in asthma, which is defined as a chronic inflammatory disease of the lung. In this study, we investigated whether embelin (Emb), the major component of Ardisia japonica BL. (AJB), exhibits anti-inflammatory effects on allergic asthma via inhibition of NF-κB activity using A549 cells and asthmatic airway epithelial tissues. Inflammation was induced in A549 cells, a human airway epithelial cell line, by IL-1β (10 ng/ml) treatment for 4 h. The effects of Emb on NF-κB activity and COX-2 protein expression in inflamed airway epithelial cells and human asthmatic airway epithelial tissues were analyzed via western blot. The secretion levels of NF-κB-mediated cytokines/chemokines, including IL-4, 6, 9, 13, TNF-α and eotaxin, were measured by a multiplex assay. Emb significantly blocked NF-κB activity in IL-1β-treated A549 cells and human asthmatic airway epithelial tissues. COX-2 expression was also reduced in both IL-1β-treated A549 cells and asthmatic tissues Emb application. Emb significantly reduced the secretion of IL-4, IL-6 and eotaxin in human asthmatic airway epithelial tissues by inhibiting activity of NF-κB. The results of this study suggest that Emb may be used as an anti-inflammatory agent via inhibition of NF-κB and related cytokines.

  5. Stochastic model of radon daughter deposition and clearance in human bronchial airways

    International Nuclear Information System (INIS)

    Hofmann, W.

    1996-01-01

    Morphometric measurements of human airway casts have repealed that the human bronchial tree is an asymmetrically dividing network, exhibiting individual variations of airway dimensions within a given airway generation Thus, a statistical correlation exists between the linear dimensions of a given parent airway and those of the asymmetrically dividing daughter branches. This statistical relationship, however, is constrained by correlations among various geometrical parameters. i.e., the human lung is not a fully stochastic system. From a statistical analysis of these morphometric data, the following geometrical parameters could be obtained for each airway generation or bifurcation: (i) probability distributions for diameters and lengths, ratios of parent cross section to the combined cross section of both daughters, ratios of major to minor daughter diameters, and branching angles for major and minor branches; (ii) correlations of diameters and lengths; and (iii) the probability of terminating the bronchial region as a function of both diameter and generation number. Since the original lung morphometry refers to total lung capacity, airway diameters and lengths were scaled down to functional residual capacity. (author)

  6. Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

    Science.gov (United States)

    Pickles, Raymond J

    2013-01-01

    Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

  7. Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

    Energy Technology Data Exchange (ETDEWEB)

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

  8. Streptococcal acute pharyngitis

    Directory of Open Access Journals (Sweden)

    Lais Martins Moreira Anjos

    2014-07-01

    Full Text Available Acute pharyngitis/tonsillitis, which is characterized by inflammation of the posterior pharynx and tonsils, is a common disease. Several viruses and bacteria can cause acute pharyngitis; however, Streptococcus pyogenes (also known as Lancefield group A β-hemolytic streptococci is the only agent that requires an etiologic diagnosis and specific treatment. S. pyogenes is of major clinical importance because it can trigger post-infection systemic complications, acute rheumatic fever, and post-streptococcal glomerulonephritis. Symptom onset in streptococcal infection is usually abrupt and includes intense sore throat, fever, chills, malaise, headache, tender enlarged anterior cervical lymph nodes, and pharyngeal or tonsillar exudate. Cough, coryza, conjunctivitis, and diarrhea are uncommon, and their presence suggests a viral cause. A diagnosis of pharyngitis is supported by the patient's history and by the physical examination. Throat culture is the gold standard for diagnosing streptococcus pharyngitis. However, it has been underused in public health services because of its low availability and because of the 1- to 2-day delay in obtaining results. Rapid antigen detection tests have been used to detect S. pyogenes directly from throat swabs within minutes. Clinical scoring systems have been developed to predict the risk of S. pyogenes infection. The most commonly used scoring system is the modified Centor score. Acute S. pyogenes pharyngitis is often a self-limiting disease. Penicillins are the first-choice treatment. For patients with penicillin allergy, cephalosporins can be an acceptable alternative, although primary hypersensitivity to cephalosporins can occur. Another drug option is the macrolides. Future perspectives to prevent streptococcal pharyngitis and post-infection systemic complications include the development of an anti-Streptococcus pyogenes vaccine.

  9. Polystyrene nanoparticles activate ion transport in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    McCarthy J

    2011-06-01

    Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

  10. Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Davis, C.W.; Boucher, R.C.

    1994-01-01

    exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties......- secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall....

  11. Cigarette Smoke and Estrogen Signaling in Human Airway Smooth Muscle

    Directory of Open Access Journals (Sweden)

    Venkatachalem Sathish

    2015-06-01

    Full Text Available Aims: Cigarette smoke (CS in active smokers and second-hand smoke exposure exacerbate respiratory disorders such as asthma and chronic bronchitis. While women are known to experience a more asthmatic response to CS than emphysema in men, there is limited information on the mechanisms of CS-induced airway dysfunction. We hypothesize that CS interferes with a normal (protective bronchodilatory role of estrogens, thus worsening airway contractility. Methods: We tested effects of cigarette smoke extract (CSE on 17β-estradiol (E2 signaling in enzymatically-dissociated bronchial airway smooth muscle (ASM obtained from lung samples of non-smoking female patients undergoing thoracic surgery. Results: In fura-2 loaded ASM cells, CSE increased intracellular calcium ([Ca2+]i responses to 10µM histamine. Acute exposure to physiological concentrations of E2 decreased [Ca2+]i responses. However, in 24h exposed CSE cells, although expression of estrogen receptors was increased, the effect of E2 on [Ca2+]i was blunted. Acute E2 exposure also decreased store-operated Ca2+ entry and inhibited stromal interaction molecule 1 (STIM1 phosphorylation: effects blunted by CSE. Acute exposure to E2 increased cAMP, but less so in 24h CSE-exposed cells. 24h CSE exposure increased S-nitrosylation of ERα. Furthermore, 24h CSE-exposed bronchial rings showed increased bronchoconstrictor agonist responses that were not reduced as effectively by E2 compared to non-CSE controls. Conclusion: These data suggest that CS induces dysregulation of estrogen signaling in ASM, which could contribute to increased airway contractility in women exposed to CS.

  12. Beryllium concentration in pharyngeal tonsils in children

    Directory of Open Access Journals (Sweden)

    Ewa Nogaj

    2014-06-01

    Full Text Available Power plant dust is believed to be the main source of the increased presence of the element beryllium in the environment which has been detected in the atmospheric air, surface waters, groundwater, soil, food, and cigarette smoke. In humans, beryllium absorption occurs mainly via the respiratory system. The pharyngeal tonsils are located on the roof of the nasopharynx and are in direct contact with dust particles in inhaled air. As a result, the concentration levels of beryllium in the pharyngeal tonsils are likely to be a good indicator of concentration levels in the air. The presented study had two primary aims: to investigate the beryllium concentration in pharyngeal tonsils in children living in southern Poland, and the appropriate reference range for this element in children’s pharyngeal tonsils. Pharyngeal tonsils were extracted from a total of 379 children (age 2–17 years, mean 6.2 ± 2.7 years living in southern Poland. Tonsil samples were mineralized in a closed cycle in a pressure mineralizer PDS 6, using 65% spectrally pure nitric acid. Beryllium concentration was determined using the ICP-AES method with a Perkin Elmer Optima 5300DVTM. The software Statistica v. 9 was used for the statistical analysis. It was found that girls had a significantly greater beryllium concentration in their pharyngeal tonsils than boys. Beryllium concentration varies greatly, mostly according to the place of residence. Based on the study results, the reference value for beryllium in pharyngeal tonsils of children is recommended to be determined at 0.02–0.04 µg/g.

  13. Overexpression of functional TrkA receptors after internalisation in human airway smooth muscle cells.

    Science.gov (United States)

    Freund-Michel, Véronique; Frossard, Nelly

    2008-10-01

    Trafficking of the TrkA receptor after stimulation by NGF is of emerging importance in structural cells in the context of airway inflammatory diseases. We have recently reported the expression of functional TrkA receptors in human airway smooth muscle cells (HASMC). We have here studied the TrkA trafficking mechanisms in these cells. TrkA disappearance from the cell membrane was induced within 5 min of NGF (3pM) stimulation. Co-immunoprecipitation of clathrin-TrkA was revealed, and TrkA internalisation inhibited either by clathrin inhibitors or by siRNA inducing downregulation of endogenous clathrin. TrkA internalised receptors were totally degraded in lysosomes, with no recycling phenomenon. Newly synthesized TrkA receptors were thereafter re-expressed at the cell membrane within 10 h. TrkA re-synthesis was inhibited by blockade of clathrin-dependent internalisation, but not of TrkA receptors lysosomal degradation. Finally, we observed that NGF multiple stimulations progressively increased TrkA expression in HASMC, which was associated with an increase in NGF/TrkA-dependent proliferation. In conclusion, we show here the occurrence of clathrin-dependent TrkA internalisation and lysosomal degradation in the airway smooth muscle, followed by upregulated re-synthesis of functional TrkA receptors and increased proliferative effect in the human airway smooth muscle. This may have pathophysiological consequences in airway inflammatory diseases.

  14. Simulation of size-dependent aerosol deposition in a realistic model of the upper human airways

    NARCIS (Netherlands)

    Frederix, E.M.A.; Kuczaj, Arkadiusz K.; Nordlund, Markus; Belka, M.; Lizal, F.; Elcner, J.; Jicha, M.; Geurts, Bernardus J.

    An Eulerian internally mixed aerosol model is used for predictions of deposition inside a realistic cast of the human upper airways. The model, formulated in the multi-species and compressible framework, is solved using the sectional discretization of the droplet size distribution function to

  15. T cell subsets in human airways prior to and following endobronchial administration of endotoxin

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C

    2015-01-01

    BACKGROUND AND OBJECTIVES: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to deter...

  16. TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS

    Science.gov (United States)

    TRANSPORT AND DEPOSITION OF NANO-SIZE PARTICLES IN THE UPPER HUMAN RESPIRATORY AIRWAYS. Zhe Zhang*, Huawei Shi, Clement Kleinstreuer, Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910; Chong S. Kim, National Health and En...

  17. Common features of sexual dimorphism in the cranial airways of different human populations.

    Science.gov (United States)

    Bastir, Markus; Godoy, Paula; Rosas, Antonio

    2011-11-01

    Sexual dimorphism in the human craniofacial system is an important feature of intraspecific variation in recent and fossil humans. Although several studies have reported different morphological patterns of sexual dimorphism in different populations, this study searches for common morphological aspects related to functional anatomy of the respiratory apparatus. 3D geometric morphometrics were used to test the hypothesis that due to higher daily energy expenditure and associated greater respiratory air consumption as well as differences in body composition, males should have absolutely and relatively greater air passages in the bony cranial airways than females. We measured 25 3D landmarks in five populations (N = 212) of adult humans from different geographic regions. Male average cranial airways were larger in centroid sizes than female ones. Males tended to show relatively taller piriform apertures and, more consistently, relatively taller internal nasal cavities and choanae than females. Multivariate regressions and residual analysis further indicated that after standardizing to the same size, males still show relatively larger airway passages than females. Because the dimensions of the choanae are limiting factors for air transmission towards the noncranial part of the respiratory system, the identified sex-specific differences in cranial airways, possibly shared among human populations, may be linked with sex-specific differences in body size, composition, and energetics. These findings may be important to understanding trends in hominin facial evolution. Copyright © 2011 Wiley-Liss, Inc.

  18. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping, E-mail: wpxie@njmu.edu.cn; Wang, Hong, E-mail: hongwang@njmu.edu.cn

    2015-08-15

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation and migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that Ipt

  19. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Hsu-Chi; Swift, D.L. [John Hopkins Univ., Baltimore, MD (United States); Simpson, S.Q. [Univ. of New Mexico, Albuquerque, NM (United States)] [and others

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  20. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    International Nuclear Information System (INIS)

    Yeh, Hsu-Chi; Swift, D.L.; Simpson, S.Q.

    1995-01-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 μm particles in 10 human subjects and in our preliminary studies using 0.004-0.15 μm particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 μm with the nasal dimensions of each subject

  1. Simulation of deposition and activity distribution of radionuclides in human airways

    International Nuclear Information System (INIS)

    Farkas, A.; Balashazy, I.; Szoke, I.; Hofmann, W.; Golser, R.

    2002-01-01

    The aim of our research activities is the modelling of the biological processes related to the development of lung cancer at the large central-airways observed in the case of uranium miners caused by the inhalation of radionuclides (especially alpha-emitting radon decay products). Statistical data show that at the uranium miners the lung cancer has developed mainly in the 3-4.-5. airway generations and especially in the right upper lobe. Therefore, it is rather important to study the physical and biological effects in this section of the human airways to find relations between the radiation dose and the adverse health effects. These results may provide useful information about the validity or invalidity of the currently used LNT (Linear-No-Threshold) dose-effect hypothesis at low doses

  2. Human airway organoid engineering as a step toward lung regeneration and disease modeling.

    Science.gov (United States)

    Tan, Qi; Choi, Kyoung Moo; Sicard, Delphine; Tschumperlin, Daniel J

    2017-01-01

    Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

    Science.gov (United States)

    Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

    2011-09-01

    Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

  4. Hold your horses: A comparison of human laryngomalacia with analogous equine airway pathology.

    Science.gov (United States)

    Lawrence, Rachael J; Butterell, Matthew J; Constable, James D; Daniel, Matija

    2018-02-01

    Laryngomalacia is the most common cause of stridor in infants. Dynamic airway collapse is also a well-recognised entity in horses and an important cause of surgical veterinary intervention. We compare the aetiology, clinical features and management of human laryngomalacia with equine dynamic airway collapse. A structured review of the PubMed, the Ovid Medline and the Cochrane Collaboration databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Systemic Reviews). There are numerous equine conditions that cause dynamic airway collapse defined specifically by the anatomical structures involved. Axial Deviation of the Aryepiglottic Folds (ADAF) is the condition most clinically analogous to laryngomalacia in humans, and is likewise most prevalent in the immature equine airway. Both conditions are managed either conservatively, or if symptoms require it, with surgical intervention. The operative procedures performed for ADAF and laryngomalacia are technically comparable. Dynamic collapse of the equine larynx, especially ADAF, is clinically similar to human laryngomalacia, and both are treated in a similar fashion. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Oxytetracycline Inhibits Mucus Secretion and Inflammation in Human Airway Epithelial Cells.

    Science.gov (United States)

    Shah, Said Ahmad; Ishinaga, Hajime; Takeuchi, Kazuhiko

    2017-01-01

    Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 μg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1β gene expression and IL-1β protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases. © 2017 S. Karger AG, Basel.

  6. GM-CSF production from human airway smooth muscle cells is potentiated by human serum

    Directory of Open Access Journals (Sweden)

    Maria B. Sukkar

    2000-01-01

    Full Text Available Recent evidence suggests that airway smooth muscle cells (ASMC actively participate in the airway inflammatory process in asthma. Interleukin–1β (IL–1β and tumour necrosis factor–α (TNF–α induce ASMC to release inflammatory mediators in vitro. ASMC mediator release in vivo, however, may be influenced by features of the allergic asthmatic phenotype. We determined whether; (1 allergic asthmatic serum (AAS modulates ASMC mediator release in response to IL–1β and TNF–α, and (2 IL–1β/TNF–α prime ASMC to release mediators in response to AAS. IL–5 and GMCSF were quantified by ELISA in culture supernatants of; (1 ASMC pre-incubated with either AAS, non-allergic non-asthmatic serum (NAS or MonomedTM (a serum substitute and subsequently stimulated with IL–1β and TNF–α and (2 ASMC stimulated with IL–1β/TNF–α and subsequently exposed to either AAS, NAS or MonomedTM. IL-1g and TNF–α induced GM-CSF release in ASMC pre-incubated with AAS was not greater than that in ASMC pre-incubated with NAS or MonomedTM. IL–1β and TNF–α, however, primed ASMC to release GM-CSF in response to human serum. GM-CSF production following IL–1β/TNF–α and serum exposure (AAS or NAS was significantly greater than that following IL–1β /TNF–α and MonomedTM exposure or IL–1β/TNF–α exposure only. Whilst the potentiating effects of human serum were not specific to allergic asthma, these findings suggest that the secretory capacity of ASMC may be up-regulated during exacerbations of asthma, where there is evidence of vascular leakage.

  7. PHARYNGITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T.A. Polunina

    2011-01-01

    Full Text Available Inflammatory disease of the throat — is a widespread pathology in childhood. The complex treatment of pharyngitis often includes solutions for gargling, sprays, tablets for sucking, hard candy or lozenges containing a variety of anti-inflammatory components. Their use reduces the severity of pain and the time treatment, but does not preclude the use of anti-inflammatory drugs for systemic effects. Key words: pharyhgitis, sore throat, treatment, children (Pediatric Pharmacology. — 2011; 8 (5: 106–108.

  8. Fetal human airway smooth muscle cell production of leukocyte chemoattractants is differentially regulated by fluticasone.

    Science.gov (United States)

    Pearson, Helen; Britt, Rodney D; Pabelick, Christine M; Prakash, Y S; Amrani, Yassine; Pandya, Hitesh C

    2015-12-01

    Adult human airway smooth muscle (ASM) produce cytokines involved in recruitment and survival of leukocytes within airway walls. Cytokine generation by adult ASM is glucocorticoid-sensitive. Whether developing lung ASM produces cytokines in a glucocorticoid-sensitive fashion is unknown. Cultured fetal human ASM cells stimulated with TNF-α (0-20 ng/ml) were incubated with TNF-α receptor-blocking antibodies, fluticasone (1 and 100 nm), or vehicle. Supernatants and cells were assayed for the production of CCL5, CXCL10, and CXCL8 mRNA and protein and glucocorticoid receptor phosphorylation. CCL5, CXCL10, and CXCL8 mRNA and protein production by fetal ASM cell was significantly and dose-dependently following TNF-α treatment. Cytokine mRNA and protein production were effectively blocked by TNF-α R1 and R2 receptor neutralizing antibodies but variably inhibited by fluticasone. TNF-α-induced TNF-R1 and R2 receptor mRNA expression was only partially attenuated by fluticasone. Glucocorticoid receptor phosphorylation at serine (Ser) 211 but not at Ser 226 was enhanced by fluticasone. Production of CCL5, CXCL10, and CXCL8 by fetal ASM appears to involve pathways that are both qualitatively and mechanistically distinct to those described for adult ASM. The findings imply developing ASM has potential to recruit leukocyte into airways and, therefore, of relevance to childhood airway diseases.

  9. Regional aerosol deposition in human upper airways: Progress report, June 1, 1988--February 28, 1989

    International Nuclear Information System (INIS)

    Swift, D.L.

    1989-01-01

    The objective of this research program is to elucidate important factors which influence overall and local deposition of aerosols in the human airways above the trachea, including nasal airways, oral passage, pharynx and larynx. The intent is to develop information which can be used for exposure models for radon from unattached radon progeny (/approximately/1nm) up to 10 μm. Special emphasis is upon flow rate and airway dimensions as influenced by age and respiratory condition, as no experimental data presently exist for age-related deposition. Because of ethical and practical considerations associated with measuring aerosol deposition in children and difficulties of measuring local deposition in vivo, our experimental approach is to construct faithful replicate models of the airways for several ages of humans in which detailed studies of deposition can be carried out with well-characterized aerosols. Initial studies of overall deposition of ultrafine aerosols in an adult model have been carried out using replicate nasal passage models provided from this laboratory. These studies demonstrate a significant deposition percent for particle sizes approaching that of unattached radon progeny (40--50%), decreasing as particle size approaches 0.1 μm. Studies of the effect of flow rate indicate that higher deposition percent is realized at lower flow rate over the range from 4--60 lmin -1

  10. Oscillatory flow in the human airways from the mouth through several bronchial generations

    International Nuclear Information System (INIS)

    Banko, Andrew J.; Coletti, Filippo; Elkins, Christopher J.; Eaton, John K.

    2016-01-01

    Highlights: • Oscillatory flow in the human airways is studied experimentally. • The realistic anatomy is obtained from the CT scan of a healthy adult. • Integral parameters are calculated to quantify streamwise and lateral dispersion. • Flow in real human anatomy is qualitatively different from idealized models. - Abstract: The time-varying flow is studied experimentally in an anatomically accurate model of the human airways from the mouth through several generations of bronchial branching. The airway geometry is obtained from the CT scan of a healthy adult male of normal height and build. The three-component, three-dimensional mean velocity field is obtained throughout the entire model using phase-locked Magnetic Resonance Velocimetry. A pulsatile pump drives a sinusoidal waveform (inhalation and exhalation) with frequency and stroke-length such that the mean trachea Reynolds number at peak inspiration is 4200 and the Womersley number is 7. Integral parameters are defined to quantify the degree of velocity profile non-uniformity (related to axial dispersion) and secondary flow strength (lateral dispersion). It is found that the extrathoracic airways significantly modify the tracheal flow and that the flow at the first bifurcation is highly asymmetric. The effect of flow oscillation is to produce time dependent flow features which are asymmetric with respect to the acceleration and deceleration periods surrounding peak inhalation and exhalation. This is most pronounced in regions of separation and on the secondary flow structure, which are sensitive to local attributes of the real anatomy. This is reflected in the integral parameters, which behave non-monotonically between successive bronchial generations. In general, the measured oscillatory flow in a realistic anatomy confirms many trends derived from idealized models but also possesses qualitatively different large scale flow structures as compared to idealized representations of the upper airways.

  11. Computational Thermodynamics Analysis of Vaporizing Fuel Droplets in the Human Upper Airways

    Science.gov (United States)

    Zhang, Zhe; Kleinstreuer, Clement

    The detailed knowledge of air flow structures as well as particle transport and deposition in the human lung for typical inhalation flow rates is an important precursor for dosimetry-and-health-effect studies of toxic particles as well as for targeted drug delivery of therapeutic aerosols. Focusing on highly toxic JP-8 fuel aerosols, 3-D airflow and fluid-particle thermodynamics in a human upper airway model starting from mouth to Generation G3 (G0 is the trachea) are simulated using a user-enhanced and experimentally validated finite-volume code. The temperature distributions and their effects on airflow structures, fuel vapor deposition and droplet motion/evaporation are discussed. The computational results show that the thermal effect on vapor deposition is minor, but it may greatly affect droplet deposition in human airways.

  12. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Science.gov (United States)

    Wu, Qun; Jiang, Di; Minor, Maisha; Chu, Hong Wei

    2014-01-01

    The use of electronic cigarettes (e-cigarettes) is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV) infection. We examined the effects of e-cigarette liquid (e-liquid) on pro-inflammatory cytokine (e.g., IL-6) production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1) in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  13. Electronic cigarette liquid increases inflammation and virus infection in primary human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available The use of electronic cigarettes (e-cigarettes is rapidly increasing in the United States, especially among young people since e-cigarettes have been perceived as a safer alternative to conventional tobacco cigarettes. However, the scientific evidence regarding the human health effects of e-cigarettes on the lung is extremely limited. The major goal of our current study is to determine if e-cigarette use alters human young subject airway epithelial functions such as inflammatory response and innate immune defense against respiratory viral (i.e., human rhinovirus, HRV infection.We examined the effects of e-cigarette liquid (e-liquid on pro-inflammatory cytokine (e.g., IL-6 production, HRV infection and host defense molecules (e.g., short palate, lung, and nasal epithelium clone 1, SPLUNC1 in primary human airway epithelial cells from young healthy non-smokers. Additionally, we examined the role of SPLUNC1 in lung defense against HRV infection using a SPLUNC1 knockout mouse model. We found that nicotine-free e-liquid promoted IL-6 production and HRV infection. Addition of nicotine into e-liquid further amplified the effects of nicotine-free e-liquid. Moreover, SPLUNC1 deficiency in mice significantly increased lung HRV loads. E-liquid inhibited SPLUNC1 expression in primary human airway epithelial cells. These findings strongly suggest the deleterious health effects of e-cigarettes in the airways of young people. Our data will guide future studies to evaluate the impact of e-cigarettes on lung health in human populations, and help inform the public about potential health risks of e-cigarettes.

  14. Life-threatening systemic toxicity and airway compromise from a common European adder bite to the tongue

    DEFF Research Database (Denmark)

    Hoegberg, L C G; Jessen, C L; Lambertsen, K

    2009-01-01

    , pharyngeal and facial oedema compromised the airway, leading to respiratory failure, concomitant with circulatory failure related to hypoxaemia and systemic toxic effects. Acute tracheotomy secured the airway, and two doses of antivenom successfully treated the systemic, toxic effects. The reaction...

  15. Exposure to ozone modulates human airway protease/antiprotease balance contributing to increased influenza A infection.

    Directory of Open Access Journals (Sweden)

    Matthew J Kesic

    Full Text Available Exposure to oxidant air pollution is associated with increased respiratory morbidities and susceptibility to infections. Ozone is a commonly encountered oxidant air pollutant, yet its effects on influenza infections in humans are not known. The greater Mexico City area was the primary site for the spring 2009 influenza A H1N1 pandemic, which also coincided with high levels of environmental ozone. Proteolytic cleavage of the viral membrane protein hemagglutinin (HA is essential for influenza virus infectivity. Recent studies suggest that HA cleavage might be cell-associated and facilitated by the type II transmembrane serine proteases (TTSPs human airway trypsin-like protease (HAT and transmembrane protease, serine 2 (TMPRSS2, whose activities are regulated by antiproteases, such as secretory leukocyte protease inhibitor (SLPI. Based on these observations, we sought to determine how acute exposure to ozone may modulate cellular protease/antiprotease expression and function, and to define their roles in a viral infection. We utilized our in vitro model of differentiated human nasal epithelial cells (NECs to determine the effects of ozone on influenza cleavage, entry, and replication. We show that ozone exposure disrupts the protease/antiprotease balance within the airway liquid. We also determined that functional forms of HAT, TMPRSS2, and SLPI are secreted from human airway epithelium, and acute exposure to ozone inversely alters their expression levels. We also show that addition of antioxidants significantly reduces virus replication through the induction of SLPI. In addition, we determined that ozone-induced cleavage of the viral HA protein is not cell-associated and that secreted endogenous proteases are sufficient to activate HA leading to a significant increase in viral replication. Our data indicate that pre-exposure to ozone disrupts the protease/antiprotease balance found in the human airway, leading to increased influenza susceptibility.

  16. Direct numerical simulation of particle laden flow in a human airway bifurcation model

    International Nuclear Information System (INIS)

    Stylianou, Fotos S.; Sznitman, Josué; Kassinos, Stavros C.

    2016-01-01

    Highlights: • An anatomically realistic model of a human airway bifurcation is constructed. • Direct numerical simulations are used to study laminar and turbulent airflow. • Aerosol deposition in the bifurcation is studied with lagrangian particle tracking. • Carinal vortices forming during steady expiration are reported for the first time. • Stokes number determines deposition differences between inspiration and expiration. - Abstract: During the delivery of inhaled medicines, and depending on the size distribution of the particles in the formulation, airway bifurcations are areas of preferential deposition. Previous studies of laminar flow through airway bifurcations point to an interplay of inertial and centrifugal forces that leads to rich flow phenomena and controls particle deposition patterns. However, recent computational studies have shown that the airflow in the upper human airways is turbulent during much of the respiratory cycle. The question of how the presence of turbulence modifies these effects remains open. In this study, we perform for the first time Direct Numerical Simulations (DNS) of fully developed turbulent flow through a single human airway bifurcation model, emulating steady prolonged inspiration and expiration. We use the rich information obtained from the DNS in order to identify key structures in the flow field and scrutinize their role in determining deposition patterns in the bifurcation. We find that the vortical structures present in the bifurcation during expiration differ from those identified during inspiration. While Dean vortices are present in both cases, a set of three dimensional “carinal vortices” are identified only during expiration. A set of laminar simulations in the same geometries, but at lower Reynolds numbers, allow us to identify key differences in aerosol deposition patterns between laminar and turbulent respiration. We also report deposition fractions for representative Stokes numbers for both

  17. Airflow structures and nano-particle deposition in a human upper airway model

    Science.gov (United States)

    Zhang, Z.; Kleinstreuer, C.

    2004-07-01

    Considering a human upper airway model, or equivalently complex internal flow conduits, the transport and deposition of nano-particles in the 1-150 nm diameter range are simulated and analyzed for cyclic and steady flow conditions. Specifically, using a commercial finite-volume software with user-supplied programs as a solver, the Euler-Euler approach for the fluid-particle dynamics is employed with a low-Reynolds-number k- ω model for laminar-to-turbulent airflow and the mass transfer equation for dispersion of nano-particles or vapors. Presently, the upper respiratory system consists of two connected segments of a simplified human cast replica, i.e., the oral airways from the mouth to the trachea (Generation G0) and an upper tracheobronchial tree model of G0-G3. Experimentally validated computational fluid-particle dynamics results show the following: (i) transient effects in the oral airways appear most prominently during the decelerating phase of the inspiratory cycle; (ii) selecting matching flow rates, total deposition fractions of nano-size particles for cyclic inspiratory flow are not significantly different from those for steady flow; (iii) turbulent fluctuations which occur after the throat can persist downstream to at least Generation G3 at medium and high inspiratory flow rates (i.e., Qin⩾30 l/min) due to the enhancement of flow instabilities just upstream of the flow dividers; however, the effects of turbulent fluctuations on nano-particle deposition are quite minor in the human upper airways; (iv) deposition of nano-particles occurs to a relatively greater extent around the carinal ridges when compared to the straight tubular segments in the bronchial airways; (v) deposition distributions of nano-particles vary with airway segment, particle size, and inhalation flow rate, where the local deposition is more uniformly distributed for large-size particles (say, dp=100 nm) than for small-size particles (say, dp=1 nm); (vi) dilute 1 nm particle

  18. Assessment of the storz video Macintosh laryngoscope for use in difficult airways: A human simulator study.

    Science.gov (United States)

    Bair, Aaron E; Olmsted, Kalani; Brown, Calvin A; Barker, Tobias; Pallin, Daniel; Walls, Ron M

    2010-10-01

    Video laryngoscopy has been shown to improve glottic exposure when compared to direct laryngoscopy in operating room studies. However, its utility in the hands of emergency physicians (EPs) remains undefined. A simulated difficult airway was used to determine if intubation by EPs using a video Macintosh system resulted in an improved glottic view, was easier, was faster, or was more successful than conventional direct laryngoscopy. Emergency medicine (EM) residents and attending physicians at two academic institutions performed endotracheal intubation in one normal and two identical difficult airway scenarios. With the difficult scenarios, the participants used video laryngoscopy during the second case. Intubations were performed on a medium-fidelity human simulator. The difficult scenario was created by limiting cervical spine mobility and inducing trismus. The primary outcome was the proportion of direct versus video intubations with a grade I or II Cormack-Lehane glottic view. Ease of intubation (self-reported via 10-cm visual analog scale [VAS]), time to intubation, and success rate were also recorded. Descriptive statistics as well as medians with interquartile ranges (IQRs) are reported where appropriate. The Wilcoxon matched pairs signed-rank test was used for comparison testing of nonparametric data. Participants (n = 39) were residents (59%) and faculty. All had human intubation experience; 51% reported more than 100 prior intubations. On difficult laryngoscopy, a Cormack-Lehane grade I or II view was obtained in 20 (51%) direct laryngoscopies versus 38 (97%) of the video-assisted laryngoscopies (p < 0.01). The median VAS score for difficult airways was 50 mm (IQR = 28–73 mm) for direct versus 18 mm (IQR = 9–50 mm) for video (p < 0.01). The median time to intubation in difficult airways was 25 seconds (IQR = 16–44 seconds) for direct versus 20 seconds (IQR = 12–35 seconds) for video laryngoscopy (p < 0.01). All intubations were successful without

  19. Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells

    Science.gov (United States)

    Ding, Bi-Sen; Gomi, Kazunori; Rafii, Shahin; Crystal, Ronald G.; Walters, Matthew S.

    2015-01-01

    ABSTRACT Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell–endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal ‘crosstalk’ between human airway basal cells and endothelial cells that regulates proliferation of basal cells. PMID:26116571

  20. Human mast cell and airway smooth muscle cell interactions: implications for asthma.

    Science.gov (United States)

    Page, S; Ammit, A J; Black, J L; Armour, C L

    2001-12-01

    Asthma is characterized by inflammation, hyperresponsiveness, and remodeling of the airway. Human mast cells (HMCs) play a central role in all of these changes by releasing mediators that cause exaggerated bronchoconstriction, induce human airway smooth muscle (HASM) cell proliferation, and recruit and activate inflammatory cells. Moreover, the number of HMCs present on asthmatic HASM is increased compared with that on nonasthmatic HASM. HASM cells also have the potential to actively participate in the inflammatory process by synthesizing cytokines and chemokines and expressing surface molecules, which have the capacity to perpetuate the inflammatory mechanisms present in asthma. This review specifically examines how the mediators of HMCs have the capacity to modulate many functions of HASM; how the synthetic function of HASM, particularly through the release and expression of stem cell factor, has the potential to influence HMC number and activation in an extraordinarily potent and proinflammatory manner; and how these interactions between HMCs and HASM have potential consequences for airway structure and inflammation relevant to the disease process of asthma.

  1. Quantitative imaging of the human upper airway: instrument design and clinical studies

    Science.gov (United States)

    Leigh, M. S.; Armstrong, J. J.; Paduch, A.; Sampson, D. D.; Walsh, J. H.; Hillman, D. R.; Eastwood, P. R.

    2006-08-01

    Imaging of the human upper airway is widely used in medicine, in both clinical practice and research. Common imaging modalities include video endoscopy, X-ray CT, and MRI. However, no current modality is both quantitative and safe to use for extended periods of time. Such a capability would be particularly valuable for sleep research, which is inherently reliant on long observation sessions. We have developed an instrument capable of quantitative imaging of the human upper airway, based on endoscopic optical coherence tomography. There are no dose limits for optical techniques, and the minimally invasive imaging probe is safe for use in overnight studies. We report on the design of the instrument and its use in preliminary clinical studies, and we present results from a range of initial experiments. The experiments show that the instrument is capable of imaging during sleep, and that it can record dynamic changes in airway size and shape. This information is useful for research into sleep disorders, and potentially for clinical diagnosis and therapies.

  2. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro

    International Nuclear Information System (INIS)

    Tapparel, Caroline; Sobo, Komla; Constant, Samuel; Huang, Song; Van Belle, Sandra; Kaiser, Laurent

    2013-01-01

    New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs

  3. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tapparel, Caroline, E-mail: Caroline.Tapparel@hcuge.ch [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Sobo, Komla [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Constant, Samuel; Huang, Song [Epithelix sárl, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva (Switzerland); Van Belle, Sandra; Kaiser, Laurent [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland)

    2013-11-15

    New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs.

  4. Computational model of soft tissues in the human upper airway.

    Science.gov (United States)

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  5. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Pettigrew, Melinda M; Ahearn, Christian P; Gent, Janneane F; Kong, Yong; Gallo, Mary C; Munro, James B; D'Mello, Adonis; Sethi, Sanjay; Tettelin, Hervé; Murphy, Timothy F

    2018-04-03

    Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.

  6. Increased proinflammatory responses from asthmatic human airway smooth muscle cells in response to rhinovirus infection

    Directory of Open Access Journals (Sweden)

    King Nicholas JC

    2006-05-01

    Full Text Available Abstract Background Exacerbations of asthma are associated with viral respiratory tract infections, of which rhinoviruses (RV are the predominant virus type. Airway smooth muscle is important in asthma pathogenesis, however little is known about the potential interaction of RV and human airway smooth muscle cells (HASM. We hypothesised that rhinovirus induction of inflammatory cytokine release from airway smooth muscle is augmented and differentially regulated in asthmatic compared to normal HASM cells. Methods HASM cells, isolated from either asthmatic or non-asthmatic subjects, were infected with rhinovirus. Cytokine production was assayed by ELISA, ICAM-1 cell surface expression was assessed by FACS, and the transcription regulation of IL-6 was measured by luciferase activity. Results RV-induced IL-6 release was significantly greater in HASM cells derived from asthmatic subjects compared to non-asthmatic subjects. This response was RV specific, as 5% serum- induced IL-6 release was not different in the two cell types. Whilst serum stimulated IL-8 production in cells from both subject groups, RV induced IL-8 production in only asthmatic derived HASM cells. The transcriptional induction of IL-6 was differentially regulated via C/EBP in the asthmatic and NF-κB + AP-1 in the non-asthmatic HASM cells. Conclusion This study demonstrates augmentation and differential transcriptional regulation of RV specific innate immune response in HASM cells derived from asthmatic and non-asthmatics, and may give valuable insight into the mechanisms of RV-induced asthma exacerbations.

  7. A Numerical Study of Water Loss Rate Distributions in MDCT-based Human Airway Models

    Science.gov (United States)

    Wu, Dan; Miyawaki, Shinjiro; Tawhai, Merryn H.; Hoffman, Eric A.; Lin, Ching-Long

    2015-01-01

    Both three-dimensional (3D) and one-dimensional (1D) computational fluid dynamics (CFD) methods are applied to study regional water loss in three multi-detector row computed-tomography (MDCT)-based human airway models at the minute ventilations of 6, 15 and 30 L/min. The overall water losses predicted by both 3D and 1D models in the entire respiratory tract agree with available experimental measurements. However, 3D and 1D models reveal different regional water loss rate distributions due to the 3D secondary flows formed at bifurcations. The secondary flows cause local skewed temperature and humidity distributions on inspiration acting to elevate the local water loss rate; and the secondary flow at the carina tends to distribute more cold air to the lower lobes. As a result, the 3D model predicts that the water loss rate first increases with increasing airway generation, and then decreases as the air approaches saturation, while the 1D model predicts a monotonic decrease of water loss rate with increasing airway generation. Moreover, the 3D (or 1D) model predicts relatively higher water loss rates in lower (or upper) lobes. The regional water loss rate can be related to the non-dimensional wall shear stress (τ*) by the non-dimensional mass transfer coefficient (h0*) as h0* = 1.15 τ*0.272, R = 0.842. PMID:25869455

  8. From single cilia to collective waves in human airway ciliated tissues

    Science.gov (United States)

    Cicuta, Pietro; Chioccioli, Maurizio; Feriani, Luigi; Pellicciotta, Nicola; Kotar, Jurij

    I will present experimental results on activity of motile cilia on various scales: from waveforms on individual cilia to the synchronised motion in cilia carpets of airway cells. Model synthetic experiments have given us an understanding of how cilia could couple with each other through forces transmitted by the fluid, and thus coordinate to beat into well organized waves (previous work is reviewed in Annu. Rev. Condens. Matter Phys. 7, 1-26 (2016)). Working with live imaging of airway human cells at the different scales, we can now test whether the biological system satisfies the ``simple'' behavior expected of the fluid flow coupling, or if other factors of mechanical forces transmission need to be accounted for. In general being able to link from the scale of molecular biological activity up to the phenomenology of collective dynamics requires to understand the relevant physical mechanism. This understanding then allows informed diagnostics (and perhaps therapeutic) approaches to a variety of diseases where mucociliary clearance in the airways is compromised. We have started exploring particularly cystic fibrosis, where the rheological properties of the mucus are affected and prevent efficient cilia synchronization. ERC Grant HydroSync.

  9. Lateral Pharyngeal Diverticulum presenting with Dysphagia ...

    African Journals Online (AJOL)

    Lateral pharyngeal diverticulum (Pharyngocele) is the protrusion of pharyngeal mucosa through the pharyngeal wall, usually through either of two weak areas in the pharyngeal wall as an acquired or congenital case. Lateral diverticula are very rare and not to be mistaken for the rather more frequent and abundantly ...

  10. Gastroesophageal reflux and pharyngeal function

    International Nuclear Information System (INIS)

    Ekberg, O.; Lindgren, S.; Malmoe Allmaenna Sjukhus

    1986-01-01

    Pharyngeal function and gastroesophageal reflux were compared in 84 dysphagic patients examined clinically and radiologically. Cricopharyngeal muscle incoordination, assessed cineradiographically, was revealed in 5 of 41 patients (12%) without and 17 of 43 patients (40%) with gastroesophageal reflux assessed clinically (p<0.05). Thus, there was a postive correlation between dysfunction of the cricopharyngeal muscle and gastroesophageal reflux. There was no correlation with other types of pharyngeal dysfunction. Our results support the assumption of a positive relationship between gastroesophageal reflux and pharyngeal function in terms of cricopharyngeal dysfunction. The pathogenesis of this relation was, however, not revealed. (orig.)

  11. Gastroesophageal reflux and pharyngeal function

    Energy Technology Data Exchange (ETDEWEB)

    Ekberg, O.; Lindgren, S.

    Pharyngeal function and gastroesophageal reflux were compared in 84 dysphagic patients examined clinically and radiologically. Cricopharyngeal muscle incoordination, assessed cineradiographically, was revealed in 5 of 41 patients (12%) without and 17 of 43 patients (40%) with gastroesophageal reflux assessed clinically (p<0.05). Thus, there was a postive correlation between dysfunction of the cricopharyngeal muscle and gastroesophageal reflux. There was no correlation with other types of pharyngeal dysfunction. Our results support the assumption of a positive relationship between gastroesophageal reflux and pharyngeal function in terms of cricopharyngeal dysfunction. The pathogenesis of this relation was, however, not revealed.

  12. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

    Directory of Open Access Journals (Sweden)

    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  13. The classical Starling resistor model often does not predict inspiratory airflow patterns in the human upper airway.

    Science.gov (United States)

    Owens, Robert L; Edwards, Bradley A; Sands, Scott A; Butler, James P; Eckert, Danny J; White, David P; Malhotra, Atul; Wellman, Andrew

    2014-04-15

    The upper airway is often modeled as a classical Starling resistor, featuring a constant inspiratory airflow, or plateau, over a range of downstream pressures. However, airflow tracings from clinical sleep studies often show an initial peak before the plateau. To conform to the Starling model, the initial peak must be of small magnitude or dismissed as a transient. We developed a method to simulate fast or slow inspirations through the human upper airway, to test the hypothesis that this initial peak is a transient. Eight subjects [4 obstructive sleep apnea (OSA), 4 controls] slept in an "iron lung" and wore a nasal mask connected to a continuous/bilevel positive airway pressure machine. Downstream pressure was measured using an epiglottic catheter. During non-rapid eye movement (NREM) sleep, subjects were hyperventilated to produce a central apnea, then extrathoracic pressure was decreased slowly (∼2-4 s) or abruptly (resistor model, the upper airway exhibits marked NED in some subjects.

  14. Local deposition patterns of inhaled radon progeny in human bronchial airways

    International Nuclear Information System (INIS)

    Heistracher, T.; Hofmann, W.; Balashazy, I.

    1996-01-01

    The local distribution of radon decay products deposited within bronchial bifurcations, particularly the formation of hot spots, may be more relevant for the determination of cellular doses in bronchial tissue than the commonly computed deposition efficiency, which is conceptually equivalent to the assumption of a uniform nuclide distribution. It is well known that the initial states of lung cancer in humans preferably occur in upper airways close to the cardinal location. In this study we use a recently developed geometric approach of a physiologically realistic bifurcation to demonstrate the site sensitivity of radon progeny deposition for two particle sizes, which are representative of the unattached and attached fraction of radon progeny

  15. Response of cultured human airway epithelial cells to X-rays and energetic α-particles

    International Nuclear Information System (INIS)

    Yang, T.C.; Holley, W.R.; Curtis, S.B.; Gruenert, D.C.; California Univ., San Francisco, CA

    1990-01-01

    Radon and its progeny, which emit α-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of α-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D 0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D 0 value, was about 24 μm 2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (∼ 180 μm 2 ), suggesting that an average of 7.5 α-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion. (author)

  16. Human factors in the development of complications of airway management: preliminary evaluation of an interview tool.

    Science.gov (United States)

    Flin, R; Fioratou, E; Frerk, C; Trotter, C; Cook, T M

    2013-08-01

    The 4th National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society (NAP4) analysed reports of serious events arising from airway management during anaesthesia, intensive care and the emergency department. We conducted supplementary telephone interviews with 12 anaesthetists who had reported to NAP4, aiming to identify causal factors using a method based on the Human Factors Investigation Tool (HFIT). We identified contributing human factors in all cases (median [range] 4.5 [1-10] per case). The most frequent related to: situation awareness (failures to anticipate, wrong decision) (nine cases); job factors (e.g. task difficulty; staffing, time pressure) (eight cases); and person factors (e.g. tiredness, hunger, stress) (six cases). Protective factors, such as teamwork and communication, were also revealed. The post-report HFIT interview method identified relevant human factors and this approach merits further testing as part of the investigation of anaesthetic incidents. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

  17. Bioaerosols from a food waste composting plant affect human airway epithelial cell remodeling genes.

    Science.gov (United States)

    Chang, Min-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-12-24

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 10(2) conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5-10 μm) having higher endotoxin levels than did fine particles (0.5-2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21 WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers.

  18. Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

    Science.gov (United States)

    Chang, Ming-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-01-01

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5–10 μm) having higher endotoxin levels than did fine particles (0.5–2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers. PMID:24368426

  19. The chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells.

    Science.gov (United States)

    Kelsen, Steven G; Aksoy, Mark O; Yang, Yi; Shahabuddin, Syed; Litvin, Judith; Safadi, Fayez; Rogers, Thomas J

    2004-09-01

    Activation of the chemokine receptor CXCR3 by its cognate ligands induces several differentiated cellular responses important to the growth and migration of a variety of hematopoietic and structural cells. In the human respiratory tract, human airway epithelial cells (HAEC) release the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. Simultaneous expression of CXCR3 by HAEC would have important implications for the processes of airway inflammation and repair. Accordingly, in the present study we sought to determine whether HAEC also express the classic CXCR3 chemokine receptor CXCR3-A and its splice variant CXCR3-B and hence may respond in autocrine fashion to its ligands. We found that cultured HAEC (16-HBE and tracheocytes) constitutively expressed CXCR3 mRNA and protein. CXCR3 mRNA levels assessed by expression array were approximately 35% of beta-actin expression. In contrast, CCR3, CCR4, CCR5, CCR8, and CX3CR1 were <5% beta-actin. Both CXCR3-A and -B were expressed. Furthermore, tracheocytes freshly harvested by bronchoscopy stained positively for CXCR3 by immunofluorescence microscopy, and 68% of cytokeratin-positive tracheocytes (i.e., the epithelial cell population) were positive for CXCR3 by flow cytometry. In 16-HBE cells, CXCR3 receptor density was approximately 78,000 receptors/cell when assessed by competitive displacement of 125I-labeled IP-10/CXCL10. Finally, CXCR3 ligands induced chemotactic responses and actin reorganization in 16-HBE cells. These findings indicate constitutive expression by HAEC of a functional CXC chemokine receptor, CXCR3. Our data suggest the possibility that autocrine activation of CXCR3 expressed by HAEC may contribute to airway inflammation and remodeling in obstructive lung disease by regulating HAEC migration.

  20. Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha.

    Science.gov (United States)

    Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

    1995-09-15

    Tumour necrosis factor-alpha (TNF alpha) is implicated in the pathogenesis of asthma; however, little is known of its direct effect on smooth muscle reactivity. We investigated the effect of TNF alpha on the responsiveness of human bronchial tissue to electrical field stimulation in vitro. Incubation of non-sensitized tissue with 1 nM, 3 nM and 10 nM TNF alpha significantly increased responsiveness to electrical field stimulation (113 +/- 8, 110 +/- 4 and 112 +/- 2% respectively) compared to control (99 +/- 2%) (P 0.05) nor were responses to exogenous acetylcholine (93 +/- 4% versus 73 +/- 7%, n = 3, P = 0.38). These results show that TNF alpha causes an increase in responsiveness of human bronchial tissue and that this occurs prejunctionally on the parasympathetic nerve pathway. This is the first report of a cytokine increasing human airway tissue responsiveness.

  1. Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS.

    Directory of Open Access Journals (Sweden)

    Marco Schlepütz

    Full Text Available The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS respond to electric field stimulation (EFS and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM caused bronchoconstriction in human (4 from 7 and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC. However, this effect was notably smaller in human responder (30 ± 7.1% than in guinea pig (79 ± 5.1% PCLS. The transient receptor potential (TRP channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

  2. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease

    Directory of Open Access Journals (Sweden)

    Hotzel Helmut

    2008-01-01

    Full Text Available Abstract Background Recurrent airway obstruction (RAO in horses is a naturally occurring dust-induced disease mainly characterized by bronchiolitis which shows histological and pathophysiological similarities to human chronic obstructive pulmonary disease (COPD. In human COPD previous investigations indicated an association with Chlamydophila psittaci infection. The present study was designed (1 to clarify a possible role of this infectious agent in RAO and (2 to investigate the suitability of this equine disorder as a model for human COPD. Methods Clinico-pathological parameters of a total of 45 horses (25 horses with clinical signs of RAO and 20 clinically healthy controls were compared to histological findings in lung tissue samples and infection by Chlamydiaceae using light microscopy, immunohistochemistry, and PCR. Results Horses with clinical signs of RAO vs. controls revealed more inflammatory changes in histology (p = 0.01, and a higher detection rate of Chlamydia psittaci antigens in all cells (p OmpA sequencing identified Chlamydophila psittaci (n = 9 and Chlamydophila abortus (n = 13 in both groups with no significant differences. Within the group of clinically healthy horses subgroups with no changes (n = 15 and slight inflammation of the small airways (n = 5 were identified. Also in the group of animals with RAO subgroups with slight (n = 16 and severe (n = 9 bronchiolitis could be formed. These four subgroups can be separated in parts by the number of cells positive for Chlamydia psittaci antigens. Conclusion Chlamydophila psittaci or abortus were present in the lung of both clinically healthy horses and those with RAO. Immunohistochemistry revealed acute chlamydial infections with inflammation in RAO horses, whereas in clinically healthy animals mostly persistent chlamydial infection and no inflammatory reactions were seen. Stable dust as the known fundamental abiotic factor in RAO is comparable to smoking in human disease. These

  3. Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells

    Science.gov (United States)

    Yadav, Umesh CS; Ramana, KV; Srivastava, SK

    2013-01-01

    Aldose reductase (AR), a glucose metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30μM) than glucose. Acrolein, a major endogenous lipid peroxidation product as well as component of environmental pollutant and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells SAECs. Exposure of SAECs to varying concentrations of acrolein caused cell-death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low (5 to 10 μM) but not high (>10 μM) concentrations of acrolein-induced SAECs cell death. AR inhibition protected SAECs from low dose (5 μM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail-moment, and annexin-V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of pro-apoptotic proteins Bax and Bad from cytosol to the mitochondria, and that of Bcl2 and BclXL from mitochondria to cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPK) such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), stress-activated protein kinases/c-jun NH2-terminal kinases (SAPK/JNK) and p38MAPK, and c-jun were transiently activated in airway epithelial cells by acrolein in a concentration and time-dependent fashion, which were significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells. PMID:23770200

  4. Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells.

    Science.gov (United States)

    Yadav, Umesh C S; Ramana, K V; Srivastava, Satish K

    2013-12-01

    Aldose reductase (AR), a glucose-metabolizing enzyme, reduces lipid aldehydes and their glutathione conjugates with more than 1000-fold efficiency (Km aldehydes 5-30 µM) relative to glucose. Acrolein, a major endogenous lipid peroxidation product as well as a component of environmental pollutants and cigarette smoke, is known to be involved in various pathologies including atherosclerosis, airway inflammation, COPD, and age-related disorders, but the mechanism of acrolein-induced cytotoxicity is not clearly understood. We have investigated the role of AR in acrolein-induced cytotoxicity in primary human small airway epithelial cells (SAECs). Exposure of SAECs to varying concentrations of acrolein caused cell death in a concentration- and time-dependent manner. AR inhibition by fidarestat prevented the low-dose (5-10 µM) but not the high-dose (>10 µM) acrolein-induced SAEC death. AR inhibition protected SAECs from low-dose (5 µM) acrolein-induced cellular reactive oxygen species (ROS). Inhibition of acrolein-induced apoptosis by fidarestat was confirmed by decreased condensation of nuclear chromatin, DNA fragmentation, comet tail moment, and annexin V fluorescence. Further, fidarestat inhibited acrolein-induced translocation of the proapoptotic proteins Bax and Bad from the cytosol to the mitochondria and that of Bcl2 and BclXL from the mitochondria to the cytosol. Acrolein-induced cytochrome c release from mitochondria was also prevented by AR inhibition. The mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases 1 and 2, stress-activated protein kinase/c-Jun NH2-terminal kinase, and p38MAPK, and c-Jun were transiently activated in airway epithelial cells by acrolein in a concentration- and time-dependent fashion, which was significantly prevented by AR inhibition. These results suggest that AR inhibitors could prevent acrolein-induced cytotoxicity in the lung epithelial cells. Copyright © 2013 Elsevier Inc. All rights

  5. Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

    Science.gov (United States)

    Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

    2011-06-01

    Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

  6. In vitro assessment of human airway toxicity from major aldehydes in automotive emissions

    Energy Technology Data Exchange (ETDEWEB)

    Grafstroem, R.C. [Karolinska Inst., Stockholm (Sweden). Inst. of Environmental Medicine

    1997-09-01

    Automotive exhausts can significantly contribute to the levels of reactive aldehydes, including formaldehyde, acetaldehyde and acrolein, in urban air. The use of alcohols as an alternative fuel for gasoline or diesel may further increase these emissions. Since it is unclear if aldehyde inhalation may induce pathological states, including cancer, in human airways, the toxic properties of the above-mentioned aldehydes were studied in cultured target cell types. Each aldehyde modified vital cellular functions in a dose-dependent manner, and invariably inhibited growth and induced abnormal terminal differentiation. Decreases of cellular thiols and increases of intracellular Ca{sup 2+} were observed, and moreover, variable types and amounts of short-lived or persistent genetic damage were induced. The concentrations required for specified levels of a particular type of injury varied up to 10000-fold among the aldehydes. Overall, distinctive patterns of cytopathological activity were observed, which differed both qualitatively and quantitatively among the aldehydes. Finally, aldehydes inhibited DNA repair processes and increased cytotoxicity and mutagenesis in synergy with other known toxicants, indicating that aldehydes may also enhance damage by other constituents in automotive exhausts. In summary, the aldehydes, notably {sup m}u{sup M}-mM formaldehyde, caused pathological effects and induced mechanisms that relate to acute toxicity and cancer development in airway epithelial cells. Since `no-effect` levels may not exist for carcinogenic agents, the overall results support a need for elimination of aldehydes in automotive exhausts. 41 refs

  7. Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.

    Science.gov (United States)

    Mao, Suifang; Shah, Alok S; Moninger, Thomas O; Ostedgaard, Lynda S; Lu, Lin; Tang, Xiao Xiao; Thornell, Ian M; Reznikov, Leah R; Ernst, Sarah E; Karp, Philip H; Tan, Ping; Keshavjee, Shaf; Abou Alaiwa, Mahmoud H; Welsh, Michael J

    2018-02-06

    Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gα i and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses. Copyright © 2018 the Author(s). Published by PNAS.

  8. Staphylococcus aureus α-Toxin Induces Actin Filament Remodeling in Human Airway Epithelial Model Cells.

    Science.gov (United States)

    Ziesemer, Sabine; Eiffler, Ina; Schönberg, Alfrun; Müller, Christian; Hochgräfe, Falko; Beule, Achim G; Hildebrandt, Jan-Peter

    2018-04-01

    Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus α-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity that are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeletons. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin-depolymerizing factor cofilin. We used recombinant wild-type hemolysin A (rHla) and a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue. Our results indicate that rHla-mediated changes in cofilin phosphorylation require the formation of functional Hla pores in the host cell membrane. Formation of functional transmembrane pores induced hypophosphorylation of cofilin at Ser3, which was mediated by rHla-induced attenuation of p21-activated protein kinase and LIM kinase activities. Because dephosphorylation of pSer3-cofilin results in activation of this actin-depolymerizing factor, treatment of cells with rHla resulted in loss of actin stress fibers from the cells and destabilization of cell shape followed by the appearance of paracellular gaps in the cell layers. Activation of protein kinase A or activation of small GTPases (Rho, Rac, Cdc42) do not seem to be involved in this response.

  9. Cigarette smoke modulates expression of human rhinovirus-induced airway epithelial host defense genes.

    Directory of Open Access Journals (Sweden)

    David Proud

    Full Text Available Human rhinovirus (HRV infections trigger acute exacerbations of chronic obstructive pulmonary disease (COPD and asthma. The human airway epithelial cell is the primary site of HRV infection and responds to infection with altered expression of multiple genes, the products of which could regulate the outcome to infection. Cigarette smoking aggravates asthma symptoms, and is also the predominant risk factor for the development and progression of COPD. We, therefore, examined whether cigarette smoke extract (CSE modulates viral responses by altering HRV-induced epithelial gene expression. Primary cultures of human bronchial epithelial cells were exposed to medium alone, CSE alone, purified HRV-16 alone or to HRV-16+ CSE. After 24 h, supernatants were collected and total cellular RNA was isolated. Gene array analysis was performed to examine mRNA expression. Additional experiments, using real-time RT-PCR, ELISA and/or western blotting, validated altered expression of selected gene products. CSE and HRV-16 each induced groups of genes that were largely independent of each other. When compared to gene expression in response to CSE alone, cells treated with HRV+CSE showed no obvious differences in CSE-induced gene expression. By contrast, compared to gene induction in response to HRV-16 alone, cells exposed to HRV+CSE showed marked suppression of expression of a number of HRV-induced genes associated with various functions, including antiviral defenses, inflammation, viral signaling and airway remodeling. These changes were not associated with altered expression of type I or type III interferons. Thus, CSE alters epithelial responses to HRV infection in a manner that may negatively impact antiviral and host defense outcomes.

  10. Research of transport and deposition of aerosol in human airway replica

    Science.gov (United States)

    Lizal, Frantisek; Jedelsky, Jan; Elcner, Jakub; Durdina, Lukas; Halasova, Tereza; Mravec, Filip; Jicha, Miroslav

    2012-04-01

    Growing concern about knowledge of aerosol transport in human lungs is caused by great potential of use of inhaled pharmaceuticals. Second substantial motive for the research is an effort to minimize adverse effects of particular matter emitted by traffic and industry on human health. We created model geometry of human lungs to 7th generation of branching. This model geometry was used for fabrication of two physical models. The first one is made from thin walled transparent silicone and it allows a measurement of velocity and size of aerosol particles by Phase Doppler Anemometry (PDA). The second one is fabricated by stereolithographic method and it is designed for aerosol deposition measurements. We provided a series of measurements of aerosol transport in the transparent model and we ascertained remarkable phenomena linked with lung flow. The results are presented in brief. To gather how this phenomena affects aerosol deposition in human lungs we used the second model and we developed a technique for deposition fraction and deposition efficiency assessment. The results confirmed that non-symmetric and complicated shape of human airways essentially affects transport and deposition of aerosol. The research will now focus on deeper insight in aerosol deposition.

  11. Research of transport and deposition of aerosol in human airway replica

    Directory of Open Access Journals (Sweden)

    Mravec Filip

    2012-04-01

    Full Text Available Growing concern about knowledge of aerosol transport in human lungs is caused by great potential of use of inhaled pharmaceuticals. Second substantial motive for the research is an effort to minimize adverse effects of particular matter emitted by traffic and industry on human health. We created model geometry of human lungs to 7th generation of branching. This model geometry was used for fabrication of two physical models. The first one is made from thin walled transparent silicone and it allows a measurement of velocity and size of aerosol particles by Phase Doppler Anemometry (PDA. The second one is fabricated by stereolithographic method and it is designed for aerosol deposition measurements. We provided a series of measurements of aerosol transport in the transparent model and we ascertained remarkable phenomena linked with lung flow. The results are presented in brief. To gather how this phenomena affects aerosol deposition in human lungs we used the second model and we developed a technique for deposition fraction and deposition efficiency assessment. The results confirmed that non-symmetric and complicated shape of human airways essentially affects transport and deposition of aerosol. The research will now focus on deeper insight in aerosol deposition.

  12. Estrogen receptor beta signaling inhibits PDGF induced human airway smooth muscle proliferation.

    Science.gov (United States)

    Ambhore, Nilesh Sudhakar; Katragadda, Rathnavali; Raju Kalidhindi, Rama Satyanarayana; Thompson, Michael A; Pabelick, Christina M; Prakash, Y S; Sathish, Venkatachalem

    2018-04-20

    Airway smooth muscle (ASM) cell hyperplasia driven by persistent inflammation is a hallmark feature of remodeling in asthma. Sex steroid signaling in the lungs is of considerable interest, given epidemiological data showing more asthma in pre-menopausal women and aging men. Our previous studies demonstrated that estrogen receptor (ER) expression increases in asthmatic human ASM; however, very limited data are available regarding differential roles of ERα vs. ERβ isoforms in human ASM cell proliferation. In this study, we evaluated the effect of selective ERα and ERβ modulators on platelet-derived growth factor (PDGF)-stimulated ASM proliferation and the mechanisms involved. Asthmatic and non-asthmatic primary human ASM cells were treated with PDGF, 17β-estradiol, ERα-agonist and/or ERβ-agonist and/or G-protein-coupled estrogen receptor 30 (GPR30/GPER) agonist and proliferation was measured using MTT and CyQuant assays followed by cell cycle analysis. Transfection of small interfering RNA (siRNA) ERα and ERβ significantly altered the human ASM proliferation. The specificity of siRNA transfection was confirmed by Western blot analysis. Gene and protein expression of cell cycle-related antigens (PCNA and Ki67) and C/EBP were measured by RT-PCR and Western analysis, along with cell signaling proteins. PDGF significantly increased ASM proliferation in non-asthmatic and asthmatic cells. Treatment with PPT showed no significant effect on PDGF-induced proliferation, whereas WAY interestingly suppressed proliferation via inhibition of ERK1/2, Akt, and p38 signaling. PDGF-induced gene expression of PCNA, Ki67 and C/EBP in human ASM was significantly lower in cells pre-treated with WAY. Furthermore, WAY also inhibited PDGF-activated PCNA, C/EBP, cyclin-D1, and cyclin-E. Overall, we demonstrate ER isoform-specific signaling in the context of ASM proliferation. Activation of ERβ can diminish remodeling in human ASM by inhibiting pro-proliferative signaling pathways

  13. Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts

    Directory of Open Access Journals (Sweden)

    Luketich James D

    2004-12-01

    Full Text Available Abstract Background Non-neuronal cells, including those derived from lung, are reported to express nicotinic acetylcholine receptors (nAChR. We examined nAChR subunit expression in short-term cultures of human airway cells derived from a series of never smokers, ex-smokers, and active smokers. Methods and Results At the mRNA level, human bronchial epithelial (HBE cells and airway fibroblasts expressed a range of nAChR subunits. In multiple cultures of both cell types, mRNA was detected for subunits that constitute functional muscle-type and neuronal-type pentomeric receptors. Two immortalized cell lines derived from HBE cells also expressed muscle-type and neuronal-type nAChR subunits. Airway fibroblasts expressed mRNA for three muscle-type subunits (α1, δ, and ε significantly more often than HBE cells. Immunoblotting of HBE cell and airway fibroblast extracts confirmed that mRNA for many nAChR subunits is translated into detectable levels of protein, and evidence of glycosylation of nAChRs was observed. Some minor differences in nAChR expression were found based on smoking status in fibroblasts or HBE cells. Nicotine triggered calcium influx in the immortalized HBE cell line BEAS2B, which was blocked by α-bungarotoxin and to a lesser extent by hexamethonium. Activation of PKC and MAPK p38, but not MAPK p42/44, was observed in BEAS2B cells exposed to nicotine. In contrast, nicotine could activate p42/44 in airway fibroblasts within five minutes of exposure. Conclusions These results suggest that muscle-type and neuronal-type nAChRs are functional in airway fibroblasts and HBE cells, that prior tobacco exposure does not appear to be an important variable in nAChR expression, and that distinct signaling pathways are observed in response to nicotine.

  14. Pharyngeal Dystonia Mimicking Spasmodic Dysphonia.

    Science.gov (United States)

    Shi, Lucy L; Simpson, C Blake; Hapner, Edie R; Jinnah, Hyder A; Johns, Michael M

    2018-03-01

    The aim of this study was to describe the presentation of pharyngeal dystonia (PD), which can occur as a focal or segmental dystonia with a primarily pharyngeal involvement for the discussion of treatment methods for controlling consequent symptoms. PD is specific to speech-related tasks. A retrospective medical record review of four patients with PD was performed. All patients were initially misdiagnosed with adductor spasmodic dysphonia and failed standard treatment with botulinum toxin type A (BTX). On laryngoscopy, the patients were discovered to have segmental or focal dystonia primarily affecting the pharyngeal musculature contributing to their vocal manifestations. A novel treatment regimen was designed, which involved directing BTX injections into the muscles involved in spasmodic valving at the oropharyngeal level. After titrating to an optimal dose, all patients showed improvement in their voice and speech with only mild dysphagia. These patients have maintained favorable results with repeat injections at 6- to 12-week intervals. PD, or dystonia with predominant pharyngeal involvement, is a rare entity with vocal manifestations that are not well described. It can be easily mistaken for spasmodic dysphonia. PD is specific to speech-related tasks. A novel method of BTX injections into the involved muscles results in a significant improvement in voice without significant dysphagia. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

  15. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    NARCIS (Netherlands)

    Larsen, J.M.; Steen-Jensen, D.B.; Laursen, J.M.; Sondergaard, J.N.; Musavian, H.S.; Butt, T.M.; Brix, S.

    2012-01-01

    Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties

  16. Characteristics of turbulent particle transport in human airways under steady and cyclic flows

    International Nuclear Information System (INIS)

    Jedelsky, Jan; Lizal, Frantisek; Jicha, Miroslav

    2012-01-01

    Highlights: ► PDA data allow to estimate PSD of particle velocity fluctuations in realistic model. ► PSD of micron-sized particles is independent of their size up to 700 Hz. ► Such particles follow air flow and turb. diffusion contributes to their deposition. ► Cyclic flow PSDs contain more TKE at high freq. than equivalent steady-flow PSDs. ► Exp. breathing phase differs from insp. phase at high frequency part of the spectra. - Abstract: Motion of monodispersed aerosol particles suspended in air flow has been studied on realistic transparent model of human airways using Phase Doppler Particle Analyser (P/DPA). Time-resolved velocity data for particles in size range 1–8 μm were processed using Fuzzy Slotting Technique to estimate the power spectral density (PSD) of velocity fluctuations. The optimum processing setup for our data was found and recommendations for future experiments to improve PSD quality were suggested. Typical PSD plots at mainstream positions of the trachea and the upper bronchi are documented and differences among (1) steady-flow regimes and equivalent cyclic breathing regimes, (2) inspiration and expiration breathing phase and (3) behaviour of particles of different sizes are described in several positions of the airway model. Systematically higher level of velocity fluctuations in the upper part of the frequency range (30–500 Hz) was found for cyclic flows in comparison with corresponding steady flows. Expiratory flows in both the steady and cyclic cases produce more high-frequency fluctuations compared to inspiratory flows. Negligible differences were found for flow of particles in the inspected size range 1–8 μm at frequencies below 500 Hz. This finding was explained by Stokes number analysis. Implied match of the air and particle flows thereby indicates turbulent diffusion as important deposition mechanism and confirms the capability to use the P/DPA data as the air flow velocity estimate.

  17. Human Lung Mast Cell Products Regulate Airway Smooth Muscle CXCL10 Levels.

    Science.gov (United States)

    Alkhouri, H; Cha, V; Tong, K; Moir, L M; Armour, C L; Hughes, J M

    2014-01-01

    In asthma, the airway smooth muscle (ASM) produces CXCL10 which may attract CXCR3(+) mast/T cells to it. Our aim was to investigate the effects of mast cell products on ASM cell CXCL10 production. ASM cells from people with and without asthma were stimulated with IL-1 β , TNF- α , and/or IFN γ and treated with histamine (1-100  μ M) ± chlorpheniramine (H1R antagonist; 1  μ M) or ranitidine (H2R antagonist; 50  μ M) or tryptase (1 nM) ± leupeptin (serine protease inhibitor; 50  μ M), heat-inactivated tryptase, or vehicle for 4 h or 24 h. Human lung mast cells (MC) were isolated and activated with IgE/anti-IgE and supernatants were collected after 2 h or 24 h. The supernatants were added to ASM cells for 48 h and ASM cell CXCL10 production detected using ELISA (protein) and real-time PCR (mRNA). Histamine reduced IL-1 β /TNF- α -induced CXCL10 protein, but not mRNA, levels independent of H1 and H2 receptor activation, whereas tryptase and MC 2 h supernatants reduced all cytokine-induced CXCL10. Tryptase also reduced CXCL10 levels in a cell-free system. Leupeptin inhibited the effects of tryptase and MC 2 h supernatants. MC 24 h supernatants contained TNF- α and amplified IFN γ -induced ASM cell CXCL10 production. This is the first evidence that MC can regulate ASM cell CXCL10 production and its degradation. Thus MC may regulate airway myositis in asthma.

  18. MicroRNA Mediated Chemokine Responses in Human Airway Smooth Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Mythili Dileepan

    Full Text Available Airway smooth muscle (ASM cells play a critical role in the pathophysiology of asthma due to their hypercontractility and their ability to proliferate and secrete inflammatory mediators. microRNAs (miRNAs are gene regulators that control many signaling pathways and thus serve as potential therapeutic alternatives for many diseases. We have previously shown that miR-708 and miR-140-3p regulate the MAPK and PI3K signaling pathways in human ASM (HASM cells following TNF-α exposure. In this study, we investigated the regulatory effect of these miRNAs on other asthma-related genes. Microarray analysis using the Illumina platform was performed with total RNA extracted from miR-708 (or control miR-transfected HASM cells. Inhibition of candidate inflammation-associated gene expression was further validated by qPCR and ELISA. The most significant biologic functions for the differentially expressed gene set included decreased inflammatory response, cytokine expression and signaling. qPCR revealed inhibition of expression of CCL11, CXCL10, CCL2 and CXCL8, while the release of CCL11 was inhibited in miR-708-transfected cells. Transfection of cells with miR-140-3p resulted in inhibition of expression of CCL11, CXCL12, CXCL10, CCL5 and CXCL8 and of TNF-α-induced CXCL12 release. In addition, expression of RARRES2, CD44 and ADAM33, genes known to contribute to the pathophysiology of asthma, were found to be inhibited in miR-708-transfected cells. These results demonstrate that miR-708 and miR-140-3p exert distinct effects on inflammation-associated gene expression and biological function of ASM cells. Targeting these miRNA networks may provide a novel therapeutic mechanism to down-regulate airway inflammation and ASM proliferation in asthma.

  19. Endogenous laminin is required for human airway smooth muscle cell maturation

    Directory of Open Access Journals (Sweden)

    Tran Thai

    2006-09-01

    Full Text Available Abstract Background Airway smooth muscle (ASM contraction underlies acute bronchospasm in asthma. ASM cells can switch between a synthetic-proliferative phenotype and a contractile phenotype. While the effects of extracellular matrix (ECM components on modulation of ASM cells to a synthetic phenotype have been reported, the role of ECM components on maturation of ASM cells to a contractile phenotype in adult lung is unclear. As both changes in ECM components and accumulation of contractile ASM are features of airway wall remodelling in asthma, we examined the role of the ECM protein, laminin, in the maturation of contractile phenotype in human ASM cells. Methods Human ASM cells were made senescence-resistant by stable expression of human telomerase reverse transcriptase. Maturation to a contractile phenotype was induced by 7-day serum deprivation, as assessed by immunoblotting for desmin and calponin. The role of laminin on ASM maturation was investigated by comparing the effects of exogenous laminin coated on culture plates, and of soluble laminin peptide competitors. Endogenous expression of laminin chains during ASM maturation was also measured. Results Myocyte binding to endogenously expressed laminin was required for ASM phenotype maturation, as laminin competing peptides (YIGSR or GRGDSP significantly reduced desmin and calponin protein accumulation that otherwise occurs with prolonged serum deprivation. Coating of plastic cell culture dishes with different purified laminin preparations was not sufficient to further promote accumulation of desmin or calponin during 7-day serum deprivation. Expression of α2, β1 and γ1 laminin chains by ASM cells was specifically up-regulated during myocyte maturation, suggesting a key role for laminin-2 in the development of the contractile phenotype. Conclusion While earlier reports suggest exogenously applied laminin slows the spontaneous modulation of ASM to a synthetic phenotype, we show for the

  20. The effect of inhaled menthol on upper airway resistance in humans: A randomized controlled crossover study

    Directory of Open Access Journals (Sweden)

    Effie J Pereira

    2013-01-01

    Full Text Available BACKGROUND: Menthol (l-menthol is a naturally-occurring cold receptor agonist commonly used to provide symptomatic relief for upper airway congestion. Menthol can also reduce the sensation of dyspnea. It is unclear whether the physiological action of menthol in dyspnea reduction is through its cold receptor agonist effect or whether associated mechanical changes occur in the upper airway.

  1. Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs.

    Science.gov (United States)

    Hasaneen, Nadia A; Zucker, Stanley; Cao, Jian; Chiarelli, Christian; Panettieri, Reynold A; Foda, Hussein D

    2005-09-01

    Airway smooth muscle (ASM) proliferation and migration are major components of airway remodeling in asthma. Asthmatic airways are exposed to mechanical strain, which contributes to their remodeling. Matrix metalloproteinase (MMP) plays an important role in remodeling. In the present study, we examined if the mechanical strain of human ASM (HASM) cells contributes to their proliferation and migration and the role of MMPs in this process. HASM were exposed to mechanical strain using the FlexCell system. HASM cell proliferation, migration and MMP release, activation, and expression were assessed. Our results show that cyclic strain increased the proliferation and migration of HASM; cyclic strain increased release and activation of MMP-1, -2, and -3 and membrane type 1-MMP; MMP release was preceded by an increase in extracellular MMP inducer; Prinomastat [a MMP inhibitor (MMPI)] significantly decreased cyclic strain-induced proliferation and migration of HASM; and the strain-induced increase in the release of MMPs was accompanied by an increase in tenascin-C release. In conclusion, cyclic mechanical strain plays an important role in HASM cell proliferation and migration. This increase in proliferation and migration is through an increase in MMP release and activation. Pharmacological MMPIs should be considered in the pursuit of therapeutic options for airway remodeling in asthma.

  2. Pharyngeal diameter in various head and neck positions during exercise in sport horses

    Science.gov (United States)

    2014-01-01

    Background In equine athletes, dynamic stenotic disorders of the upper airways are often the cause for abnormal respiratory noises and/or poor performance. There are hypotheses, that head and neck flexion may influence the morphology and function of the upper airway and thus could even induce or deteriorate disorders of the upper respiratory tract. Especially the pharynx, without osseous or cartilaginous support is prone to changes in pressure and airflow during exercise. The objective of this study was to develop a method for measuring the pharyngeal diameter in horses during exercise, in order to analyse whether a change of head-neck position may have an impact on the pharyngeal diameter. Results Under the assumption that the width of the epiglottis remains constant in healthy horses, the newly developed method for calculating the pharyngeal diameter in horses during exercise is unsusceptible against changes of the viewing-angle and distance between the endoscope and the structures, which are to be assessed. The quotient of the width of the epiglottis and the perpendicular from a fixed point on the dorsal pharynx to the epiglottis could be used to determine the pharyngeal diameter. The percentage change of this quotient (pharynx-epiglottis-ratio; PE-ratio) in the unrestrained head-neck position against the reference position was significantly larger than that of any other combination of the head-neck positions investigated. A relation between the percentage change in PE-ratio and the degree of head and neck flexion could not be confirmed. Conclusions It could be shown, that the pharyngeal diameter is reduced through the contact position implemented by the rider in comparison to the unrestrained head and neck position. An alteration of the pharyngeal diameter depending on the degree of head and neck flexion (represented by ground and withers angle) could not be confirmed. PMID:24886465

  3. Comparison of vectorial ion transport in primary murine airway and human sinonasal air-liquid interface cultures, models for studies of cystic fibrosis, and other airway diseases.

    Science.gov (United States)

    Zhang, Shaoyan; Fortenberry, James A; Cohen, Noam A; Sorscher, Eric J; Woodworth, Bradford A

    2009-01-01

    The purpose of this study was to compare vectorial ion transport within murine trachea, murine nasal septa, and human sinonasal cultured epithelium. Our hypothesis is that murine septal epithelium, rather than trachea, will more closely mimic the electrophysiology properties of human sinonasal epithelium. Epithelium from murine trachea, murine septa, and human sinonasal tissue were cultured at an air-liquid interface to confluence and full differentiation. A limited number of homozygous dF508 epithelia were also cultured. Monolayers were mounted in modified Ussing chambers to investigate pharmacologic manipulation of ion transport. The change in forskolin-stimulated current (delta-I(SC), expressed as micro-A/cm(2)) in murine septal (n = 19; 16.84 +/- 2.09) and human sinonasal (n = 18; 12.15 +/- 1.93) cultures was significantly increased over murine tracheal cultures (n = 15; 6.75 +/- 1.35; p = 0.035 and 0.0005, respectively). Forskolin-stimulated I(SC) was inhibited by the specific cystic fibrosis transmembrane regulator (CFTR) inhibitor INH-172 (5 microM). No forskolin-stimulated I(SC) was shown in cultures of dF508 homozygous murine septal epithelium (n = 3). Murine septal I(SC) was largely inhibited by amiloride (12.03 +/- 0.66), whereas human sinonasal cultures had a very limited response (0.70 +/- 0.47; p < 0.0001). The contribution of CFTR to stimulated chloride current as measured by INH-172 was highly significantly different between all groups (murine septa, 19.51 +/- 1.28; human sinonasal, 11.12 +/- 1.58; murine trachea, 4.85 +/- 0.49; p < 0.0001). Human sinonasal and murine septal epithelial cultures represent a useful model for studying CFTR activity and may provide significant advantages over lower airway tissues for investigating upper and lower respiratory pathophysiology.

  4. Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

    National Research Council Canada - National Science Library

    Gao1, Radharaman Ray2, Yan Xiao3, Peter E. Barker3 and Prab, Xiugong

    2006-01-01

    .... In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE...

  5. Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles

    International Nuclear Information System (INIS)

    Tal, Tamara L.; Simmons, Steven O.; Silbajoris, Robert; Dailey, Lisa; Cho, Seung-Hyun; Ramabhadran, Ram; Linak, William; Reed, William; Bromberg, Philip A.; Samet, James M.

    2010-01-01

    Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

  6. [The use of the antidepressant citalopran for the treatment of chronic pharyngitis and pharyngeal neurosis].

    Science.gov (United States)

    Milinevskiĭ, I V; Shabaldina, E V; Shamova, I P; Shabaldin, A V

    2011-01-01

    The analysis of the efficacy of citalopran for the treatment of chronic pharyngitis and pharyngeal neurosis was carried out. The positive outcome of the treatment was documented in 95% of the patients.

  7. Tracheal intubation with a flexible fibreoptic scope or the McGrath videolaryngoscope in simulated difficult airway scenarios

    DEFF Research Database (Denmark)

    Jepsen, Cecilie H; Gätke, Mona R; Thøgersen, Bente

    2014-01-01

    Grath videolaryngoscope and FFE. The participants then performed tracheal intubation on a SimMan manikin once with the McGrath videolaryngoscope and once with the FFE in three difficult airway scenarios: (1) pharyngeal obstruction; (2) pharyngeal obstruction and cervical rigidity; (3) tongue oedema. MAIN OUTCOME MEASURES...

  8. Response of Differentiated Human Airway Epithelia to Alcohol Exposure and Klebsiella pneumoniae Challenge

    Directory of Open Access Journals (Sweden)

    Sammeta V. Raju

    2013-07-01

    Full Text Available Alcohol abuse has been associated with increased susceptibility to pulmonary infection. It is not fully defined how alcohol contributes to the host defense compromise. Here primary human airway epithelial cells were cultured at an air-liquid interface to form a differentiated and polarized epithelium. This unique culture model allowed us to closely mimic lung infection in the context of alcohol abuse by basolateral alcohol exposure and apical live bacterial challenge. Application of clinically relevant concentrations of alcohol for 24 h did not significantly alter epithelial integrity or barrier function. When apically challenged with viable Klebsiella pneumoniae, the cultured epithelia had an enhanced tightness which was unaffected by alcohol. Further, alcohol enhanced apical bacterial growth, but not bacterial binding to the cells. The cultured epithelium in the absence of any treatment or stimulation had a base-level IL-6 and IL-8 secretion. Apical bacterial challenge significantly elevated the basolateral secretion of inflammatory cytokines including IL-2, IL-4, IL-6, IL-8, IFN-γ, GM-CSF, and TNF-α. However, alcohol suppressed the observed cytokine burst in response to infection. Addition of adenosine receptor agonists negated the suppression of IL-6 and TNF-α. Thus, acute alcohol alters the epithelial cytokine response to infection, which can be partially mitigated by adenosine receptor agonists.

  9. Differential effects of airway anesthesia on ozone-induced pulmonary responses in human subjects.

    Science.gov (United States)

    Schelegle, E S; Eldridge, M W; Cross, C E; Walby, W F; Adams, W C

    2001-04-01

    We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on lung volume decrements, rapid shallow breathing, and subjective symptoms of breathing discomfort induced by the acute inhalation of 0.30 ppm ozone for 65 min in 22 ozone-sensitive healthy human subjects. After 50 min of ozone inhalation FEV(1) was reduced 24%, breathing frequency was increased 40%, tidal volume was decreased 31%, and total subjective symptom score was increased (71.2, compared with 3.8 for filtered air exposure). Inhalation of tetracaine aerosol resulted in marked reductions in ozone-induced subjective symptoms of throat tickle and/or irritation (92.1%), cough (78.5%), shortness of breath (72.5%), and pain on deep inspiration (69.4%). In contrast, inhalation of tetracaine aerosol (mass median aerodynamic diameter of 3.52 microm with a geometric standard deviation of 1.92) resulted in only minor and inconsistent rectification of FEV(1) decrements (5.0%) and breathing frequency (-3.8%) that was not significantly different from that produced by saline aerosol alone (FEV(1), 5.1% and breathing frequency, -2.7%). Our data are consistent with afferent endings located within the large conducting airways of the tracheobronchial tree being primarily responsible for ozone-induced subjective symptoms and provides strong evidence that ozone-induced inhibition of maximal inspiratory effort is not dependent on conscious sensations of inspiratory discomfort.

  10. IMAGE-BASED IN VIVO QUANTITATIVE ASSESSMENT OF HUMAN AIRWAY OPENING AND CONTRACTILITY BY FIBER OPTICAL NASOPHARYNGOSCOPY IN HEALTHY AND ASTHMATIC SUBJECTS

    Directory of Open Access Journals (Sweden)

    LINHONG DENG

    2013-04-01

    Full Text Available Assessment of human airway lumen opening is important in diagnosing and understanding the mechanisms of airway dysfunctions such as the excessive airway narrowing in asthma and chronic obstructive pulmonary disease (COPD. Although there are indirect methods to evaluate the airway calibre, direct in vivo measurement of the airway calibre has not been commonly available. With recent advent of the flexible fiber optical nasopharyngoscope with video recording it has become possible to directly visualize the passages of upper and lower airways. However, quantitative analysis of the recorded video images has been technically challenging. Here, we describe an automatic image processing and analysis method that allows for batch analysis of the images recorded during the endoscopic procedure, thus facilitates image-based quantification of the airway opening. Video images of the airway lumen of volunteer subject were acquired using a fiber optical nasopharyngoscope, and subsequently processed using Gaussian smoothing filter, threshold segmentation, differentiation, and Canny image edge detection, respectively. Thus the area of the open airway lumen was identified and computed using a predetermined converter of the image scale to true dimension of the imaged object. With this method we measured the opening/narrowing of the glottis during tidal breathing with or without making "Hee" sound or cough. We also used this method to measure the opening/narrowing of the primary bronchus of either healthy or asthmatic subjects in response to histamine and/or albuterol treatment, which also provided an indicator of the airway contractility. Our results demonstrate that the image-based method accurately quantified the area change waveform of either the glottis or the bronchus as observed by using the optical nasopharygoscope. Importantly, the opening/narrowing of the airway lumen generally correlated with the airflow and resistance of the airways, and could

  11. Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle dysfunction following intermittent hypoxia in females.

    Science.gov (United States)

    O'Halloran, Ken D; Lewis, Philip; McDonald, Fiona

    2017-11-01

    Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control disorder more common in men than women. The reasons for the sex difference in prevalence are multifactorial, but are partly attributable to protective effects of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is characterized by repeated occlusions of the pharyngeal airway during sleep. Dysfunction of the upper airway muscles controlling airway calibre and collapsibility is implicated in the pathophysiology of OSAS, and sex differences in the neuro-mechanical control of upper airway patency are described. It is widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of OSAS due to recurrent apnoea, drives many of the morbid consequences characteristic of the disorder. In rodents, exposure to CIH-related redox stress causes upper airway muscle weakness and fatigue, associated with mitochondrial dysfunction. Of interest, in adults, there is female resilience to CIH-induced muscle dysfunction. Conversely, exposure to CIH in early life, results in upper airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age. Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult female upper airway muscle, an effect partially restored by oestrogen replacement therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists with evidence of substantially greater loss of performance in male muscle during acute exposure to severe hypoxic stress. Sex differences in upper airway muscle physiology may have relevance to human OSAS. The oestrogen-oestrogen receptor α axis represents a potential therapeutic target in OSAS, particularly in post-menopausal women. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Generation of Distal Airway Epithelium from Multipotent Human Foregut Stem Cells.

    Science.gov (United States)

    Hannan, Nicholas R F; Sampaziotis, Fotios; Segeritz, Charis-Patricia; Hanley, Neil A; Vallier, Ludovic

    2015-07-15

    Collectively, lung diseases are one of the largest causes of premature death worldwide and represent a major focus in the field of regenerative medicine. Despite significant progress, only few stem cell platforms are currently available for cell-based therapy, disease modeling, and drug screening in the context of pulmonary disorders. Human foregut stem cells (hFSCs) represent an advantageous progenitor cell type that can be used to amplify large quantities of cells for regenerative medicine applications and can be derived from any human pluripotent stem cell line. Here, we further demonstrate the application of hFSCs by generating a near homogeneous population of early pulmonary endoderm cells coexpressing NKX2.1 and FOXP2. These progenitors are then able to form cells that are representative of distal airway epithelium that express NKX2.1, GATA6, and cystic fibrosis transmembrane conductance regulator (CFTR) and secrete SFTPC. This culture system can be applied to hFSCs carrying the CFTR mutation Δf508, enabling the development of an in vitro model for cystic fibrosis. This platform is compatible with drug screening and functional validations of small molecules, which can reverse the phenotype associated with CFTR mutation. This is the first demonstration that multipotent endoderm stem cells can differentiate not only into both liver and pancreatic cells but also into lung endoderm. Furthermore, our study establishes a new approach for the generation of functional lung cells that can be used for disease modeling as well as for drug screening and the study of lung development.

  13. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  14. Effects of bile acids on human airway epithelial cells: implications for aerodigestive diseases

    Directory of Open Access Journals (Sweden)

    Adil Aldhahrani

    2017-03-01

    Full Text Available Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B. The immortalised human bronchial epithelial cell line (BEAS-2B was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids. Post-challenge concentrations of interleukin (IL-8, IL-6 and granulocyte−macrophage colony-stimulating factor were measured using commercial ELISA kits. The viability of the BEAS-2B cells was measured using CellTiter-Blue and MTT assays. Lithocholic acid, deoxycholic acid, chenodeoxycholic acid and cholic acid were successfully used to stimulate cultured BEAS-2B cells at different concentrations. A concentration of lithocholic acid above 10 μmol·L−1 causes cell death, whereas deoxycholic acid, chenodeoxycholic acid and cholic acid above 30 μmol·L−1 was required for cell death. Challenge with bile acids at physiological levels also led to a significant increase in the release of IL-8 and IL6 from BEAS-2B. Aspiration of bile acids could potentially cause cell damage, cell death and inflammation in vivo. This is relevant to an integrated gastrointestinal and lung physiological paradigm of chronic lung disease, where reflux and aspiration are described in both chronic lung diseases and allograft injury.

  15. PPARγ ligand ciglitazone inhibits TNFα-induced ICAM-1 in human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Chien-Da Huang

    2014-08-01

    Full Text Available Background: Modification of human airway smooth muscle (ASM function by proinflammatory cytokines has been regarded as a potential mechanism underlying bronchial hyperresponsiveness in asthma. Human ASM cells express intercellular adhesion molecule (ICAM-1 in response to cytokines. Synthetic ligands for peroxisome proliferator-activated receptor (PPARγ reportedly possess anti-inflammatory and immunomodulatory properties. In this study, we examined whether ciglitazone, a synthetic PPARγ ligand, can modulate the basal and tumor necrosis factor (TNFα-induced ICAM1 gene expression in human ASM cells. Methods: Human ASM cells were treated with TNFα. ICAM-1 expression was assessed by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR analysis. PPARγ activity was inhibited by target-specific small interfering (si RNA targeting PPARγ and GW9662, a PPARγ antagonist. Activity of nuclear factor (NF-κB was assessed by using immunoblot analysis, immune-confocal images, and electrophoretic mobility shift assay (EMSA. Results: By flow cytometry, ciglitazone alone had no effect on ICAM-1 expression in ASM cells, but inhibited ICAM-1 expression in response to TNFα (10 ng/ml in a dose-dependent manner (1-10 μM. It also inhibited TNFα-induced ICAM1 gene expression by RT-PCR analysis. Knockdown of PPARγ gene by target-specific siRNA targeting PPARγ enhanced ICAM-1 expression and the inhibitory effect of ciglitazone on TNFα-induced ICAM-1 expression was reversed by PPARγ siRNA and GW9662. SN-50 (10 μg/ml, an inhibitor for nuclear translocation of NF-κB, inhibited TNFα-induced ICAM-1 expression. Ciglitazone did not prevent TNFα-induced degradation of the cytosolic inhibitor of NF-κB (IκB, but inhibited the nuclear translocation of p65 induced by TNFα and suppressed the NF-κB/DNA binding activity. Conclusion: These findings suggest that ciglitazone inhibits TNFα-induced ICAM1 gene expression in human ASM cells through

  16. Pharyngeal squamous cell papilloma in adult Japanese: comparison with laryngeal papilloma in clinical manifestations and HPV infection.

    Science.gov (United States)

    Hirai, Ryoji; Makiyama, Kiyoshi; Higuti, Yusho; Ikeda, Atsuo; Miura, Masatoshi; Hasegawa, Hisashi; Kinukawa, Noriko; Ikeda, Minoru

    2012-10-01

    A number of reports have investigated the relationship between laryngeal papilloma and human papilloma virus (HPV) infection. On the other hand, it is unclear whether the HPV infection is involved in the occurrence of pharyngeal papilloma. We hypothesized that HPV infection was involved in the occurrence of pharyngeal papilloma similarly to laryngeal papilloma. To verify this hypothesis, we investigated the presence of HPV infection. Furthermore, clinical manifestations of pharyngeal papilloma, which had rarely been reported, were discussed. A male-to-female ratio, solitary or multiple occurrences, and koilocytosis were examined in cases with pharyngeal papilloma. HPV DNA was examined with unfixed surgically resected specimens of pharyngeal papilloma. A screening test by the liquid-phase hybridization method was carried out for the HPV high-risk group (16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, and 68) and HPV low-risk group (6, 11, 42, 43, 44). As a control, 15 cases with laryngeal papilloma for which the same screening test was carried out were employed. Pharyngeal papilloma occurred as a solitary lesion more often, whereas laryngeal papilloma occurred as multiple tumors more frequently. The HPV infection rate was 0% in pharyngeal papilloma cases, which was in stark contrast with 66.7% in the HPV low-risk group in laryngeal papilloma cases. Pharyngeal papilloma occurred as a solitary lesion in females more frequently. Contrary to our hypothesis, the involvement of HPV infection was unlikely in the occurrence of pharyngeal papilloma.

  17. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    International Nuclear Information System (INIS)

    Matsuzaki, Shinichi; Ishizuka, Tamotsu; Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo; Komachi, Mayumi; Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko; Dobashi, Kunio; Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki; Mori, Masatomo; Okajima, Fumikazu

    2011-01-01

    Highlights: → The involvement of extracellular acidification in airway remodeling was investigated. → Extracellular acidification alone induced CTGF production in human ASMCs. → Extracellular acidification enhanced TGF-β-induced CTGF production in human ASMCs. → Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. → OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-β-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G q/11 protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP 3 ) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G q/11 protein and inositol-1,4,5-trisphosphate-induced Ca 2+ mobilization in human ASMCs.

  18. Differential responses of human dendritic cells to metabolites from the oral/airway microbiome.

    Science.gov (United States)

    Whiteson, K; Agrawal, S; Agrawal, A

    2017-06-01

    Small molecule metabolites that are produced or altered by host-associated microbial communities are emerging as significant immune response modifiers. However, there is a key gap in our knowledge of how oral microbial metabolites affect the immune response. Here, we examined the effects of metabolites from five bacterial strains found commonly in the oral/airway microbial communities of humans. The five strains, each isolated from cystic fibrosis patient sputum, were Pseudomonas aeruginosa FLR01 non-mucoid (P1) and FLR02 mucoid (P2) forms, Streptococcus pneumoniae (Sp), S. salivarius (Ss) and Rothia mucilaginosa (Rm). The effect of bacterial metabolites on dendritic cell (DC) activation, T cell priming and cytokine secretion was determined by exposing DCs to bacterial supernatants and individual metabolites of interest. Supernatants from P1 and P2 induced high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-12 and IL-6 from DCs and primed T cells to secrete interferon (IFN)-γ, IL-22 compared to supernatants from Sp, Ss and Rm. Investigations into the composition of supernatants using gas chromatography-mass spectroscopy (GC-MS) revealed signature metabolites for each of the strains. Supernatants from P1 and P2 contained high levels of putrescine and glucose, while Sp and Ss contained high levels of 2,3-butanediol. The individual metabolites replicated the results of whole supernatants, although the magnitudes of their effects were reduced significantly. Altogether, our data demonstrate for the first time that the signature metabolites produced by different bacteria have different effects on DC functions. The identification of signature metabolites and their effects on the host immune system can provide mechanistic insights into diseases and may also be developed as biomarkers. © 2017 British Society for Immunology.

  19. Streptococcal Pharyngitis and Appendicitis in Children.

    Science.gov (United States)

    Nielsen, Jason W; Abel, Stuart A; Kenney, Brian

    2018-01-01

    Several pathologies, including pharyngitis, are associated with abdominal pain that can mimic appendicitis. We sought to further understand the link between appendicitis-like symptoms and streptococcal (strep) pharyngitis. All patients undergoing ultrasound imaging for appendicitis in our emergency department during 2013 were reviewed (n = 1572). A total of 207 patients were identified who underwent both ultrasound for appendicitis and testing for strep pharyngitis. Demographic and outcomes data between rule out appendicitis patients who underwent strep testing and those who did not were compared. Strep testing was more common in younger patients (mean age = 8.26 vs 10.26 years P appendicitis and 35 (16.9%) patients tested positive for strep pharyngitis. No cases of concurrent strep pharyngitis and appendicitis were identified. The negative appendectomy rate in the strep pharyngitis tested group was 38.5% (5/13), compared with 7.7% (23/296) ( P = .003) in the nontested group. The appendicitis rate among the strep tested group was 3.8% (8/207) compared with 20% (273/1365) in the nontested group ( P appendicitis, and had a higher rate of negative appendectomy. A diagnosis of concurrent appendicitis and strep pharyngitis is rare. In cases of patients with sufficient symptoms to warrant testing for strep pharyngitis a diagnosis of appendicitis is less likely and surgical intervention leads to higher negative appendectomy rates.

  20. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    Science.gov (United States)

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

  1. Numerical modelling of local deposition patients, activity distributions and cellular hit probabilities of inhaled radon progenies in human airways

    International Nuclear Information System (INIS)

    Farkas, A.; Balashazy, I.; Szoeke, I.

    2003-01-01

    The general objective of our research is modelling the biophysical processes of the effects of inhaled radon progenies. This effort is related to the rejection or support of the linear no threshold (LNT) dose-effect hypothesis, which seems to be one of the most challenging tasks of current radiation protection. Our approximation and results may also serve as a useful tool for lung cancer models. In this study, deposition patterns, activity distributions and alpha-hit probabilities of inhaled radon progenies in the large airways of the human tracheobronchial tree are computed. The airflow fields and related particle deposition patterns strongly depend on the shape of airway geometry and breathing pattern. Computed deposition patterns of attached an unattached radon progenies are strongly inhomogeneous creating hot spots at the carinal regions and downstream of the inner sides of the daughter airways. The results suggest that in the vicinity of the carinal regions the multiple hit probabilities are quite high even at low average doses and increase exponentially in the low-dose range. Thus, even the so-called low doses may present high doses for large clusters of cells. The cell transformation probabilities are much higher in these regions and this phenomenon cannot be modeled with average burdens. (authors)

  2. Genetic modification of adeno-associated viral vector type 2 capsid enhances gene transfer efficiency in polarized human airway epithelial cells.

    Science.gov (United States)

    White, April F; Mazur, Marina; Sorscher, Eric J; Zinn, Kurt R; Ponnazhagan, Selvarangan

    2008-12-01

    Cystic fibrosis (CF) is a common genetic disease characterized by defects in the expression of the CF transmembrane conductance regulator (CFTR) gene. Gene therapy offers better hope for the treatment of CF. Adeno-associated viral (AAV) vectors are capable of stable expression with low immunogenicity. Despite their potential in CF gene therapy, gene transfer efficiency by AAV is limited because of pathophysiological barriers in these patients. Although a few AAV serotypes have shown better transduction compared with the AAV2-based vectors, gene transfer efficiency in human airway epithelium has still not reached therapeutic levels. To engineer better AAV vectors for enhanced gene delivery in human airway epithelium, we developed and characterized mutant AAV vectors by genetic capsid modification, modeling the well-characterized AAV2 serotype. We genetically incorporated putative high-affinity peptide ligands to human airway epithelium on the GH loop region of AAV2 capsid protein. Six independent mutant AAV were constructed, containing peptide ligands previously reported to bind with high affinity for known and unknown receptors on human airway epithelial cells. The vectors were tested on nonairway cells and nonpolarized and polarized human airway epithelial cells for enhanced infectivity. One of the mutant vectors, with the peptide sequence THALWHT, not only showed the highest transduction in undifferentiated human airway epithelial cells but also indicated significant transduction in polarized cells. Interestingly, this modified vector was also able to infect cells independently of the heparan sulfate proteoglycan receptor. Incorporation of this ligand on other AAV serotypes, which have shown improved gene transfer efficiency in the human airway epithelium, may enhance the application of AAV vectors in CF gene therapy.

  3. Effect of Clark's twin-block appliance (CTB and non-extraction fixed mechano-therapy on the pharyngeal dimensions of growing children

    Directory of Open Access Journals (Sweden)

    Batool Ali

    2015-12-01

    Full Text Available Abstract Introduction: Narrow airway dimensions due to mandibular deficiency can predispose an individual to severe respiratory distress. Hence, treatment with mandibular advancement devices at an early age might help improving the pharyngeal passage and reduce the risk of respiratory difficulties. Therefore, the aim of the current study was to evaluate the mean changes in the pharyngeal dimensions of children with mandibular deficiency treated with Clark's twin-block appliance (CTB followed by fixed orthodontic treatment. Methods: Orthodontic records of 42 children with mandibular deficiency were selected. Records comprised three lateral cephalograms taken at the start of CTB treatment, after CTB removal and at the end of fixed appliance treatment, and were compared with 32 controls from the Bolton-Brush study. Friedman test was used to compare pre-treatment, mid-treatment and post-treatment pharyngeal dimensions. Wilcoxon signed rank test was used to compare the airway between pre-treatment and post follow-up controls. Mann-Whitney U test was applied to compare the mean changes in pharyngeal dimensions between treatment group and controls from T2 to T0. Post-hoc Dunnet T3 test was used for multiple comparisons of treatment outcomes after CTB and fixed appliances, taking a p-value of ≤ 0.05 as statistically significant. Results: Superior pharyngeal space (p < 0.001 and upper airway thickness (p = 0.035 were significantly increased after CTB, and the change in superior pharyngeal space remained stable after fixed mechano-therapy. Conclusion: CTB can have a positive effect in improving pharyngeal space and the resultant increase in airway remains stable on an average of two and a half years.

  4. Propagation of respiratory viruses in human airway epithelia reveals persistent virus-specific signatures.

    Science.gov (United States)

    Essaidi-Laziosi, Manel; Brito, Francisco; Benaoudia, Sacha; Royston, Léna; Cagno, Valeria; Fernandes-Rocha, Mélanie; Piuz, Isabelle; Zdobnov, Evgeny; Huang, Song; Constant, Samuel; Boldi, Marc-Olivier; Kaiser, Laurent; Tapparel, Caroline

    2018-06-01

    The leading cause of acute illnesses, respiratory viruses, typically cause self-limited diseases, although severe complications can occur in fragile patients. Rhinoviruses (RVs), respiratory enteroviruses (EVs), influenza virus, respiratory syncytial viruses (RSVs), and coronaviruses are highly prevalent respiratory pathogens, but because of the lack of reliable animal models, their differential pathogenesis remains poorly characterized. We sought to compare infections by respiratory viruses isolated from clinical specimens using reconstituted human airway epithelia. Tissues were infected with RV-A55, RV-A49, RV-B48, RV-C8, and RV-C15; respiratory EV-D68; influenza virus H3N2; RSV-B; and human coronavirus (HCoV)-OC43. Replication kinetics, cell tropism, effect on tissue integrity, and cytokine secretion were compared. Viral adaptation and tissue response were assessed through RNA sequencing. RVs, RSV-B, and HCoV-OC43 infected ciliated cells and caused no major cell death, whereas H3N2 and EV-D68 induced ciliated cell loss and tissue integrity disruption. H3N2 was also detected in rare goblet and basal cells. All viruses, except RV-B48 and HCoV-OC43, altered cilia beating and mucociliary clearance. H3N2 was the strongest cytokine inducer, and HCoV-OC43 was the weakest. Persistent infection was observed in all cases. RNA sequencing highlighted perturbation of tissue metabolism and induction of a transient but important immune response at 4 days after infection. No majority mutations emerged in the viral population. Our results highlight the differential in vitro pathogenesis of respiratory viruses during the acute infection phase and their ability to persist under immune tolerance. These data help to appreciate the range of disease severity observed in vivo and the occurrence of chronic respiratory tract infections in immunocompromised hosts. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Design, characterization and use of replicate human upper airways for radon dosimetry studies

    International Nuclear Information System (INIS)

    Swift, D.L.; Cheng, Y.S.; Su, Y.F.; Yeh, H.C.

    1992-01-01

    The size distribution of inhaled radon progeny aerosols is a significant factor in dosimetry. The role of the airways above the trachea is an important determinant of the respiratory distribution of both attached and unattached progeny aerosols. In order to provide information on the effect of particle size and breathing conditions on the overall and local deposition, we have developed a method to produce a replicate airway model from an in vivo magnetic resonance imaging coronal scan. The model consists of a sandwich of methacrylate elements, each element having the thickness of the scan interval. The transition between successive scan outlines traced on the front and back surfaces of each element is handsculpted in the plastic. The hollow model of the nasal passages thus produced has been characterized both morphologically and fluid-mechanically and has a flow resistance typical of a normal adult. The model has several distinct advantages for studies of radon progeny aerosol deposition. After exposure to a radioaerosol (or to an aerosol of an otherwise measurable substance) the individual elements can be separated to determine local deposition. The dimensions of specific upper-airway regions can be changed by replacing a small number of elements. The model has been incorporated in an exposure system for determining overall nandregional deposition of aerosols whose median diameter is approximately 1.7 nm. Measurements at several flow rates are presented to demonstrate use of the model in radon dosimetry. The model should also be useful for determining the airway deposition of other environmental aerosols

  6. Surfactant Proteins A, B, C and D in the Human Nasal Airway

    DEFF Research Database (Denmark)

    Gaunsbaek, Maria Q; Kjeldsen, Anette D; Svane-Knudsen, Viggo

    2014-01-01

    Aims: To investigate the presence of surfactant protein (SP) A, B, C and D in nasal airways and to determine whether the proteins exert their main functions in nasal secretions or in the deeper layers of the nasal mucosa. Methods: Volunteers were recruited from the Department of ENT Head and Neck...

  7. Effect of acute metabolic acid/base shifts on the human airway calibre.

    NARCIS (Netherlands)

    Brijker, F.; Elshout, F.J.J. van den; Heijdra, Y.F.; Bosch, F.H.; Folgering, H.T.M.

    2001-01-01

    Acute metabolic alkalosis (NaHCO(3)), acidosis (NH(4)Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24-56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid-base shifts were determined

  8. Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Shaikh N

    2017-06-01

    Full Text Available Nooreen Shaikh,1,2 Malcolm Johnson,3 David A Hall,4 Kian Fan Chung,1,2 John H Riley,3 Sally Worsley,5 Pankaj K Bhavsar1,2 1Experimental Studies, National Heart and Lung Institute, Imperial College London, 2Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, 3Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, 4Fibrosis and Lung Injury Development Planning Unit, GlaxoSmithKline, Stevenage, 5Respiratory Research & Development, GlaxoSmithKline, Uxbridge, UK Background: Intracellular mechanisms of action of umeclidinium (UMEC, a long-acting muscarinic receptor antagonist, and vilanterol (VI, a long-acting β2-adrenoceptor (β2R agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs. Materials and methods: ASMCs from tracheas of healthy lung-transplant donors were treated with VI, UMEC, UMEC and VI combined, or control compounds (salmeterol, propranolol, ICI 118.551, or methacholine [MCh]. Cyclic adenosine monophosphate (cAMP was measured using an enzyme-linked immunosorbent assay, intracellular free calcium ([Ca2+]i using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2 messenger RNA using real-time quantitative polymerase chain reaction. Results: VI and salmeterol (10–12–10–6 M induced cAMP production from ASMCs in a concentration-dependent manner, which was greater for VI at all concentrations. β2R antagonism by propranolol or ICI 118.551 (10–12–10–4 M resulted in concentration-dependent inhibition of VI-induced cAMP production, and ICI 118.551 was more potent. MCh (5×10–6 M, 30 minutes attenuated VI-induced cAMP production (P<0.05, whereas pretreatment with UMEC (10–8 M, 1 hour restored the magnitude of VI-induced cAMP production. ASMC stimulation with MCh (10–11–5×10–6 M resulted in a concentration-dependent increase in [Ca2+]i, which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca2+]i release was greater with UMEC + VI versus

  9. Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH-impedance monitoring

    Science.gov (United States)

    Desjardin, Marie; Roman, Sabine; des Varannes, Stanislas Bruley; Gourcerol, Guillaume; Coffin, Benoit; Ropert, Alain; Mion, François

    2013-01-01

    Background Pharyngeal pH probes and pH-impedance catheters have been developed for the diagnosis of laryngo-pharyngeal reflux. Objective To determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events. Methods 24-h pH-impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows, according to impedance patterns. Results Only 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Conclusions This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus. PMID:24917995

  10. LOCAL TREATMENT FEATURES OF PHARYNGITIS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    E. А. Lebedinskaya

    2014-01-01

    Full Text Available This paper reviews causes and treatment methods for inflammatory forms of pharynx pathology in children. It is shown that the primary cause of pharyngitis pathogenesis is the dysfunction of immunogenic resistance of pharyngeal mucous membrane. It is mucosal immune system that blocks viral and bacterial infections. Taking into account functional principles of mucosal immune system allows creating a personal programme of immunoreabilitation based on physiological and complex principles. At the same time in pediatric practice not only drug efficacy, but also its safety, ease of use and flavor become increasingly important. In this regard possibilities and advantages of locally applied antiseptics for acute pharyngitis treatment in children are considered.

  11. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

    Science.gov (United States)

    Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

    2012-09-01

    Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO2 NPs (size range 4-33 nm), two preparations of CeO2 NPs (9-36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15-240 μg/cm2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm2, in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO2 and CeO2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured nanomaterials.

  12. Comparative effects of metal oxide nanoparticles on human airway epithelial cells and macrophages

    International Nuclear Information System (INIS)

    Rotoli, Bianca Maria; Bussolati, Ovidio; Costa, Anna Luisa; Blosi, Magda; Di Cristo, Luisana; Zanello, Pier Paolo; Bianchi, Massimiliano G.; Visigalli, Rossana; Bergamaschi, Enrico

    2012-01-01

    Among nanomaterials of industrial relevance, metal-based nanoparticles (NPs) are widely used, but their effects on airway cells are relatively poorly characterized. To compare the effects of metal NPs on cells representative of the lung-blood barrier, Calu-3 epithelial cells and Raw264.7 macrophages were incubated with three industrially relevant preparations of TiO 2 NPs (size range 4–33 nm), two preparations of CeO 2 NPs (9–36 nm) and CuO NPs (25 nm). While Raw264.7 were grown on standard plasticware, Calu-3 cells were seeded on permeable filters, where they form a high-resistance monolayer, providing an in vitro model of the airway barrier. Metal NPs, obtained from industrial sources, were characterized under the conditions adopted for the biological tests. Cytotoxicity was assessed with resazurin method in both epithelial and macrophage cells, while epithelial barrier permeability was monitored measuring the trans-epithelial electrical resistance (TEER). In macrophages, titania and ceria had no significant effect on viability in the whole range of nominal doses tested (15–240 μg/cm 2 of monolayer), while CuO NPs produced a marked viability loss. Moreover, only CuO NPs, but not the other NPs, lowered TEER of Calu-3 monolayers, pointing to the impairment of the epithelial barrier. TEER decreased by 30 % at the dose of 10 μg/cm 2 of CuO NPs, compared to untreated control, and was abolished at doses ≥80 μg/cm 2 , in strict correlation with changes in cell viability. These results indicate that (1) CuO NPs increase airway epithelium permeability even at relatively low doses and are significantly toxic for macrophages and airway epithelial cells, likely through the release of Cu ions in the medium; (2) TiO 2 and CeO 2 NPs do not affect TEER and exhibit little acute toxicity for airway epithelial cells and macrophages; and (3) TEER measurement can provide a simple method to assess the impairment of in vitro airway epithelial barrier model by manufactured

  13. Study of cyclic and steady particle motion in a realistic human airway model using phase-Doppler anemometry

    Science.gov (United States)

    Jedelský, Jan; Lízal, František; Jícha, Miroslav

    2012-04-01

    Transport and deposition of particles in human airways has been of research interest for many years. Various experimental methods such as constant temperature anemometry, particle image velocimetry and laser-Doppler based techniques were employed for study of aerosol transport in the past. We use Phase-Doppler Particle Analyser (P/DPA) for time resolved size and velocity measurement of liquid aerosol particles in a size range 1 to 8 μm. The di-2ethylhexyl sabacate (DEHS) particles were produced by condensation monodisperse aerosol generator. A thin-wall transparent model of human airways with non-symmetric bifurcations and non-planar geometry containing parts from throat to 3rd-4th generation of bronchi was fabricated for the study. Several cyclic (sinusoidal) breathing regimes were simulated using pneumatic breathing mechanism. Analogous steady-flow regimes were also investigated and used for comparison. An analysis of the particle velocity data was performed with aim to gain deeper understanding of the transport phenomena in the realistic bifurcating airway system. Flows of particles of different sizes in range 1 - 10 μm was found to slightly differ for extremely high Stokes numbers. Differences in steady and cyclic turbulence intensities were documented in the paper. Systematically higher turbulence intensity was found for cyclic flows and mainly in the expiration breathing phase. Negligible differences were found for behaviour of different particle size classes in the inspected range 1 to 8 μm. Possibility of velocity spectra estimation of air flow using the P/DPA data is discussed.

  14. Study of cyclic and steady particle motion in a realistic human airway model using phase-Doppler anemometry

    Directory of Open Access Journals (Sweden)

    Jícha Miroslav

    2012-04-01

    Full Text Available Transport and deposition of particles in human airways has been of research interest for many years. Various experimental methods such as constant temperature anemometry, particle image velocimetry and laser-Doppler based techniques were employed for study of aerosol transport in the past. We use Phase-Doppler Particle Analyser (P/DPA for time resolved size and velocity measurement of liquid aerosol particles in a size range 1 to 8 μm. The di-2ethylhexyl sabacate (DEHS particles were produced by condensation monodisperse aerosol generator. A thin-wall transparent model of human airways with non-symmetric bifurcations and non-planar geometry containing parts from throat to 3rd-4th generation of bronchi was fabricated for the study. Several cyclic (sinusoidal breathing regimes were simulated using pneumatic breathing mechanism. Analogous steady-flow regimes were also investigated and used for comparison. An analysis of the particle velocity data was performed with aim to gain deeper understanding of the transport phenomena in the realistic bifurcating airway system. Flows of particles of different sizes in range 1 – 10 μm was found to slightly differ for extremely high Stokes numbers. Differences in steady and cyclic turbulence intensities were documented in the paper. Systematically higher turbulence intensity was found for cyclic flows and mainly in the expiration breathing phase. Negligible differences were found for behaviour of different particle size classes in the inspected range 1 to 8 μm. Possibility of velocity spectra estimation of air flow using the P/DPA data is discussed.

  15. CXCR3 surface expression in human airway epithelial cells: cell cycle dependence and effect on cell proliferation.

    Science.gov (United States)

    Aksoy, Mark O; Yang, Yi; Ji, Rong; Reddy, P J; Shahabuddin, Syed; Litvin, Judith; Rogers, Thomas J; Kelsen, Steven G

    2006-05-01

    We recently demonstrated that human bronchial epithelial cells (HBEC) constitutively express the CXC chemokine receptor CXCR3, which when activated, induces directed cell migration. The present study in HBEC examined the relative expression of the CXCR3 splice variants CXCR3-A and -B, cell cycle dependence of CXCR3 expression, and the effects of the CXCR3 ligand, the interferon-gamma-inducible CXC chemokine I-TAC/CXCL11, on DNA synthesis and cell proliferation. Both CXCR3-A and -B mRNA, assessed by real-time RT-PCR, were expressed in normal HBEC (NHBEC) and the HBEC line 16-HBE. However, CXCR3-B mRNA was 39- and 6-fold greater than CXCR3-A mRNA in NHBEC and 16-HBE, respectively. Although most HBEC (>80%) assessed by flow cytometry and immunofluorescence microscopy contained intracellular CXCR3, only a minority (75%) were in the S + G(2)/M phases of the cell cycle. Stimulation of CXCR3 with I-TAC enhanced thymidine incorporation and cell proliferation and increased p38 and ERK1/2 phosphorylation. These data indicate that 1) human airway epithelial cells primarily express CXCR3-B mRNA, 2) surface expression of CXCR3 is largely confined to the S + G(2)/M phases of the cell cycle, and 3) activation of CXCR3 induces DNA synthesis, cell proliferation, and activation of MAPK pathways. We speculate that activation of CXCR3 exerts a mitogenic effect in HBEC, which may be important during airway mucosal injury in obstructive airway diseases such as asthma and chronic obstructive pulmonary disease.

  16. Human airway eosinophils exhibit preferential reduction in STAT signaling capacity and increased CISH expression.

    Science.gov (United States)

    Burnham, Mandy E; Koziol-White, Cynthia J; Esnault, Stephane; Bates, Mary E; Evans, Michael D; Bertics, Paul J; Denlinger, Loren C

    2013-09-15

    Allergic asthma, a chronic respiratory disorder marked by inflammation and recurrent airflow obstruction, is associated with elevated levels of IL-5 family cytokines and elevated numbers of eosinophils (EOS). IL-5 family cytokines elongate peripheral blood EOS (EOS(PB)) viability, recruit EOS(PB) to the airways, and, at higher concentrations, induce degranulation and reactive oxygen species generation. Although airway EOS (EOS(A)) remain signal ready in that GM-CSF treatment induces degranulation, treatment of EOS(A) with IL-5 family cytokines no longer confers a survival advantage. Because the IL-5 family receptors have common signaling capacity, but are uncoupled from EOS(A) survival, whereas other IL-5 family induced endpoints remain functional, we tested the hypothesis that EOS(A) possess a JAK/STAT-specific regulatory mechanism (because JAK/STAT signaling is critical to EOS survival). We found that IL-5 family-induced STAT3 and STAT5 phosphorylation is attenuated in EOS(A) relative to blood EOS from airway allergen-challenged donors. However, IL-5 family-induced ERK1/2 phosphorylation is not altered between EOS(A) and EOS from airway allergen-challenged donors. These observations suggest EOS(A) possess a regulatory mechanism for suppressing STAT signaling distinct from ERK1/2 activation. Furthermore, we found, in EOS(PB), IL-5 family cytokines induce members of the suppressors of cytokine signaling (SOCS) genes, CISH and SOCS1. Additionally, following allergen challenge, EOS(A) express significantly more CISH and SOCS1 mRNA and CISH protein than EOS(PB) counterparts. In EOS(PB), long-term pretreatment with IL-5 family cytokines, to varying degrees, attenuates IL-5 family-induced STAT5 phosphorylation. These data support a model in which IL-5 family cytokines trigger a selective downregulation mechanism in EOS(A) for JAK/STAT pathways.

  17. Pharyngeal weakness and upper esophageal sphincter opening in patients with unilateral vocal fold immobility.

    Science.gov (United States)

    Domer, Amanda S; Leonard, Rebecca; Belafsky, Peter C

    2014-10-01

    To evaluate pharyngeal strength and upper esophageal sphincter opening in patients with unilateral vocal fold immobility (UVFI). Case control study. Charts of individuals with UVFI who underwent a videofluoroscopic swallow study were reviewed. To exclude confounding variables associated with pharyngeal weakness, inclusion was limited to patients with iatrogenic and idiopathic UVFI. Data abstracted included patient demographics, etiology of UVFI, pharyngeal constriction ratio (PCR), and upper esophageal sphincter (UES) opening (UESmax). Data were compared to age/gender-matched controls with no history of dysphagia or UVFI. Discrete variables were analyzed using a chi-square test of independence, and an independent samples t test was used to compare the UVFI and control groups (P = 0.05). A one-way analysis of variance (ANOVA) was used to compare iatrogenic and idiopathic UVFI groups. The mean age of the cohort (n = 25) was 61 (±14 SD) years and 52% was female. The etiologies of UVFI were iatrogenic (n = 17) and idiopathic (n = 8). Thirty-eight percent of UVFI patients (n = 25) aspirated compared to 0% of controls (P  0.05). Individuals with UVFI of iatrogenic and idiopathic etiologies with subjective dysphagia demonstrate objective evidence of pharyngeal weakness. The increased prevalence of aspiration in this population may not be solely the result of impaired airway protection. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  18. PQN-75 is expressed in the pharyngeal gland cells of Caenorhabditis elegans and is dispensable for germline development

    Directory of Open Access Journals (Sweden)

    Jesse D. Rochester

    2017-09-01

    Full Text Available In Caenorhabditis elegans, five pharyngeal gland cells reside in the terminal bulb of the pharynx and extend anterior processes to five contact points in the pharyngeal lumen. Pharyngeal gland cells secrete mucin-like proteins thought to facilitate digestion, hatching, molting and assembly of the surface coat of the cuticle, but supporting evidence has been sparse. Here we show pharyngeal gland cell expression of PQN-75, a unique protein containing an N-terminal signal peptide, nucleoporin (Nup-like phenylalanine/glycine (FG repeats, and an extensive polyproline repeat domain with similarities to human basic salivary proline-rich pre-protein PRB2. Imaging of C-terminal tagged PQN-75 shows localization throughout pharyngeal gland cell processes but not the pharyngeal lumen; instead, aggregates of PQN-75 are occasionally found throughout the pharynx, suggesting secretion from pharyngeal gland cells into the surrounding pharyngeal muscle. PQN-75 does not affect fertility and brood size in C. elegans but confers some degree of stress resistance and thermotolerance through unknown mechanisms.

  19. Impact of varying physical activity levels on airway sensitivity and bronchodilation in healthy humans.

    Science.gov (United States)

    Smith, Joshua R; Kurti, Stephanie P; Johnson, Ariel M; Kolmer, Sarah A; Harms, Craig

    2015-12-01

    The purpose of this study was to determine if the amount of physical activity influences airway sensitivity and bronchodilation in healthy subjects across a range of physical activity levels. Thirty healthy subjects (age, 21.9 ± 2.6 years; 13 men/17 women) with normal pulmonary function reported to the laboratory on 2 separate occasions where they were randomized to breathe either hypertonic saline (HS) (nebulized hypertonic saline (25%) for 20 min) or HS followed by 5 deep inspirations (DIs), which has been reported to bronchodilate the airways. Pulmonary function tests (PFTs) were performed prior to both conditions and following the HS breathing or 5 DIs. Moderate to vigorous physical activity (MVPA) level was measured via accelerometer worn for 7 days. Following the HS breathing, forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) significantly decreased from baseline by -11.8% ± 8.4% and -9.3% ± 6.7%, respectively. A 2-segment linear model determined significant relationships between MVPA and percent change in FEV1 (r = 0.50) and FVC (r = 0.55). MVPA above ∼497 and ∼500 min/week for FEV1 and FVC, respectively, resulted in minor additional improvements (p > 0.05) in PFTs following the HS breathing. Following the DIs, FEV1 and FVC decreased (p 0.05) to MVPA. In conclusion, these data demonstrate that higher MVPA levels attenuated airway sensitivity but not bronchodilation in healthy subjects.

  20. Electrostatic Charge Effects on Pharmaceutical Aerosol Deposition in Human Nasal–Laryngeal Airways

    Directory of Open Access Journals (Sweden)

    Jinxiang Xi

    2014-01-01

    Full Text Available Electrostatic charging occurs in most aerosol generation processes and can significantly influence subsequent particle deposition rates and patterns in the respiratory tract through the image and space forces. The behavior of inhaled aerosols with charge is expected to be most affected in the upper airways, where particles come in close proximity to the narrow turbinate surface, and before charge dissipation occurs as a result of high humidity. The objective of this study was to quantitatively evaluate the deposition of charged aerosols in an MRI-based nasal–laryngeal airway model. Particle sizes of 5 nm–30 µm and charge levels ranging from neutralized to ten times the saturation limit were considered. A well-validated low Reynolds number (LRN k–ω turbulence model and a discrete Lagrangian tracking approach that accounted for electrostatic image force were employed to simulate the nasal airflow and aerosol dynamics. For ultrafine aerosols, electrostatic charge was observed to exert a discernible but insignificant effect. In contrast, remarkably enhanced depositions were observed for micrometer particles with charge, which could be one order of magnitude larger than no-charge depositions. The deposition hot spots shifted towards the anterior part of the upper airway as the charge level increased. Results of this study have important implications for evaluating nasal drug delivery devices and for assessing doses received from pollutants, which often carry a certain level of electric charges.

  1. Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses

    Science.gov (United States)

    Jazaeri Farsani, Seyed Mohammad; Deijs, Martin; Dijkman, Ronald; Molenkamp, Richard; Jeeninga, Rienk E; Ieven, Margareta; Goossens, Herman; van der Hoek, Lia

    2015-01-01

    Background Currently, virus discovery is mainly based on molecular techniques. Here, we propose a method that relies on virus culturing combined with state-of-the-art sequencing techniques. The most natural ex vivo culture system was used to enable replication of respiratory viruses. Method Three respiratory clinical samples were tested on well-differentiated pseudostratified tracheobronchial human airway epithelial (HAE) cultures grown at an air–liquid interface, which resemble the airway epithelium. Cells were stained with convalescent serum of the patients to identify infected cells and apical washes were analyzed by VIDISCA-454, a next-generation sequencing virus discovery technique. Results Infected cells were observed for all three samples. Sequencing subsequently indicated that the cells were infected by either human coronavirus OC43, influenzavirus B, or influenzavirus A. The sequence reads covered a large part of the genome (52%, 82%, and 57%, respectively). Conclusion We present here a new method for virus discovery that requires a virus culture on primary cells and an antibody detection. The virus in the harvest can be used to characterize the viral genome sequence and cell tropism, but also provides progeny virus to initiate experiments to fulfill the Koch's postulates. PMID:25482367

  2. Streptococcal pharyngitis and rheumatic heart disease: the superantigen hypothesis revisited.

    Science.gov (United States)

    Hurst, Jacklyn R; Kasper, Katherine J; Sule, Akshay N; McCormick, John K

    2018-07-01

    Streptococcus pyogenes is a human-specific and globally prominent bacterial pathogen that despite causing numerous human infections, this bacterium is normally found in an asymptomatic carrier state. This review provides an overview of both bacterial and human factors that likely play an important role in nasopharyngeal colonization and pharyngitis, as well as the development of acute rheumatic fever and rheumatic heart disease. Here we highlight a recently described role for bacterial superantigens in promoting acute nasopharyngeal infection, and discuss how these immune system activating toxins could be crucial to initiate the autoimmune process in rheumatic heart disease. Copyright © 2018. Published by Elsevier B.V.

  3. Pakistan prevalence survey in acute pharyngitis

    International Nuclear Information System (INIS)

    Rathi, S. K.

    2014-01-01

    Objective: To study the prevalence of Group A beta haemolytic Streptococcus in patients with acute pharyngitis and correlation of Modified Centor Score and Rapid Antigen Detection Test. Methods: The multi-centre, prospective, cross-sectional study was conducted in 8 major cities of Pakistan between June 2012 and February 2013, and comprised patients presenting with acute pharyngitis. The subjects were above 3 years of age presenting to primary care physician with sore throat, temperature over 100.4 (degree) F, tonsillar exudates and/or cervical adenopathy (duration of symptoms 4. Conclusion: The prevalence of Group A beta haemolytic Streptococcus as a cause of acute pharyngitis was 25.3%. Modified Centor Score had a strong positive correlation with Rapid Antigen Detection Test in identifying Group A beta haemolytic Streptococcus as a cause of acute pharyngitis. (author)

  4. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    Energy Technology Data Exchange (ETDEWEB)

    Lasalvia, Maria [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Castellani, Stefano [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); D’Antonio, Palma [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Perna, Giuseppe [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Carbone, Annalucia [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy); Colia, Anna Laura; Maffione, Angela Bruna [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Capozzi, Vito [Department of Clinical and Experimental Medicine, University of Foggia, Foggia (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Bari, Bari (Italy); Conese, Massimo, E-mail: massimo.conese@unifg.it [Department of Medical and Surgical Sciences, University of Foggia, Foggia (Italy)

    2016-10-15

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in

  5. Human airway epithelial cells investigated by atomic force microscopy: A hint to cystic fibrosis epithelial pathology

    International Nuclear Information System (INIS)

    Lasalvia, Maria; Castellani, Stefano; D’Antonio, Palma; Perna, Giuseppe; Carbone, Annalucia; Colia, Anna Laura; Maffione, Angela Bruna; Capozzi, Vito; Conese, Massimo

    2016-01-01

    The pathophysiology of cystic fibrosis (CF) airway disease stems from mutations in the CF Transmembrane Conductance Regulator (CFTR) gene, leading to a chronic respiratory disease. Actin cytoskeleton is disorganized in CF airway epithelial cells, likely contributing to the CF-associated basic defects, i.e. defective chloride secretion and sodium/fluid hypersorption. In this work, we aimed to find whether this alteration could be pointed out by means of Atomic Force Microscopy (AFM) investigation, as roughness and Young's elastic module. Moreover, we also sought to determine whether disorganization of actin cytoskeleton is linked to hypersoption of apical fluid. Not only CFBE41o- (CFBE) cells, immortalized airway epithelial cells homozygous for the F508del CFTR allele, showed a different morphology in comparison with 16HBE14o- (16HBE) epithelial cells, wild-type for CFTR, but also they displayed a lack of stress fibers, suggestive of a disorganized actin cytoskeleton. AFM measurements showed that CFBE cells presented a higher membrane roughness and decreased rigidity as compared with 16HBE cells. CFBE overexpressing wtCFTR became more elongated than the parental CFBE cell line and presented actin stress fibers. CFBE cells absorbed more fluid from the apical compartment. Study of fluid absorption with the F-actin-depolymerizing agent Latrunculin B demonstrated that actin cytoskeletal disorganization increased fluid absorption, an effect observed at higher magnitude in 16HBE than in CFBE cells. For the first time, we demonstrate that actin cytoskeleton disorganization is reflected by AFM parameters in CF airway epithelial cells. Our data also strongly suggest that the lack of stress fibers is involved in at least one of the early step in CF pathophysiology at the levels of the airways, i.e. fluid hypersorption. - Highlights: • CF bronchial epithelial (CFBE) cells show a disorganized actin cytoskeleton. • CFBE cells present high roughness and low rigidity in the

  6. COMPUTED TOMOGRAPHIC EVALUATION OF CANINE PHARYNGEAL NEOPLASIA

    OpenAIRE

    Carozzi, Gregorio

    2016-01-01

    Computed tomography (CT) is commonly used to investigate head tumours in dogs, and is a fundamental part of the diagnostic work-up, for diagnosis, staging and planning therapy in neoplastic disease. Nasal diseases, either neoplastic or non-neoplastic diseases, oral neoplasia, brain disease, thyroid or carotid body neoplasia have been extensively studied. However little information are available for lesions of the pharyngeal area. In this thesis, cases of dogs affected by pharyngeal neoplas...

  7. Downregulation of SLC7A7 Triggers an Inflammatory Phenotype in Human Macrophages and Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Bianca Maria Rotoli

    2018-03-01

    Full Text Available Lysinuric protein intolerance (LPI is a recessively inherited aminoaciduria caused by mutations of SLC7A7, the gene encoding y+LAT1 light chain of system y+L for cationic amino acid transport. The pathogenesis of LPI is still unknown. In this study, we have utilized a gene silencing approach in macrophages and airway epithelial cells to investigate whether complications affecting lung and immune system are directly ascribable to the lack of SLC7A7 or, rather, mediated by an abnormal accumulation of arginine in mutated cells. When SLC7A7/y+LAT1 was silenced in human THP-1 macrophages and A549 airway epithelial cells by means of short interference RNA (siRNA, a significant induction of the expression and release of the inflammatory mediators IL1β and TNFα was observed, no matter the intracellular arginine availability. This effect was mainly regulated at transcriptional level through the activation of NFκB signaling pathway. Moreover, since respiratory epithelial cells are the important sources of chemokines in response to pro-inflammatory stimuli, the effect of IL1β has been addressed on SLC7A7 silenced A549 cells. Results obtained indicated that the downregulation of SLC7A7/y+LAT1 markedly strengthened the stimulatory effect of the cytokine on CCL5/RANTES expression and release without affecting the levels of CXCL8/IL8. Consistently, also the conditioned medium of silenced THP-1 macrophages activated airway epithelial cells in terms of CCL5/RANTES expression due to the presence of elevated amount of proinflammatory cytokines. In conclusion, our results point to a novel thus far unknown function of SLC7A7/y+LAT1, that, under physiological conditions, besides transporting arginine, may act as a brake to restrain inflammation.

  8. Numerical investigation of inspiratory airflow in a realistic model of the human tracheobronchial airways and a comparison with experimental results.

    Science.gov (United States)

    Elcner, Jakub; Lizal, Frantisek; Jedelsky, Jan; Jicha, Miroslav; Chovancova, Michaela

    2016-04-01

    In this article, the results of numerical simulations using computational fluid dynamics (CFD) and a comparison with experiments performed with phase Doppler anemometry are presented. The simulations and experiments were conducted in a realistic model of the human airways, which comprised the throat, trachea and tracheobronchial tree up to the fourth generation. A full inspiration/expiration breathing cycle was used with tidal volumes 0.5 and 1 L, which correspond to a sedentary regime and deep breath, respectively. The length of the entire breathing cycle was 4 s, with inspiration and expiration each lasting 2 s. As a boundary condition for the CFD simulations, experimentally obtained flow rate distribution in 10 terminal airways was used with zero pressure resistance at the throat inlet. CCM+ CFD code (Adapco) was used with an SST k-ω low-Reynolds Number RANS model. The total number of polyhedral control volumes was 2.6 million with a time step of 0.001 s. Comparisons were made at several points in eight cross sections selected according to experiments in the trachea and the left and right bronchi. The results agree well with experiments involving the oscillation (temporal relocation) of flow structures in the majority of the cross sections and individual local positions. Velocity field simulation in several cross sections shows a very unstable flow field, which originates in the tracheal laryngeal jet and propagates far downstream with the formation of separation zones in both left and right airways. The RANS simulation agrees with the experiments in almost all the cross sections and shows unstable local flow structures and a quantitatively acceptable solution for the time-averaged flow field.

  9. Post-extubation airway obstruction. Literature review

    Directory of Open Access Journals (Sweden)

    Álvaro SÁNCHEZ-TABERNERO

    2017-03-01

    Full Text Available Introduction and objective: airway obstruction after extubation in any surgery is a critical event with low incidence, which may require reintubation or tracheostomy, which often otolaryngologist is required. Objective: To determine the prevalence of BVA and its causes through systematic literature review. Method: Literature review in PubMed, Scopus and Cochrane clinical trials, meta-analysis, reviews and case series and control over airway obstruction after extubation that requires reintubation in adults. Results: 6 studies and one clinical practice guidelines were selected. The most common cause of extubation failure is blocking the airway for various reasons (pharyngeal muscle weakness residual effect -often farmacologycal-, laryngospasm, vocal cord paralysis, edema of upper respiratory tract, cervical postoperative hematoma, foreign bodies or secretions. Most cases of re-intubation occurred within 2 hours after extubation. Conclusions: The most common cause of failure after general anesthesia extubation is blocking the airway generally caused by residual neuromuscular blocking effect. Airway obstruction risk increases in airway and head and neck surgery. Difficult intubation guidlines have improved performance and reduced adverse events and similar strategies must be implemented in extubation. The procedure extubation and reintubation should be documented. Working groups airway must be multidisciplinary and include specialists in otolaryngology.

  10. Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

    Science.gov (United States)

    Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

    2011-01-01

    To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

  11. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors.

    Science.gov (United States)

    Burgess, J K; Ketheson, A; Faiz, A; Limbert Rempel, K A; Oliver, B G; Ward, J P T; Halayko, A J

    2018-01-16

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness of hTERT immortalisation of human ASM cells as a research tool. Specifically we compared proliferative capacity, inflammatory mediator release and extracellular matrix (ECM) production in hTERT immortalised and parent primary ASM cells from asthmatic and non-asthmatic donors. Our studies revealed no significant differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis between donor-matched parent and hTERT immortalised ASM cell lines. However, deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in immortalised ASM cells compared to corresponding primary cells. Notably, previously reported differences in proliferation and inflammatory mediator release between asthmatic and non-asthmatic ASM cells were retained, but excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM cells. This study shows that hTERT immortalised ASM cells mirror primary ASM cells in proliferation and inflammatory profile characteristics. Moreover, we demonstrate both strengths and weaknesses of this immortalised cell model as a representation of primary ASM cells for future asthma pathophysiological research.

  12. Objective classification of different head and neck positions and their influence on the radiographic pharyngeal diameter in sport horses

    Science.gov (United States)

    2014-01-01

    Background Various head and neck positions in sport horses are significant as they can interfere with upper airway flow mechanics during exercise. Until now, research has focused on subjectively described head and neck positions. The objective of this study was to develop an objective, reproducible method for quantifying head and neck positions accurately. Results Determining the angle between the ridge of the nose and the horizontal plane (ground angle) together with the angle between the ridge of nose and the line connecting the neck and the withers (withers angle) has provided values that allow precise identification of three preselected head and neck positions for performing sport horses. The pharyngeal diameter, determined on lateral radiographs of 35 horses, differed significantly between the established flexed position and the remaining two head and neck positions (extended and neutral). There was a significant correlation between the pharyngeal diameter and the ground angle (Spearman’s rank correlation coefficient −0.769, p horses. The ground angle and the withers angle show significant correlation with the measured pharyngeal diameter in resting horses. Hence, these angles provide an appropriate method for assessing the degree of head and neck flexion. Further research is required to examine the influence of increasing head and neck flexion and the related pharyngeal diameter on upper airway function in exercising horses. PMID:24886564

  13. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota.

    Science.gov (United States)

    Larsen, Jeppe Madura; Steen-Jensen, Daniel Bisgaard; Laursen, Janne Marie; Søndergaard, Jonas Nørskov; Musavian, Hanieh Sadat; Butt, Tariq Mahmood; Brix, Susanne

    2012-01-01

    Recent studies using culture-independent methods have characterized the human airway microbiota and report microbial communities distinct from other body sites. Changes in these airway bacterial communities appear to be associated with inflammatory lung disease, yet the pro-inflammatory properties of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella spp. vs. Actinomyces spp.) reflecting their pro-inflammatory effects on DCs. Co-culture experiments found that Prevotella spp. were able to reduce Haemophillus influenzae-induced IL-12p70 in DCs, whereas no effect was observed on IL-23 and IL-10 production. This study demonstrates intrinsic differences in DC stimulating properties of bacteria associated with the airway microbiota.

  14. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  15. Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with Obstructive Sleep Apnea.

    Science.gov (United States)

    Sands, Scott A; Edwards, Bradley A; Terrill, Philip I; Taranto-Montemurro, Luigi; Azarbarzin, Ali; Marques, Melania; Hess, Lauren B; White, David P; Wellman, Andrew

    2018-05-01

    Therapies for obstructive sleep apnea (OSA) could be administered on the basis of a patient's own phenotypic causes ("traits") if a clinically applicable approach were available. Here we aimed to provide a means to quantify two key contributors to OSA-pharyngeal collapsibility and compensatory muscle responsiveness-that is applicable to diagnostic polysomnography. Based on physiological definitions, pharyngeal collapsibility determines the ventilation at normal (eupneic) ventilatory drive during sleep, and pharyngeal compensation determines the rise in ventilation accompanying a rising ventilatory drive. Thus, measuring ventilation and ventilatory drive (e.g., during spontaneous cyclic events) should reveal a patient's phenotypic traits without specialized intervention. We demonstrate this concept in patients with OSA (N = 29), using a novel automated noninvasive method to estimate ventilatory drive (polysomnographic method) and using "gold standard" ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized physiological measurements using continuous positive airway pressure manipulation were employed for further comparison. The validity of nasal pressure as a ventilation surrogate was also tested (N = 11). Polysomnography-derived collapsibility and compensation estimates correlated favorably with those quantified using gold standard ventilatory drive (R = 0.83, P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive airway pressure manipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001; respectively). Polysomnographic estimates effectively stratified patients into high versus low subgroups (accuracy, 69-86% vs. ventilatory drive measures; P < 0.05). Traits were near-identical using nasal pressure versus pneumotach (N = 11, R ≥ 0.98, both traits; P < 0.001). Phenotypes of pharyngeal dysfunction in OSA are evident from spontaneous changes in ventilation and

  16. Study of the flow unsteadiness in the human airway using large eddy simulation

    Science.gov (United States)

    Bernate, Jorge A.; Geisler, Taylor S.; Padhy, Sourav; Shaqfeh, Eric S. G.; Iaccarino, Gianluca

    2017-08-01

    The unsteady flow in a patient-specific geometry of the airways is studied. The geometry comprises the oral cavity, orophrarynx, larynx, trachea, and the bronchial tree extending to generations 5-8. Simulations are carried out for a constant inspiratory flow rate of 60 liters/min, corresponding to a Reynolds number of 4213 for a nominal tracheal diameter of 2 cm. The computed mean flow field is compared extensively with magnetic resonance velocimetry measurements by Banko et al. [Exp. Fluids 56, 117 (2015), 10.1007/s00348-015-1966-y] carried out in the same computed-tomography-based geometry, showing good agreement. In particular, we focus on the dynamics of the flow in the bronchial tree. After becoming unsteady at a constriction in the oropharynx, the flow is found to be chaotic, exhibiting fluctuations with broad-band spectra even at the most distal airways in which the Reynolds numbers are as low as 300. An inertial range signature is present in the trachea but not in the bronchial tree where a narrower range of scales is observed. The unsteadiness is attributed to the convection of turbulent structures produced at the larynx as well as to local kinetic energy production throughout the bronchial tree. Production occurs predominantly at shear layers bounding geometry-induced separation regions.

  17. Levcromakalim- and isoprenaline-induced relaxation of human isolated airways--role of the epithelium and of K+ channel activation.

    Science.gov (United States)

    Black, J L; Johnson, P R; McKay, K O; Carey, D; Armour, C L

    1994-06-01

    In this study we have investigated the mechanism of action of levcromakalim and isoprenaline in human isolated airways with respect to the K+ channels they activate and the possibility that these smooth muscle relaxants activate K+ channels on the airway epithelium. Mechanical removal of the epithelial layer (mean percentage of epithelium present 20 +/- 3%, n = 20 tissues) did not affect the relaxation responses to levcromakalim or isoprenaline, either in terms of maximal relaxation or sensitivity. Whilst having no effect on isoprenaline-induced relaxation, studied from basal tone, the ATP-sensitive K+ channel blocker BRL 31660 (10, 30 and 50 microM) reduced relaxation responses induced (from basal tone) by levcromakalim from 74 +/- 6% (of the maximal response to isoprenaline) to 48 +/- 12% (n = 7), 9 +/- 9% (n = 4) and 0 (n = 4), respectively. Charybdotoxin, a blocker of high conductance Ca(2+)-activated K+ channels, at concentrations of 30 and 100 nM, had no effect on either levcromakalim- or or isoprenaline-induced relaxation responses and yet charybdotoxin was active at KCa channels in outside-out patches of hippocampal granule cells. Moreover, tetraethylammonium (10 mM) inhibited neither isoprenaline- nor levcromakalim-induced relaxation. This study has demonstrated that the relaxation responses elicited in human bronchus to isoprenaline and levcromakalim are likely to be the result of direct effects on the smooth muscle with no contribution from epithelial receptors or K+ channels. The actions of levcromakalim appear to be mediated only via activation of KATP channels. Further, we have made the important observation that, under the experimental conditions of our study, isoprenaline does not activate the KCa channel to produce relaxation in human bronchus.

  18. Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-α and dexamethasone

    Directory of Open Access Journals (Sweden)

    Walseth Timothy F

    2008-03-01

    Full Text Available Abstract Background CD38 is expressed in human airway smooth muscle (HASM cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-α. CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-α. Regulation of CD38 expression in HASM cells involves the transcription factor NF-κB, and glucocorticoids inhibit this expression through NF-κB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene. Methods We cloned a putative 3 kb promoter fragment of the human cd38 gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative cd38 promoter region revealed one NF-κB and several AP-1 and glucocorticoid response element (GRE motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-κB and some of the AP-1 sites, or the promoter with mutations of the NF-κB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies. Results TNF-α induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-κB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-α. The binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-κB site and some of the six AP-1 sites was increased by TNF-α, and to

  19. Systems Biology Investigations of Pseudomonas aeruginosa Evolution in Association with Human Airway Infections

    DEFF Research Database (Denmark)

    Pedersen, Søren Damkiær

    Most knowledge about evolutionary adaptation has been gained from experimental evolution studies, in which organisms have been allowed to evolve under simple, well-defined conditions in the laboratory. While these studies have provided novel insight into the fundamental processes of evolutionary....... aeruginosa DK2 clone lineage during 200,000 generations of evolution in the CF airways from its entrance in the clinic in the 1970’ies until the end of 2010. Genetic analysis showed that the DK2 lineage between 1973 and 2007 accumulated mutations in a near-linear manner with an overall genomic signature...... included fixation of mutations in the rpoD gene encoding the principle sigma factor σ70. The findings presented in this thesis provide insight into the genetic mechanisms and evolutionary processes that shape the adaptation of bacteria colonizing complex natural environments. Increased knowledge...

  20. Human Airway Eosinophils Exhibit Preferential Reduction in STAT Signaling Capacity and Increased CISH Expression1

    Science.gov (United States)

    Burnham, Mandy E.; Koziol-White, Cynthia J.; Esnault, Stephane; Bates, Mary E.; Evans, Michael D.; Bertics, Paul J.; Denlinger, Loren C.

    2013-01-01

    Allergic asthma, a chronic respiratory disorder marked by inflammation and recurrent airflow obstruction, is associated with elevated levels of Interleukin-5 (IL-5) family cytokines, and elevated numbers of eosinophils (EOS). IL-5 family cytokines elongate peripheral blood EOS (EOSPB) viability, recruit EOSPB to the airways, and at higher concentrations, induce degranulation and reactive oxygen species (ROS) generation. While, EOSA remain signal ready in that GM-CSF treatment induces degranulation, treatment of EOSA with IL-5 family cytokines no longer confers a survival advantage. Since the IL-5 family receptors have common signaling capacity, but are uncoupled from EOSA survival while other IL-5 family induced endpoints remain functional, we tested the hypothesis that EOSA possess a JAK/STAT specific regulatory mechanism (since JAK/STAT signaling is critical to EOS survival). We found that IL-5 family-induced STAT3 and STAT5 phosphorylation is attenuated in EOSA relative to blood EOS from airway allergen-challenged donors (EOSCPB). However, IL-5 family induced ERK1/2 phosphorylation is not altered between EOSA and EOSCPB. These observations suggest EOSA possess a regulatory mechanism for suppressing STAT signaling distinct from ERK1/2 activation. Furthermore, we found, in EOSPB, IL-5 family cytokines induce members of the suppressors of cytokine signaling (SOCS) genes, CISH and SOCS1. Additionally, following allergen challenge, EOSA express significantly more CISH and SOCS1 mRNA and CISH protein than EOSPB counterparts. In EOSPB, long-term pretreatment with IL-5 family cytokines, to varying degrees, attenuates IL-5 family induced STAT5 phosphorylation. These data support a model wherein IL-5 family cytokines trigger a selective down-regulation mechanism in EOSA for JAK/STAT pathways. PMID:23956426

  1. Tuberculose faringolaríngea Laryngo-pharyngeal Tuberculosis

    Directory of Open Access Journals (Sweden)

    Leonardo Conrado Barbosa de Sá

    2007-12-01

    Full Text Available A apresentação faringolaríngea da tuberculose como forma isolada da doença é rara, entretanto, nos últimos anos, com o aumento progressivo do número de casos de tuberculose em geral, a possibilidade dessas localizações aumentou. OBJETIVO: Descrever caso de tuberculose faringolaríngea primária em paciente grávida e imunocompetente. RELATORIO DE CASO: Paciente do sexo feminino, 30 anos, com história de odinofagia há 10 meses, sem qualquer sintoma sistêmico ou outras queixas referentes às vias aéreas superiores. Apresentava lesão granulomatosa em orofaringe e laringe, e o resultado da biópsia revelou bacilos álcool-ácido resistentes. Exames clínico e radiológico do aparelho respiratório sem alterações. Realizado tratamento anti-tuberculose por nove meses com resolução completa do quadro. CONCLUSÃO: Autores realçam a importância epidemiológica da tuberculose e a necessidade de um alto grau de suspeição de lesões das vias aéreas superiores para o diagnóstico precoce da doença.Tuberculosis of the Larynx and pharynx only is rare. However, in the last few years, the number of tuberculosis cases in general have had a dramatic increase, thus increasing the possibility of isolated laryngo-pharyngeal lesions. AIM: To report a case of isolated laryngo-pharyngeal tuberculosis in a pregnant, immunocompetent host. CASE REPORT: A 30- year-old pregnant female had complained of odynophagia for the last ten months. There were no other respiratory or systemic symptoms. An oro-pharyngeal granulomatous lesion was found, and the biopsy revealed acid-fast bacilli. There were no clinical or radiologic pulmonary findings. She was submitted successfully to an tuberculosis treatment protocol for nine months. CONCLUSIONS: The authors point out the epidemiological importance of tuberculosis and the need for a higher degree of suspicion when dealing with uncommon upper airway lesions to make an early diagnosis.

  2. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP) and CCL11/eotaxin-1 in human asthmatic airways.

    Science.gov (United States)

    Nino, Gustavo; Huseni, Shehlanoor; Perez, Geovanny F; Pancham, Krishna; Mubeen, Humaira; Abbasi, Aleeza; Wang, Justin; Eng, Stephen; Colberg-Poley, Anamaris M; Pillai, Dinesh K; Rose, Mary C

    2014-01-01

    Thymic stromal lymphoproetin (TSLP) is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral) and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state. Primary human bronchial epithelial cells (HBEC) from control (n = 3) and asthmatic (n = 3) donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI) conditions and treated apically with dsRNA (viral surrogate) or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC) from normal (n = 3) and asthmatic (n = 3) donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20) vs. non-asthmatic uninfected controls (n = 20). Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay. Our data demonstrate that: 1) Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2) TSLP exposure induces unidirectional (apical) secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3) Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1. There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  3. Directional secretory response of double stranded RNA-induced thymic stromal lymphopoetin (TSLP and CCL11/eotaxin-1 in human asthmatic airways.

    Directory of Open Access Journals (Sweden)

    Gustavo Nino

    Full Text Available Thymic stromal lymphoproetin (TSLP is a cytokine secreted by the airway epithelium in response to respiratory viruses and it is known to promote allergic Th2 responses in asthma. This study investigated whether virally-induced secretion of TSLP is directional in nature (apical vs. basolateral and/or if there are TSLP-mediated effects occurring at both sides of the bronchial epithelial barrier in the asthmatic state.Primary human bronchial epithelial cells (HBEC from control (n = 3 and asthmatic (n = 3 donors were differentiated into polarized respiratory tract epithelium under air-liquid interface (ALI conditions and treated apically with dsRNA (viral surrogate or TSLP. Sub-epithelial effects of TSLP were examined in human airway smooth muscle cells (HASMC from normal (n = 3 and asthmatic (n = 3 donors. Clinical experiments examined nasal airway secretions obtained from asthmatic children during naturally occurring rhinovirus-induced exacerbations (n = 20 vs. non-asthmatic uninfected controls (n = 20. Protein levels of TSLP, CCL11/eotaxin-1, CCL17/TARC, CCL22/MDC, TNF-α and CXCL8 were determined with a multiplex magnetic bead assay.Our data demonstrate that: 1 Asthmatic HBEC exhibit an exaggerated apical, but not basal, secretion of TSLP after dsRNA exposure; 2 TSLP exposure induces unidirectional (apical secretion of CCL11/eotaxin-1 in asthmatic HBEC and enhanced CCL11/eotaxin-1 secretion in asthmatic HASMC; 3 Rhinovirus-induced asthma exacerbations in children are associated with in vivo airway secretion of TSLP and CCL11/eotaxin-1.There are virally-induced TSLP-driven secretory immune responses at both sides of the bronchial epithelial barrier characterized by enhanced CCL11/eotaxin-1 secretion in asthmatic airways. These results suggest a new model of TSLP-mediated eosinophilic responses in the asthmatic airway during viral-induced exacerbations.

  4. Airway stents

    Science.gov (United States)

    Keyes, Colleen

    2018-01-01

    Stents and tubes to maintain the patency of the airways are commonly used for malignant obstruction and are occasionally employed in benign disease. Malignant airway obstruction usually results from direct involvement of bronchogenic carcinoma, or by extension of carcinomas occurring in the esophagus or the thyroid. External compression from lymph nodes or metastatic disease from other organs can also cause central airway obstruction. Most malignant airway lesions are surgically inoperable due to advanced disease stage and require multimodality palliation, including stent placement. As with any other medical device, stents have significantly evolved over the last 50 years and deserve an in-depth understanding of their true capabilities and complications. Not every silicone stent is created equal and the same holds for metallic stents. Herein, we present an overview of the topic as well as some of the more practical and controversial issues surrounding airway stents. We also try to dispel the myths surrounding stent removal and their supposed use only in central airways. At the end, we come to the long-held conclusion that stents should not be used as first line treatment of choice, but after ruling out the possibility of curative surgical resection or repair. PMID:29707506

  5. Defective Resensitization in Human Airway Smooth Muscle Cells Evokes β-Adrenergic Receptor Dysfunction in Severe Asthma.

    Directory of Open Access Journals (Sweden)

    Manveen K Gupta

    Full Text Available β2-adrenergic receptor (β2AR agonists (β2-agonist are the most commonly used therapy for acute relief in asthma, but chronic use of these bronchodilators paradoxically exacerbates airway hyper-responsiveness. Activation of βARs by β-agonist leads to desensitization (inactivation by phosphorylation through G-protein coupled receptor kinases (GRKs which mediate β-arrestin binding and βAR internalization. Resensitization occurs by dephosphorylation of the endosomal βARs which recycle back to the plasma membrane as agonist-ready receptors. To determine whether the loss in β-agonist response in asthma is due to altered βAR desensitization and/or resensitization, we used primary human airway smooth muscle cells (HASMCs isolated from the lungs of non-asthmatic and fatal-asthmatic subjects. Asthmatic HASMCs have diminished adenylyl cyclase activity and cAMP response to β-agonist as compared to non-asthmatic HASMCs. Confocal microscopy showed significant accumulation of phosphorylated β2ARs in asthmatic HASMCs. Systematic analysis of desensitization components including GRKs and β-arrestin showed no appreciable differences between asthmatic and non-asthmatic HASMCs. However, asthmatic HASMC showed significant increase in PI3Kγ activity and was associated with reduction in PP2A activity. Since reduction in PP2A activity could alter receptor resensitization, endosomal fractions were isolated to assess the agonist ready β2ARs as a measure of resensitization. Despite significant accumulation of β2ARs in the endosomes of asthmatic HASMCs, endosomal β2ARs cannot robustly activate adenylyl cyclase. Furthermore, endosomes from asthmatic HASMCs are associated with significant increase in PI3Kγ and reduced PP2A activity that inhibits β2AR resensitization. Our study shows that resensitization, a process considered to be a homeostasis maintaining passive process is inhibited in asthmatic HASMCs contributing to β2AR dysfunction which may underlie

  6. Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Taissia G Popova

    Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

  7. Chemotaxis and Binding of Pseudomonas aeruginosa to Scratch-Wounded Human Cystic Fibrosis Airway Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Christian Schwarzer

    Full Text Available Confocal imaging was used to characterize interactions of Pseudomonas aeruginosa (PA, expressing GFP or labeled with Syto 11 with CF airway epithelial cells (CFBE41o-, grown as confluent monolayers with unknown polarity on coverglasses in control conditions and following scratch wounding. Epithelia and PAO1-GFP or PAK-GFP (2 MOI were incubated with Ringer containing typical extracellular salts, pH and glucose and propidium iodide (PI, to identify dead cells. PAO1 and PAK swam randomly over and did not bind to nonwounded CFBE41o- cells. PA migrated rapidly (began within 20 sec, maximum by 5 mins and massively (10-80 fold increase, termed "swarming", but transiently (random swimming after 15 mins, to wounds, particularly near cells that took up PI. Some PA remained immobilized on cells near the wound. PA swam randomly over intact CFBE41o- monolayers and wounded monolayers that had been incubated with medium for 1 hr. Expression of CFTR and altered pH of the media did not affect PA interactions with CFBE41o- wounds. In contrast, PAO1 swarming and immobilization along wounds was abolished in PAO1 (PAO1ΔcheYZABW, no expression of chemotaxis regulatory components cheY, cheZ, cheA, cheB and cheW and greatly reduced in PAO1 that did not express amino acid receptors pctA, B and C (PAO1ΔpctABC and in PAO1 incubated in Ringer containing a high concentration of mixed amino acids. Non-piliated PAKΔpilA swarmed normally towards wounded areas but bound infrequently to CFBE41o- cells. In contrast, both swarming and binding of PA to CFBE41o- cells near wounds were prevented in non-flagellated PAKΔfliC. Data are consistent with the idea that (i PA use amino acid sensor-driven chemotaxis and flagella-driven swimming to swarm to CF airway epithelial cells near wounds and (ii PA use pili to bind to epithelial cells near wounds.

  8. Phenotype and Functional Features of Human Telomerase Reverse Transcriptase Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic Donors

    NARCIS (Netherlands)

    Burgess, J. K.; Ketheson, A.; Faiz, A.; Rempel, K. A. Limbert; Oliver, B. G.; Ward, J. P. T.; Halayko, A. J.

    2018-01-01

    Asthma is an obstructive respiratory disease characterised by chronic inflammation with airway hyperresponsiveness. In asthmatic airways, there is an increase in airway smooth muscle (ASM) cell bulk, which differs from non-asthmatic ASM in characteristics. This study aimed to assess the usefulness

  9. ATP Release from Human Airway Epithelial Cells Exposed to Staphylococcus aureus Alpha-Toxin

    Directory of Open Access Journals (Sweden)

    Romina Baaske

    2016-12-01

    Full Text Available Airway epithelial cells reduce cytosolic ATP content in response to treatment with S. aureus alpha-toxin (hemolysin A, Hla. This study was undertaken to investigate whether this is due to attenuated ATP generation or to release of ATP from the cytosol and extracellular ATP degradation by ecto-enzymes. Exposure of cells to rHla did result in mitochondrial calcium uptake and a moderate decline in mitochondrial membrane potential, indicating that ATP regeneration may have been attenuated. In addition, ATP may have left the cells through transmembrane pores formed by the toxin or through endogenous release channels (e.g., pannexins activated by cellular stress imposed on the cells by toxin exposure. Exposure of cells to an alpha-toxin mutant (H35L, which attaches to the host cell membrane but does not form transmembrane pores, did not induce ATP release from the cells. The Hla-mediated ATP-release was completely blocked by IB201, a cyclodextrin-inhibitor of the alpha-toxin pore, but was not at all affected by inhibitors of pannexin channels. These results indicate that, while exposure of cells to rHla may somewhat reduce ATP production and cellular ATP content, a portion of the remaining ATP is released to the extracellular space and degraded by ecto-enzymes. The release of ATP from the cells may occur directly through the transmembrane pores formed by alpha-toxin.

  10. Pharyngeal branchial cyst: magnetic resonance findings

    Energy Technology Data Exchange (ETDEWEB)

    Cerezal, L.; Canga, A. [Department of Radiology of the ' Santa Cruz' Hospital Liencres, Cantabria (Spain); Morales, C. [Department of Otorhinolaryngology of the ' Sierrallana' Hospital Torrelavega, Cantabria (Spain); Abascal, F.; Usamentiaga, E.; Bustamante, M. [Department of Radiology of the University Hospital ' Marques de Valdecilla' , Av. de Valdecilla s/n Santander 39008 (Spain); Olcinas, O. [Department of Pathology of the University Hospital ' Marques de Valdecilla' , Av. de Valdecilla s/n Santander 39008 (Spain)

    1998-11-01

    An unusual case of pharyngeal cyst in a 25-year-old man studied by Magnetic Resonance (MR) is described. Anatomic location and pathological findings indicated the second branchial pouch origin. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  11. Pharyngeal branchial cyst: magnetic resonance findings

    International Nuclear Information System (INIS)

    Cerezal, L.; Canga, A.; Morales, C.; Abascal, F.; Usamentiaga, E.; Bustamante, M.; Olcinas, O.

    1998-01-01

    An unusual case of pharyngeal cyst in a 25-year-old man studied by Magnetic Resonance (MR) is described. Anatomic location and pathological findings indicated the second branchial pouch origin. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  12. Altered pharyngeal muscles in Parkinson disease.

    Science.gov (United States)

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

    2012-06-01

    Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

  13. Topical Therapy of Acute Pharyngitis in Children

    Directory of Open Access Journals (Sweden)

    Yu.K. Bolbot

    2015-02-01

    Full Text Available The paper discusses the methods of topical antiinflammatory therapy for acute pharyngitis in children. The analysis of the complex of mechanisms (antiinflammatory, local analgesic ones of Tantum Verde® action and method of its application are provided.

  14. The New Perilaryngeal Airway (CobraPLA™)1 Is as Efficient as the Laryngeal Mask Airway (LMA™)2, But Provides Better Airway Sealing Pressures

    Science.gov (United States)

    Akça, Ozan; Wadhwa, Anupama; Sengupta, Papiya; Durrani, Jaleel; Hanni, Keith; Wenke, Mary; Yücel, Yüksel; Lenhardt, Rainer; Doufas, Anthony G.; Sessler, Daniel I.

    2006-01-01

    The Laryngeal Mask Airway (LMA) is a frequently-used efficient airway device, yet it sometimes seals poorly, thus reducing the efficacy of positive-pressure ventilation. The Perilaryngeal Airway (CobraPLA) is a novel airway device with a larger pharyngeal cuff (when inflated). We tested the hypothesis that the CobraPLA was superior to LMA with regard to insertion time and airway sealing pressure and comparable to LMA in airway adequacy and recovery characteristics. After midazolam and fentanyl, 81 ASA I-II outpatients having elective surgery were randomized to receive an LMA or CobraPLA. Anesthesia was induced with propofol (2.5 mg/kg, IV), and the airway inserted. We measured 1) insertion time; 2) adequacy of the airway (no leak at 15-cm-H2O peak pressure or tidal volume of 5 ml/kg); 3) airway sealing pressure; 4) number of repositioning attempts; and 5) sealing quality (no leak at tidal volume of 8 ml/kg). At the end of surgery, gastric insufflation, postoperative sore throat, dysphonia, and dysphagia were evaluated. Data were compared with unpaired t-tests, chi-square tests, or Fisher’s Exact tests; P<0.05 was significant. Patient characteristics, insertion times, airway adequacy, number of repositioning attempts, and recovery were similar in each group. Airway sealing pressure was significantly greater with CobraPLA (23±6 cm H2O) than LMA (18±5 cm H2O, P<0.001). The CobraPLA has insertion characteristics similar to LMA, but better airway sealing capabilities. PMID:15281543

  15. Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics.

    Science.gov (United States)

    Pourmehran, Oveis; Gorji, Tahereh B; Gorji-Bandpy, Mofid

    2016-10-01

    Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to minimize undesired side effects due to systemic distribution in the organism. Using magnetic drug particles under the influence of an external magnetic field, the drug particles are navigated toward the target region. Herein, computational fluid dynamics was used to simulate the air flow and magnetic particle deposition in a realistic human airway geometry obtained by CT scan images. Using discrete phase modeling and one-way coupling of particle-fluid phases, a Lagrangian approach for particle tracking in the presence of an external non-uniform magnetic field was applied. Polystyrene (PMS40) particles were utilized as the magnetic drug carrier. A parametric study was conducted, and the influence of particle diameter, magnetic source position, magnetic field strength and inhalation condition on the particle transport pattern and deposition efficiency (DE) was reported. Overall, the results show considerable promise of MDT in deposition enhancement at the target region (i.e., left lung). However, the positive effect of increasing particle size on DE enhancement was evident at smaller magnetic field strengths (Mn [Formula: see text] 1.5 T), whereas, at higher applied magnetic field strengths, increasing particle size has a inverse effect on DE. This implies that for efficient MTD in the human respiratory system, an optimal combination of magnetic drug career characteristics and magnetic field strength has to be achieved.

  16. Change in Posterior Pharyngeal Space After Counterclockwise Rotational Orthognathic Surgery for Class II Dentofacial Deformity Diagnosed With Obstructive Sleep Apnea Based on Cephalometric Analysis.

    Science.gov (United States)

    Jeong, Woo Shik; Kim, Young Chul; Chung, Yoo Sam; Lee, Chang Yeol; Choi, Jong Woo

    2017-07-01

    Although maxillomandibular advancement (MMA) is an orthognathic surgical procedure used to manage obstructive sleep apnea (OSA) in individuals who are noncompliant with continuous positive airway pressure therapy, simple MMA encounters problems in terms of aesthetic outcomes in Asian populations with preexisting dentoalveolar protrusion. Our current prospective investigation describes changes in posterior pharyngeal space and aesthetic outcomes after counterclockwise rotational orthognathic surgery, which is known to be quite difficult in terms of the maintenance of the skeletal stability in skeletal class II patients with OSA. This prospective study investigated the surgical outcome of patients who suffered from OSA following counterclockwise rotational orthognathic surgery. The patients were skeletal class II patients who underwent orthognathic surgery between March 2013 and December 2014. Cephalometric posterior airway analysis and a questionnaire for facial perception were used to assess pharyngeal airway and patient perception of facial appearance. A total of 14 patients were included. Satisfactory results were achieved without complications in all OSA patients. The airway parameters for anteroposterior length significantly increased. Thirteen patients answered a questionnaire on their facial appearance, and the visual analog scale averaged 7.31 points, indicating a favorable facial appearance. Counterclockwise rotational orthognathic surgery without maxilla advancement for the correction of OSA can effectively increase the posterior pharyngeal space, with favorable aesthetic results. With thoughtful application, this novel approach may be an alternative to standard approaches for the correction of OSA using orthognathic surgery.

  17. Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

    Science.gov (United States)

    Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

    2014-01-01

    As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

  18. Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study

    DEFF Research Database (Denmark)

    Lajer, C B; Nielsen, F C; Friis-Hansen, L

    2011-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs, which regulate mRNA translation/decay, and may serve as biomarkers. We characterised the expression of miRNAs in clinically sampled oral and pharyngeal squamous cell carcinoma (OSCC and PSCC) and described the influence of human papilloma virus (HPV)....

  19. Counseling a Patient with the Antenatal Diagnosis of a Cerebellar Abnormality and a Pharyngeal Cyst

    Directory of Open Access Journals (Sweden)

    Lissa Francois

    2014-11-01

    Full Text Available Introduction - Prenatal counseling with regards to the prognosis of a cerebellar abnormality is hindered not only by the diverse clinical presentations but also by the presence of subtle findings. We present a case of a distinct combination of asymmetric cerebellar hypoplasia secondary to an anterior meningoencephalocele through a clival defect that caused a severe airway obstruction in the newborn. Case Description - A 21-year-old gravida 4 para 0 mother with a dichorionic–diamniotic twin pregnancy was referred for a second trimester sonographic survey. An asymmetric cerebellar hypoplasia, mega cisterna magna, and a pharyngeal cystic mass were noted on twin A. Magnetic resonance imaging report confirmed posterior fossa abnormalities and shed no light on the differential diagnosis of the cystic mass. The pregnancy ended by Cesarean delivery at 32 weeksʼ gestation after a preterm premature rupture of the membranes. Twin A had a severe airway obstruction. Postnatal evaluation confirmed a midline anterior meningoencephalocele through a defect in the clivus. The microarray chromosomal analysis demonstrated a 5q15 variant with uncertain clinical significance. Conclusion - Antenatal recognition of the unique combination of a cerebellar hypoplasia with a pharyngeal cyst can impact the prenatal counseling as well as neonatal management.

  20. The detection of pharyngeal incoordination and aspiration by radiosalivagram in cerebral palsy

    Energy Technology Data Exchange (ETDEWEB)

    Baikie, G.; Reddihough, D.; Olinsky, A.; South, M.J.; Bowe, J.; Cook, D.J. [Royal Children`s Hospital, Parkville, VIC, (Australia)

    1997-09-01

    Full text: Children with cerebral palsy (CP) may have abnormal respiratory function because of aspiration pneumonitis, chest deformity, upper airways obstruction or central respiratory control abnormalities. The diagnosis of aspiration has long confounded clinicians and is often made indirectly after exclusion of other causes of respiratory disease in susceptible individuals. The radiosalivagram is a technique which permits the demonstration of aspiration of pharyngeal contents in individuals with pharyngeal incoordination. It is a simple procedure which provides both qualitative and quantitative evidence of aspiration. Over an hour and while supine, 20 mL of {sup 99m}Tc-sulphur colloid is instilled into the pharynx via a thin plastic tube using a syringe pump. The neck, thorax and upper abdomen are imaged continuously In normal individuals, radioactivity is demonstrated in the pharynx, oesophagus and stomach; in the presence of pharyngeal incoordination, radioactivity is seen within one or both main bronchi and adjacent lung fields. The rate of clearance from the lungs varies and can be quantified. We have studied 31 children with severe non-ambulant CR The time to first aspiration, maximum quantity aspirated, and retention of aspirated material at 2h have been determined. These data have been compared with measurements of respiratory function. Preliminary results of this ongoing study reveal a broad range of outcomes. Seventeen children (17/31) had aspiration, in 15/17 aspiration was unilateral and in 14/17 there was spontaneous early clearance. The investigation was well tolerated by patients. The radiosalivagram is a simple, quantifiable investigation for demonstrating or excluding pharyngeal incoordination and aspiration in children with unexplained respiratory disease.

  1. The detection of pharyngeal incoordination and aspiration by radiosalivagram in cerebral palsy

    International Nuclear Information System (INIS)

    Baikie, G.; Reddihough, D.; Olinsky, A.; South, M.J.; Bowe, J.; Cook, D.J.

    1997-01-01

    Full text: Children with cerebral palsy (CP) may have abnormal respiratory function because of aspiration pneumonitis, chest deformity, upper airways obstruction or central respiratory control abnormalities. The diagnosis of aspiration has long confounded clinicians and is often made indirectly after exclusion of other causes of respiratory disease in susceptible individuals. The radiosalivagram is a technique which permits the demonstration of aspiration of pharyngeal contents in individuals with pharyngeal incoordination. It is a simple procedure which provides both qualitative and quantitative evidence of aspiration. Over an hour and while supine, 20 mL of 99m Tc-sulphur colloid is instilled into the pharynx via a thin plastic tube using a syringe pump. The neck, thorax and upper abdomen are imaged continuously In normal individuals, radioactivity is demonstrated in the pharynx, oesophagus and stomach; in the presence of pharyngeal incoordination, radioactivity is seen within one or both main bronchi and adjacent lung fields. The rate of clearance from the lungs varies and can be quantified. We have studied 31 children with severe non-ambulant CR The time to first aspiration, maximum quantity aspirated, and retention of aspirated material at 2h have been determined. These data have been compared with measurements of respiratory function. Preliminary results of this ongoing study reveal a broad range of outcomes. Seventeen children (17/31) had aspiration, in 15/17 aspiration was unilateral and in 14/17 there was spontaneous early clearance. The investigation was well tolerated by patients. The radiosalivagram is a simple, quantifiable investigation for demonstrating or excluding pharyngeal incoordination and aspiration in children with unexplained respiratory disease

  2. Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part I: Theory and model validation.

    Science.gov (United States)

    Kolanjiyil, Arun V; Kleinstreuer, Clement

    2016-12-01

    Computational predictions of aerosol transport and deposition in the human respiratory tract can assist in evaluating detrimental or therapeutic health effects when inhaling toxic particles or administering drugs. However, the sheer complexity of the human lung, featuring a total of 16 million tubular airways, prohibits detailed computer simulations of the fluid-particle dynamics for the entire respiratory system. Thus, in order to obtain useful and efficient particle deposition results, an alternative modeling approach is necessary where the whole-lung geometry is approximated and physiological boundary conditions are implemented to simulate breathing. In Part I, the present new whole-lung-airway model (WLAM) represents the actual lung geometry via a basic 3-D mouth-to-trachea configuration while all subsequent airways are lumped together, i.e., reduced to an exponentially expanding 1-D conduit. The diameter for each generation of the 1-D extension can be obtained on a subject-specific basis from the calculated total volume which represents each generation of the individual. The alveolar volume was added based on the approximate number of alveoli per generation. A wall-displacement boundary condition was applied at the bottom surface of the first-generation WLAM, so that any breathing pattern due to the negative alveolar pressure can be reproduced. Specifically, different inhalation/exhalation scenarios (rest, exercise, etc.) were implemented by controlling the wall/mesh displacements to simulate realistic breathing cycles in the WLAM. Total and regional particle deposition results agree with experimental lung deposition results. The outcomes provide critical insight to and quantitative results of aerosol deposition in human whole-lung airways with modest computational resources. Hence, the WLAM can be used in analyzing human exposure to toxic particulate matter or it can assist in estimating pharmacological effects of administered drug-aerosols. As a practical

  3. Effect of variation of geometric parameters on the flow within a synthetic models of lower human airways

    Science.gov (United States)

    Espinosa Moreno, Andres Santiago; Duque Daza, Carlos Alberto

    2017-11-01

    The effects of variation of two geometric parameters, such as bifurcation angle and carina rounding radius, during the respiratory inhalation process, are studied numerically using two synthetic models of lower human airways. Laminar flow simulations were performed for six angles and three rounding radius, for 500, 1000, 1500 and 2000 for Reynolds numbers. Numerical results showed the existence of a direct relationship between the deformation of the velocity profiles (effect produced by the bifurcation) and the vortical structures observed through the secondary flow patterns. It is observed that the location of the vortices (and their related saddle point) is associated with the displacement of the velocity peak. On the other hand, increasing the angle and the rounding radius seems to bring about a growth of the pressure drop, which in turn displaces the distribution and peaks of the maximum shear stresses of the carina, that is, of the bifurcation point. Some physiological effects associated with the phenomena produced by these geometric variations are also discussed.

  4. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

    Energy Technology Data Exchange (ETDEWEB)

    Albino, C.C., E-mail: ccalbino@uol.com.b [Instituto de Diabetes e Endocrinologia de Maringa, PR (Brazil); Graf, H.; Paz-Filho, G. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital das Clinicas. Servico de Endocrinologia e Metabologia; Diehl, L.A. [Universidade Estadual de Londrina (UEL), PR (Brazil); Olandoski, M.; Sabbag, A. [Pontificia Univ. Catolica do Parana (PUCPR), Curitiba, PR (Brazil). Nucleo de Bioestatistica; Buchpiguel, C. [Universidade de Sao Paulo (USP), SP (Brazil). Dept. de Radiologia

    2006-03-15

    Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of {sup 131}I for treating MNG. Euthyroid patients with MNG (69.3 +- 62.0 mL, 20 females, 2 males, 64 +- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq {sup 131}I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +- 17.6%) and II (21.6 +- 17.8%), but not in group III (2.7 +- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +- 18.1%) and II (37.4 +- 27.1%), but not in group III (19.0 +- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed {sup 131}I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus {sup 131}I (author)

  5. IFN-γ, IL-4 and IL-13 modulate responsiveness of human airway smooth muscle cells to IL-13

    Directory of Open Access Journals (Sweden)

    Michoud Marie-Claire

    2008-12-01

    Full Text Available Abstract Background IL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6. The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13. Methods Cultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine. Results IL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression. Conclusion Pre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine

  6. Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

    International Nuclear Information System (INIS)

    Albino, C.C.; Graf, H.; Paz-Filho, G.; Olandoski, M.; Sabbag, A.; Buchpiguel, C.

    2006-01-01

    Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131 I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131 I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6%) and II (21.6 ± 17.8%), but not in group III (2.7 ± 15.3%). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1%) and II (37.4 ± 27.1%), but not in group III (19.0 ± 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131 I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131 I (author)

  7. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Halayko Andrew J

    2009-09-01

    Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

  8. Induction of hyperresponsiveness in human airway tissue by neutrophils--mechanism of action.

    Science.gov (United States)

    Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

    1996-05-01

    The two main features of asthma are bronchial hyperresponsiveness and inflammation. The inflammatory response in asthma consists of infiltration and activation of a variety of inflammatory cells including neutrophils. Our previous studies have shown that stimulated neutrophil supernatants cause hyperresponsiveness of human bronchial tissue in vitro. To investigate the effect of the sensitization status of the tissue and the albumin concentration used to prepare supernatants on the response of human bronchial tissue to stimulated neutrophil supernatants. Neutrophil supernatants were prepared from human isolated blood in the presence of varying concentrations of albumin (0%, 0.1% and 4%). Neutrophil supernatants were added to sensitized and non-sensitized human isolated bronchial tissue which was stimulated with electrical field stimulation (EFS) (20 s every 4 min). Receptor antagonists specific for the prostaglandin and thromboxane (10(-7) M GR32191), platelet activating factor (10(-6) M WEB 2086), leukotriene D4 (10(-6) M MK-679) and neurokinin A (10(-7) M SR48968) receptors were used to identify neutrophil products responsible for the effects observed in the bronchial tissue. In non-sensitized human bronchial tissue, stimulated neutrophil supernatants induced a direct contraction in the presence of 0% and 0.1% but not 4% albumin. This contraction was due to leukotriene D4 as MK-679 completely inhibited the contraction. In contrast, stimulated neutrophil supernatants increased responsiveness of sensitized human bronchial tissue to EFS. The increased responsiveness was observed only in the presence of 0.1% albumin, with the site of modulation likely to be prejunctional on the parasympathetic nerve. The increased responsiveness was not inhibited by any of the antagonists tested. Sensitization status of the tissue and albumin concentration effect the responsiveness of human bronchial tissue to stimulated neutrophil supernatant. Our results suggest a possible role for

  9. Pharyngeal video fluoroscopy: Selected unusual cases

    International Nuclear Information System (INIS)

    Conoley, P.M.; Fox, D.R.

    1987-01-01

    The videotape in this exhibit presents cases illustrative of the use of pharyngeal video fluoroscopy in diagnostic evaluations and therapeutic decision-making in a variety of speech and swallowing disorders of adults and children. Clinical problems addressed include an interesting compensatory speech mechanism in a cleft-palate patient, a preoperative candidate for a Lefort procedure, uncontrolled nasality in a singer, and dysphagia in an antimony worker

  10. Pulmonary Renal Syndrome After Streptococcal Pharyngitis

    Directory of Open Access Journals (Sweden)

    Gopi Mara-Koosham PhD

    2016-04-01

    Full Text Available Pulmonary renal syndrome is a class of small vessel vasculitides that are characterized by the dual presentation of diffuse alveolar hemorrhage (DAH and glomerulonephritis. Pulmonary renal syndrome has multiple etiologies, but its development has been rarely reported following infection with group A streptococcus. We present the case of a 36-year-old Native American male who was transferred to our facility due to refractory hypoxic respiratory failure. He had been diagnosed with streptococcal pharyngitis 2 weeks prior to admission. Given the presence of hemoptysis, bronchoscopy was performed and was consistent with DAH. Urinalysis demonstrated hematuria and proteinuria, in the setting of elevated creatinine and blood urea nitrogen. Additionally, antistreptolysin O titer was positive. Given the constellation of laboratory findings and history of streptococcal pharyngitis, the patient was diagnosed with PRS secondary to streptococcal infection. High-dose methylprednisolone was initiated with concomitant plasmapheresis. He was extubated successfully after his respiratory status improved and was eventually discharged home after making a full recovery within 2 weeks after admission. This case illustrates the importance of clinically relevant sequelae of streptococcal infection as well as the appropriate treatment of PRS secondary to streptococcal pharyngitis with plasmapheresis and intravenous corticosteroids.

  11. Divergent pro-inflammatory profile of human dendritic cells in response to commensal and pathogenic bacteria associated with the airway microbiota

    DEFF Research Database (Denmark)

    Larsen, Jeppe Madura; Steen-Jensen, Daniel Bisgaard; Laursen, Janne Marie

    2012-01-01

    of individual bacterial species are unknown. In this study, we compared the immune stimulatory capacity on human monocyte-derived dendritic cells (DCs) of selected airway commensal and pathogenic bacteria predominantly associated with lungs of asthma or COPD patients (pathogenic Haemophillus spp. and Moraxella...... spp.), healthy lungs (commensal Prevotella spp.) or both (commensal Veillonella spp. and Actinomyces spp.). All bacteria were found to induce activation of DCs as demonstrated by similar induction of CD83, CD40 and CD86 surface expression. However, asthma and COPD-associated pathogenic bacteria...... provoked a 3-5 fold higher production of IL-23, IL-12p70 and IL-10 cytokines compared to the commensal bacteria. Based on the differential cytokine production profiles, the studied airway bacteria could be segregated into three groups (Haemophilus spp. and Moraxella spp. vs. Prevotella spp. and Veillonella...

  12. Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

    International Nuclear Information System (INIS)

    Zaccone, Eric J.; Goldsmith, W. Travis; Shimko, Michael J.; Wells, J.R.; Schwegler-Berry, Diane; Willard, Patsy A.; Case, Shannon L.; Thompson, Janet A.; Fedan, Jeffrey S.

    2015-01-01

    Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (R t ) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na + transport, without affecting Cl − transport or Na + ,K + -pump activity. R t was unaffected. Na + transport recovered 18 h after exposure. Concentrations (100–360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. - Highlights: • Butter flavoring vapor effects on human cultured airway epithelium were studied. • Na transport was reduced by a 6-h exposure to 25 ppm diacetyl and 2,3-pentanedione. • Na transport recovered 18 h after exposure. • > 60 ppm transepithelial voltage and resistance were abolished; cells were damaged. • Cells metabolized diacetyl and 2,3-pentanedione into acetoin and 2-OH-3-pentanone.

  13. Preferential Generation of 15-HETE-PE Induced by IL-13 Regulates Goblet Cell Differentiation in Human Airway Epithelial Cells.

    Science.gov (United States)

    Zhao, Jinming; Minami, Yoshinori; Etling, Emily; Coleman, John M; Lauder, Sarah N; Tyrrell, Victoria; Aldrovandi, Maceler; O'Donnell, Valerie; Claesson, Hans-Erik; Kagan, Valerian; Wenzel, Sally

    2017-12-01

    Type 2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase-1 (15LO1) is induced by the type 2 cytokine IL-13 in human airway epithelial cells (HAECs) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15-HETE-phosphatidylethanolamine (15-HETE-PE), and 13-hydroxyoctadecadienoic acid (13-HODE). In this study, we investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, as well as its influence on goblet cell differentiation in HAECs. Primary HAECs obtained from bronchial brushings of asthmatic and healthy subjects were cultured under air-liquid interface culture supplemented with arachidonic acid and linoleic acid (10 μM each) and exposed to IL-13 for 7 days. Short interfering RNA transfection and 15LO1 inhibition were applied to suppress 15LO1 expression and activity. IL-13 stimulation induced expression of 15LO1 and preferentially generated 15-HETE-PE in vitro, both of which persisted after removal of IL-13. 15LO1 inhibition (by short interfering RNA and chemical inhibitor) decreased IL-13-induced forkhead box protein A3 (FOXA3) expression and enhanced FOXA2 expression. These changes were associated with reductions in both mucin 5AC and periostin. Exogenous 15-HETE-PE stimulation (alone) recapitulated IL-13-induced FOXA3, mucin 5AC, and periostin expression. The results of this study confirm the central importance of 15LO1 and its primary product, 15-HETE-PE, for epithelial cell remodeling in HAECs.

  14. Upper airway obstruction and pulmonary abnormalities due to lymphoproliferative disease following bone marrow transplantation in children

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, B.D. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105 (United States)]|[Departments of Radiology and Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Heslop, H.E. [Department of Hematology/Oncology, St. Jude Children`s Research Hospital, Department of Pediatrics, University of Tennessee, Memphis, Tennessee (United States); Kaste, S.C. [Department of Diagnostic Imaging, St. Jude Children`s Research Hospital, Department of Radiology, University of Tennessee, Memphis, Tennessee (United States); Bodner, S. [Department of Pathology, St. Jude Children`s Research Hospital, Department of Pathology, University of Tennessee, Memphis, Tennessee (United States)

    1998-07-01

    We report three patients who developed severe supraglottic airway obstruction due to Epstein-Barr virus lymphoproliferative disease following allogeneic bone marrow transplantation. In addition to enlarged pharyngeal lymphoid tissue seen in all three patients, two had supraglottic airway narrowing and two developed pulmonary lymphoproliferative disease. They were treated with unmanipulated T cells or EBV-specific cytotoxic T lymphocytes. Life-threatening upper airway obstruction is a radiologically detectable complication of allogeneic bone marrow transplantation in children. (orig.) With 3 figs., 1 tab., 12 refs.

  15. Negative Pressure Pulmonary Edema Following use of Laryngeal Mask Airway (LMA

    Directory of Open Access Journals (Sweden)

    Yesim Bayraktar

    2013-06-01

    Full Text Available Negative pressure pulmonary edema (NPPE following upper airway obstruction is a non-cardiogenic pulmonary edema. The first cause in the etiology of NPPE is developed laryngospasm after intubation or extubation, while the other causes are epiglotitis, croup, hiccups, foreign body aspiration, pharyngeal hematoma and oropharyngeal tumors.The Late diagnosis and treatment causes high morbidity and mortality. The protection of the airway and maintainance of arterial oxygenation will be life saving.In this article we aimed to report  a case of negative pressure pulmonary edema, resolved succesfully after treatment, following use of laryngeal mask airway (LMA.

  16. Biodiesel exhaust-induced cytotoxicity and proinflammatory mediator production in human airway epithelial cells.

    Science.gov (United States)

    Mullins, Benjamin J; Kicic, Anthony; Ling, Kak-Ming; Mead-Hunter, Ryan; Larcombe, Alexander N

    2016-01-01

    Increasing use of biodiesel has prompted research into the potential health effects of biodiesel exhaust exposure. Few studies directly compare the health consequences of mineral diesel, biodiesel, or blend exhaust exposures. Here, we exposed human epithelial cell cultures to diluted exhaust generated by the combustion of Australian ultralow-sulfur-diesel (ULSD), unprocessed canola oil, 100% canola biodiesel (B100), and a blend of 20% canola biodiesel mixed with 80% ULSD. The physicochemical characteristics of the exhaust were assessed and we compared cellular viability, apoptosis, and levels of interleukin (IL)-6, IL-8, and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) in exposed cultured cells. Different fuel types produced significantly different amounts of exhaust gases and different particle characteristics. All exposures resulted in significant apoptosis and loss of viability when compared with control, with an increasing proportion of biodiesel being correlated with a decrease in viability. In most cases, exposure to exhaust resulted in an increase in mediator production, with the greatest increases most often in response to B100. Exposure to pure canola oil (PCO) exhaust did not increase mediator production, but resulted in a significant decrease in IL-8 and RANTES in some cases. Our results show that canola biodiesel exhaust exposure elicits inflammation and reduces viability of human epithelial cell cultures in vitro when compared with ULSD exhaust exposure. This may be related to an increase in particle surface area and number in B100 exhaust when compared with ULSD exhaust. Exposure to PCO exhaust elicited the greatest loss of cellular viability, but virtually no inflammatory response, likely due to an overall increase in average particle size. © 2014 Wiley Periodicals, Inc.

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  18. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast ... Facebook Twitter ...

  19. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    International Nuclear Information System (INIS)

    Pei, Qing-Mei; Jiang, Ping; Yang, Min; Qian, Xue-Jiao; Liu, Jiang-Bo; Kim, Sung-Ho

    2016-01-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  20. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Qing-Mei, E-mail: 34713316@qq.com [Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China); Jiang, Ping, E-mail: jiangping@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Yang, Min, E-mail: YangMin@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Qian, Xue-Jiao, E-mail: qianxuejiao@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Liu, Jiang-Bo, E-mail: LJB1984@163.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China); Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com [Department of Respiration, Tianjin First Central Hospital, Tianjin (China)

    2016-10-01

    Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation

  1. Clinical analysis of pharyngeal musculature and genioglossus exercising to treat obstructive sleep apnea and hypopnea syndrome.

    Science.gov (United States)

    Tang, Shi-xiong; Qing, Jing; Wang, Yao-wen; Chai, Liang; Zhang, Wei-min; Ye, Xian-wang; Zhang, Jie; Huang, Yi-qin; Cheng, Peng

    2015-11-01

    mild and moderate OSAHS patients who do not want to take surgery and continuous positive airway pressure (CPAP) treatment. In addition, exercising pharyngeal musculature and genioglossus can be considered as remedial treatment of OSAHS to surgery and other therapies.

  2. Clinical analysis of pharyngeal musculature and genioglossus exercising to treat obstructive sleep apnea and hypopnea syndrome*#

    Science.gov (United States)

    TANG, Shi-xiong; QING, Jing; WANG, Yao-wen; CHAI, Liang; ZHANG, Wei-min; Ye, Xian-wang; Zhang, Jie; Huang, Yi-qin; Cheng, Peng

    2015-01-01

    surgical complications, and especially mild and moderate OSAHS patients who do not want to take surgery and continuous positive airway pressure (CPAP) treatment. In addition, exercising pharyngeal musculature and genioglossus can be considered as remedial treatment of OSAHS to surgery and other therapies. PMID:26537211

  3. A simple procedure for measuring pharyngeal sensitivity: a contribution to the diagnosis of sleep apnoea

    OpenAIRE

    Dematteis, M; Levy, P; Pepin, J

    2005-01-01

    Background: Patients with severe apnoea may have an impaired pharyngeal dilating reflex related to decreased pharyngeal sensitivity. The accuracy of a simple new procedure to measure pharyngeal sensitivity and to diagnose sleep disordered breathing (SDB) was investigated.

  4. Scavenger receptors in human airway epithelial cells: role in response to double-stranded RNA.

    Directory of Open Access Journals (Sweden)

    Audrey Dieudonné

    Full Text Available Scavenger receptors and Toll-like receptors (TLRs cooperate in response to danger signals to adjust the host immune response. The TLR3 agonist double stranded (dsRNA is an efficient activator of innate signalling in bronchial epithelial cells. In this study, we aimed at defining the role played by scavenger receptors expressed by bronchial epithelial cells in the control of the innate response to dsRNA both in vitro and in vivo. Expression of several scavenger receptor involved in pathogen recognition was first evaluated in human bronchial epithelial cells in steady-state and inflammatory conditions. Their implication in the uptake of dsRNA and the subsequent cell activation was evaluated in vitro by competition with ligand of scavenger receptors including maleylated ovalbumin and by RNA silencing. The capacity of maleylated ovalbumin to modulate lung inflammation induced by dsRNA was also investigated in mice. Exposure to tumor necrosis factor-α increased expression of the scavenger receptors LOX-1 and CXCL16 and the capacity to internalize maleylated ovalbumin, whereas activation by TLR ligands did not. In contrast, the expression of SR-B1 was not modulated in these conditions. Interestingly, supplementation with maleylated ovalbumin limited dsRNA uptake and inhibited subsequent activation of bronchial epithelial cells. RNA silencing of LOX-1 and SR-B1 strongly blocked the dsRNA-induced cytokine production. Finally, administration of maleylated ovalbumin in mice inhibited the dsRNA-induced infiltration and activation of inflammatory cells in bronchoalveolar spaces and lung draining lymph nodes. Together, our data characterize the function of SR-B1 and LOX-1 in bronchial epithelial cells and their implication in dsRNA-induced responses, a finding that might be relevant during respiratory viral infections.

  5. Lipids in airway secretions

    International Nuclear Information System (INIS)

    Bhaskar, K.R.; DeFeudis O'Sullivan, D.; Opaskar-Hincman, H.; Reid, L.M.

    1987-01-01

    Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analysed, by thin layer chromatography, lipids present in airway mucus under 'normal' and hypersecretory (pathological) conditions.The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced ''in vitro'' by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO 2 , (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14 C acetate and 14 C palmitate were incorporated into lipids secreted ''in vitro'' by canine tracheal explants indicating that they are synthesised by the airway. (author)

  6. Dioscorin pre-treatment protects A549 human airway epithelial cells from hydrogen peroxide-induced oxidative stress.

    Science.gov (United States)

    Hsu, Jeng-Yuan; Chu, Jao-Jia; Chou, Ming-Chih; Chen, Ya-Wen

    2013-10-01

    Hydrogen peroxide (H(2)O(2)) is a highly reactive oxygen species involved in lung and bronchial epithelium injury. Increased H(2)O(2) levels have been reported in expired breath condensates of patients with inflammatory airway diseases such as chronic obstructive pulmonary disease. Protecting airway epithelial cells from oxidative stress is an important task in the prevention and management of airway diseases. Previous studies demonstrate that yam (Dioscorea batatas Decne) has antioxidant and anti-trypsin activities. This study evaluated the validity of dioscorin in vitro. The results showed that dioscorin attenuated the alteration of H(2)O(2) on G2/M cell cycle arrest. This might be associated with the activation of IκB and subsequent inactivation of NF-κB. Furthermore, dioscorin suppressed IL-8 secretion and reduced changes of adhesion molecule expressions in H(2)O(2)-injured A549 cells. These results help in understanding the potential of traditional Chinese herbal medicine as treatment for airway inflammatory diseases.

  7. Culturing the Unculturable: Human Coronavirus HKU1 Infects, Replicates, and Produces Progeny Virions in Human Ciliated Airway Epithelial Cell Cultures

    NARCIS (Netherlands)

    Pyrc, Krzysztof; Sims, Amy C.; Dijkman, Ronald; Jebbink, Maarten; Long, Casey; Deming, Damon; Donaldson, Eric; Vabret, Astrid; Baric, Ralph; van der Hoek, Lia; Pickles, Raymond

    2010-01-01

    Culturing newly identified human lung pathogens from clinical sample isolates can represent a daunting task, with problems ranging from low levels of pathogens to the presence of growth suppressive factors in the specimens, compounded by the lack of a suitable tissue culture system. However, it is

  8. Fluid structure interaction simulations of the upper airway in obstructive sleep apnea patients before and after maxillomandibular advancement surgery.

    Science.gov (United States)

    Chang, Kwang K; Kim, Ki Beom; McQuilling, Mark W; Movahed, Reza

    2018-06-01

    The purpose of this study was to analyze pharyngeal airflow using both computational fluid dynamics (CFD) and fluid structure interactions (FSI) in obstructive sleep apnea patients before and after maxillomandibular advancement (MMA) surgery. The airflow characteristics before and after surgery were compared with both CFD and FSI. In addition, the presurgery and postsurgery deformations of the airway were evaluated using FSI. Digitized pharyngeal airway models of 2 obstructive sleep apnea patients were generated from cone-beam computed tomography scans before and after MMA surgery. CFD and FSI were used to evaluate the pharyngeal airflow at a maximum inspiration rate of 166 ml per second. Standard steady-state numeric formulations were used for airflow simulations. Airway volume increased, pressure drop decreased, maximum airflow velocity decreased, and airway resistance dropped for both patients after the MMA surgery. These findings occurred in both the CFD and FSI simulations. The FSI simulations showed an area of marked airway deformation in both patients before surgery, but this deformation was negligible after surgery for both patients. Both CFD and FSI simulations produced airflow results that indicated less effort was needed to breathe after MMA surgery. The FSI simulations demonstrated a substantial decrease in airway deformation after surgery. These beneficial changes positively correlated with the large improvements in polysomnography outcomes after MMA surgery. Copyright © 2018 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  9. Causes and consequences of anterior pharyngeal pouch after total laryngectomy.

    Science.gov (United States)

    Anderson, S; Hogan, D; Panizza, B

    2014-07-01

    To assess the frequency of anterior pharyngeal pouch formation after total laryngectomy, and to discuss the causes and consequences of anterior pharyngeal pouch formation. A prospective, observational study of 43 patients undergoing total laryngectomy. Data collected included laryngeal defect closure type, tumour staging and demographic information. A barium swallow was performed on day 7-14 after surgery to assess for anterior pharyngeal pouch formation and fistula formation. The incidence of anterior pharyngeal pouch formation was 47 per cent. Patients who did not have an anterior pharyngeal pouch on swallow imaging assessment were less likely to develop a pharyngo-cutaneous fistula. There was no statistically significant association between laryngeal defect closure type and anterior pharyngeal pouch formation. The anterior pharyngeal pouch is a dynamic phenomenon best investigated with a fluoroscopic swallow imaging study. Its causes are multi-factorial. Absence of an anterior pharyngeal pouch appears to confer protection against pharyngo-cutaneous fistula formation, hastening commencement of adjuvant therapy and an oral diet.

  10. Interaction of Mycobacterium leprae with human airway epithelial cells: adherence, entry, survival, and identification of potential adhesins by surface proteome analysis.

    Science.gov (United States)

    Silva, Carlos A M; Danelishvili, Lia; McNamara, Michael; Berredo-Pinho, Márcia; Bildfell, Robert; Biet, Franck; Rodrigues, Luciana S; Oliveira, Albanita V; Bermudez, Luiz E; Pessolani, Maria C V

    2013-07-01

    This study examined the in vitro interaction between Mycobacterium leprae, the causative agent of leprosy, and human alveolar and nasal epithelial cells, demonstrating that M. leprae can enter both cell types and that both are capable of sustaining bacterial survival. Moreover, delivery of M. leprae to the nasal septum of mice resulted in macrophage and epithelial cell infection in the lung tissue, sustaining the idea that the airways constitute an important M. leprae entry route into the human body. Since critical aspects in understanding the mechanisms of infection are the identification and characterization of the adhesins involved in pathogen-host cell interaction, the nude mouse-derived M. leprae cell surface-exposed proteome was studied to uncover potentially relevant adhesin candidates. A total of 279 cell surface-exposed proteins were identified based on selective biotinylation, streptavidin-affinity purification, and shotgun mass spectrometry; 11 of those proteins have been previously described as potential adhesins. In vitro assays with the recombinant forms of the histone-like protein (Hlp) and the heparin-binding hemagglutinin (HBHA), considered to be major mycobacterial adhesins, confirmed their capacity to promote bacterial attachment to epithelial cells. Taking our data together, they suggest that the airway epithelium may act as a reservoir and/or portal of entry for M. leprae in humans. Moreover, our report sheds light on the potentially critical adhesins involved in M. leprae-epithelial cell interaction that may be useful in designing more effective tools for leprosy control.

  11. Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol.

    Science.gov (United States)

    Neilson, Louise; Mankus, Courtney; Thorne, David; Jackson, George; DeBay, Jason; Meredith, Clive

    2015-10-01

    Development of physiologically relevant test methods to analyse potential irritant effects to the respiratory tract caused by e-cigarette aerosols is required. This paper reports the method development and optimisation of an acute in vitro MTT cytotoxicity assay using human 3D reconstructed airway tissues and an aerosol exposure system. The EpiAirway™ tissue is a highly differentiated in vitro human airway culture derived from primary human tracheal/bronchial epithelial cells grown at the air-liquid interface, which can be exposed to aerosols generated by the VITROCELL® smoking robot. Method development was supported by understanding the compatibility of these tissues within the VITROCELL® system, in terms of airflow (L/min), vacuum rate (mL/min) and exposure time. Dosimetry tools (QCM) were used to measure deposited mass, to confirm the provision of e-cigarette aerosol to the tissues. EpiAirway™ tissues were exposed to cigarette smoke and aerosol generated from two commercial e-cigarettes for up to 6 h. Cigarette smoke reduced cell viability in a time dependent manner to 12% at 6 h. E-cigarette aerosol showed no such decrease in cell viability and displayed similar results to that of the untreated air controls. Applicability of the EpiAirway™ model and exposure system was demonstrated, showing little cytotoxicity from e-cigarette aerosol and different aerosol formulations when compared directly with reference cigarette smoke, over the same exposure time. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Adrenomedullin stimulates cyclic AMP production in the airway epithelial cells of guinea-pigs and in the human epithelial cell line

    Directory of Open Access Journals (Sweden)

    Takashi Kawaguchi

    1999-01-01

    Full Text Available This study was designed to examine the effects of adrenomedullin (AM on airway epithelial cells. Primary cultures of guinea-pig tracheal epithelial cells and the human bronchiolar epithelial cell line NCI-H441 were used. Intracellular cyclic adenosine monophosphate (cAMP, cyclic guanosine monophosphate (cGMP, prostaglandin E2 (PGE2, and stable end-products of nitric oxide were assayed. Adrenomedullin (10−6 mol/L stimulated cAMP production in guinea-pig epithelial cells. Indomethacin (10−5 mol/L significantly decreased the basal level of intracellular cAMP in guinea-pig epithelial cells, but not in NCI-H441 cells. However, AM did not stimulate production of PGE2, a major product that can increase cAMP formation. In the case of NCI-H441 cells, AM (10−8 – 10−6 mol/L did not significantly affect intracellular cGMP levels or nitrite content in conditioned medium. Adrenomedullin and calcitonin gene-related peptide (CGRP each stimulated cAMP production in NCI-H441 cells, but AM-stimulated cAMP production was antagonized by the CGRP fragment CGRP8–37. These findings suggest that AM stimulates cAMP production and functionally competes with CGRP for binding sites in airway epithelial cells, at least in human epithelial cells, but that it does not stimulate the release of PGE2 and nitric oxide. Though cyclooxygenase products contribute to some extent to cAMP formation in guinea-pigs, AM independently stimulates intracellular cAMP formation in airway epithelial cells.

  13. A preliminary evaluation of myoelectrical energy distribution of the front neck muscles in pharyngeal phase during normal swallowing.

    Science.gov (United States)

    Mingxing Zhu; Wanzhang Yang; Samuel, Oluwarotimi Williams; Yun Xiang; Jianping Huang; Haiqing Zou; Guanglin Li

    2016-08-01

    Pharyngeal phase is a central hub of swallowing in which food bolus pass through from the oral cavity to the esophageal. Proper understanding of the muscular activities in the pharyngeal phase is useful for assessing swallowing function and the occurrence of dysphagia in humans. In this study, high-density (HD) surface electromyography (sEMG) was used to study the muscular activities in the pharyngeal phase during swallowing tasks involving three healthy male subjects. The root mean square (RMS) of the HD sEMG data was computed by using a series of segmented windows as myoelectrical energy. And the RMS of each window covering all channels (16×5) formed a matrix. During the pharyngeal phase of swallowing, three of the matrixes were chosen and normalized to obtain the HD energy maps and the statistical parameter. The maps across different viscosity levels offered the energy distribution which showed the muscular activities of the left and right sides of the front neck muscles. In addition, the normalized average RMS (NARE) across different viscosity levels revealed a left-right significant correlation (r=0.868±0.629, pstronger correlation when swallowing water. This pilot study suggests that HD sEMG would be a potential tool to evaluate muscular activities in pharyngeal phase during normal swallowing. Also, it might provide useful information for dysphagia diagnosis.

  14. Modelling the effect of non-uniform radon progeny activities on transformation frequencies in human bronchial airways

    International Nuclear Information System (INIS)

    Fakir, H.; Hofmann, W.; Aubineau-Laniece, I.

    2006-01-01

    The effects of radiological and morphological source heterogeneities in straight and Y-shaped bronchial airways on hit frequencies and Micro-dosimetric quantities in epithelial cells have been investigated previously. The goal of the present study is to relate these physical quantities to transformation frequencies in sensitive target cells and to radon-induced lung cancer risk. Based on an effect-specific track length model, computed linear energy transfer (LET) spectra were converted to corresponding transformation frequencies for different activity distributions and source - target configurations. Average transformation probabilities were considerably enhanced for radon progeny accumulations and target cells at the carinal ridge, relative to uniform activity distributions and target cells located along the curved and straight airway portions at the same exposure level. Although uncorrelated transformation probabilities produce a linear dose - effect relationship, correlated transformations first increase depending on the LET, but then decrease significantly when exceeding a defined number of hits or cumulative exposure level. (authors)

  15. Dioscorin protects tight junction protein expression in A549 human airway epithelium cells from dust mite damage.

    Science.gov (United States)

    Fu, Lin Shien; Ko, Ying Hsien; Lin, Kuo Wei; Hsu, Jeng Yuan; Chu, Jao Jia; Chi, Chin Shiang

    2009-12-01

    In addition to being an allergen, the trypsin activity of dust mite extract also destroys the tight junctions of bronchial epithelium. Such damage can lead to airway leakage, which increases airway exposure to allergens, irritants, and other pathogens. Dioscorin, the storage protein of yam, demonstrates anti-trypsin activity, as well as other potential anti-inflammatory effects. This study investigated the protective role of dioscorin for tight junctions. The immunofluorescence stains of zonula occludens (ZO-1), E-cadherin (EC) and desmoplakin (DP) proteins were compared. A cultured A549 cell line was used as a control and A549 cells were incubated with mite extract 100 mg/mL for 16 h, with or without dioscorin 100 mg/mL pretreatment for 8 h and with dioscorin 100 mg/mL alone for 16 h. Western blot was performed to detect changes in ZO-1, EC, and DP in the treated A549 cell lines. Loss of tight junction protein expression (ZO-1, EC, DP) was demonstrated after 16-h mite extract incubation. The defect could be restored if cells were pretreated with dioscorin for 8 h. In addition, dioscorin did not cause damage to the A549 cell lines in terms of cell survival or morphology. Western blot showed no change in the amount of tight junction protein under various conditions. Dioscorin is a potential protector of airway damage caused by mite extract.

  16. Transient Dynamics Simulation of Airflow in a CT-Scanned Human Airway Tree: More or Fewer Terminal Bronchi?

    Directory of Open Access Journals (Sweden)

    Shouliang Qi

    2017-01-01

    Full Text Available Using computational fluid dynamics (CFD method, the feasibility of simulating transient airflow in a CT-based airway tree with more than 100 outlets for a whole respiratory period is studied, and the influence of truncations of terminal bronchi on CFD characteristics is investigated. After an airway model with 122 outlets is extracted from CT images, the transient airflow is simulated. Spatial and temporal variations of flow velocity, wall pressure, and wall shear stress are presented; the flow pattern and lobar distribution of air are gotten as well. All results are compared with those of a truncated model with 22 outlets. It is found that the flow pattern shows lobar heterogeneity that the near-wall air in the trachea is inhaled into the upper lobe while the center flow enters the other lobes, and the lobar distribution of air is significantly correlated with the outlet area ratio. The truncation decreases airflow to right and left upper lobes and increases the deviation of airflow distributions between inspiration and expiration. Simulating the transient airflow in an airway tree model with 122 bronchi using CFD is feasible. The model with more terminal bronchi decreases the difference between the lobar distributions at inspiration and at expiration.

  17. Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness.

    Science.gov (United States)

    Devouassoux, Gilles; Lévy, Patrick; Rossini, Eliane; Pin, Isabelle; Fior-Gozlan, Michèle; Henry, Mireille; Seigneurin, Daniel; Pépin, Jean-Louis

    2007-03-01

    Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

  18. Diacetyl and 2,3-pentanedione exposure of human cultured airway epithelial cells: Ion transport effects and metabolism of butter flavoring agents

    Energy Technology Data Exchange (ETDEWEB)

    Zaccone, Eric J. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Goldsmith, W. Travis [Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States); Shimko, Michael J. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Wells, J.R.; Schwegler-Berry, Diane; Willard, Patsy A.; Case, Shannon L.; Thompson, Janet A. [Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States); Fedan, Jeffrey S. [Department of Pharmaceutical Sciences, West Virginia University, Morgantown, WV (United States); Pathology and Physiology Research Branch, National Institute for Occupational Safety and Health, Morgantown, WV (United States)

    2015-12-15

    Inhalation of butter flavoring by workers in the microwave popcorn industry may result in “popcorn workers' lung.” In previous in vivo studies rats exposed for 6 h to vapor from the flavoring agents, diacetyl and 2,3-pentanedione, acquired flavoring concentration-dependent damage of the upper airway epithelium and airway hyporeactivity to inhaled methacholine. Because ion transport is essential for lung fluid balance, we hypothesized that alterations in ion transport may be an early manifestation of butter flavoring-induced toxicity. We developed a system to expose cultured human bronchial/tracheal epithelial cells (NHBEs) to flavoring vapors. NHBEs were exposed for 6 h to diacetyl or 2,3-pentanedione vapors (25 or ≥ 60 ppm) and the effects on short circuit current and transepithelial resistance (R{sub t}) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na{sup +} transport, without affecting Cl{sup −} transport or Na{sup +},K{sup +}-pump activity. R{sub t} was unaffected. Na{sup +} transport recovered 18 h after exposure. Concentrations (100–360 ppm) of diacetyl and 2,3-pentanedione reported earlier to give rise in vivo to epithelial damage, and 60 ppm, caused death of NHBEs 0 h post-exposure. Analysis of the basolateral medium indicated that NHBEs metabolize diacetyl and 2,3-pentanedione to acetoin and 2-hydroxy-3-pentanone, respectively. The results indicate that ion transport is inhibited transiently in airway epithelial cells by lower concentrations of the flavorings than those that result in morphological changes of the cells in vivo or in vitro. - Highlights: • Butter flavoring vapor effects on human cultured airway epithelium were studied. • Na transport was reduced by a 6-h exposure to 25 ppm diacetyl and 2,3-pentanedione. • Na transport recovered 18 h after exposure. • > 60 ppm transepithelial voltage and resistance were abolished; cells were damaged. • Cells metabolized diacetyl and 2,3-pentanedione

  19. Effect of titanium dioxide nanoparticles (TiO2 NPs) on the expression of mucin genes in human airway epithelial cells.

    Science.gov (United States)

    Kim, Gui Ok; Choi, Yoon Seok; Bae, Chang Hoon; Song, Si-Youn; Kim, Yong-Dae

    2017-01-01

    Titanium dioxide nanoparticles (TiO 2 NPs) are utilized with growing frequency for a wide variety of industrial applications. Recently, acute and chronic exposures to TiO 2 NPs have been found to induce inflammatory response in the human respiratory tract. However, the effect and mechanism underlying the induction of major airway mucins by TiO 2 NPs have not been elucidated. This study was conducted to characterize the effect of TiO 2 NPs, and the mechanism involved, on the expressions of airway mucins in human airway epithelial cells. In NCI-H292 cells and primary cultures of normal nasal epithelial cells, the effects of TiO 2 NPs and signaling pathway for airway mucin genes were investigated by reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassays and immunoblot analysis using several specific inhibitors and small interfering RNAs (siRNAs). TiO 2 NPs increased MUC5B expression and activated the phosphorylations of extracellular signal-related kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (an ERK1/2 MAPK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited TiO 2 NPs-induced MUC5B expression. And knockdown of ERK1, ERK2 and p38 MAPK using siRNAs significantly blocked TiO 2 NPs-induced MUC5B mRNA expression. Furthermore, Toll-like receptor 4 (TLR4) mRNA expression was increased by TiO 2 NPs, and knockdown by TLR4 siRNA significantly attenuated TiO 2 NPs-induced MUC5B mRNA expression and the TiO 2 NPs-induced phosphorylations of ERK1/2 and p38 MAPK. These results demonstrate for the first time that TiO 2 NPs induce MUC5B expression via TLR4-dependent ERK1/2 and p38 MAPK signaling pathways in respiratory epithelium.

  20. Tumor necrosis factor-alpha enhances mRNA expression and secretion of interleukin-6 in cultured human airway smooth muscle cells

    NARCIS (Netherlands)

    S. McKay (Sue); S.J. Hirst (Stuart); M. Bertrand-de Haas (Marion); J.C. de Jongste (Johan); H.C. Hoogsteden (Henk); P.R. Saxena (Pramod Ranjan); H.S. Sharma (Hari)

    2000-01-01

    textabstractAirway smooth muscle (ASM) is considered to be an end-target cell for the effects of mediators released during airway wall inflammation. Several reports suggest that activated ASM may be capable of generating various proinflammatory cytokines. We

  1. Computationally efficient analysis of particle transport and deposition in a human whole-lung-airway model. Part II: Dry powder inhaler application.

    Science.gov (United States)

    Kolanjiyil, Arun V; Kleinstreuer, Clement; Sadikot, Ruxana T

    2017-05-01

    Pulmonary drug delivery is becoming a favored route for administering drugs to treat both lung and systemic diseases. Examples of lung diseases include asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD) as well as respiratory distress syndrome (ARDS) and pulmonary fibrosis. Special respiratory drugs are administered to the lungs, using an appropriate inhaler device. Next to the pressurized metered-dose inhaler (pMDI), the dry powder inhaler (DPI) is a frequently used device because of the good drug stability and a minimal need for patient coordination. Specific DPI-designs and operations greatly affect drug-aerosol formation and hence local lung deposition. Simulating the fluid-particle dynamics after use of a DPI allows for the assessment of drug-aerosol deposition and can also assist in improving the device configuration and operation. In Part I of this study a first-generation whole lung-airway model (WLAM) was introduced and discussed to analyze particle transport and deposition in a human respiratory tract model. In the present Part II the drug-aerosols are assumed to be injected into the lung airways from a DPI mouth-piece, forming the mouth-inlet. The total as well as regional particle depositions in the WLAM, as inhaled from a DPI, were successfully compared with experimental data sets reported in the open literature. The validated modeling methodology was then employed to study the delivery of curcumin aerosols into lung airways using a commercial DPI. Curcumin has been implicated to possess high therapeutic potential as an antioxidant, anti-inflammatory and anti-cancer agent. However, efficacy of curcumin treatment is limited because of the low bioavailability of curcumin when ingested. Hence, alternative drug administration techniques, e.g., using inhalable curcumin-aerosols, are under investigation. Based on the present results, it can be concluded that use of a DPI leads to low lung deposition efficiencies because large amounts of

  2. Posture of the head and pharyngeal swallowing

    International Nuclear Information System (INIS)

    Ekberg, O.

    1986-01-01

    Closure of the laryngeal vestibule during swallowing is important for protection of the airways. The present investigation included 53 patients with dysphagia examined cineradiographically with the head held in resting posture, flexion and extension. The ability to protect the airways by the downward movement of the epiglottis and by obliteration of the laryngeal vestibule was studied in different postures of the head. Of 35 patients with normal laryngeal obliteration with the head in resting position 10 showed a defective closure at swallowing in extension. In 18 patients with defective closure of the laryngeal vestibule in resting position 9 were improved on flexion and two on extension of the head. In one patient with defectie closure of the laryngeal vestibule in resting position swallowing in flexion showed an aggravated dysfunction. In our other patients the defective closure became more marked on extension. Four patients had less effective downward movement of the epiglottis with the head in extension. Of 10 patients with defective epiglottic movement with the head in resting position two were improved on tilting the head forwards. The results show that the position of the head influences the closure of the airways during swallowing. Patients with defective protection of the laryngeal vestibule should be instructed to swallow with the head tilted forwards. (orig.)

  3. Significance of Interleukin-6 Signaling in the Resistance of Pharyngeal Cancer to Irradiation and the Epidermal Growth Factor Receptor Inhibitor

    International Nuclear Information System (INIS)

    Chen, C.-C.; Chen, W.-C.; Lu, C.-H.; Wang, W.-H.; Lin, P.-Y.; Lee, K.-D.; Chen, M.-F.

    2010-01-01

    Purpose: Tumor eradication by chemoradiotherapy for pharyngeal cancer has not been particularly successful. Targeting epithelial growth factor receptor (EGFR) could be a potential treatment strategy providing additional benefits, but only a subset of these tumors gives a clinically significant response to EGFR inhibitors. The aim has been to identify the role of interleukin-6 (IL-6) signaling and its predictive power in the treatment response of pharyngeal cancer. Methods and Materials: Human pharyngeal cancer cell lines, including the hypopharyngeal cancer cell line FaDu and its derived cell line FaDu-C225-R, were selected. Changes in tumor growth, response to treatment, and responsible signaling pathway were investigated in vitro. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining, and correlations were made between levels of IL-6, IL-6 receptor (IL-6R), p-AKT, and p-STAT3 expression and the clinical outcome of patients. Results: In vitro, either extrinsic IL-6 stimulation of cancer cells or intrinsically activated IL-6 signaling detected in FADu-C225-R cells results in resistance to irradiation and EGFR inhibitor. Blocking IL-6 signaling attenuated aggressive tumor behavior and sensitized the cells to treatments. The responsible mechanisms included decreased p-STAT3, less nuclear translocation of EGFR, and subsequently attenuated epithelial-mesenchymal transition. Regarding clinical data, staining of p-STAT3 and IL-6 was significantly linked with lower response rates to treatments and shorter survival in pharyngeal cancer patients. Conclusions: IL-6 and p-STAT3 may be significant predictors of pharyngeal carcinoma, and regulating IL-6 signaling can be considered a promising therapeutic approach.

  4. The effects of gas humidification with high-flow nasal cannula on cultured human airway epithelial cells.

    Science.gov (United States)

    Chidekel, Aaron; Zhu, Yan; Wang, Jordan; Mosko, John J; Rodriguez, Elena; Shaffer, Thomas H

    2012-01-01

    Humidification of inspired gas is important for patients receiving respiratory support. High-flow nasal cannula (HFNC) effectively provides temperature and humidity-controlled gas to the airway. We hypothesized that various levels of gas humidification would have differential effects on airway epithelial monolayers. Calu-3 monolayers were placed in environmental chambers at 37°C with relative humidity (RH) 90% (HFNC) for 4 and 8 hours with 10 L/min of room air. At 4 and 8 hours, cell viability and transepithelial resistance measurements were performed, apical surface fluid was collected and assayed for indices of cell inflammation and function, and cells were harvested for histology (n = 6/condition). Transepithelial resistance and cell viability decreased over time (P < 0.001) between HFNC and dry groups (P < 0.001). Total protein secretion increased at 8 hours in the dry group (P < 0.001). Secretion of interleukin (IL)-6 and IL-8 in the dry group was greater than the other groups at 8 hours (P < 0.001). Histological analysis showed increasing injury over time for the dry group. These data demonstrate that exposure to low humidity results in reduced epithelial cell function and increased inflammation.

  5. The Effects of Gas Humidification with High-Flow Nasal Cannula on Cultured Human Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Aaron Chidekel

    2012-01-01

    Full Text Available Humidification of inspired gas is important for patients receiving respiratory support. High-flow nasal cannula (HFNC effectively provides temperature and humidity-controlled gas to the airway. We hypothesized that various levels of gas humidification would have differential effects on airway epithelial monolayers. Calu-3 monolayers were placed in environmental chambers at 37°C with relative humidity (RH 90% (HFNC for 4 and 8 hours with 10 L/min of room air. At 4 and 8 hours, cell viability and transepithelial resistance measurements were performed, apical surface fluid was collected and assayed for indices of cell inflammation and function, and cells were harvested for histology (n=6/condition. Transepithelial resistance and cell viability decreased over time (P<0.001 between HFNC and dry groups (P<0.001. Total protein secretion increased at 8 hours in the dry group (P<0.001. Secretion of interleukin (IL-6 and IL-8 in the dry group was greater than the other groups at 8 hours (P<0.001. Histological analysis showed increasing injury over time for the dry group. These data demonstrate that exposure to low humidity results in reduced epithelial cell function and increased inflammation.

  6. Effects of pharyngeal electrical stimulation on swallowing performance.

    Science.gov (United States)

    Takeishi, Ryosuke; Magara, Jin; Watanabe, Masahiro; Tsujimura, Takanori; Hayashi, Hirokazu; Hori, Kazuhiro; Inoue, Makoto

    2018-01-01

    Pharyngeal electrical stimulation (PEStim) has been found to facilitate voluntary swallowing. This study investigated how PEStim contributed to modulation of swallowing function in 15 healthy humans. In the involuntary swallowing test, water was injected onto the pharynx at 0.05 ml/s and the onset latency of the first swallow was measured. In the voluntary swallowing test, subjects swallowed their own saliva as quickly as possible for 30 s and the number of swallows was counted. Voluntary and involuntary swallowing was evaluated before (baseline), immediately after, and every 10 min after 10-min PEStim for 60 min. A voluntary swallowing test with simultaneous 30-s PEStim was also conducted before and 60 min after 10-min PEStim. The number of voluntary swallows with simultaneous PEStim significantly increased over 60 min after 10-min PEStim compared with the baseline. The onset latency of the first swallow in the involuntary swallowing test was not affected by 10-min PEStim. The results suggest that PEStim may have a long-term facilitatory effect on the initiation of voluntary swallowing in healthy humans, but not on peripherally-evoked swallowing. The physiological implications of this modulation are discussed.

  7. A study of the post-surgical volumetric changes of oropharyngeal visceral cavity, upper airway and the respiratory function of in mandibular setback surgery

    International Nuclear Information System (INIS)

    Ooto, Hiroyuki

    2007-01-01

    It has been reported that the narrowing of pharyngeal airway caused by mandibular setback surgery may associate the upper respiratory tract dysfunctions such as sleep apnea/hypopnea. However, there has been no clear relevance between morphological changes of pharyngeal airway in two dimensional evaluation and the onset of postoperative upper airway dysfunction. The aim of this study is to evaluate volumetric change and relevance of oropharyngeal visceral cavity and upper airway with three-dimensional CT (3DCT) and upper airway function before and after mandibular setback surgery. Thirty three patients (6 males and 27 females) who have had mandibular setback surgery were allocated in this study. The difference between pre- and postoperative position of mandibular bone and hyoid bone as well as volume of airway, and oropharyngeal visceral cavity were measured using 3DCT remodeling images. The evaluation of upper airway function was performed Polysomnograph (PSG) pre- and post surgically. These data were corrected just before the operation, just before discharge (10.2±1.8 days after the operation) and 1 year later. After mandibular setback surgery, the volume of airway and oropharyngeal visceral cavity had significantly decreased. However, there was no correlation in the quantity of mandibular setback and reduction of airway volume. PSG, aggravation of apnea hypopnea index (AHI) was confirmed among 7 out of 26 samples (27%) in the postoperative early stage. In addition, aggravation of minimum SpO 2 , desaturation index and outbreak time of snoring were detected. At the early stage of postoperation, the airway volume decreased and the airway function took a turn for the worse. On the other hand both were recognized to have tendency to recover after 1 year. In this study, there was no correlation in the amount of change of the volume of the airway, oropharyngeal visceral cavity and aggravation of upper airway function. Moreover it was suggested that age and other

  8. Variability of the pharyngeal phase of swallow in the cat.

    Directory of Open Access Journals (Sweden)

    Daniel G Spearman

    Full Text Available The pharyngeal phase of swallow has been thought to be a stereotypical motor behavior.This is a prospective, preclinical, hypothesis driven, one group by three-task design.We sought to compare the effects of pharyngeal swabbing, water only, and water plus punctate mechanical stimulation on the spatiotemporal features of the pharyngeal phase of swallow in the cat. Swallow was elicited under these three conditions in six anaesthetized cats. Electromyographic activity was recorded from seven muscles used to evaluate swallow: mylohyoid, geniohyoid, thyrohyoid, thyroarytenoid, thyropharyngeus, cricopharyngeus, and parasternal.Pharyngeal swabbing in comparison to the other stimulus conditions, results in decreases in post-swallow cricopharyngeus activity (upper esophageal sphincter; a significant increase in parasternal (schluckatmung; swallow breath activity; and increases in thyrohyoid (laryngeal elevator, thyroarytenoid (laryngeal adductor and parasternal muscles burst duration. Pearson correlations were found of moderate strength between 19% of burst duration comparisons and weak to moderate relationships between 29% of burst amplitude comparisons. However, there were no positive significant relationships between phase durations and electromyogram amplitudes between any of the muscles studied during swallow.The results support the concept that a stereotypical behavior, such as pharyngeal swallowing in animal models, can be modified by sensory feedback from pharyngeal mucosal mechanoreceptors. Furthermore, differences in swallow phase durations and amplitudes provide evidence that separate regulatory mechanisms exist which regulate spatial and temporal aspects of the behavior.

  9. Measurement of pharyngeal sensory cortical processing: technique and physiologic implications

    Directory of Open Access Journals (Sweden)

    Ringelstein E Bernd

    2009-07-01

    Full Text Available Abstract Background Dysphagia is a major complication of different diseases affecting both the central and peripheral nervous system. Pharyngeal sensory impairment is one of the main features of neurogenic dysphagia. Therefore an objective technique to examine the cortical processing of pharyngeal sensory input would be a helpful diagnostic tool in this context. We developed a simple paradigm to perform pneumatic stimulation to both sides of the pharyngeal wall. Whole-head MEG was employed to study changes in cortical activation during this pharyngeal stimulation in nine healthy subjects. Data were analyzed by means of synthetic aperture magnetometry (SAM and the group analysis of individual SAM data was performed using a permutation test. Results Our results revealed bilateral activation of the caudolateral primary somatosensory cortex following sensory pharyngeal stimulation with a slight lateralization to the side of stimulation. Conclusion The method introduced here is simple and easy to perform and might be applicable in the clinical setting. The results are in keeping with previous findings showing bihemispheric involvement in the complex task of sensory pharyngeal processing. They might also explain changes in deglutition after hemispheric strokes. The ipsilaterally lateralized processing is surprising and needs further investigation.

  10. Airway Clearance Techniques (ACTs)

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    Full Text Available ... specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway ... on their own. Share Facebook Twitter Email More options Print Share Facebook Twitter Email Print Permalink All ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Make a Charitable Gift Our Corporate Supporters Workplace Engagement DONATE YOUR PROPERTY eCards for a Cure About ... airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  13. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  14. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Physical Therapy Coughing and Huffing High-Frequency Chest Wall Oscillation Positive Expiratory Pressure Clinical Trials Clinical Trials ... clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to ...

  15. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH ... clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to ...

  16. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... a range of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage ... LEGACY GIFT Sponsor a Participant CF Climb CF Cycle for Life Great Strides Xtreme Hike Participate In ...

  17. Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

    Directory of Open Access Journals (Sweden)

    Ping-Ho Chen

    2017-01-01

    Full Text Available Global reports estimate 600 million betel quid (BQ chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN, are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN and genetic factors (MAO and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future.

  18. Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

    Science.gov (United States)

    Mahmood, Qaisar; Chiang, Tai-An

    2017-01-01

    Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD) but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO) gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future. PMID:29376073

  19. On the relation of nasal cycling with nasal airway dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Guilmette, R A; Wolff, R K

    1988-12-01

    The size and configuration of the nasal airways of humans change with time as a result of the normal process of congestion/decongestion of the erectile tissue of the nasal mucosa. To determine the extent to which airway areas change in vivo, we used magnetic resonance imaging (MRI) to quantitate both the cross-sectional area and perimeter of coronal sections of the entire nasal airway of a human subject. Changes in airway size or patency were indexed to measured changes in unilateral nasal airway resistance determined by posterior rhino manometry. The results of this study in which two MRI scans were performed for presumed left-side patency and two for right-side patency, showed that changes in nasal airway resistance were difficult to ascribe to systematic changes In the sizes of the airways. (author)

  20. On the relation of nasal cycling with nasal airway dimensions

    International Nuclear Information System (INIS)

    Guilmette, R.A.; Wolff, R.K.

    1988-01-01

    The size and configuration of the nasal airways of humans change with time as a result of the normal process of congestion/decongestion of the erectile tissue of the nasal mucosa. To determine the extent to which airway areas change in vivo, we used magnetic resonance imaging (MRI) to quantitate both the cross-sectional area and perimeter of coronal sections of the entire nasal airway of a human subject. Changes in airway size or patency were indexed to measured changes in unilateral nasal airway resistance determined by posterior rhino manometry. The results of this study in which two MRI scans were performed for presumed left-side patency and two for right-side patency, showed that changes in nasal airway resistance were difficult to ascribe to systematic changes In the sizes of the airways. (author)

  1. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

    Winkler Wille, Mathilde Marie; Pedersen, Jesper Holst; Dirksen, Asger

    2013-01-01

    Rationale – Chronic Obstructive Pulmonary Disease (COPD) is a combination of chronic bronchitis and emphysema, which both may lead to airway obstruction. Under normal circumstances, airway dimensions vary as a function of inspiration level. We aim to study the influence of COPD and emphysema......-20% (mild), 20%-30% (moderate) or >30% (severe). Spirometry was performed annually and participants were divided into severity groups according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Data were analysed in a mixed effects regression model with log(airway lumen diameter...... and emphysema, respectively. Conclusions – Airway distensibility decreases significantly with increasing severity of both GOLD status and emphysema, indicating that in COPD the dynamic change in airway calibre during respiration is compromised. Chronic bronchitis and emphysema appear to be interacting...

  2. Hybrid Lipid/Polymer Nanoparticles for Pulmonary Delivery of siRNA: Development and Fate Upon In Vitro Deposition on the Human Epithelial Airway Barrier.

    Science.gov (United States)

    d'Angelo, Ivana; Costabile, Gabriella; Durantie, Estelle; Brocca, Paola; Rondelli, Valeria; Russo, Annapina; Russo, Giulia; Miro, Agnese; Quaglia, Fabiana; Petri-Fink, Alke; Rothen-Rutishauser, Barbara; Ungaro, Francesca

    2017-10-16

    Nowadays, the downregulation of genes involved in the pathogenesis of severe lung diseases through local siRNA delivery appears an interesting therapeutic approach. In this study, we propose novel hybrid lipid-polymer nanoparticles (hNPs) consisting of poly(lactic-co-glycolic) acid (PLGA) and dipalmitoyl phosphatidylcholine (DPPC) as siRNA inhalation system. A panel of DPPC/PLGA hNPs was prepared by emulsion/solvent diffusion and fully characterized. A combination of model siRNAs against the sodium transepithelial channel (ENaC) was entrapped in optimized hNPs comprising or not poly(ethylenimine) (PEI) as third component. siRNA-loaded hNPs were characterized for encapsulation efficiency, release kinetics, aerodynamic properties, and stability in artificial mucus (AM). The fate and cytotoxicity of hNPs upon aerosolization on a triple cell co-culture model (TCCC) mimicking human epithelial airway barrier were assessed. Finally, the effect of siRNA-loaded hNPs on ENaC protein expression at 72 hours was evaluated in A549 cells. Optimized muco-inert hNPs encapsulating model siRNA with high efficiency were produced. The developed hNPs displayed a hydrodynamic diameter of ∼150 nm, a low polydispersity index, a negative ζ potential close to -25 mV, and a peculiar triphasic siRNA release lasting for 5 days, which slowed down in the presence of PEI. siRNA formulations showed optimal in vitro aerosol performance after delivery with a vibrating mesh nebulizer. Furthermore, small-angle X-ray scattering analyses highlighted an excellent stability upon incubation with AM, confirming the potential of hNPs for direct aerosolization on mucus-lined airways. Studies in TCCC confirmed that fluorescent hNPs are internalized inside airway epithelial cells and do not exert any cytotoxic or acute proinflammatory effect. Finally, a prolonged inhibition of ENaC protein expression was observed in A549 cells upon treatment with siRNA-loaded hNPs. Results demonstrate the great potential

  3. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  4. CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways.

    Science.gov (United States)

    Shahabuddin, Syed; Ji, Rong; Wang, Ping; Brailoiu, Eugene; Dun, Na; Yang, Yi; Aksoy, Mark O; Kelsen, Steven G

    2006-07-01

    Human airway epithelial cells (HAEC) constitutively express the CXC chemokine receptor CXCR3, which regulates epithelial cell movement. In diseases such as chronic obstructive pulmonary disease and asthma, characterized by denudation of the epithelial lining, epithelial cell migration may contribute to airway repair and reconstitution. This study compared the potency and efficacy of three CXCR3 ligands, I-TAC/CXCL11, IP-10/CXCL10, and Mig/CXCL9, as inducers of chemotaxis in HAEC and examined the underlying signaling pathways involved. Studies were performed in cultured HAEC from normal subjects and the 16-HBE cell line. In normal HAEC, the efficacy of I-TAC-induced chemotaxis was 349 +/- 88% (mean +/- SE) of the medium control and approximately one-half the response to epidermal growth factor, a highly potent chemoattractant. In normal HAEC, Mig, IP-10, and I-TAC induced chemotaxis with similar potency and a rank order of efficacy of I-TAC = IP-10 > Mig. Preincubation with pertussis toxin completely blocked CXCR3-induced migration. Of interest, intracellular [Ca(2+)] did not rise in response to I-TAC, IP-10, or Mig. I-TAC induced a rapid phosphorylation (5-10 min) of two of the three MAPKs, i.e., p38 and ERK1/2. Pretreatment of HAEC with the p38 inhibitor SB 20358 or the PI3K inhibitor wortmannin dose-dependently inhibited the chemotactic response to I-TAC. In contrast, the ERK1/2 inhibitor U0126 had no effect on chemotaxis. These data indicate that in HAEC, CXCR3-mediated chemotaxis involves a G protein, which activates both the p38 MAPK and PI3K pathways in a calcium-independent fashion.

  5. Pharyngeal and cervical cancer incidences significantly correlate with personal UV doses among whites in the United States.

    Science.gov (United States)

    Godar, Dianne E; Tang, Rong; Merrill, Stephen J

    2014-09-01

    Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer's incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state's average annual personal UV dose. We refer to our data as 'white' rather than 'Caucasian,' which is a specific subgroup of whites, and 'black' rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. The value of CT measurement of normal human mandible, hyoid and the airway area at the hyoid level

    International Nuclear Information System (INIS)

    Chen Changliang; Zhang Jia; Ge Pingjiang; Zhang Siyi

    2004-01-01

    Objective: To determine the normal value and clinical significance of the lengths and angles of both mandible and hyoid, and their relationship with cervical vertebra as well as the transverse area of the airway at the hyoid level using CT. Methods: Several lines and angles on the CT images were measured in 68 normal subjects. Line A was the length between both free ends of the mandible; line B was the distance from the body of the mandible to line A; Line C was the distance from line A to the anterior aspect of the cervical vertebra. α 1 was the angle between the middle of mandible body and its two free ends. Line a was the distance between two free ends of greater horn of hyoid bone. Line b was the distance from hyoid to line a. Line c was the distance from line a to the cervical vertebra. α 2 was the angle between the middle of hyoid body and its two free ends. S stood for the area of the airway at the hyoid level. SPSS 11.5 statistical analysis package was used to analyze the results. Results: The average and median distance/angle of various measurements were as follows: line A was (89.28±5.90) mm and 88.70 mm, line B was (62.61±5.78) mm and 62.50 mm, line C was (9.29±3.29) mm and 4.20 mm, α 1 was (71.25±6.77) degree and 71.05 degree, line a was (38.69 ± 6.07) mm and 39.90 mm, line b was (28.79 ± 4.37) mm and 28.50 mm, line c was (1.91 ± 3.03) mm and 1.75 mm, α 2 was (68.47 ± 15.71) degree and 66.95 degree. The average S was (436.14 ± 160.37) mm 2 and median was 431.75 mm 2 . Conclusion: It is easy to measure the three lines and the two angles of mandible and hyoid. The measurement is of vital importance in the diagnosis and treatment for obstructive sleep apnea syndrome

  7. TREATMENT FOR ACUTE PHARYNGITIS AND TONSILLOPHARYNGITIS AMONG SICKLY CHILDREN

    Directory of Open Access Journals (Sweden)

    G.A. Samsygina

    2007-01-01

    Full Text Available Among the sickly children, pharyngitis and tonsillopharyngitis are quite often accompanied by pain and scratch in a throat, which is anguished for a child themselves and causes parents to worry. In the therapy for the indicated pathology, a certain place is held by a local antibiotic fusafungine. In the article, the author studies the effects of fusafungine on tonsillitis/tonsillopharyngitis and pharyngitis, running with pain in a throat, among the sickly children aged between 3 and 15. The research was carried on in 42 centers of different Russian regions and became a part of the multicentered research according to «Chibis» program. 2,609 children were examined, 1,907 of who Received fusafungine and 702 children did not. Among 78,1% of the children, the authors noted the phenomena of pharyngitis, rhinopharyngitis and acute tonsillopharyngitis. As the research showed the symptoms of rhinopharyngitis and tonsillopharync gitis were reliably arrested much faster, when applying fusafungine, thus, the clinical effects mostly emerged after 4th–5th day of the therapy. The acquired data allowed one to recommend the inclusion of fusafungine into the therapy for acute rhinopharyngitis, pharyngitis and tonsillopharyngitis among the sickly children.Key words: rhinopharyngitis, pharyngitis, tonsillopharyngitis, fusafungine, children, treatment.

  8. [Etiological analysis and individualized treatment of pharyngeal paraesthesia].

    Science.gov (United States)

    Lou, Zhengcai; Gong, Xuhong; Lou, Fangyi; He, Lanjuan; Zhu, Qiaoying

    2009-07-01

    To analyze the nosazontology of pharyngeal paraesthesia and investigate the treatment. Two hundred and twelve misdiagnosed pharyngeal paraesthesia patients were investigated by history inquiry, routine examination, 24-hour esophageal pH monitoring, barium X-ray of the oesophagus, anxieties-athymic private measuring scale, coefficient of variation of the R-R (CVR-R), bioavailable testosterone detection (Bio-T), erection experiment and questionnaire about man climacteric syndrome. The concomitant symptoms and positions of pharyngeal paresthesia were also studied. We adopted individuallized sequential multi-therapy for every patient according to the cause of disease. The cause of disease within 212 cases of pharyngeal paraesthesia included 62 psychic trauma, 32 endocrine system disease, 106 upper gastrointestinal disease, circulatory disease, 9 circulatory disease, 3 idiopathic. With individualized treatment, 110 cases had fully recovered, 63 cases excellence and 31 cases utility, and the efficiency rate was 96.23%. Pharyngeal paraesthesia can be caused by several factors. Thorough examination and comprehensive analysis should be applied to those incurable patient who has been treated for a long time. Short course of treatment and irrational drug use are the main causes of short-term recurrence and unsatisfactory curative effect.

  9. McIsaac criteria for diagnosis of acute group-A β-hemolytic streptococcal pharyngitis

    Directory of Open Access Journals (Sweden)

    Imanuel Y. Malino

    2013-10-01

    Conclusion A McIsaac criteria total score of <4 is favorable for excluding a diagnosis of GABHS pharyngitis. A McIsaac total criteria score of ≥4 requires further examination to confirm a diagnosis of GABHS pharyngitis.

  10. Streptococcus pyogenes pharyngeal colonization resulting in recurrent, prepubertal vulvovaginitis.

    Science.gov (United States)

    Hansen, Megan T; Sanchez, Veronica T; Eyster, Kathleen; Hansen, Keith A

    2007-10-01

    Recurrent, prepubertal, vaginal infections are an uncommon, troublesome problem for the patient and her family. Failure of initial therapy to alleviate vulvovaginitis may be related to vulvar skin disease, foreign body, sexual abuse, pinworms, reactions to medications, anatomic anomalies, or allergies. This report describes a case of recurrent Streptococcus pyogenes vulvovaginitis secondary to presumed vaginal re-inoculation from pharyngeal colonization. A 4-yr-old presented with one year of culture proven, recurrent Streptococcus pyogenes vulvovaginitis. Her symptoms repeatedly resolved with penicillin therapy, but continued to recur following cessation of antibiotic therapy. Evaluation included physical examination, trans-abdominal pelvic ultrasound, and vaginoscopy which all revealed normal upper and lower genital tract anatomy. Both the patient and her mother demonstrated culture proven, Group A Streptococcus pharyngeal colonization. Because of the possibility of repeated inoculations of the vaginal area from the colonized pharynx, they were both treated for decolonization with a regimen of amoxicillin and rifampin for ten days. Following this therapy there was resolution of vaginal symptoms with no further recurrence. Follow-up pharyngeal culture done on both mother and child on their last visit were negative for Group A Streptococcus. This case demonstrated an unusual specific cause of recurrent vaginitis resulting from presumed self or maternal re-inoculation with group A beta-hemolytic streptococcus from pharyngeal colonization. Group A beta-hemolytic streptococcus are consistently sensitive to penicillin, but up to 25% of acute pharyngitis cases treated with penicillin having continued asymptomatic, bacterial carriage within the nasopharynx. Thus initial alleviation of symptoms in a patient with Group A beta-hemolytic vulvovaginitis treated with penicillin, can have continued asymptomatic pharyngeal colonization which can result in recurrence of the

  11. Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model.

    Science.gov (United States)

    Sisler, Jennifer D; Pirela, Sandra V; Friend, Sherri; Farcas, Mariana; Schwegler-Berry, Diane; Shvedova, Anna; Castranova, Vincent; Demokritou, Philip; Qian, Yong

    2015-01-01

    The printer is one of the most common office equipment. Recently, it was reported that toner formulations for printing equipment constitute nano-enabled products (NEPs) and contain engineered nanomaterials (ENMs) that become airborne during printing. To date, insufficient research has been performed to understand the potential toxicological properties of printer-emitted particles (PEPs) with several studies using bulk toner particles as test particles. These studies demonstrated the ability of toner particles to cause chronic inflammation and fibrosis in animal models. However, the toxicological implications of inhalation exposures to ENMs emitted from laser printing equipment remain largely unknown. The present study investigates the toxicological effects of PEPs using an in vitro alveolar-capillary co-culture model with Human Small Airway Epithelial Cells (SAEC) and Human Microvascular Endothelial Cells (HMVEC). Our data demonstrate that direct exposure of SAEC to low concentrations of PEPs (0.5 and 1.0 µg/mL) caused morphological changes of actin remodeling and gap formations within the endothelial monolayer. Furthermore, increased production of reactive oxygen species (ROS) and angiogenesis were observed in the HMVEC. Analysis of cytokine and chemokine levels demonstrates that interleukin (IL)-6 and MCP-1 may play a major role in the cellular communication observed between SAEC and HMVEC and the resultant responses in HMVEC. These data indicate that PEPs at low, non-cytotoxic exposure levels are bioactive and affect cellular responses in an alveolar-capillary co-culture model, which raises concerns for potential adverse health effects.

  12. Ultraviolet Radiation Exposure and the Incidence of Oral, Pharyngeal and Cervical Cancer and Melanoma: An Analysis of the SEER Data.

    Science.gov (United States)

    Adams, Spencer; Lin, Jie; Brown, Derek; Shriver, Craig D; Zhu, Kangmin

    2016-01-01

    Based on the hypothesis that ultraviolet radiation (UVR) exposure can cause DNA damage that may activate dormant viruses such as human papilloma virus, a recent ecological study, which estimated state-level UVR exposure, reported positive correlations between annual UVR exposure and the incidence of oral, pharyngeal, and cervical cancer in 16 U.S. states using the International Agency for Research on Cancer (IARC) data. The purpose of the current study was to further investigate whether the annual UVR level, estimated on a county level, is associated with incidence rates of such cancers using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 data. If UVR exposure is associated with incidence of these cancer types, we would expect to see a similar or stronger association with melanoma because UVR exposure is a well-demonstrated risk factor for this disease. Thus, we also included melanoma in the study. The study subjects were White and Black individuals with oral, pharyngeal, cervical cancer or melanoma diagnosed between 1973 and 2011 from the SEER 18 data. UVR was estimated at the county level and grouped into high-, medium- and low-exposure levels. Age-adjusted incidence rates of cancer were calculated and compared among the UVR exposure groups. The comparisons were also stratified by sex and race. There was an inverse association between UVR exposure and incidence of oral, pharyngeal, and cervical cancer. The inverse association was also observed for melanoma. When stratified by race and sex, the inverse associations remained except for melanoma among Blacks. In contrast to a previous study, our study found that there were inverse associations between UVR exposure and the incidence of oral, pharyngeal, and cervical cancer, as well as of melanoma. Our findings are in agreement with several other published studies reporting no positive correlation between UVR exposure and the incidence rates of oral, pharyngeal, and cervical

  13. The neuropharmacology of upper airway motor control in the awake and asleep states: implications for obstructive sleep apnoea

    Directory of Open Access Journals (Sweden)

    Horner Richard L

    2001-08-01

    Full Text Available Abstract Obstructive sleep apnoea is a common and serious breathing problem that is caused by effects of sleep on pharyngeal muscle tone in individuals with narrow upper airways. There has been increasing focus on delineating the brain mechanisms that modulate pharyngeal muscle activity in the awake and asleep states in order to understand the pathogenesis of obstructive apnoeas and to develop novel neurochemical treatments. Although initial clinical studies have met with only limited success, it is proposed that more rational and realistic approaches may be devised for neurochemical modulation of pharyngeal muscle tone as the relevant neurotransmitters and receptors that are involved in sleep-dependent modulation are identified following basic experiments.

  14. Airway management in neuroanesthesiology.

    Science.gov (United States)

    Aziz, Michael

    2012-06-01

    Airway management for neuroanesthesiology brings together some key principles that are shared throughout neuroanesthesiology. This article appropriately targets the cervical spine with associated injury and the challenges surrounding airway management. The primary focus of this article is on the unique airway management obstacles encountered with cervical spine injury or cervical spine surgery, and unique considerations regarding functional neurosurgery are addressed. Furthermore, topics related to difficult airway management for those with rheumatoid arthritis or pituitary surgery are reviewed. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Effect of Perinatal secondhand tobacco smoke exposure on in vivo and intrinsic airway structure/function in non-human primates

    International Nuclear Information System (INIS)

    Joad, Jesse P.; Kott, Kayleen S.; Bric, John M.; Peake, Janice L.; Pinkerton, Kent E.

    2009-01-01

    Infants exposed to second hand smoke (SHS) experience more problems with wheezing. This study was designed to determine if perinatal SHS exposure increases intrinsic and/or in vivo airway responsiveness to methacholine and whether potential structural/cellular alterations in the airway might explain the change in responsiveness. Pregnant rhesus monkeys were exposed to filtered air (FA) or SHS (1 mg/m 3 total suspended particulates) for 6 h/day, 5 days/week starting at 50 days gestational age. The mother/infant pairs continued the SHS exposures postnatally. At 3 months of age each infant: 1) had in vivo lung function measurements in response to inhaled methacholine, or 2) the right accessory lobe filled with agarose, precision-cut to 600 μm slices, and bathed in increasing concentrations of methacholine. The lumenal area of the central airway was determined using videomicrometry followed by fixation and histology with morphometry. In vivo tests showed that perinatal SHS increases baseline respiratory rate and decreases responsiveness to methacholine. Perinatal SHS did not alter intrinsic airway responsiveness in the bronchi. However in respiratory bronchioles, SHS exposure increased airway responsiveness at lower methacholine concentrations but decreased it at higher concentrations. Perinatal SHS did not change eosinophil profiles, epithelial volume, smooth muscle volume, or mucin volume. However it did increase the number of alveolar attachments in bronchi and respiratory bronchioles. In general, as mucin increased, airway responsiveness decreased. We conclude that perinatal SHS exposure alters in vivo and intrinsic airway responsiveness, and alveolar attachments

  16. Co-morbidity and treatment outcomes of elderly pharyngeal cancer patients : A matched control study

    NARCIS (Netherlands)

    Peters, Thomas T. A.; Langendijk, Johannes A.; Plaat, Boudewijn; Wedman, Jan; Roodenburg, Jan L. N.; van Dijk, Boukje A. C.; Sluiter, Wim J.; van der Laan, Bernard F. A. M.; Halmos, Gyorgy

    2011-01-01

    Treatment choice in elderly pharyngeal cancer patient is disputed. This study was aimed to asses association of co-morbidity, complications and survival in different treatment modalities of pharyngeal cancer patients. Retrospective analysis of pharyngeal cancer patients, diagnosed between 1997 and

  17. Evaluation of pharyngeal volume and compliance of OSAHS patients using 3D CT and volume measurement

    International Nuclear Information System (INIS)

    Lan, Zhijie

    2004-01-01

    The intrinsic properties such as baseline caliber and compliance of the upper airway are thought to be important in the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS).The author attempted using imaging methods to evaluate both baseline caliber and compliance in normal individuals and OSAHS patients, and to localize the obstructive sites in OSAHS patients. Critical closing pressure (P crit ) and minimally effective therapeutical pressure (P eff ) were measured and computed tomography (CT) scan of pharynx was performed during wakefulness and drug-induced sleep with P crit , 0 cm H 2 O and P eff being given through a nose mask system. 7 normal individuals (age, 32.2±6.5 y's and body mass index, 23.6±5.4 kg/m 2 ) and 13 OSAHS patients (age, 33.3±6.4 y's and body mass index, 25.9±6.0 kg/m 2 ) were studied. 3D images of pharyngeal airway were reconstructed, and volume of each subdivision of pharynx was measured. Volume, average area and compliance of each subdivision were compared between the two groups. On an air-mode view of 3D image, the outline of pharynx was shown as transparent tubal structure, on which the narrowing collapse of airway at any level or any direction can be easily identified. Anatomy of pharynx could be easily understood on the virtual endoscopic mode. During wakefulness, the average area of the upper (1.20±0.26 cm 2 vs. 1.57±0.17 cm 2 , P 2 vs. 2.58±0.27 cm 2 , P 2 vs. 1.45±0.18 cm 2 , P 2 vs. 2.44±0.26 cm 2 ). The compliance of the middle part (0.28±0.15/cmH 2 O vs. 0.13±0.07/cmH 2 O, P<0.05) of pharynx was significantly higher in OSAHS patients than in normal individuals. The data suggested that OSAHS patients have a narrower and more collapsible pharynx compared to the normal subjects. The method of the present study is valid to evaluate both morphology and function of the upper airway. (author)

  18. Gaseous distention of the hypopharynx and cervical esophagus with nasal CPAP: a mimicker of pharyngeal perforation and esophageal atresia

    Energy Technology Data Exchange (ETDEWEB)

    Walor, David; Berdon, Walter; Holt, Peter D.; Fox, Matthew [Columbia University Medical Center, Department of Radiology, New York, NY (United States); Children' s Hospital of New York, New York, NY (United States); Anderson, Nicole [Columbia University Medical Center, Department of Neonatology, New York, NY (United States); Children' s Hospital of New York, New York, NY (United States)

    2005-12-01

    Nasal continuous positive airway pressure (CPAP) has been used since 1975 as the initial treatment for respiratory distress syndrome (RDS) in very premature infants. Gaseous distention of the abdomen (CPAP belly) is a common secondary effect of CPAP. Gaseous distention of the hypopharynx is also common. To determine the incidence of hypopharyngeal distention in infants on CPAP. We performed a retrospective review of the chest radiographs of 57 premature infants treated with CPAP during a 4-week period to find the presence and degree of hypopharyngeal distention. Of the 57 radiographs, 14 (25%) revealed gaseous distention of the hypopharynx and/or cervical esophagus. On occasion, this raised concern for pharyngeal perforation or esophageal atresia. Awareness that CPAP-related hypopharyngeal distention is common should help radiologists avoid erroneous consideration of esophageal atresia or hypopharyngeal perforation. (orig.)

  19. Gaseous distention of the hypopharynx and cervical esophagus with nasal CPAP: a mimicker of pharyngeal perforation and esophageal atresia

    International Nuclear Information System (INIS)

    Walor, David; Berdon, Walter; Holt, Peter D.; Fox, Matthew; Anderson, Nicole

    2005-01-01

    Nasal continuous positive airway pressure (CPAP) has been used since 1975 as the initial treatment for respiratory distress syndrome (RDS) in very premature infants. Gaseous distention of the abdomen (CPAP belly) is a common secondary effect of CPAP. Gaseous distention of the hypopharynx is also common. To determine the incidence of hypopharyngeal distention in infants on CPAP. We performed a retrospective review of the chest radiographs of 57 premature infants treated with CPAP during a 4-week period to find the presence and degree of hypopharyngeal distention. Of the 57 radiographs, 14 (25%) revealed gaseous distention of the hypopharynx and/or cervical esophagus. On occasion, this raised concern for pharyngeal perforation or esophageal atresia. Awareness that CPAP-related hypopharyngeal distention is common should help radiologists avoid erroneous consideration of esophageal atresia or hypopharyngeal perforation. (orig.)

  20. Severe angioedema in myxedema coma: a difficult airway in a rare endocrine emergency.

    Science.gov (United States)

    Lee, Christopher H; Wira, Charles R

    2009-10-01

    Myxedema coma is the most lethal manifestation of hypothyroidism. It is a true medical emergency and can result in profound hemodynamic instability and airway compromise. Myxedema coma currently remains a diagnostic challenge due to the rarity of cases seen today, and failure to promptly initiate therapy with replacement thyroid hormone can be fatal. As thyroid hormone therapy can take days or weeks to reverse the manifestations of myxedema coma, interim supportive therapy is critical while awaiting clinical improvement. Some patients will require endotracheal intubation in the emergency department (ED), and physicians should be aware that unanticipated posterior pharyngeal edema in myxedema coma could severely complicate airway management. Although mechanical ventilation is a well-described adjunctive therapy for myxedema coma, reports of the potential difficulty in securing a definitive airway in these patients are rare. We describe a case of an unidentified woman who presented to the ED with myxedema coma requiring urgent endotracheal intubation and was found to have extensive posterior pharyngeal angioedema inconsistent with her relatively benign external examination. This case highlights the typical features of myxedema coma and discusses our necessity for a rescue device in definitive endotracheal tube placement. Emergency physicians should anticipate a potentially difficult airway in all myxedema coma patients regardless of the degree of external facial edema present.

  1. Effects of prostaglandin E2 and cAMP elevating drugs on GM-CSF release by cultured human airway smooth muscle cells. Relevance to asthma therapy.

    Science.gov (United States)

    Lazzeri, N; Belvisi, M G; Patel, H J; Yacoub, M H; Chung, K F; Mitchell, J A

    2001-01-01

    Human airway smooth muscle (HASM) cells release granulocyte macrophage-colony stimulating factor (GM-CSF) and express cyclooxygenase (COX)-2 (resulting in the release of prostaglandin [PG] E2) after stimulation with cytokines. Because COX-2 activity can regulate a number of inflammatory processes, we have assessed its effects, as well as those of agents that modulate cyclic adenosine monophosphate (cAMP), on GM-CSF release by HASM cells. Cells stimulated with a combination of proinflammatory cytokines (interleukin-1beta and tumor necrosis factor-alpha each at 10 ng/ml) for 24 h released significant amounts of PGE2 (measured by radioimmunoassay) and GM-CSF (measured by enzyme-linked immunosorbent assay). Indomethacin and other COX-1/COX-2 inhibitors caused concentration-dependent inhibitions of PGE2 concomitantly with increases in GM-CSF formation. Addition of exogenous PGE2 or the beta2-agonist fenoterol, which increase cAMP, to cytokine-treated HASM cells had no effect on GM-CSF release unless COX activity was first blocked with indomethacin. The type 4 phosphodiesterase inhibitors rolipram and SB 207499 both caused concentration-dependent reductions in GM-CSF production. Thus, when HASM cells are activated with cytokines they release PGE2, which acts as a "braking mechanism" to limit the coproduction of GM-CSF. Moreover, agents that elevate cAMP also reduce GM-CSF formation by these cells.

  2. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening.

    Science.gov (United States)

    An, Steven S; Askovich, Peter S; Zarembinski, Thomas I; Ahn, Kwangmi; Peltier, John M; von Rechenberg, Moritz; Sahasrabudhe, Sudhir; Fredberg, Jeffrey J

    2011-01-13

    A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20) and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Using a high-throughput fluorescence polarization (FP) assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM). Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  3. A novel small molecule target in human airway smooth muscle for potential treatment of obstructive lung diseases: a staged high-throughput biophysical screening

    Directory of Open Access Journals (Sweden)

    von Rechenberg Moritz

    2011-01-01

    Full Text Available Abstract Background A newly identified mechanism of smooth muscle relaxation is the interaction between the small heat shock protein 20 (HSP20 and 14-3-3 proteins. Focusing upon this class of interactions, we describe here a novel drug target screening approach for treating airflow obstruction in asthma. Methods Using a high-throughput fluorescence polarization (FP assay, we screened a library of compounds that could act as small molecule modulators of HSP20 signals. We then applied two quantitative, cell-based biophysical methods to assess the functional efficacy of these molecules and rank-ordered their abilities to relax isolated human airway smooth muscle (ASM. Scaling up to the level of an intact tissue, we confirmed in a concentration-responsive manner the potency of the cell-based hit compounds. Results Among 58,019 compound tested, 268 compounds caused 20% or more reduction of the polarized emission in the FP assay. A small subset of these primary screen hits, belonging to two scaffolds, caused relaxation of isolated ASM cell in vitro and attenuated active force development of intact tissue ex vivo. Conclusions This staged biophysical screening paradigm provides proof-of-principle for high-throughput and cost-effective discovery of new small molecule therapeutic agents for obstructive lung diseases.

  4. Pharyngeal transit time measured by scintigraphic and biomagnetic method

    International Nuclear Information System (INIS)

    Miquelin, C.A.; Braga, F.J.H.N.; Baffa, O.

    1996-01-01

    A comparative evaluation between scintigraphic and biomagnetic method to measure the pharyngeal transit is presented. Three volunteers have been studied. The aliment (yogurt) was labeled with 9 9 m Technetium for the scintigraphic test and with ferrite for the biomagnetic one. The preliminary results indicate a difference between the values obtained, probably due to the biomagnetic detector resolution

  5. Chronic Pharyngitis And Multiple Soft Palate Peforation In An HIV ...

    African Journals Online (AJOL)

    This report is at advocating the need for repeated investigation and screening for HIV particularly when there is persistent clinical feature strongly suggestive of AIDS. Should we even start to contemplate therapeutic of antiretroviral dugs in some cases? KEY WORDS: Chronic pharyngitis, Soft palate perforation, AIDS, HIV ...

  6. Fluconazole resistant opportunistic oro-pharyngeal candida and non ...

    African Journals Online (AJOL)

    Background: Oro-Pharyngeal Candidiasis (OPC) continues to be considered the most common opportunistic fungal disease in HIV/AIDS patients globally. Azole antifungal agent has become important in the treatment of mucosal candidiasis in HIV patients. Presently, antifungal drug resistance is fast becoming a major ...

  7. Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke

    DEFF Research Database (Denmark)

    Bath, Philip M W; Scutt, Polly; Love, Jo

    2016-01-01

    BACKGROUND AND PURPOSE: Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. METHODS...

  8. MRI analysis on soft tissue around upper airway in obese adolescent patients with obstructive sleep apnea syndrome

    International Nuclear Information System (INIS)

    Zhang Zhengjiao; Yuan Haibo; Peng Liping; Li Dan; Hua Shucheng

    2012-01-01

    Objective: To investigate the correlation of soft tissue structure of upper airway with the pathogenesis of obstructive sleep apnea syndrome (OSAS) in adolescents age group by analyzing magnetic resonance imaging (MRI) of upper airway. Methods: The subjects were divided into obese OSAS, obese controls and normal weight controls groups according to the results from polysomnography and body mass index measurements; Upper airway was scanned by MRI sagittally and axially; upper airway at all levels and soft tissue was analyzed by Amira Medical image analysis system. Results: Tongue volumes in obese OSAS and obese controls were significantly greater than that in normal weight controls (P<0.05); tonsil and adenoid volumes in obese OSAS were significantly higher than those in two control groups (P<0.05 or P<0.001), but no significant difference was found between two control groups. The volumes of lateral pharyngeal wall in obese OSAS were higher than those in obese controls and normal weight controls (P<0.05 or P<0.001), and they were higher in obese controls compared with normal weight controls (P<0.05). In obese OSAS group, positive correlations were found between volumes of lateral pharyngeal wall and apnea/hypopnea index (AHI) (r=0.879, P<0.01), as well volumes of tonsils and AHI (r=0.824, P<0.01). Conclusion: Obesity can increase the soft tissue volumes around upper airway, there by increase the upper airway obstruction; lateral pharyngeal wall and adenoid volumes play major roles in evaluating the severity of OSAS in adolescents. (authors)

  9. Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: Further mechanistic studies

    International Nuclear Information System (INIS)

    Becker, Susanne; Mundandhara, Sailaja; Devlin, Robert B.; Madden, Michael

    2005-01-01

    In order to better understand how ambient air particulate matter (PM) affect lung health, the two main airway cell types likely to interact with inhaled particles, alveolar macrophages (AM) and airway epithelial cells have been exposed to particles in vitro and followed for endpoints of inflammation, and oxidant stress. Separation of Chapel Hill PM 10 into fine and coarse size particles revealed that the main proinflammatory response (TNF, IL-6, COX-2) in AM was driven by material present in the coarse PM, containing 90-95% of the stimulatory material in PM10. The particles did not affect expression of hemoxygenase-1 (HO-1), a sensitive marker of oxidant stress. Primary cultures of normal human bronchial epithelial cells (NHBE) also responded to the coarse fraction with higher levels of IL-8 and COX-2, than induced by fine or ultrafine PM. All size PM induced oxidant stress in NHBE, while fine PM induced the highest levels of HO-1 expression. The production of cytokines in AM by both coarse and fine particles was blocked by the toll like receptor 4 (TLR4) antagonist E5531 involved in the recognition of LPS and Gram negative bacteria. The NHBE were found to recognize coarse and fine PM through TLR2, a receptor with preference for recognition of Gram positive bacteria. Compared to ambient PM, diesel PM induced only a minimal cytokine response in both AM and NHBE. Instead, diesel suppressed LPS-induced TNF and IL-8 release in AM. Both coarse and fine ambient air PM were also found to inhibit LPS-induced TNF release while silica, volcanic ash or carbon black had no inhibitory effect. Diesel particles did not affect cytokine mRNA induction nor protein accumulation but interfered with the release of cytokine from the cells. Ambient coarse and fine PM, on the other hand, inhibited both mRNA induction and protein production. Exposure to coarse and fine PM decreased the expression of TLR4 in the macrophages. Particle-induced decrease in TLR4 and hyporesponsiveness to LPS

  10. INHIBITION OF PROTEIN TYROSINE PHOSPHATASE ACTIVITY MEDIATES EPIDERMAL GROWTH FACTOR RECEPTOR SIGNALING IN HUMAN AIRWAY EPITHELIAL CELLS

    Science.gov (United States)

    Epidemiological studies have implicated zinc in the toxicity of ambient particulate matter (PM) inhalation. We previously showed that exposure to metal-laden PM inhibits protein tyrosine phosphatase (PTP) activity in human primary bronchial epithelial cells (HAEC) and leads t...

  11. Regulation of cyclooxygenase-2 expression by cAMP response element and mRNA stability in a human airway epithelial cell line exposed to zinc

    Science.gov (United States)

    Exposure to zinc-laden particulate matter in ambient and occupational settings has been associated with proinflammatory responses in the lung. Cyclooxygenase 2-derived eicosanoids are important modulators of airway inflammation. In this study, we characterized the transcriptional...

  12. Obstetric airway management

    African Journals Online (AJOL)

    of stomach contents into the lungs during obstetric anesthesia.8 ... Both of the mortalities occurred secondary to solid ... The large number of deaths ... subcategories of patients as a first-line airway device, and are increasingly being ... outline the problems with obstetric airway management, and then focus on a few of the ...

  13. Diagnosis and management of group A streptococcal pharyngitis and associated complications [digest].

    Science.gov (United States)

    Vazquez, Michelle N; Sanders, Jennifere E; Wilson, Bryan

    2017-12-21

    Although group A Streptococcus (GAS) pharyngitis is the most common cause of bacterial pharyngitis in children and adolescents, many viral and bacterial infections mimic the symptoms of GAS pharyngitis. Emergency clinicians must recognize the symptomatology of GAS pharyngitis and use appropriate means of diagnosis and treatment to promote good antibiotic stewardship. This issue reviews the signs and symptoms of GAS pharyngitis, as well as associated complications, and provides recommendations for appropriate treatment that focuses on reducing the severity and duration of symptoms, reducing the incidence of nonsuppurative complications, and reducing transmission. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

  14. A lateral cephalometric study of pharyngeal cavity in Korean adults

    International Nuclear Information System (INIS)

    Lee, Sang Rae

    1976-01-01

    A study was performed to investigate the size of pharyngeal cavity and sexual differences between Korean adult mal e and female by introducing linear analysis of the lateral cephalogram. The radiograms were composed of 46 adult male aged 24.64 and 52 adult female aged 22.74 respectively. In order to study and measure the pharyngeal area, the following skeletal landmarks were selected: S,N,A,Ptm, B,H,H', M ,S-N, FH and CV, and the angle CV-FH was measured to provide a factor for correction of error resulting from improper he ad positioning of subjects, especially in the relative positions of A and H, while radiography. All points to be measured were projected at right angles to the Frankfort plane. For the purpose of measuring the anteroposterior dimensions of pharyngeal cavity the distances were measured in A-Ptm, A-S, S-Ptm and CV-H, and vertical measurements were made in SN-A, SN-PNS, SN-H' and M-H. The obtained results were as follows: 1. The pharyngeal cavity is broader in the vertical than in the anteroposterior diameter in both sex and the maximum sexual differences were showed in the distances between SN and H', and minimal sexual differences in the distances between S and Ptm. 2. In general, the measurements of male were larger than those of female in the anteroposterior dimensions of pharyngea l cavity, but the distances between A and S, between CV and H showed significant sexual differences when evaluated statistically. 3. All of the measurements were larger in male than in female in vertical dimensions of pharyngeal cavity, and there were statistical significances of sexual differences in all variables.

  15. A lateral cephalometric study of pharyngeal cavity in Korean adults

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Rae [Department of Dental Radiology, College of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    1976-11-15

    A study was performed to investigate the size of pharyngeal cavity and sexual differences between Korean adult mal e and female by introducing linear analysis of the lateral cephalogram. The radiograms were composed of 46 adult male aged 24.64 and 52 adult female aged 22.74 respectively. In order to study and measure the pharyngeal area, the following skeletal landmarks were selected: S,N,A,Ptm, B,H,H', M ,S-N, FH and CV, and the angle CV-FH was measured to provide a factor for correction of error resulting from improper he ad positioning of subjects, especially in the relative positions of A and H, while radiography. All points to be measured were projected at right angles to the Frankfort plane. For the purpose of measuring the anteroposterior dimensions of pharyngeal cavity the distances were measured in A-Ptm, A-S, S-Ptm and CV-H, and vertical measurements were made in SN-A, SN-PNS, SN-H' and M-H. The obtained results were as follows: 1. The pharyngeal cavity is broader in the vertical than in the anteroposterior diameter in both sex and the maximum sexual differences were showed in the distances between SN and H', and minimal sexual differences in the distances between S and Ptm. 2. In general, the measurements of male were larger than those of female in the anteroposterior dimensions of pharyngea l cavity, but the distances between A and S, between CV and H showed significant sexual differences when evaluated statistically. 3. All of the measurements were larger in male than in female in vertical dimensions of pharyngeal cavity, and there were statistical significances of sexual differences in all variables.

  16. Airway smooth muscle cells : regulators of airway inflammation

    NARCIS (Netherlands)

    Zuyderduyn, Suzanne

    2007-01-01

    Airways from asthmatic subjects are more responsive to bronchoconstrictive stimuli than airways from healthy subjects. Airway smooth muscle (ASM) cells mediate contraction of the airways by responding to the bronchoconstrictive stimuli, which was thought to be the primary role of ASM cells. In this

  17. Role of H2O2 in the Oxidative Effects of Zinc Exposure in Human Airway Epithelial Cells

    Science.gov (United States)

    Human exposure to particulate matter (PM) is a global environmental health concern. Zinc (Zn(2+)) is a ubiquitous respiratory toxicant that has been associated with PM health effects. However, the molecular mechanism of Zn(2+) toxicity is not fully understood. H202 and Zn(2+) hav...

  18. 21 CFR 868.1780 - Inspiratory airway pressure meter.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inspiratory airway pressure meter. 868.1780 Section 868.1780 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... meter. (a) Identification. An inspiratory airway pressure meter is a device used to measure the amount...

  19. Inactivation of Bmp4 from the Tbx1 Expression Domain Causes Abnormal Pharyngeal Arch Artery and Cardiac Outflow Tract Remodeling

    Science.gov (United States)

    Nie, Xuguang; Brown, Christopher B.; Wang, Qin; Jiao, Kai

    2011-01-01

    Maldevelopment of outflow tract and aortic arch arteries is among the most common forms of human congenital heart diseases. Both Bmp4 and Tbx1 are known to play critical roles during cardiovascular development. Expression of these two genes partially overlaps in pharyngeal arch areas in mouse embryos. In this study, we applied a conditional gene inactivation approach to test the hypothesis that Bmp4 expressed from the Tbx1 expression domain plays a critical role for normal development of outflow tract and pharyngeal arch arteries. We showed that inactivation of Bmp4 from Tbx1-expressing cells leads to the spectrum of deformities resembling the cardiovascular defects observed in human DiGeorge syndrome patients. Inactivation of Bmp4 from the Tbx1 expression domain did not cause patterning defects, but affected remodeling of outflow tract and pharyngeal arch arteries. Our further examination revealed that Bmp4 is required for normal recruitment/differentiation of smooth muscle cells surrounding the PAA4 and survival of outflow tract cushion mesenchymal cells. PMID:21123999

  20. The influence of monoamine oxidase variants on the risk of betel quid-associated oral and pharyngeal cancer.

    Science.gov (United States)

    Chen, Ping-Ho; Huang, Bin; Shieh, Tien-Yu; Wang, Yan-Hsiung; Chen, Yuk-Kwan; Wu, Ju-Hui; Huang, Jhen-Hao; Chen, Chun-Chia; Lee, Ka-Wo

    2014-01-01

    Betel quid (BQ) and areca nut (AN) (major BQ ingredient) are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs) and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO) gene by inducing reactive oxygen species (ROS). The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

  1. The Influence of Monoamine Oxidase Variants on the Risk of Betel Quid-Associated Oral and Pharyngeal Cancer

    Directory of Open Access Journals (Sweden)

    Ping-Ho Chen

    2014-01-01

    Full Text Available Betel quid (BQ and areca nut (AN (major BQ ingredient are group I human carcinogens illustrated by International Agency for Research on Cancer and are closely associated with an elevated risk of oral potentially malignant disorders (OPMDs and cancers of the oral cavity and pharynx. The primary alkaloid of AN, arecoline, can be metabolized via the monoamine oxidase (MAO gene by inducing reactive oxygen species (ROS. The aim of this study was to investigate whether the variants of the susceptible candidate MAO genes are associated with OPMDs and oral and pharyngeal cancer. A significant trend of MAO-A mRNA expression was found in in vitro studies. Using paired human tissues, we confirmed the significantly decreased expression of MAO-A and MAO-B in cancerous tissues when compared with adjacent noncancerous tissues. Moreover, we determined that MAO-A single nucleotide polymorphism variants are significantly linked with oral and pharyngeal cancer patients in comparison to OPMDs patients [rs5953210 risk G-allele, odds ratio = 1.76; 95% confidence interval = 1.02-3.01]. In conclusion, we suggested that susceptible MAO family variants associated with oral and pharyngeal cancer may be implicated in the modulation of MAO gene activity associated with ROS.

  2. 3D Reconstruction of the Human Airway Mucosa In Vitro as an Experimental Model to Study NTHi Infections.

    Directory of Open Access Journals (Sweden)

    Pasquale Marrazzo

    Full Text Available We have established an in vitro 3D system which recapitulates the human tracheo-bronchial mucosa comprehensive of the pseudostratified epithelium and the underlying stromal tissue. In particular, we reported that the mature model, entirely constituted of primary cells of human origin, develops key markers proper of the native tissue such as the mucociliary differentiation of the epithelial sheet and the formation of the basement membrane. The infection of the pseudo-tissue with a strain of NonTypeable Haemophilus influenzae results in bacteria association and crossing of the mucus layer leading to an apparent targeting of the stromal space where they release large amounts of vesicles and form macro-structures. In summary, we propose our in vitro model as a reliable and potentially customizable system to study mid/long term host-pathogen processes.

  3. Effect of controlled human exposure to diesel exhaust and allergen on airway surfactant protein D, myeloperoxidase and club (Clara) cell secretory protein 16.

    Science.gov (United States)

    Biagioni, B J; Tam, S; Chen, Y-W R; Sin, D D; Carlsten, C

    2016-09-01

    Air pollution is a major cause of global morbidity and mortality. Air pollution and aeroallergens aggravate respiratory illness, but the variable effects of air pollutants and allergens in the lung are poorly understood. To determine the effects of diesel exhaust (DE) and bronchial allergen challenge as single and dual exposures on aspects of innate immunity in the airway as reflected by surfactant protein D (SPD), myeloperoxidase (MPO) and club (Clara) cell secretory protein 16 (CC16) in 18 atopic individuals. In this double-blind, randomized crossover study, atopic individuals were exposed to DE or filtered air, followed by endobronchial allergen or saline 1 hour after inhalational exposure. Bronchoalveolar lavage, bronchial washings, nasal lavage and blood samples were obtained 48 hours after exposures and assayed for CC16, MPO and SPD by ELISA. In bronchial samples, the concentration of SPD increased from 53.3 to 91.8 ng/mL after endobronchial allergen, with no additional contribution from DE. MPO also increased significantly in response to allergen (6.8 to 14.7 ng/mL), and there was a small additional contribution from exposure to DE. The concentration of CC16 decreased from 340.7 to 151.0 ng/mL in response to DE, with minor contribution from allergen. These changes were not reflected in nasal lavage fluid or plasma samples. These findings suggest that allergen and DE variably influence different aspects of the innate immune response of the lung. SPD and MPO, known markers of allergic inflammation in the lung, are strongly increased by allergen while DE has a minor effect therein. DE induces a loss of CC16, a protective protein, while allergen has a minor effect therein. Results support site- and exposure-specific responses in the human lung upon multiple exposures. © 2016 John Wiley & Sons Ltd.

  4. Polarized secretion of interleukin (IL-6 and IL-8 by human airway epithelia 16HBE14o- cells in response to cationic polypeptide challenge.

    Directory of Open Access Journals (Sweden)

    Alison Wai-ming Chow

    Full Text Available BACKGROUND: The airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-L-arginine. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human bronchial epithelial cells, 16HBE14o- cells, were "chemically injured" by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-kappaB pathways. CONCLUSIONS/SIGNIFICANCE: The results clearly demonstrate that damage to the bronchial epithelia by poly-L-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

  5. Innate immune receptors in human airway smooth muscle cells: activation by TLR1/2, TLR3, TLR4, TLR7 and NOD1 agonists.

    Directory of Open Access Journals (Sweden)

    Anne Månsson Kvarnhammar

    Full Text Available BACKGROUND: Pattern-recognition receptors (PRRs, including Toll-like receptors (TLRs, NOD-like receptors (NLRs and RIG-I-like receptors (RLRs, recognize microbial components and trigger a host defense response. Respiratory tract infections are common causes of asthma exacerbations, suggesting a role for PRRs in this process. The present study aimed to examine the expression and function of PRRs on human airway smooth muscle cells (HASMCs. METHODS: Expression of TLR, NLR and RLR mRNA and proteins was determined using real-time RT-PCR, flow cytometry and immunocytochemistry. The functional responses to ligand stimulation were investigated in terms of cytokine and chemokine release, cell surface marker expression, proliferation and proteins regulating the contractile state. RESULTS: HASMCs expressed functional TLR2, TLR3, TLR4, TLR7 and NOD1. Stimulation with the corresponding agonists Pam3CSK4, poly(I:C, LPS, R-837 and iE-DAP, respectively, induced IL-6, IL-8 and GM-CSF release and up-regulation of ICAM-1 and HLA-DR, while poly(I:C also affected the release of eotaxin and RANTES. The proliferative response was slightly increased by LPS. Stimulation, most prominently with poly(I:C, down-regulated myosin light chain kinase and cysteinyl leukotriene 1 receptor expression and up-regulated β2-adrenoceptor expression. No effects were seen for agonist to TLR2/6, TLR5, TLR8, TLR9, NOD2 or RIG-I/MDA-5. CONCLUSION: Activation of TLR2, TLR3, TLR4, TLR7 and NOD1 favors a synthetic phenotype, characterized by an increased ability to release inflammatory mediators, acquire immunomodulatory properties by recruiting and interacting with other cells, and reduce the contractile state. The PRRs might therefore be of therapeutic use in the management of asthma and infection-induced disease exacerbations.

  6. Effects of nitrogen-doped multi-walled carbon nanotubes compared to pristine multi-walled carbon nanotubes on human small airway epithelial cells.

    Science.gov (United States)

    Mihalchik, Amy L; Ding, Weiqiang; Porter, Dale W; McLoughlin, Colleen; Schwegler-Berry, Diane; Sisler, Jennifer D; Stefaniak, Aleksandr B; Snyder-Talkington, Brandi N; Cruz-Silva, Rodolfo; Terrones, Mauricio; Tsuruoka, Shuji; Endo, Morinobu; Castranova, Vincent; Qian, Yong

    2015-07-03

    Nitrogen-doped multi-walled carbon nanotubes (ND-MWCNTs) are modified multi-walled carbon nanotubes (MWCNTs) with enhanced electrical properties that are used in a variety of applications, including fuel cells and sensors; however, the mode of toxic action of ND-MWCNT has yet to be fully elucidated. In the present study, we compared the interaction of ND-MWCNT or pristine MWCNT-7 with human small airway epithelial cells (SAEC) and evaluated their subsequent bioactive effects. Transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction suggested the presence of N-containing defects in the lattice of the nanotube. The ND-MWCNTs were determined to be 93.3% carbon, 3.8% oxygen, and 2.9% nitrogen. A dose-response cell proliferation assay showed that low doses of ND-MWCNT (1.2μg/ml) or MWCNT-7 (0.12μg/ml) increased cellular proliferation, while the highest dose of 120μg/ml of either material decreased proliferation. ND-MWCNT and MWCNT-7 appeared to interact with SAEC at 6h and were internalized by 24h. ROS were elevated at 6 and 24h in ND-MWCNT exposed cells, but only at 6h in MWCNT-7 exposed cells. Significant alterations to the cell cycle were observed in SAEC exposed to either 1.2μg/ml of ND-MWCNT or MWCNT-7 in a time and material-dependent manner, possibly suggesting potential damage or alterations to cell cycle machinery. Our results indicate that ND-MWCNT induce effects in SAEC over a time and dose-related manner which differ from MWCNT-7. Therefore, the physicochemical characteristics of the materials appear to alter their biological effects. Published by Elsevier Ireland Ltd.

  7. Age-Related Changes in Pharyngeal Lumen Size: A Retrospective MRI Analysis.

    Science.gov (United States)

    Molfenter, Sonja M; Amin, M R; Branski, R C; Brumm, J D; Hagiwara, M; Roof, S A; Lazarus, C L

    2015-06-01

    Age-related loss of muscle bulk and strength (sarcopenia) is often cited as a potential mechanism underlying age-related changes in swallowing. Our goal was to explore this phenomenon in the pharynx, specifically, by measuring pharyngeal wall thickness and pharyngeal lumen area in a sample of young versus older women. MRI scans of the neck were retrospectively reviewed from 60 women equally stratified into three age groups (20s, 60s, 70+). Four de-identified slices were extracted per scan for randomized, blinded analysis: one mid-sagittal and three axial slices were selected at the anterior inferior border of C2 and C3, and at the pit of the vallecula. Pixel-based measures of pharyngeal wall thickness and pharyngeal lumen area were completed using ImageJ and then converted to metric units. Measures of pharyngeal wall thickness and pharyngeal lumen area were compared between age groups with one-way ANOVAs using Sidak adjustments for post-hoc pairwise comparisons. A significant main effect for age was observed across all variables whereby pharyngeal wall thickness decreased and pharyngeal lumen area increased with advancing age. Pairwise comparisons revealed significant differences between 20s versus 70+ for all variables and 20s versus 60s for all variables except those measured at C2. Effect sizes ranged from 0.54 to 1.34. Consistent with existing sacropenia literature, the pharyngeal muscles appear to atrophy with age and consequently, the size of the pharyngeal lumen increases.

  8. Airway Clearance Techniques (ACTs)

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    Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  9. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments and Therapies People with cystic fibrosis are living ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

  10. Airway Clearance Techniques (ACTs)

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    Full Text Available ... There are different ways to clear your airways. Most are easy to do. Infants and toddlers will ... best ACT is the one that you are most likely to perform as part of your daily ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments and Therapies People with cystic fibrosis are living longer and ... to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of Breathing Technique ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... about the needs of people with cystic fibrosis so that they make smart decisions about CF-related ... then move the mucus out of the airways so it can be coughed out. These medications can ...

  13. Airway Clearance Techniques (ACTs)

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    Full Text Available ... in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care Guidelines Chronic Medications to Maintain Lung ...

  14. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The ... Home Life With CF Treatments and Therapies Airway Clearance ...

  15. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: March 2018 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  16. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway Clearance Therapies Clinical Care ... attack bacteria. Choose What's Best for You Your respiratory therapist or another member of your CF care ...

  17. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Clinician Career Development Awards Clinician Training Awards Mutation Analysis Program Network News Network News: June 2018 Network ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  18. Airway Clearance Techniques (ACTs)

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    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that ... into the smaller airways to attack bacteria. Choose What's Best for You Your respiratory therapist or another ...

  19. Airway Clearance Techniques (ACTs)

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    Full Text Available ... decisions about your health care. CF Genetics: The Basics CF Mutations Video Series Find Out More About ... of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and ...

  20. Airway Clearance Techniques (ACTs)

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    Full Text Available ... that help thin and move the mucus, and antibiotics. Bronchodilators should be inhaled before you start ACTs. This medication helps to widen your airways (bronchi) by relaxing the ...

  1. Airway Clearance Techniques (ACTs)

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    Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  2. Airway Clearance Techniques (ACTs)

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    Full Text Available ... in part to specialized CF care and a range of treatment options. Airway Clearance Active Cycle of ... a cure for CF and supports a broad range of research initiatives to tackle the disease from ...

  3. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy ... clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest Wall ...

  4. Airway Clearance Techniques (ACTs)

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    Full Text Available ... huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how ... What is CF? About Cystic Fibrosis CF Genetics Diagnosis Testing for CF Life With CF Caring for ...

  5. Airway Clearance Techniques (ACTs)

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    Full Text Available ... CFTR Modulator Therapies Mucus Thinners Nebulizer Care at Home Vascular Access Devices PICCs and Ports Partnerships for ... Facebook Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance ...

  6. Airway Clearance Techniques (ACTs)

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    Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ultimately help find a ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic ...

  7. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing ... Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest Wall Oscillation ( ...

  8. Airway Clearance Techniques (ACTs)

    Science.gov (United States)

    ... infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway ... Positive Expiratory Pressure High-Frequency Chest Wall Oscillation (the Vest) Follow ...

  9. Evolutionary Trends of the Pharyngeal Dentition in Cypriniformes (Actinopterygii: Ostariophysi)

    OpenAIRE

    Pasco-Viel, Emmanuel; Charles, Cyril; Chevret, Pascale; Semon, Marie; Tafforeau, Paul; Viriot, Laurent; Laudet, Vincent

    2010-01-01

    Background : The fish order Cypriniformes is one of the most diverse ray-finned fish groups in the world with more than 3000 recognized species. Cypriniformes are characterized by a striking distribution of their dentition: namely the absence of oral teeth and presence of pharyngeal teeth on the last gill arch (fifth ceratobranchial). Despite this limited localisation, the diversity of tooth patterns in Cypriniformes is astonishing. Here we provide a further description of this diversity usin...

  10. Airway management in trauma.

    Science.gov (United States)

    Langeron, O; Birenbaum, A; Amour, J

    2009-05-01

    Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration.

  11. Theoretical calculations of the deposition of non-spherical particles in the upper airways of the human lung

    International Nuclear Information System (INIS)

    Sturm, Robert; Hofmann, Werner

    2009-01-01

    In the contribution presented here a computer model for the description of non-spherical particle deposition in the upper human respiratory tract is introduced. The theoretical approach is mainly based on the principle of the aerodynamic diameter, whose calculation was carried out according to most current scientific findings. With the help of this parameter deposition patterns for various particle categories (fibers and oblate disks) and breathing conditions (sitting, light-work and hard-work breathing) were simulated. Concerning cylindrical fibers with a diameter ≥ 1 μm, an increase of the aspect ratio β (i.e. particle length/particle diameter) causes a significant enhancement of deposition in the uppermost regions of the respiratory tract (oropharynx, larynx, trachea). This effect is additionally intensified by an increase of the inhalative flow. Regarding the oblate disks with a diameter ≥ 1 μm, any decrease of the aspect ratio leads to an enhancement of deposition in the deeper lung regions, representing an effect contrary to that observed for fibers. An increase of the inhalative flow only induces a limited decrease of the effect. (orig.)

  12. Diagnosis of Swallowing Disorders: How We Interpret Pharyngeal Manometry.

    Science.gov (United States)

    Cock, Charles; Omari, Taher

    2017-03-01

    We provide an overview of the clinical application of novel pharyngeal high-resolution impedance manometry (HRIM) with pressure flow analysis (PFA) in our hands with example cases. In our Centre, we base our interpretation of HRIM recordings upon a qualitative assessment of pressure-impedance waveforms during individual swallows, as well as a quantitative assessment of averaged PFA swallow function variables. We provide a description of two global swallowing efficacy measures, the swallow risk index (SRI), reflecting global swallowing dysfunction (higher SRI = greater aspiration risk) and the post-swallow impedance ratio (PSIR) detecting significant post-swallow bolus residue. We describe a further eight swallow function variables specific to the hypopharynx and upper esophageal sphincter (UES), assessing hypo-pharyngeal distension pressure, contractility, bolus presence and flow timing, and UES basal tone, relaxation, opening and contractility. Pharyngeal HRIM has now come of age, being applicable for routine clinical practice to assess the biomechanics of oropharyngeal swallowing dysfunction. In the future, it may guide treatment strategies and allow more objective longitudinal follow-up on clinical outcomes.

  13. Sternocleidomastoid flap augmentation of the pharyngeal closure after total laryngectomy.

    Science.gov (United States)

    Ibrahim, Sherif Gabr; Wahba, Basim Metwally; Elbatawi, Ahmed Mahmoud; Eltelety, Ahmad Mohamed

    2017-08-01

    The objective of the study was to evaluate the effect of sternocleidomastoid (SCM) flap augmentation of the pharyngeal closure after total laryngectomy on the incidence of pharyngocutaneous fistula (PCF). Thirty patients with T4a laryngeal carcinoma and none of them receiving primary radiotherapy previously were divided into two equal groups. Group A patients had SCM flap augmentation of the pharyngeal closure after total laryngectomy. Group B patients had the standard pharyngeal closure without augmentation. Both groups were followed up for 30 days postoperatively for the development of PCF. The use of the SCM added about extra 15 min to the surgical procedure in all patients (p laryngectomy. Three patients in each group developed PCF either early (10 days or less postoperatively) or late (more than 10 days but less than 30 days postoperatively). There was no statistically significant difference in the length of hospital stay between the two groups. The use of SCM flap did not reduce the incidence of PCF after total laryngectomy.

  14. Laryngeal sensation and pharyngeal delay time after (chemo)radiotherapy.

    Science.gov (United States)

    Maruo, Takashi; Fujimoto, Yasushi; Ozawa, Kikuko; Hiramatsu, Mariko; Suzuki, Atsushi; Nishio, Naoki; Nakashima, Tsutomu

    2014-08-01

    The objective of the study was to evaluate the association between changes in laryngeal sensation and initiation of swallowing reflex or swallowing function before and after (chemo)radiotherapy. A prospective study was conducted in a tertiary referral university hospital. Thirteen patients who received (chemo)radiotherapy for treatment of laryngeal or hypopharyngeal cancer were included. Laryngeal sensation was evaluated at the tip of the epiglottis before and 1, 3 months, and 1 year after (chemo)radiotherapy. Videofluoroscopy was performed at the same time. Quantitative determinations included changes in laryngeal sensation, computed analysis of pharyngeal delay time, the distance and velocity of hyoid bone movement during the phase of hyoid excursion, and pharyngeal residue rate (the proportion of the bolus that was left as residue in the pharynx at the first swallow). Laryngeal sensation significantly deteriorated 1 month after (chemo)radiotherapy, but there was a tendency to return to pretreatment levels 1 year after treatment. Neither pharyngeal delay time nor displacement of the hyoid bone changed significantly before and after (chemo)radiotherapy. In addition, there was no significant difference in the mean velocity of hyoid bone movement and the amount of stasis in the pharynx at the first swallow before and after (chemo)radiotherapy. After (chemo)radiotherapy, laryngeal sensation deteriorated. But, in this study, videofluoroscopy showed that swallowing reflex and function were maintained.

  15. Comparative effectiveness of instructional methods: oral and pharyngeal cancer examination.

    Science.gov (United States)

    Clark, Nereyda P; Marks, John G; Sandow, Pamela R; Seleski, Christine E; Logan, Henrietta L

    2014-04-01

    This study compared the effectiveness of different methods of instruction for the oral and pharyngeal cancer examination. A group of thirty sophomore students at the University of Florida College of Dentistry were randomly assigned to three training groups: video instruction, a faculty-led hands-on instruction, or both video and hands-on instruction. The training intervention involved attending two sessions spaced two weeks apart. The first session used a pretest to assess students' baseline didactic knowledge and clinical examination technique. The second session utilized two posttests to assess the comparative effectiveness of the training methods on didactic knowledge and clinical technique. The key findings were that students performed the clinical examination significantly better with the combination of video and faculty-led hands-on instruction (p<0.01). All students improved their clinical exam skills, knowledge, and confidence in performing the oral and pharyngeal cancer examination independent of which training group they were assigned. Utilizing both video and interactive practice promoted greater performance of the clinical technique on the oral and pharyngeal cancer examination.

  16. [Effects of transient receptor potential melastatin 8 cation channels on inflammatory reaction induced by cold temperatures in human airway epithelial cells].

    Science.gov (United States)

    Li, Min-chao; Perelman, Juliy M; Kolosov, Victor P; Zhou, Xiang-dong

    2011-10-01

    To explore the role of transient receptor potential melastatin 8 cation channels (TRPM8) in cold-induced production of inflammatory factors in airway epithelial cells and related signal transduction mechanism. The 16HBE human airway epithelial cells were stimulated with cold temperature (18°C). In intervention experiments, cells were pretreated with TRPM8 channel antagonist BCTC, protein kinase C (PKC) specific inhibitor calphostin C and transfected with TRPM8 shRNA or control shRNA respectively, and thereafter cold stimulation was applied. Cells were divided into 6 groups: a control group (incubated at 37°C), a cold stimulation group, a cold stimulation + BCTC group, a cold stimulation + TRPM8 shRNA group, a cold stimulation + control shRNA group, a cold stimulation + calphostin C group. Western blot was performed to show the extent of knockdown in TRPM8 protein expression in the TRPM8 shRNA transfected cells. Dynamics of relative concentration of intracellular Ca(2+) in the former 5 groups were measured by calcium imaging techniques. Images were taken at one frame per 10 seconds. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α mRNA and protein were detected by real-time PCR and ELISA respectively. The highest relative concentration of intracellular calcium in cold stimulation group (2.36 ± 0.24) was higher than that of control group (1.01 ± 0.02) (t = 12.52, P cold stimulation group (t = 6.69 and 9.12, all P cold stimulation group[0.66 ± 0.16, 0.77 ± 0.15, 0.73 ± 0.09 and (92 ± 13) ng/L, (125 ± 22) ng/L, (88 ± 12) ng/L ] were significantly higher than those in control group [0.37 ± 0.08, 0.32 ± 0.07, 0.48 ± 0.10 and (52 ± 8) ng/L, (50 ± 9) ng/L, (61 ± 8) ng/L] (t = 3.20 - 6.26, all P cold stimulation + BCTC group [0.42 ± 0.09, 0.52 ± 0.13, 0.52 ± 0.12 and (72 ± 8) ng/L, (92 ± 14) ng/L, (68 ± 11) ng/L], cold stimulation + TRPM8 shRNA group [0.41 ± 0.10, 0.49 ± 0.08, 0.50 ± 0.08 and (60 ± 12) ng/L, (89 ± 14) ng

  17. Toward the modeling of mucus draining from the human lung: role of the geometry of the airway tree

    International Nuclear Information System (INIS)

    Mauroy, Benjamin; Merckx, Jacques; Flaud, Patrice; Fausser, Christian; Pelca, Dominique

    2011-01-01

    Mucociliary clearance and cough are the two main natural mucus draining methods in the bronchial tree. If they are affected by a pathology, they can become insufficient or even ineffective, then therapeutic draining of mucus plays a critical role to keep mucus levels in the lungs acceptable. The manipulations of physical therapists are known to be very efficient clinically but they are mostly empirical since the biophysical mechanisms involved in these manipulations have never been studied. We develop in this work a model of mucus clearance in idealized rigid human bronchial trees and focus our study on the interaction between (1) tree geometry, (2) mucus physical properties and (3) amplitude of flow rate in the tree. The mucus is considered as a Bingham fluid (gel-like) which is moved upward in the tree thanks to its viscous interaction with air flow. Our studies point out the important roles played both by the geometry and by the physical properties of mucus (yield stress and viscosity). More particularly, the yield stress has to be overcome to make mucus flow. Air flow rate and yield stress determine the maximal possible mucus thickness in each branch of the tree at equilibrium. This forms a specific distribution of mucus in the tree whose characteristics are strongly related to the multi-scaled structure of the tree. The behavior of any mucus distribution is then dependent on this distribution. Finally, our results indicate that increasing air flow rates ought to be more efficient to drain mucus out of the bronchial tree while minimizing patient discomfort

  18. House dust mite major allergens Der p 1 and Der p 5 activate human airway-derived epithelial cells by protease-dependent and protease-independent mechanisms

    Directory of Open Access Journals (Sweden)

    Timmerman J André B

    2006-03-01

    Full Text Available Abstract House dust mite allergens (HDM cause bronchoconstriction in asthma patients and induce an inflammatory response in the lungs due to the release of cytokines, chemokines and additional mediators. The mechanism how HDM components achieve this is largely unknown. The objective of this study was to assess whether HDM components of Dermatophagoides pteronissinus with protease activity (Der p 1 and unknown enzymatic activity (Der p 2, Der p 5 induce biological responses in a human airway-derived epithelial cell line (A549, and if so, to elucidate the underlying mechanism(s of action. A549 cells were incubated with HDM extract, Der p 1, recombinant Der p 2 and recombinant Der p 5. Cell desquamation was assessed by microscopy. The proinflammatory cytokines, IL-6 and IL-8, were measured by ELISA. Intracellular Ca2+ levels were assessed in A549 cells and in mouse fibroblasts expressing the human protease activated receptor (PAR1, PAR2 or PAR4. HDM extract, Der p 1 and Der p 5 dose-dependently increased the production of IL-6 and IL-8. Added simultaneously, Der p 1 and Der p 5 further increased the production of IL-6 and IL-8. The action of Der p 1 was blocked by cysteine-protease inhibitors, while that of Der p 5 couldn't be blocked by either serine- or cysteine protease inhibitors. Der p 5 only induced cell shrinking, whereas HDM extract and Der p1 also induced cell desquamation. Der p 2 had no effect on A549 cells. Der p 1's protease activity causes desquamation and induced the release of IL6 and IL-8 by a mechanism independent of Ca2+ mobilisation and PAR activation. Der p 5 exerts a protease-independent activation of A549 that involves Ca2+ mobilisation and also leads to the production of these cytokines. Together, our data indicate that allergens present in HDM extracts can trigger protease-dependent and protease-independent signalling pathways in A549 cells.

  19. Details of regional particle deposition and airflow structures in a realistic model of human tracheobronchial airways: two-phase flow simulation.

    Science.gov (United States)

    Rahimi-Gorji, Mohammad; Gorji, Tahereh B; Gorji-Bandpy, Mofid

    2016-07-01

    In the present investigation, detailed two-phase flow modeling of airflow, transport and deposition of micro-particles (1-10µm) in a realistic tracheobronchial airway geometry based on CT scan images under various breathing conditions (i.e. 10-60l/min) was considered. Lagrangian particle tracking has been used to investigate the particle deposition patterns in a model comprising mouth up to generation G6 of tracheobronchial airways. The results demonstrated that during all breathing patterns, the maximum velocity change occurred in the narrow throat region (Larynx). Due to implementing a realistic geometry for simulations, many irregularities and bending deflections exist in the airways model. Thereby, at higher inhalation rates, these areas are prone to vortical effects which tend to entrap the inhaled particles. According to the results, deposition fraction has a direct relationship with particle aerodynamic diameter (for dp=1-10µm). Enhancing inhalation flow rate and particle size will largely increase the inertial force and consequently, more particle deposition is evident suggesting that inertial impaction is the dominant deposition mechanism in tracheobronchial airways. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Differential Roles of Hydrogen Peroxide in Adaptive and Inflammatory Gene Expression Induced by Exposure of Human Airway Epithelial Cells to Zn2+

    Science.gov (United States)

    Oxidant stress is believed to play an important role in particulate matter (PM)–mediated toxicity in the respiratory tract. Zinc (Zn2+) is a ubiquitous component of PM that has been shown to induce adverse responses such as inflammatory and adaptive gene expression in airway epit...

  1. Infection with human H1N1 influenza virus affects the expression of sialic acids of metaplastic mucous cells in the ferret airways

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Martel, Cyril Jean-Marie; Aasted, Bent

    2009-01-01

    Glycans terminating in sialic acids serve as receptors for influenza viruses. In this study ferrets were infected with influenza virus A/New Caledonia/20/99, and the in situ localization of sialic acids linked a2-3 and a2-6 in the airways was investigated in infected and non-infected animals by use...

  2. CT demonstration of pharyngeal narrowing in adult obstructive sleep apnea

    International Nuclear Information System (INIS)

    Bohlman, M.E.; Haponik, E.F.; Smith, P.L.; Allen, R.P.; Bleecker, E.R.; Goldman, S.M.

    1983-01-01

    Sleep apnea is a major cause of daytime hypersomnolence. Among the proposed etiologies, focal obstruction of the airways at the level of the pharynx has been suggested but not proven. Using computed tomography, the cross-sectional area of the airway can be readily assessed. Thirty-three adults with clinically proven sleep apnea and 12 normal adults underwent systematic computed tomography of the neck. Significant airway narrowing was demonstrated in all the patients with obstructive sleep apnea, whereas no such narrowing was seen in the controls. In 11, the narrowing was at a single level, whereas in 22 patients two or more levels were affected. This study has shown that a structurally abnormal airway may serve as an anatomic substrate for the development of sleep apnea. On the basis of this evidence, uvulopalatopharyngoplasty has been performed in two patients with relief of symptoms in one

  3. Digital Morphometrics: A New Upper Airway Phenotyping Paradigm in OSA.

    Science.gov (United States)

    Schwab, Richard J; Leinwand, Sarah E; Bearn, Cary B; Maislin, Greg; Rao, Ramya Bhat; Nagaraja, Adithya; Wang, Stephen; Keenan, Brendan T

    2017-08-01

    OSA is associated with changes in pharyngeal anatomy. The goal of this study was to objectively and reproducibly quantify pharyngeal anatomy by using digital morphometrics based on a laser ruler and to assess differences between subjects with OSA and control subjects and associations with the apnea-hypopnea index (AHI). To the best of our knowledge, this study is the first to use digital morphometrics to quantify intraoral risk factors for OSA. Digital photographs were obtained by using an intraoral laser ruler and digital camera in 318 control subjects (mean AHI, 4.2 events/hour) and 542 subjects with OSA (mean AHI, 39.2 events/hour). The digital morphometric paradigm was validated and reproducible over time and camera distances. A larger modified Mallampati score and having a nonvisible airway were associated with a higher AHI, both unadjusted (P digital morphometrics is an accurate, high-throughput, and noninvasive technique to identify anatomic OSA risk factors. Morphometrics may also provide a more reproducible and standardized measurement of the Mallampati score. Digital morphometrics represent an efficient and cost-effective method of examining intraoral crowding and tongue size when examining large populations, genetics, or screening for OSA. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  4. Interleukin (IL) 36 gamma induces mucin 5AC, oligomeric mucus/gel-forming expression via IL-36 receptor-extracellular signal regulated kinase 1 and 2, and p38-nuclear factor kappa-light-chain-enhancer of activated B cells in human airway epithelial cells.

    Science.gov (United States)

    Bae, Chang Hoon; Choi, Yoon Seok; Na, Hyung Gyun; Song, Si-Youn; Kim, Yong-Dae

    2018-03-01

    Mucin 5AC, oligomeric mucus/gel-forming (MUC5AC) expression is significantly increased in allergic and inflammatory airway diseases. Interleukin (IL) 36 gamma is predominantly expressed in airway epithelial cells and plays an important role in innate and adaptive immune responses. IL-36 gamma is induced by many inflammatory mediators, including cytokines and bacterial and viral infections. However, the association between IL-36 gamma and mucin secretion in human airway epithelial cells has not yet been fully investigated. The objective of this study was to determine whether IL-36 gamma might play a role in the regulation of mucin secretion in airway epithelial cells. We investigated the effect and brief signaling pathway of IL-36 gamma on MUC5AC expression in human airway epithelial cells. Enzyme immunoassay, immunoblot analysis, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (PCR), and real-time PCR were performed in mucin-producing human airway epithelial NCI-H292 cells and in human nasal epithelial cells after pretreatment with IL-36 gamma, several specific inhibitors, or small interfering RNAs (siRNA). IL-36 gamma induced MUC5AC expression and activated the phosphorylation of extracellular signal regulated kinase (ERK) 1 and 2, p38, and nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-kappa B). IL-36 receptor antagonist significantly attenuated these effects. The specific inhibitor and siRNA of ERK1, ERK2, p38, and NF-kappa B significantly attenuated IL-36 gamma induced MUC5AC expression. These results indicated that IL-36 gamma induced MUC5AC expression via the IL-36 receptor-mediated ERK1/2 and p38/NF-kappa B pathway in human airway epithelial cells.

  5. Airway exploration in children

    Directory of Open Access Journals (Sweden)

    Fernando GÓMEZ-SÁEZ

    2018-03-01

    Full Text Available Introduction and objective: The management of the airways represents a constant challenge in pediatric practice. In the last years, bronchoscopy has become an essential technique in the diagnosis and treatment of various abnormalities of the child's respiratory system. The special characteristics of the pediatric airway and the differentiated pathology it presents give pediatric bronchoscopy its own entity. Pediatric bronchoscopy is a safe technique with many applications, both diagnostic and therapeutic. The use of both types of bronchoscopes (flexible and rigid allows to take advantage of each one of them. Flexible bronchoscopy in pediatrics is a relatively simple and low-risk procedure that provides anatomical and dynamic information on the airways, as well as cytological and microbiological studies. The simplicity and low risk of this technique, in addition to not requiring general anesthesia, allows it to be performed even at the head of the patient, which has led to an increasingly extensive field of indications. The purpose of this article is to provide a review on the timeliness of the pediatric bronchoscopy procedure, especially about its indications. Method: Narrative review. Conclusion: The endoscopic examination of the airway is a cost-effective technique in pediatrics, with little complications and can offer very valuable diagnostic information, as well as perform certain therapeutic procedures. It is recommended that all professionals involved in the management of patients with airway pathology should know their indications, contraindications, complications, as well as their therapeutic applications.

  6. Supplemental Carbon Dioxide Stabilizes the Upper Airway in Volunteers Anesthetized with Propofol.

    Science.gov (United States)

    Ruscic, Katarina Jennifer; Bøgh Stokholm, Janne; Patlak, Johann; Deng, Hao; Simons, Jeroen Cedric Peter; Houle, Timothy; Peters, Jürgen; Eikermann, Matthias

    2018-05-10

    Propofol impairs upper airway dilator muscle tone and increases upper airway collapsibility. Preclinical studies show that carbon dioxide decreases propofol-mediated respiratory depression. We studied whether elevation of end-tidal carbon dioxide (PETCO2) via carbon dioxide insufflation reverses the airway collapsibility (primary hypothesis) and impaired genioglossus muscle electromyogram that accompany propofol anesthesia. We present a prespecified, secondary analysis of previously published experiments in 12 volunteers breathing via a high-flow respiratory circuit used to control upper airway pressure under propofol anesthesia at two levels, with the deep level titrated to suppression of motor response. Ventilation, mask pressure, negative pharyngeal pressure, upper airway closing pressure, genioglossus electromyogram, bispectral index, and change in end-expiratory lung volume were measured as a function of elevation of PETCO2 above baseline and depth of propofol anesthesia. PETCO2 augmentation dose-dependently lowered upper airway closing pressure with a decrease of 3.1 cm H2O (95% CI, 2.2 to 3.9; P < 0.001) under deep anesthesia, indicating improved upper airway stability. In parallel, the phasic genioglossus electromyogram increased by 28% (23 to 34; P < 0.001). We found that genioglossus electromyogram activity was a significant modifier of the effect of PETCO2 elevation on closing pressure (P = 0.005 for interaction term). Upper airway collapsibility induced by propofol anesthesia can be reversed in a dose-dependent manner by insufflation of supplemental carbon dioxide. This effect is at least partly mediated by increased genioglossus muscle activity.

  7. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  8. Airway remodeling and its reversibility in equine asthma

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Lavoie

    2017-06-01

    Full Text Available Despite effective therapies for controlling its clinical manifestations, human asthma remains an incurable disease. It is now recognized that inflammation induced structural changes (remodeling of the airways are responsible for the progressive loss of lung function in asthmatic patients. However, the peripheral airways, where most of the remodeling occurs in severe asthmatic patients, cannot be safely sampled in humans, and therefore, little is known of the effects of current therapies at reversing the established asthmatic remodeling, especially those occurring in the peripheral airways. Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, experiments in which the disease is artificially induced have been shown to have limited translational potential for humans. To the contrary, horses naturally suffer from an asthma-like condition which shares marked similarities with human asthma making this model unique to investigate the kinetics, reversibility, as well as the physiological consequences of tissue remodeling (Bullone and Lavoie 2015. We reported an increased deposition of smooth muscle, collagen and elastic fibers in the peripheral airways of affected horses, which was correlated with the lung function (Herszberg et al., 2006; Setlakwe et al., 2014. The airway subepithelial collagen depositions were almost completely reversed with 6 to 12 months of treatment with either antigen avoidance or inhaled corticosteroids (ICS administration, and there was a modest (30% on average decrease in airway smooth muscle (Leclere et al., 2011. A recent study also found that ICS combined with long-acting ß2-agonists drugs (LABA and ICS monotherapy similarly induced a 30% decrease of the airway smooth muscle mass at 3 months (Buollone, 2017. However, only ICS/LABA and antigen avoidance decreased airway luminal neutrophilia. The findings indicate the enhance therapeutic effect of ICS

  9. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buhl, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Cepeda Sarabia, A. M.; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; de Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Fink Wagner, A.; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garcés, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzmán, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Lodrup Carlsen, K. C.; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; de Manuel Keenoy, E.; Masjedi, M. R.; Melen, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Momas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Radier Pontal, F.; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schünemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

  10. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    NARCIS (Netherlands)

    Bousquet, J.; Addis, A.; Adcock, I.; Agache, I.; Agusti, A.; Alonso, A.; Annesi-Maesano, I.; Anto, J. M.; Bachert, C.; Baena-Cagnani, C. E.; Bai, C.; Baigenzhin, A.; Barbara, C.; Barnes, P. J.; Bateman, E. D.; Beck, L.; Bedbrook, A.; Bel, E. H.; Benezet, O.; Bennoor, K. S.; Benson, M.; Bernabeu-Wittel, M.; Bewick, M.; Bindslev-Jensen, C.; Blain, H.; Blasi, F.; Bonini, M.; Bonini, S.; Boulet, L. P.; Bourdin, A.; Bourret, R.; Bousquet, P. J.; Brightling, C. E.; Briggs, A.; Brozek, J.; Buh, R.; Bush, A.; Caimmi, D.; Calderon, M.; Calverley, P.; Camargos, P. A.; Camuzat, T.; Canonica, G. W.; Carlsen, K. H.; Casale, T. B.; Cazzola, M.; Sarabia, A. M. Cepeda; Cesario, A.; Chen, Y. Z.; Chkhartishvili, E.; Chavannes, N. H.; Chiron, R.; Chuchalin, A.; Chung, K. F.; Cox, L.; Crooks, G.; Crooks, M. G.; Cruz, A. A.; Custovic, A.; Dahl, R.; Dahlen, S. E.; De Blay, F.; Dedeu, T.; Deleanu, D.; Demoly, P.; Devillier, P.; Didier, A.; Dinh-Xuan, A. T.; Djukanovic, R.; Dokic, D.; Douagui, H.; Dubakiene, R.; Eglin, S.; Elliot, F.; Emuzyte, R.; Fabbri, L.; Wagner, A. Fink; Fletcher, M.; Fokkens, W. J.; Fonseca, J.; Franco, A.; Frith, P.; Furber, A.; Gaga, M.; Garces, J.; Garcia-Aymerich, J.; Gamkrelidze, A.; Gonzales-Diaz, S.; Gouzi, F.; Guzman, M. A.; Haahtela, T.; Harrison, D.; Hayot, M.; Heaney, L. G.; Heinrich, J.; Hellings, P. W.; Hooper, J.; Humbert, M.; Hyland, M.; Iaccarino, G.; Jakovenko, D.; Jardim, J. R.; Jeandel, C.; Jenkins, C.; Johnston, S. L.; Jonquet, O.; Joos, G.; Jung, K. S.; Kalayci, O.; Karunanithi, S.; Keil, T.; Khaltaev, N.; Kolek, V.; Kowalski, M. L.; Kull, I.; Kuna, P.; Kvedariene, V.; Le, L. T.; Carlsen, K. C. Lodrup; Louis, R.; MacNee, W.; Mair, A.; Majer, I.; Manning, P.; Keenoy, E. de Manuel; Masjedi, M. R.; Meten, E.; Melo-Gomes, E.; Menzies-Gow, A.; Mercier, G.; Mercier, J.; Michel, J. P.; Miculinic, N.; Mihaltan, F.; Milenkovic, B.; Molimard, M.; Mamas, I.; Montilla-Santana, A.; Morais-Almeida, M.; Morgan, M.; N'Diaye, M.; Nafti, S.; Nekam, K.; Neou, A.; Nicod, L.; O'Hehir, R.; Ohta, K.; Paggiaro, P.; Palkonen, S.; Palmer, S.; Papadopoulos, N. G.; Papi, A.; Passalacqua, G.; Pavord, I.; Pigearias, B.; Plavec, D.; Postma, D. S.; Price, D.; Rabe, K. F.; Pontal, F. Radier; Redon, J.; Rennard, S.; Roberts, J.; Robine, J. M.; Roca, J.; Roche, N.; Rodenas, F.; Roggeri, A.; Rolland, C.; Rosado-Pinto, J.; Ryan, D.; Samolinski, B.; Sanchez-Borges, M.; Schunemann, H. J.; Sheikh, A.; Shields, M.; Siafakas, N.; Sibille, Y.; Similowski, T.; Small, I.; Sola-Morales, O.; Sooronbaev, T.; Stelmach, R.; Sterk, P. J.; Stiris, T.; Sud, P.; Tellier, V.; To, T.; Todo-Bom, A.; Triggiani, M.; Valenta, R.; Valero, A. L.; Valiulis, A.; Valovirta, E.; Van Ganse, E.; Vandenplas, O.; Vasankari, T.; Vestbo, J.; Vezzani, G.; Viegi, G.; Visier, L.; Vogelmeier, C.; Vontetsianos, T.; Wagstaff, R.; Wahn, U.; Wallaert, B.; Whalley, B.; Wickman, M.; Williams, D. M.; Wilson, N.; Yawn, B. P.; Yiallouros, P. K.; Yorgancioglu, A.; Yusuf, O. M.; Zar, H. J.; Zhong, N.; Zidarn, M.; Zuberbier, T.

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will

  11. Continuous Positive Airway Pressure (CPAP)

    Science.gov (United States)

    ... ENT Doctor Near You Continuous Positive Airway Pressure (CPAP) Continuous Positive Airway Pressure (CPAP) Patient Health Information ... relations staff at newsroom@entnet.org . What Is CPAP? The most common and effective nonsurgical treatment for ...

  12. Cephalomteric changes in airway dimensions with twin block therapy in growing Class II patients

    Science.gov (United States)

    Vinoth, Santhana Krishnan; Thomas, Ashwin Varghese; Nethravathy, Ramya

    2013-01-01

    Introduction: Myofunctional appliances are commonly used for correction of skeletal Class II malrelationship. These appliances influence craniofacial and nasopharyngeal dimensions. Objectives: The present study was done to evaluate changes in airway with twin block therapy. Materials and Methods: Cephalometric assessment of airway was done in 25 growing children in the age group of 11-13 years with Class II skeletal pattern. All the patients were treated with twin block appliance. Pre and post treatment lateral cephalograms were taken to evaluate the changes in different airway and craniofacial dimensions during the treatment period. The average treatment duration was 14.5 months. Results: Airway: A significant increase was observed in upper and lower pharyngeal width and area of bony nasopharynx. Craniofacial dimension: There was a significant increase in effective mandibular length, ramal length and mandibular plane angle. There was an increase in SNB angle, which resulted in decreased ANB angle. Conclusion: There was a definite improvement in airway dimension following twin block therapy PMID:23946570

  13. Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

    DEFF Research Database (Denmark)

    Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

    2012-01-01

    The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic...... inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

  14. Equine recurrent airway obstruction

    Directory of Open Access Journals (Sweden)

    Artur Niedźwiedź

    2014-10-01

    Full Text Available Equine Recurrent Airway Obstruction (RAO, also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their lives, therefore they should be properly managed. In therapy the most importanthing is to eliminate dustexposure, administration of corticosteroids and use bronchodilators to improve pulmonary function.

  15. Pharyngitis – fatal infectious disease or medical error?

    Directory of Open Access Journals (Sweden)

    Marta Rorat

    2015-08-01

    Full Text Available Reporting on adverse events is essential to create a culture of safety, which focuses on protecting doctors and patients from medical errors. We present a fatal case of Streptococcus C pharyngitis in a 56-year-old man. The clinical course and the results of additional diagnostics and autopsy showed that sepsis followed by multiple organ failure was the ultimate cause of death. The clinical course appeared fatal due to a chain of adverse events, including errors made by the physicians caring for the patient for 10 days.

  16. The principles of specifying diagnosis of malignant pharyngeal tumors

    International Nuclear Information System (INIS)

    Savyin, O.O.

    1998-01-01

    The conclusion about pharyngeal tumor was based on additional shadow of the tumor in one or several departments, thickening of the folds, narrowing of the lumen, deformity or absence of the lumen of the pyriform sinus and morgan's ventricles. ACT allowed to evaluate objectively not only localization, size, shape and structure of the growth, but also the state of the surrounding tissue (including the changes in the cartilage). ACT with 'e' sound pronunciation allowed to reveal the changes in the vocal cords which are not revealed by plain x-ray tomography

  17. Pharmacological studies of the mechanism and function of interleukin-1β-induced miRNA-146a expression in primary human airway smooth muscle

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoying

    2010-06-01

    Full Text Available Abstract Background Despite the widespread induction of miR-146a during the innate immune response little is known regarding its biogenesis, function and mechanism. We have therefore examined the role of miR-146a during the interleukin (IL-1β-stimulated IL-6 and IL-8 release and proliferation in primary human airway smooth muscle (HASM cells. Methods HASM cells were isolated from human lung re-section, cultured to a maximum of 3 - 6 passages and then exposed to IL-1β. miR-146a expression were determined by qRT-PCR, IL-6 and IL-8 release by ELISA and proliferation using bromodeoxyuridine incorporation. The role of NF-κB and the MAP kinase pathways was assessed using pharmacological inhibitors of IKK2 (TPCA-1, JNK (SP600125, p38 MAP kinase (SB203580 and MEK-1/2 (PD98059. miR-146a function was determined following transfection of HASM with inhibitors and mimics using Amaxa electroporation. Results IL-1β induced a time-dependent and prolonged 100-fold induction in miR-146a expression, which correlated with release of IL-6 and IL-8. Exposure to IL-1β had no effect upon HASM proliferation. Pharmacological studies showed that expression of primary miR-146a was regulated at the transcriptional levels by NF-κB whilst post-transcriptional processing to mature miR-146a was regulated by MEK-1/2 and JNK-1/2. Functional studies indicated that IL-1β-induced miR-146a expression does not negatively regulate IL-6 and IL-8 release or basal proliferation. However, inhibition of IL-1β-induced IL-6 and IL-8 release was observed at the super-maximal intracellular miR-146a levels obtained by transfection with miR-146a mimics and indicates that studies using miRNA mimics can produce false positive results. Mechanistic studies showed that in the presence of super-maximal levels, the action of miR-146a mimics was mediated at a step following IL-6 and IL-8 mRNA transcription and not through down-regulation of IL-1 receptor associated kinase 1 (IRAK-1 and TNF

  18. Paediatric airway management: basic aspects

    DEFF Research Database (Denmark)

    Holm-Knudsen, R J; Rasmussen, L S

    2009-01-01

    Paediatric airway management is a great challenge, especially for anaesthesiologists working in departments with a low number of paediatric surgical procedures. The paediatric airway is substantially different from the adult airway and obstruction leads to rapid desaturation in infants and small...... children. This paper aims at providing the non-paediatric anaesthesiologist with a set of safe and simple principles for basic paediatric airway management. In contrast to adults, most children with difficult airways are recognised before induction of anaesthesia but problems may arise in all children...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... NACFC Carolyn and C Richard Mattingly Leadership in Mental Health Care Award Mary M. Kontos Award NACFC Reflections ... help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway clearance. ... Instagram Email Find a Clinical Trial Help us blaze ...

  20. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... how you can help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage ...

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Team Your cystic fibrosis care team includes a group of CF health care professionals who partner with ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

  2. Airway Clearance Techniques (ACTs)

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    Full Text Available ... cystic fibrosis. CF CARE CENTER finder We provide funding for and accredit more than 120 care centers ... Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The ... Home Life With CF Treatments and Therapies Airway Clearance ...

  3. Upper airway evaluation

    International Nuclear Information System (INIS)

    Hoffman, E.A.; Gefter, W.B.; Schnall, M.; Nordberg, J.; Listerud, J.; Lenkinski, R.E.

    1988-01-01

    The authors are evaluating upper-airway sleep disorders with magnetic resonance (MR) imaging and x-ray cine computed tomography (CT). Fixed structural anatomy is visualized with multisection spin-echo MR imaging, the dynamic component with cine CT. Unique aspects of the study are described in this paper

  4. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... programs and policies to improve the lives of people with CF. Help us by raising awareness of CF, participating in a fundraising event, or volunteering ... clear your airways. Most are easy to do. Infants and toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they ...

  5. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... and Their Families When There's More Than One Person With CF in the Same School Daily Life ... Awards and Grants Career Development Awards Research Awards Training Awards CF ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ...

  6. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... infant or child manage their lung health, watch parents of children with CF and a respiratory therapist talk about the different techniques they use for airway ... Positive Expiratory Pressure High-Frequency Chest Wall Oscillation (the Vest) Follow ...

  7. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can help your infant or child manage their lung health, watch parents of children with CF and a respiratory therapist ...

  8. Dual embryonic origin and patterning of the pharyngeal skeleton in the axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Sefton, Elizabeth M; Piekarski, Nadine; Hanken, James

    2015-01-01

    The impressive morphological diversification of vertebrates was achieved in part by innovation and modification of the pharyngeal skeleton. Extensive fate mapping in amniote models has revealed a primarily cranial neural crest derivation of the pharyngeal skeleton. Although comparable fate maps of amphibians produced over several decades have failed to document a neural crest derivation of ventromedial elements in these vertebrates, a recent report provides evidence of a mesodermal origin of one of these elements, basibranchial 2, in the axolotl. We used a transgenic labeling protocol and grafts of labeled cells between GFP+ and white embryos to derive a fate map that describes contributions of both cranial neural crest and mesoderm to the axolotl pharyngeal skeleton, and we conducted additional experiments that probe the mechanisms that underlie mesodermal patterning. Our fate map confirms a dual embryonic origin of the pharyngeal skeleton in urodeles, including derivation of basibranchial 2 from mesoderm closely associated with the second heart field. Additionally, heterotopic transplantation experiments reveal lineage restriction of mesodermal cells that contribute to pharyngeal cartilage. The mesoderm-derived component of the pharyngeal skeleton appears to be particularly sensitive to retinoic acid (RA): administration of exogenous RA leads to loss of the second basibranchial, but not the first. Neural crest was undoubtedly critical in the evolution of the vertebrate pharyngeal skeleton, but mesoderm may have played a central role in forming ventromedial elements, in particular. When and how many times during vertebrate phylogeny a mesodermal contribution to the pharyngeal skeleton evolved remain to be resolved. © 2015 Wiley Periodicals, Inc.

  9. Bupivacaine Lozenge Compared with Lidocaine Spray as Topical Pharyngeal Anesthetic before Unsedated Upper Gastrointestinal Endoscopy

    DEFF Research Database (Denmark)

    Salale, Nesrin; Treldal, Charlotte; Mogensen, Stine

    2014-01-01

    Unsedated upper gastrointestinal endoscopy (UGE) can induce patient discomfort, mainly due to a strong gag reflex. The aim was to assess the effect of a bupivacaine lozenge as topical pharyngeal anesthetic compared with standard treatment with a lidocaine spray before UGE. Ninety-nine adult...... with a lidocaine spray proved to be a superior option as topical pharyngeal anesthetic before an UGE....

  10. Extraglottic airway devices: technology update

    Directory of Open Access Journals (Sweden)

    Sharma B

    2017-08-01

    Full Text Available Bimla Sharma, Chand Sahai, Jayashree Sood Department of Anaesthesiology, Pain and Perioperative Medicine, Sir Ganga Ram Hospital, New Delhi, India Abstract: Extraglottic airway devices (EADs have revolutionized the field of airway management. The invention of the laryngeal mask airway was a game changer, and since then, there have been several innovations to improve the EADs in design, functionality, safety and construction material. These have ranged from changes in the shape of the mask, number of cuffs and material used, like rubber, polyvinylchloride and latex. Phthalates, which were added to the construction material in order to increase device flexibility, were later omitted when this chemical was found to have serious adverse reproductive outcomes. The various designs brought out by numerous companies manufacturing EADs resulted in the addition of several devices to the airway market. These airway devices were put to use, many of them with inadequate or no evidence base regarding their efficacy and safety. To reduce the possibility of compromising the safety of the patient, the Difficult Airway Society (DAS formed the Airway Device Evaluation Project Team (ADEPT to strengthen the evidence base for airway equipment and vet the new extraglottic devices. A preuse careful analysis of the design and structure may help in better understanding of the functionality of a particular device. In the meantime, the search for the ideal EAD continues. Keywords: extraglottic airway devices, laryngeal mask airway, other extraglottic airway devices, safety, technology update

  11. Current status of superficial pharyngeal squamous cell carcinoma in Japan.

    Science.gov (United States)

    Rikitake, Ryoko; Ando, Mizuo; Saito, Yuki; Yoshimoto, Seiichi; Yamasoba, Tatsuya; Higashi, Takahiro

    2017-10-01

    To investigate the status and treatment of superficial pharyngeal squamous cell carcinoma in Japan. We analyzed all cases diagnosed between 2011 and 2013, as recorded in the national database of hospital-based cancer registries. We extracted data on patient sex, age, tumor locations, histology, presentation routes, initial treatments, and TNM stages. Additionally, we compared the characteristics of pharyngeal carcinoma to those of esophageal cancer. A total of 16,521 oropharyngeal and hypopharyngeal cancers from 409 institutions were included. Diagnosis of Tis tumors was infrequent, and both cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis diseases were the most commonly detected during follow-up examinations for other diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients comprised an equally high proportion of men (94 vs 92%, respectively). The most common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%). The proportion of Tis tumors diagnosed at individual institutions showed a positive correlation with the number of endoscopic treatments (r = 0.32, P squamous cell carcinoma patients in Japan. Further improvements in early diagnosis and standardized treatments are warranted.

  12. Hallucigenia's head and the pharyngeal armature of early ecdysozoans.

    Science.gov (United States)

    Smith, Martin R; Caron, Jean-Bernard

    2015-07-02

    The molecularly defined clade Ecdysozoa comprises the panarthropods (Euarthropoda, Onychophora and Tardigrada) and the cycloneuralian worms (Nematoda, Nematomorpha, Priapulida, Loricifera and Kinorhyncha). These disparate phyla are united by their means of moulting, but otherwise share few morphological characters--none of which has a meaningful fossilization potential. As such, the early evolutionary history of the group as a whole is largely uncharted. Here we redescribe the 508-million-year-old stem-group onychophoran Hallucigenia sparsa from the mid-Cambrian Burgess Shale. We document an elongate head with a pair of simple eyes, a terminal buccal chamber containing a radial array of sclerotized elements, and a differentiated foregut that is lined with acicular teeth. The radial elements and pharyngeal teeth resemble the sclerotized circumoral elements and pharyngeal teeth expressed in tardigrades, stem-group euarthropods and cycloneuralian worms. Phylogenetic results indicate that equivalent structures characterized the ancestral panarthropod and, seemingly, the ancestral ecdysozoan, demonstrating the deep homology of panarthropod and cycloneuralian mouthparts, and providing an anatomical synapomorphy for the ecdysozoan supergroup.

  13. Poststreptococcal keratouveitis associated with group C streptococcus pharyngitis

    Directory of Open Access Journals (Sweden)

    Nataneli N

    2011-09-01

    Full Text Available Nathaniel Nataneli1, Zenia P Aguilera1, Pearl S Rosenbaum1, Tamar Goldstein1,2, Martin Mayers11Department of Ophthalmology, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, Bronx, NY, USA; 2Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelPurpose: To report the first case of poststreptococcal syndrome uveitis (PSU in association with group C streptococcus (GCS.Patients and methods: Chart review of a 24-year-old man who presented with bilateral ocular redness, pain, and photophobia for 5 days and "white rings" around his eyes for a duration of 3 days. The patient further reported fever and sore throat in the preceding week. Slit-lamp examination showed bilateral keratouveitis. A thorough uveitis workup, antistreptolysin O (ASLO titer, and throat culture were obtained. The patient was treated with frequent topical steroids and systemic doxycycline. The uveitis and keratitis subsided over the next few weeks, leaving extensive peripheral keratolysis.Results: The results of laboratory diagnostic testing revealed an elevated ASLO, C-reactive protein, as well as HLA-B27 positivity. Throat cultures grew beta-hemolytic GCS; group A streptococcus was culture negative.Conclusion: GCS pharyngitis may be a causative organism of PSU.Keywords: pharyngitis, keratolysis, keratouveitis

  14. Observation the swallowing mechanism in elderly patients with pharyngeal dysphagia

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    Claudia Ximena Campo-Cañar

    2010-09-01

    Full Text Available Observation of the swallowing dynamics is an issue that demands close attention by the health professionals involved in the diagnosis and management of patients with dysphagia. This article is a review of the literature aimed to enhance the knowledge regarding the speech therapy assessment of pharyngeal dysphagia in elder adults. The disorder of the swallowing is called dysphagia and it is defined as difficulty swallowing. The dysphagia is often caused by affectation of mechanical or neuromuscular components of the swallowing mechanism. This type of disorder is likely to impact the the oral, pharyngeal and esophageal phases of the swallowing. The speech therapist should take into account assessing aspects such as level of consciousness, vital signs, whether or not the patient is ventilator dependent, means of feeding, if intubated what type of cannula, whether or not the patient uses a speaking valve (if a trach tube is present, nutritional status, the patient’s expressive and receptive language, the anatomical and physiological state of the oral motor structures. When assessing swallowing clinicians should also make sure to develop an adequate beside clinical, voice assessment and videofluoroscopy.

  15. Volumetric evaluation of pharyngeal segments in obstructive sleep apnea patients,

    Directory of Open Access Journals (Sweden)

    Marcos Marques Rodrigues

    Full Text Available Abstract Introduction Obstructive sleep apnea occurs by recurrent collapse of the upper airway during sleep, resulting in total (apnea or partial (hypopnea reduction of the airflow and has intimate relation with changes in the upper airway. Cone Beam CT allows the analysis of the upper airway and its volume by three-dimensional reconstruction. Objective To evaluate a possible correlation between the volume of the upper airway and the severity of the obstructive sleep apnea. Methods A retrospective study was performed reviewing polysomnographic data and Cone Beam CT records of 29 patients (13 males and 16 females. The correlation between the volume of the nasopharynx, the oropharynx and the total superior pharynx with the AHI was assessed by Pearson's rank correlation coefficient. Results The obstructive sleep apnea severity division was: ten patients had severe, 7 had moderate, 6 had mild and 6 of them were healthy. The correlation between the nasopharynx, the oropharynx and the total superior pharynx volumes and the Apnea-Hypopnea-Index was respectively: −0.415 (p = 0.025, 0.186 (p = 0.334 and −0329 (p = 0.089. The Spearman's rank controlled by the Body Mass Index, the age and the gender was: −0.206 (p = 0.304, −0.155 (p = 0.439 and 0.242 (p = 0.284. Conclusion There is no correlation between the volume of the airway and the obstructive sleep apnea, assessed by Apnea-Hypopnea-Index and controlled by the Body Mass Index, the age and the gender. The volume of the upper airways as an isolated parameter did not correlate to the severity of the obstructive sleep apnea syndrome, and should be evaluated together with other factors.

  16. Volumetric evaluation of pharyngeal segments in obstructive sleep apnea patients.

    Science.gov (United States)

    Rodrigues, Marcos Marques; Pereira Filho, Valfrido Antonio; Gabrielli, Mário Francisco Real; Oliveira, Talles Fernando Medeiros de; Batatinha, Júlio Américo Pereira; Passeri, Luis Augusto

    2017-01-30

    Obstructive sleep apnea occurs by recurrent collapse of the upper airway during sleep, resulting in total (apnea) or partial (hypopnea) reduction of the airflow and has intimate relation with changes in the upper airway. Cone Beam CT allows the analysis of the upper airway and its volume by three-dimensional reconstruction. To evaluate a possible correlation between the volume of the upper airway and the severity of the obstructive sleep apnea. A retrospective study was performed reviewing polysomnographic data and Cone Beam CT records of 29 patients (13 males and 16 females). The correlation between the volume of the nasopharynx, the oropharynx and the total superior pharynx with the AHI was assessed by Pearson's rank correlation coefficient. The obstructive sleep apnea severity division was: ten patients had severe, 7 had moderate, 6 had mild and 6 of them were healthy. The correlation between the nasopharynx, the oropharynx and the total superior pharynx volumes and the Apnea-Hypopnea-Index was respectively: -0.415 (p=0.025), 0.186 (p=0.334) and -0329 (p=0.089). The Spearman's rank controlled by the Body Mass Index, the age and the gender was: -0.206 (p=0.304), -0.155 (p=0.439) and 0.242 (p=0.284). There is no correlation between the volume of the airway and the obstructive sleep apnea, assessed by Apnea-Hypopnea-Index and controlled by the Body Mass Index, the age and the gender. The volume of the upper airways as an isolated parameter did not correlate to the severity of the obstructive sleep apnea syndrome, and should be evaluated together with other factors. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  17. Anti-CTGF single-chain variable fragment dimers inhibit human airway smooth muscle (ASM) cell proliferation by down-regulating p-Akt and p-mTOR levels.

    Science.gov (United States)

    Gao, Wei; Cai, Liting; Xu, Xudong; Fan, Juxiang; Xue, Xiulei; Yan, Xuejiao; Qu, Qinrong; Wang, Xihua; Zhang, Chen; Wu, Guoqiu

    2014-01-01

    Connective tissue growth factor (CTGF) contributes to airway smooth muscle (ASM) cell hyperplasia in asthma. Humanized single-chain variable fragment antibody (scFv) was well characterized as a CTGF antagonist in the differentiation of fibroblast into myofibroblast and pulmonary fibrosis in our previous studies. To further improve the bioactivity of scFv, we constructed a plasmid to express scFv-linker-matrilin-6×His fusion proteins that could self-assemble into the scFv dimers by disulfide bonds in matrilin under non-reducing conditions. An immunoreactivity assay demonstrated that the scFv dimer could highly bind to CTGF in a concentration-dependent manner. The MTT and EdU assay results revealed that CTGF (≥10 ng/mL) promoted the proliferation of ASM cells, and this effect was inhibited when the cells were treated with anti-CTGF scFv dimer. The western blot analysis results showed that increased phosphorylation of Akt and mTOR induced by CTGF could be suppressed by this scFv dimer. Based on these findings, anti-CTGF scFv dimer may be a potential agent for the prevention of airway remodeling in asthma.

  18. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  19. Effects of Laser Printer–Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts

    Science.gov (United States)

    Pirela, Sandra V.; Miousse, Isabelle R.; Lu, Xiaoyan; Castranova, Vincent; Thomas, Treye; Qian, Yong; Bello, Dhimiter; Kobzik, Lester; Koturbash, Igor; Demokritou, Philip

    2015-01-01

    Background Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing. Objectives We assessed the biological responses of a panel of human cell lines to PEPs. Methods Three physiologically relevant cell lines—small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)—were exposed to PEPs at a wide range of doses (0.5–100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. Results PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure. Conclusions The in vitro findings obtained in this study suggest that laser printer–emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders. Citation Pirela SV, Miousse IR, Lu X, Castranova V, Thomas T, Qian Y, Bello D, Kobzik L, Koturbash I, Demokritou P. 2016. Effects of laser printer–emitted engineered nanoparticles on cytotoxicity, chemokine expression, reactive oxygen species, DNA methylation, and DNA damage: a comprehensive in

  20. Upper airway muscles awake and asleep.

    Science.gov (United States)

    Sériès, Frédéric

    2002-06-01

    Upper airway (UA) structures are involved in different respiratory and non-respiratory tasks. The coordination of agonist and antagonist UA dilators is responsible for their mechanical function and their ability to maintain UA patency throughout the respiratory cycle. The activity of these muscles is linked with central respiratory activity but also depends on UA pressure changes and is greatly influenced by sleep. UA muscles are involved in determining UA resistance and stability (i.e. closing pressure), and the effect of sleep on these variables may be accounted for by its effect on tonic and phasic skeletal muscle activities. The mechanical effects of UA dilator contraction also depend on their physiological properties (capacity to generate tension in vitro, activity of the anaerobic enzymatic pathway, histo-chemical characteristics that may differ between subjects who may or may not have sleep-related obstructive breathing disorders). These characteristics may represent an adaptive process to an increased resistive loading of these muscles. The apparent discrepancy between the occurrence of UA closure and an increased capacity to generate tension in sleep apnea patients may be due to a reduction in the effectiveness of UA muscle contraction in these patients; such an increase in tissue stiffness could be accounted for by peri-muscular tissue characteristics. Therefore, understanding of UA muscle physiological characteristics should take into account its capacity for force production and its mechanical coupling with other UA tissues. Important research goals for the future will be to integrate these issues with other physiological features of the disease, such as UA size and dimension, histological characteristics of UA tissues and the effect of sleep on muscle function. Such integration will better inform understanding of the role of pharyngeal UA muscles in the pathophysiology of the sleep apnea/hypopnea syndrome.

  1. A pair of pharyngeal gustatory receptor neurons regulates caffeine-dependent ingestion in Drosophila larvae

    Directory of Open Access Journals (Sweden)

    Jaekyun Choi

    2016-07-01

    Full Text Available The sense of taste is an essential chemosensory modality that enables animals to identify appropriate food sources and control feeding behavior. In particular, the recognition of bitter taste prevents animals from feeding on harmful substances. Feeding is a complex behavior comprised of multiple steps, and food quality is continuously assessed. We here examined the role of pharyngeal gustatory organs in ingestion behavior. As a first step, we constructed a gustatory receptor-to-neuron map of the larval pharyngeal sense organs, and examined corresponding gustatory receptor neuron projections in the larval brain. Out of 22 candidate bitter compounds, we found 14 bitter compounds that elicit inhibition of ingestion in a dose-dependent manner. We provide evidence that certain pharyngeal gustatory receptor neurons are necessary and sufficient for the ingestion response of larvae to caffeine. Additionally, we show that a specific pair of pharyngeal gustatory receptor neurons, DP1, responds to caffeine by calcium imaging. In this study we show that a specific pair of gustatory receptor neurons in the pharyngeal sense organs coordinates caffeine sensing with regulation of behavioral responses such as ingestion. Our results indicate that in Drosophila larvae, the pharyngeal gustatory receptor neurons have a major role in sensing food palatability to regulate ingestion behavior. The pharyngeal sense organs are prime candidates to influence ingestion due to their position in the pharynx, and they may act as first level sensors of ingested food.

  2. Virtual 3-D 18F-FDG PET/CT panendoscopy for assessment of the upper airways of head and neck cancer patients: a feasibility study

    International Nuclear Information System (INIS)

    Buchbender, Christian; Heusner, Till A.; Treffert, Jon; Lehnerdt, Goetz; Mattheis, Stefan; Geiger, Bernhard; Bockisch, Andreas; Forsting, Michael; Antoch, Gerald

    2012-01-01

    The aim of this study was to evaluate whether a virtual 3-D 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT panendoscopy is feasible and can be used for noninvasive imaging of the upper airways and pharyngeal/laryngeal tumours. From 18 F-FDG PET/CT data sets of 40 patients (29 men, 11 women; age 61 ± 9 years) with pharyngeal or laryngeal malignancies virtual 3-D 18 F-FDG PET/CT panendoscopies were reconstructed and the image processing time was measured. The feasibility of assessing the oral cavity, nasopharynx, tongue base, soft palate, pharyngeal tonsils, epiglottis, aryepiglottic folds, piriform sinus, postcricoid space, glottis, subglottis, trachea, bronchi and oesophagus and of detecting primary tumours was tested. Results of fibre-optic bronchoscopy and histology served as the reference standard. The nasopharynx, tongue base, soft palate, pharyngeal tonsils, epiglottis, subglottis and the tracheobronchial tree were accessible in all 40, and the aryepiglottic folds, posterior hypopharyngeal wall, postcricoid space, piriform sinus, glottis, oral cavity and oesophagus in 37, 37, 37, 37, 33, 16 and 0 patients, respectively. In all 12 patients with restricted fibre-optic evaluation due to being primarily intubated, the subglottis was accessible via virtual panendoscopy. The primary tumour was depicted in 36 of 40 patients (90 %). The mean processing time for virtual 18 F-FDG PET/CT panendoscopies was 145 ± 98 s. Virtual 18 F-FDG PET/CT panendoscopy of the upper airways is technically feasible and can detect pharyngeal and laryngeal malignancies. This new tool can aid in the complete evaluation of the subglottic space in intubated patients and may be used for planning optical panendoscopies, biopsies and surgery in the future. (orig.)

  3. Incidental Mycobacterium-induced granulomatous inflammation of the follicular pharyngeal tonsils in a South African farmed ostrich (Struthio camelus

    Directory of Open Access Journals (Sweden)

    Martina R. Crole

    2013-10-01

    Full Text Available Avian mycobacteriosis (AM is a zoonotic disease caused by Mycobacterium aviumcomplex (MAC, which can spread from avians to other farmed animals such as cattle and pigs as well as to humans. This study is the first report of granulomatous inflammation, as a result of avian mycobacteriosis, in the follicular pharyngeal tonsils of a farmed ostrich. The head of an apparently healthy farmed adult ostrich was obtained after slaughter. Each pharyngeal fold displayed a large tissue mass. This tissue was routinely prepared for light microscopy and stained with haematoxylin and eosin, periodic acid Schiff, Grocott methenamine silver, Gram and Ziehl-Neelsen. Immunohistochemistry (IHC and polymerase chain reaction (PCR were performed to identify Mycobacterium spp. and Mycobacterium tuberculosis complex, respectively. Histologically, the tissue masses consisted of confluent mature micro-granulomata that were characterised by central caseous necrosis surrounded by multinucleated giant cells, macrophages and lymphoid cells and an outer mature fibrous connective tissue capsule. Within some foci of caseous necrosis were variably sized colonies of small, Gram-negative, acid-fast bacilli, which showed positive IHC labelling for Mycobacterium spp., leading to a presumptive diagnosis of AM. PCR thus proved useful in excluding the presence of notifiable Mycobacteriumspp. The significance and role of the pharyngeal tonsils of ratites in diseases such as AM warrant specific attention. Moreover, as ratites are known to present with AM infections with apparently no visible loss in body condition, as presumably occurred in the present case, it is imperative that unusual masses in apparently healthy ratites be thoroughly investigated.

  4. Anticholinergic treatment in airways diseases.

    LENUS (Irish Health Repository)

    Flynn, Robert A

    2009-10-01

    The prevalence of chronic airways diseases such as chronic obstructive pulmonary disease and asthma is increasing. They lead to symptoms such as a cough and shortness of breath, partially through bronchoconstriction. Inhaled anticholinergics are one of a number of treatments designed to treat bronchoconstriction in airways disease. Both short-acting and long-acting agents are now available and this review highlights their efficacy and adverse event profile in chronic airways diseases.

  5. Treatment and post-treatment effects of facemask therapy on the sagittal pharyngeal dimensions in Class III subjects.

    Science.gov (United States)

    Baccetti, Tiziano; Franchi, Lorenzo; Mucedero, Manuela; Cozza, Paola

    2010-06-01

    The purpose of this cephalometric study was to analyse the treatment and post-treatment craniofacial effects of a facemask (FM) combined with a bite block (BB) with specific regard to the sagittal pharyngeal dimensions in subjects with a Class III malocclusion when compared with an untreated Class III control group. The FM/BB group (22 subjects, 12 females and 10 males) had a mean age pre-treatment (T1) of 8.9 +/- 1.5 years, at the end of active treatment (T2) of 10.5 +/- 1.3 years, and post-treatment (T3) of 12.6 +/- 1.9 years. The treated group was compared with a control group of 14 subjects (6 females and 8 males) with untreated Class III malocclusions that matched the FM/BB group as to age at T1, T2, and T3, observation periods and skeletal maturation. Comparisons of the T2-T1 and T3-T1 changes between the two groups were analysed with the Mann-Whitney test. Significant favourable skeletal changes in the maxilla and mandible were observed in the treated group both after Ts2 and T3. No significant short- or long-term changes in the sagittal oropharyngeal and nasopharyngeal airway dimensions were induced by maxillary protraction in subjects with a Class III malocclusion when compared with untreated controls.

  6. The measurements of multiple slices CT on the narrow pharyngeal cavity in obstructive sleep apnea-hypopnea syndrome

    International Nuclear Information System (INIS)

    Shen Jie; Qi Ji; Yin Jianzhong

    2007-01-01

    Objective: To define the characteristic values of the pharyngeal cavity by comparing the values of measures and ratios between the patients with obstructive sleep apnea-hypopnea syndrome (OSAS) and controls. Methods: Sixty-eight OSAS patients who were diagnosed using polysomnography, and 56 healthy people were scanned by MSCT (multiple slices computed tomography) in the awake state. Then, the values were measured on the reformatted images and were compared between two groups. Results: Of the 63 values, 49 values were different between the two groups, and among those, 4 values were entered into the Discriminant Functions. These were the left-right diameter (LR) [OSAS: LR=(9.4±3.7) mm, controls: LR=(20.1±5.0) mm, t=-13.820, P=0.000] and the cross-sectional area (XSA) [OSAS: XSA=(54±27) mm 2 , controls: XSA=(164±77) mm 2 , t=-10.944, P=0.000] of RP, the heights of tongue [OSAS: (75.4±8.3) mm, controls: (58.4±9.8) mm, t=10.476, P=0.000], the lengths of uvula/the lengths of airway (OSAS: 0.139±0.039, controls: 0.154±0.048, t=-1.983, P=0.050). Conclusions: Many measures and ratios were different between the two groups, but there were overlaps between them. Measures using the Discriminant Functions can help the diagnosis of OSAS. (authors)

  7. Measurement of lung airways in three dimensions using hyperpolarized helium-3 MRI

    International Nuclear Information System (INIS)

    Peterson, Eric T; Fain, Sean B; Dai Jionghan; Holmes, James H

    2011-01-01

    Large airway measurement is clinically important in cases of airway disease and trauma. The gold standard is computed tomography (CT), which allows for airway measurement. However, the ionizing radiation dose associated with CT is a major limitation in longitudinal studies and trauma. To avoid ionizing radiation from CT, we present a method for measuring the large airway diameter in humans using hyperpolarized helium-3 (HPHe) MRI in conjunction with a dynamic 3D radial acquisition. An algorithm is introduced which utilizes the significant airway contrast for semi-automated segmentation and skeletonization which is used to derive the airway lumen diameter. The HPHe MRI method was validated with quantitative CT in an excised and desiccated porcine lung (linear regression R 2 = 0.974 and slope = 0.966 over 32 airway segments). The airway lumen diameters were then compared in 24 human subjects (22 asthmatics and 2 normals; linear regression R 2 value of 0.799 and slope = 0.768 over 309 airway segments). The feasibility for airway path analysis to areas of ventilation defect is also demonstrated.

  8. Volumetric MR imaging of the upper airway in obstructive sleep apnea syndrome

    International Nuclear Information System (INIS)

    Gefter, W.B.; Nordberg, J.E.; Hoffman, E.A.

    1989-01-01

    Structural abnormalities in the upper airway and surrounding soft tissues may contribute to the obstructive sleep apnea syndrome (OSAS). The authors have utilized MR imaging (3-mm contiguous T1-weighted sagittal images obtained with a local coil at 1.5 T) combined with a computer graphics-based analysis of three-dimensional geometry to study the upper airways of 10 awake, supine normal subjects (29--50 years-old), seven patients with OSAS (34--54 years old), and a nonapneic snorer (24 years old). Upper-airway anatomic segments were compared with regard to regional volumes, minimum cross-sectional areas, and pharyngeal wall thickness. Results to date show a smaller retropalatial airway volume in the patients with OSAS (1.8 cm 3 ± 0.8 [SEM]) and a smaller minimum cross-sectional retropalatal area in patients with OSAS (0.45 cm 2 ) than in the nonapneic snorer (0.9 cm 2 ) and the normal subjects (2.5 cm 2 ± 0.2)

  9. Impediment in upper airway stabilizing forces assessed by phrenic nerve stimulation in sleep apnea patients

    Directory of Open Access Journals (Sweden)

    Vérin E

    2005-09-01

    Full Text Available Abstract Background The forces developed during inspiration play a key role in determining upper airway stability and the occurrence of nocturnal breathing disorders. Phrenic nerve stimulation applied during wakefulness is a unique tool to assess Upper airway dynamic properties and to measure the overall mechanical effects of the inspiratory process on UA stability. Objectives To compare the flow/pressure responses to inspiratory and expiratory twitches between sleep apnea subjects and normal subjects. Methods Inspiratory and expiratory twitches using magnetic nerve stimulation completed in eleven untreated sleep apnea subjects and ten normal subjects. Results In both groups, higher flow and pressure were reached during inspiratory twitches. The two groups showed no differences in expiratory twitch parameters. During inspiration, the pressure at which flow-limitation occurred was more negative in normals than in apneic subjects, but not reaching significance (p = 0.07. The relationship between pharyngeal pressure and flow adequately fitted with a polynomial regression model providing a measurement of upper airway critical pressure during twitch. This pressure significantly decreased in normals from expiratory to inspiratory twitches (-11.1 ± 1.6 and -15.7 ± 1.0 cm H2O respectively, 95% CI 1.6–7.6, p Conclusion Inspiratory-related upper airway dilating forces are impeded in sleep apnea patients.

  10. Early adaptive developments of Pseudomonas aeruginosa after the transition from life in the environment to persistent colonization in the airways of human cystic fibrosis hosts

    DEFF Research Database (Denmark)

    Rau, Martin Holm; Hansen, Susse Kirkelund; Johansen, H. K.

    2010-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen ubiquitous to the natural environment but with the capability of moving to the host environment. Long-term infection of the airways of cystic fibrosis patients is associated with extensive genetic adaptation of P. aeruginosa, and we have studied...... cases of the initial stages of infection in order to characterize the early adaptive processes in the colonizing bacteria. A combination of global gene expression analysis and phenotypic characterization of longitudinal isolates from cystic fibrosis patients revealed well-known characteristics...... such as conversion to a mucoid phenotype by mucA mutation and increased antibiotic resistance by nfxB mutation. Additionally, upregulation of the atu operon leading to enhanced growth on leucine provides a possible example of metabolic optimization. A detailed investigation of the mucoid phenotype uncovered profound...

  11. The Laryngeal Mask Airway (LMA) as an alternative to airway ...

    African Journals Online (AJOL)

    Background: To evaluate the possibility of airway management using a laryngeal mask airway (LMA) during dental procedures on mentally retarded (MR) patients and patients with genetic diseases. Design: A prospective pilot study. Setting: University Hospital. Methods: A pilot study was designed to induce general ...

  12. Relationship between airway pathophysiology and airway inflammation in older asthmatics

    DEFF Research Database (Denmark)

    Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J

    2013-01-01

    -dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

  13. The usefulness of design of experimentation in defining the effect difficult airway factors and training have on simulator oral-tracheal intubation success rates in novice intubators.

    Science.gov (United States)

    Thomas, Frank; Carpenter, Judi; Rhoades, Carol; Holleran, Renee; Snow, Gregory

    2010-04-01

    This exploratory study examined novice intubators and the effect difficult airway factors have on pre- and posttraining oral-tracheal simulation intubation success rates. Using a two-level, full-factorial design of experimentation (DOE) involving a combination of six airway factors (curved vs. straight laryngoscope blade, trismus, tongue edema, laryngeal spasm, pharyngeal obstruction, or cervical immobilization), 64 airway scenarios were prospectively randomized to 12 critical care nurses to evaluate pre- and posttraining first-pass intubation success rates on a simulator. Scenario variables and intubation outcomes were analyzed using a generalized linear mixed-effects model to determine two-way main and interactive effects. Interactive effects between the six study factors were nonsignificant (p = 0.69). For both pre- and posttraining, main effects showed the straight blade (p = 0.006), tongue edema (p = 0.0001), and laryngeal spasm (p = 0.004) significantly reduced success rates, while trismus (p = 0.358), pharyngeal obstruction (p = 0.078), and cervical immobilization did not significantly change the success rate. First-pass intubation success rate on the simulator significantly improved (p = 0.005) from pre- (19%) to posttraining (36%). Design of experimentation is useful in analyzing the effect difficult airway factors and training have on simulator intubation success rates. Future quality improvement DOE simulator research studies should be performed to help clarify the relationship between simulator factors and patient intubation rates.

  14. The influence of upper airways diameter on the intensity of obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    Jolanta Szymańska

    2014-03-01

    Full Text Available Introduction and Objective. Obstructive sleep apnea (OSA is characterized by at least 5 ten-second-long episodes of apnea or hypopnea, per hour of sleep. This disease may lead to severe, life-threatening complications. Therefore, risk analysis and its influence on disease intensity is crucial for proper implementation of preventive treatments. Objective. To determine the relation between the intensity of OSA expressed in Apnea-Hypopnea Index (AHI, and the anterior-posterior diameter of upper airways at the levels of soft palate and tongue base. Material and Method. Medical records of 41 patients with sleep apnea (AHI>4 diagnosed through polysomnographic examination obstructive were used for the study. The data consisted of: age and gender, polysomnographic examination results (AHI, lateral cephalogram with cephalomertic analysis, together with measurements of the upper and lower pharyngeal depth according to McNamara. Statistical analysis was carried out in accordance with Pearson’s r correlation coefficient test (Statistica 8.0 software package. Results. Analysis of the influence of upper airways diameter on the intensity of OSA showed that the value of upper Airways diameter at the tongue base level had no statistically significant impact on the value of AHI (p=0.795. However, a statistically significant impact of the value of upper airways diameter on the AHI value (p=0.008 at the soft palate level was observed. Patients with OSA have narrowed upper airways diameter. The value of AHI increases with the decrease of upper diameter and is not dependent on a lower diameter value. Patients with a decreased upper airways diameter should be informed about potential breathing disorders during sleep.

  15. Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment

    DEFF Research Database (Denmark)

    Nørskov, Anders Kehlet; Rosenstock, Charlotte Valentin; Wetterslev, Jørn

    2013-01-01

    -specific assessment. Data from patients' pre-operative airway assessment are registered in the Danish Anaesthesia Database. Objective scores for intubation and mask ventilation grade the severity of airway managements. The accuracy of predicting difficult intubation and mask ventilation is measured for each group...... the examination and registration of predictors for difficult mask ventilation with a non-specified clinical airway assessment on prediction of difficult mask ventilation.Method/Design: We cluster-randomized 28 Danish departments of anaesthesia to airway assessment either by the SARI or by usual non...... that registration of the SARI and predictors for difficult mask ventilation are mandatory for the intervention group but invisible to controls....

  16. Ventilation via the 2.4 mm internal diameter Tritube® with cuff – new possibilities in airway management

    DEFF Research Database (Denmark)

    Kristensen, M S; de Wolf, M W P; Rasmussen, L S

    2017-01-01

    BACKGROUND: A small tube may facilitate tracheal intubation and improve surgical access. We describe our initial experience with the Tritube®that is a novel cuffed endotracheal tube with a 2.4 mm internal diameter. METHODS: The Tritube®was used in seven adult Ear-Nose-and Throat surgical patients...... of the intubated airway during oral, pharyngeal, laryngeal or tracheal procedures in adults. This technique has the potential to replace temporary tracheostomy, jet-ventilation or extra-corporal membrane oxygenation in selected patients....

  17. Lentiviral Vector Gene Transfer to Porcine Airways

    Directory of Open Access Journals (Sweden)

    Patrick L Sinn

    2012-01-01

    Full Text Available In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE. Interestingly, feline immunodeficiency virus (FIV-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1–based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF.

  18. Influence of x-irradiation on pharyngeal induction in the Planarian, Dugesia japonica japonica

    International Nuclear Information System (INIS)

    Asai, Etsuo

    1980-01-01

    Pharyngeal formation was examined in cases where normal or X-irradiated head pieces were transplanted into the postpharyngeal region of normal or irradiated worms. Transplantation experiments were carried out in four different combinations of hosts and grafts: (1) normal host and graft (control), (2) normal host and irradiated graft, (3) irradiated host and normal graft, (4) irradiated host and graft. In the first experiment, well developed pharynges were formed in the areas both anterior and posterior to the graft on the 14th day after transplantation. In the second experiment, formation of new pharynges was delayed compared with that in the first group. In the third experiment, only one pharynx developed in the area posterior to each graft in most cases. In the last experiment, no new pharynx appeared at all. From these results, the influence of X-rays on factors participating in pharyngeal induction was discussed. (author)

  19. Location of the levator veli palatini insertion following levator retropositioning, palatal pushback, and pharyngeal flap procedures.

    Science.gov (United States)

    Mulliken, J B; Giargiana, F A; Claybaugh, G J; Hoopes, J E

    1975-07-01

    A long-term cineradiographic follow-up study of twenty patients with velo-pharyngeal incompetence fails to demonstrate predictable retrodisplacement of the levator insertion following combined levator retropositioning, pushback, and pharyngeal flap procedures. Simple levator retropositioning gave posterior displacement in the two patients evaluated. Patients with normal or posterior levator insertions pre-operatively all demonstrated post-operative anterior displacement following pharyngeal flap procedures, either alone or in combination with pushback. Anterior levator displacement may be the result of scar contraction or division of the levator sling (during insetting of a pharyngeal flap). Pre-operative and post-operative speech evaluation demonstrated substantial improvement in all except 3 patients; 2 of the poor speech results were patients with demonstrated levator retrodisplacement on post-operative cineradiography.

  20. Fatal verminous pharyngitis and esophagitis caused by Streptocara incognita in mute swans (Cygnus olor).

    Science.gov (United States)

    Alić, A; Prasović, S; Hodzić, A; Besirović, H; Residbegović, Emina; Omeragić, J

    2013-03-01

    Streptocara spp. infections are reported to cause gastritis, proventriculitis, esophagitis, and pharyngitis in various waterfowls, especially diving ducks. In the present paper, we describe severe fatal diphtheritic pharyngitis and esophagitis caused by Streptocara incognita in three female mute swans (Cygnus olor) in Bosnia and Herzegovina. Prior to death, the swans were showing signs of lethargy, anorexia, and reluctance to move. At necropsy, in all swans severe diphtheritic pharyngitis and esophagitis with deep, dark red hemorrhagic ulcerations were observed. Numerous thin, white, up to 1-cm-long nematodes, identified as S. incognita, were observed embedded in the pharyngeal and esophageal mucosa under the diphtheritic membranes. Histopathology revealed severe fibrinonecrotic inflammation with numerous cross-sections of the parasites. To the authors' knowledge, this is the first report of severe, fatal streptocariasis in mute swans.

  1. Oral Cavity, Pharyngeal, and Laryngeal Cancer Prevention (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about factors that may influence the risk of developing oral cavity, pharyngeal, and laryngeal cancers and about approaches that may help in the prevention of these diseases.

  2. Prevalence of Beta-Hemolytic Streptococci Groups A, C, and G in Patients with Acute Pharyngitis

    Directory of Open Access Journals (Sweden)

    Trupti B Naik

    2016-01-01

    Conclusions: Although rate of pharyngitis associated with GCS and GGS is marginally lower than GAS, their carriage rate among healthy and relative higher drug resistance emphasizes the need for periodic surveillance of infection by the different serogroups of BHS.

  3. [Analysis of the characteristic of pharyngeal paraesthesia patients by high resolution manometry].

    Science.gov (United States)

    Gu, Yun; Qian, Wei

    2015-09-01

    To discuss the pressure changing characteristics of upper esophageal sphincter (UES), lower esophageal sphincter (LES) and the esophagus kinetic characteristics of pharyngeal paraesthesia patients. To take high resolution manometry in 44 cases of pharyngeal paraesthesia patients and 23 normal subjects separately. According to the RSI score,the 44 patients were divided into group A (the group without reflux, RSI 0.05). The esophagus DCI of group B was lower than that of group A and control group (P 0.05). The pharyngeal paresthesia symptoms of'patients was associated with the increasing of UES pressure. The pharyngeal paresthesia symptoms of group with reflux was related to low pressure of LES and high pressure of UES. The last part of esophagus of group with reflux had obstacles in powers, which weaken the peristalsis and declined the ability to clear the bolus and gastric reflux material.

  4. Rhinosinusitis and the lower airways

    NARCIS (Netherlands)

    Hellings, Peter W.; Hens, Greet

    2009-01-01

    The interaction between upper and lower airway disease has been recognized for centuries, with recent studies showing a direct link between upper and airway inflammation in allergic patients. The mechanisms underlying the interaction between nasal and bronchial inflammation have primarily been

  5. Anaesthesia and subglottic airway obstruction

    African Journals Online (AJOL)

    2009-07-14

    Jul 14, 2009 ... Introduction. Surgery on the upper airway remains challenging for both surgeon and ... from her upper airway obstruction rather than asthma.1 She had made a long ... patient was well oxygenated with oxygen saturation above. 95%. .... Difficulties relate to tidal volume measurement, CO2 detection and the.

  6. Experimental otitis media with effusion induced by electron beam irradiation to pharyngeal orifice of auditory tube in guinea pig

    International Nuclear Information System (INIS)

    Kokubu, Michiyo; Amatsu, Mutsuo

    1984-01-01

    The purpose of the present study was to obtain a more natural tubal insufficiency than that obtained by the conventional methods to clarify the middle ear pathology associated with tubal dysfunction. For this purpose, the pharyngeal orifice of the auditory tube in the guinea pigs was irradiated with electron beam with a dose of 2,000 rad following the preliminary experiments to determine the appropriate dose. The guinea pigs with intact drum and normal Pryer reflex were used for the present experiment series. A specially devised apparatus was used for avoiding the dipersing beam. Histopathological changes of the middle ear and auditory tube were observed in a series of single specimen with H-E staining 1, 2, 3, 6, 12 months after irradiation. In this study, middle ear with effusion was used to clarify the dynamic process of the pathological changes between the auditory tube and the middle ear. In summary, the present study revealed that the electron beam irradiation to the pharyngeal orifice caused various grades of otitis media with effusion which could be classified into three groups. Of these groups 1) and 2), 3) were likely to be corresponding with so-called serous and purulent otitis media with effusion in human respectively. Infection due to the malfunction caused by the epithelial damage of the auditory tube was an important promoting factor to change the serous type effusion for the purulent type effusion. (J.P.N.)

  7. Pharyngeal Residue Severity Rating Scales Based on Fiberoptic Endoscopic Evaluation of Swallowing: A Systematic Review.

    Science.gov (United States)

    Neubauer, Paul D; Hersey, Denise P; Leder, Steven B

    2016-06-01

    Identification of pharyngeal residue severity located in the valleculae and pyriform sinuses has always been a primary goal during fiberoptic endoscopic evaluation of swallowing (FEES). Pharyngeal residue is a clinical sign of potential prandial aspiration making an accurate description of its severity an important but difficult challenge. A reliable, validated, and generalizable pharyngeal residue severity rating scale for FEES would be beneficial. A systematic review of the published English language literature since 1995 was conducted to determine the quality of existing pharyngeal residue severity rating scales based on FEES. Databases were searched using controlled vocabulary words and synonymous free text words for topics of interest (deglutition disorders, pharyngeal residue, endoscopy, videofluoroscopy, fiberoptic technology, aspiration, etc.) and outcomes of interest (scores, scales, grades, tests, FEES, etc.). Search strategies were adjusted for syntax appropriate for each database/platform. Data sources included MEDLINE (OvidSP 1946-April Week 3 2015), Embase (OvidSP 1974-2015 April 20), Scopus (Elsevier), and the unindexed material in PubMed (NLM/NIH) were searched for relevant articles. Supplementary efforts to identify studies included checking reference lists of articles retrieved. Scales were compared using qualitative properties (sample size, severity definitions, number of raters, and raters' experience and training) and psychometric analyses (randomization, intra- and inter-rater reliability, and construct validity). Seven articles describing pharyngeal residue severity rating scales met inclusion criteria. Six of seven scales had insufficient data to support their use as evidenced by methodological weaknesses with both qualitative properties and psychometric analyses. There is a need for qualitative and psychometrically reliable, validated, and generalizable pharyngeal residue severity rating scales that are anatomically specific, image

  8. The relationship between pharyngeal morphology measured with cone-beam computed tomography and maxillary morphology measured by lateral cephalogram

    International Nuclear Information System (INIS)

    Yamaguchi, Fumie; Yamaguchi, Tetsutaro; Miyamoto, Asami; Maki, Koutaro

    2007-01-01

    This study examined the relationship between pharyngeal morphology measured with cone-beam computed tomography (CBCT) and maxillary morphology measured from lateral cephalograms. The subjects comprised 45 women, with a mean age of 27.9 years (range, 16-50 years), who attended the Department of Orthodontics at Showa University. The evaluation of pharyngeal morphology was based on 9 variables measured by CBCT: pharyngeal space volume, pharyngeal vertical length, pharyngeal sagittal length, pharyngeal coronal length, epiglottis length, epiglottis width, the distance from the genion to the hyoidale, the distance from the hyoidale to the aditus larynges base, and the distance from the aditus larynges base to the genion. Maxillary morphology was evaluated from 5 measured sites: SNA, S'-Ptm', A'-Ptm', the occiusal plane angle, and the palatal plane angle. Pearson's correlation coefficient was used to detect associations between pharyngeal and maxillary morphological variables. There were significant correlations between pharyngeal coronal length and SNA, the distance from the genion to the hyoidale and the occlusal plane angle, pharyngeal coronal length and A'-Ptm', pharyngeal vertical length and the palatal plane angle, as well as the aditus larynges base to the genion and the occlusal plane. This information has potential clinical value for better understanding obstructive sleep apnea in adult patients, and for structurally based treatments such as surgical orthodontics. (author)

  9. Relapsing polychondritis and airway involvement.

    Science.gov (United States)

    Ernst, Armin; Rafeq, Samaan; Boiselle, Phillip; Sung, Arthur; Reddy, Chakravarthy; Michaud, Gaetane; Majid, Adnan; Herth, Felix J F; Trentham, David

    2009-04-01

    To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

  10. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.

    Science.gov (United States)

    Dong, Qian; Ernst, Sarah E; Ostedgaard, Lynda S; Shah, Viral S; Ver Heul, Amanda R; Welsh, Michael J; Randak, Christoph O

    2015-05-29

    The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P(1),P(5)-di(adenosine-5') pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5'-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5'-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl(-) channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Automated method for structural segmentation of nasal airways based on cone beam computed tomography

    Science.gov (United States)

    Tymkovych, Maksym Yu.; Avrunin, Oleg G.; Paliy, Victor G.; Filzow, Maksim; Gryshkov, Oleksandr; Glasmacher, Birgit; Omiotek, Zbigniew; DzierŻak, RóŻa; Smailova, Saule; Kozbekova, Ainur

    2017-08-01

    The work is dedicated to the segmentation problem of human nasal airways using Cone Beam Computed Tomography. During research, we propose a specialized approach of structured segmentation of nasal airways. That approach use spatial information, symmetrisation of the structures. The proposed stages can be used for construction a virtual three dimensional model of nasal airways and for production full-scale personalized atlases. During research we build the virtual model of nasal airways, which can be used for construction specialized medical atlases and aerodynamics researches.

  12. Evidence of a true pharyngeal tonsil in birds: a novel lymphoid organ in Dromaius novaehollandiae and Struthio camelus (Palaeognathae

    Directory of Open Access Journals (Sweden)

    Crole Martina R

    2012-08-01

    Full Text Available Abstract Background Tonsils are secondary lymphoid organs located in the naso- and oropharynx of most mammalian species. Most tonsils are characterised by crypts surrounded by dense lymphoid tissue. However, tonsils without crypts have also been recognised. Gut-associated lymphoid tissue (GALT, although not well-organised and lacking tonsillar crypts, is abundant in the avian oropharynx and has been referred to as the “pharyngeal tonsil”. In this context the pharyngeal folds present in the oropharynx of ratites have erroneously been named the pharyngeal tonsils. This study distinguishes between the different types and arrangements of lymphoid tissue in the pharyngeal region of D. novaehollandiae and S. camelus and demonstrates that both species possess a true pharyngeal tonsil which fits the classical definition of tonsils in mammals. Results The pharyngeal tonsil (Tonsilla pharyngea of D. novaehollandiae was located on the dorsal free surface of the pharyngeal folds and covered by a small caudo-lateral extension of the folds whereas in S. camelus the tonsil was similarly located on the dorsal surface of the pharyngeal folds but was positioned retropharyngeally and encapsulated by loose connective tissue. The pharyngeal tonsil in both species was composed of lymph nodules, inter-nodular lymphoid tissue, mucus glands, crypts and intervening connective tissue septa. In S. camelus a shallow tonsillar sinus was present. Aggregated lymph nodules and inter-nodular lymphoid tissue was associated with the mucus glands on the ventral surface of the pharyngeal folds in both species and represented the Lymphonoduli pharyngeales. Similar lymphoid tissue, but more densely packed and situated directly below the epithelium, was present on the dorsal, free surface of the pharyngeal folds and represented a small, non-follicular tonsil. Conclusions The follicular pharyngeal tonsils in D. novaehollandiae and S. camelus are distinct from the pharyngeal folds in

  13. Three dimensional Cone Beam Computed Tomography Study of Pharyngeal Airway Dimensions in Different Anteroposterior Skeletal Classification Patients

    Science.gov (United States)

    2015-07-10

    CBCT Technology 7. Intended publication/meeting: Requirement for Masters in Oral Biology 8. "Required by" date: 01Jul15 9. Date of submission for...compared to Class I patients10. They divided 45 children into Class I and Class III groups. Class III patients had larger and flatter oropharyngeal...who had soft tissue pathology detected in the scans or their medical history, previous Orthognathic surgery, or a syndrome diagnosis were excluded

  14. Physiologic correlates of airspace size and airway remodeling in the smoke exposed guinea pig model

    NARCIS (Netherlands)

    Wright, J. L.; Postma, D. S.; Kerstjens, H. A. M.; Timens, W.; Whittaker, P.; Churg, A.

    2007-01-01

    Although small airway remodeling (SAR) leading to airflow obstruction is a common consequence of human cigarette smoking, the airways have been largely ignored in animal models of chronic obstructive pulmonary disease ( COPD). We examined lung structure in a guinea pig model of chronic cigarette

  15. Airway necrosis after salvage esophagectomy

    International Nuclear Information System (INIS)

    Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

    2010-01-01

    Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

  16. THE BUFFER CAPACITY OF AIRWAY EPITHELIAL SECRETIONS

    Directory of Open Access Journals (Sweden)

    Dusik eKim

    2014-06-01

    Full Text Available The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF. The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 µl volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO3- is the major buffer. Peak buffer capacity (β increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO3- secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO3- secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions.

  17. Airway fibroepithelial polyposis

    Directory of Open Access Journals (Sweden)

    Gonzalo Labarca

    2017-01-01

    Full Text Available Fibroepithelial polyps are benign lesions, frequently found in the skin and genitourinary tract. Airway involvement is rare, and few case reports have been published. Our patient was a 79 y.o. male smoker, who was referred to us with a 3-month history of dry cough. At physical examination, the patient looked well, but a chest CT showed a 6-mm polyp lesion in his trachea. A flexible bronchoscopy confirmed this lesion, and forceps biopsies were performed. Argon plasma coagulation was used to completely resect and treat the lesion. Pathological analysis revealed a fibroepithelial polyp (FP. The aim of this manuscript is to report a case of FP with bronchoscopic management and to review the current literature about this condition.

  18. Do Dysphagic Patients with an Absent Pharyngeal Swallow Have a Shorter Survival than Dysphagic Patients with Pharyngeal Swallow? Prognostic Importance of a Therapeutic Videoradiographic Swallowing Study (TVSS)

    International Nuclear Information System (INIS)

    Buelow, M.; Olsson, R.; Ekberg, O.

    2005-01-01

    Purpose: To study survival in two groups of dysphagic patients - one group unable to elicit the pharyngeal stage of swallow (APS) and another group with pharyngeal swallow (WPS) - and to compare recommendations regarding nutrition and therapeutic strategies based on the therapeutic swallowing study. Material and Methods: In this retrospective study, the records of dysphagic patients who have undergone a therapeutic videoradiographic swallowing study (TVSS) were reviewed. Forty patients without pharyngeal swallow were matched for age and gender with 40 patients with pharyngeal swallow; altogether 80 patients were included in the study. Survival was registered at 3, 12, and 72 months after the TVSS. Results: In this study, the APS group had a significantly shorter survival time compared to the WPS group when followed-up at 12 months. In the APS group, most patients (37.5% (15/40)) died within the 3 months after TVSS. At 72 months, 62.5% (25/40) of the patients in the APS group had died. In the WPS group, 5% (2/40) had died within 3 months and 47.4% (19/40) after 12 months. At 72 months, 52.5% (21/40) of the patients in the WPS group had died. Regarding nutritional and therapeutic recommendations based on TVSS, 34/40 in the APS group were recommended no oral intake. Eighteen naso-gastric tubes were placed directly after TVSS. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, and tongue exercises (in 8 patients). In the WPS group, all patients were recommended oral intake. Diet modification was recommended in 29 patients. The therapeutic strategies recommended were head-positioning, thermal tactile stimulation, tongue exercises, supraglottic swallow, and effortful swallow (in 24 patients). Conclusion: Patients unable to elicit the pharyngeal stage of swallow had a shorter survival time than patients with pharyngeal swallow, probably due to a more severe underlying disease. Tube feeding was more frequent in the APS group. Fewer

  19. Effects of Laser Printer-Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts.

    Science.gov (United States)

    Pirela, Sandra V; Miousse, Isabelle R; Lu, Xiaoyan; Castranova, Vincent; Thomas, Treye; Qian, Yong; Bello, Dhimiter; Kobzik, Lester; Koturbash, Igor; Demokritou, Philip

    2016-02-01

    Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing. We assessed the biological responses of a panel of human cell lines to PEPs. Three physiologically relevant cell lines--small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)--were exposed to PEPs at a wide range of doses (0.5-100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure. The in vitro findings obtained in this study suggest that laser printer-emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders.

  20. Posterior pharyngeal candidiasis in the absence of clinically overt oral involvement: a cross-sectional study.

    Science.gov (United States)

    Glavey, Siobhan V; Keane, Niamh; Power, Maria; O'Regan, Anthony W

    2013-12-01

    Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. Median age was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS, and 20 % of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at

  1. Therapeutic CPAP Level Predicts Upper Airway Collapsibility in Patients With Obstructive Sleep Apnea.

    Science.gov (United States)

    Landry, Shane A; Joosten, Simon A; Eckert, Danny J; Jordan, Amy S; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A

    2017-06-01

    Upper airway collapsibility is a key determinant of obstructive sleep apnea (OSA) which can influence the efficacy of certain non-continuous positive airway pressure (CPAP) treatments for OSA. However, there is no simple way to measure this variable clinically. The present study aimed to develop a clinically implementable tool to evaluate the collapsibility of a patient's upper airway. Collapsibility, as characterized by the passive pharyngeal critical closing pressure (Pcrit), was measured in 46 patients with OSA. Associations were investigated between Pcrit and data extracted from patient history and routine polysomnography, including CPAP titration. Therapeutic CPAP level, demonstrated the strongest relationship to Pcrit (r2=0.51, p CPAP level (6.2 ± 0.6 vs. 10.3 ± 0.4 cmH2O, p -2 cmH2O). A therapeutic CPAP level ≤8.0 cmH2O was sensitive (89%) and specific (84%) for detecting a mildly collapsible upper airway. When applied to the independent validation data set (n = 74), this threshold maintained high specificity (91%) but reduced sensitivity (75%). Our data demonstrate that a patient's therapeutic CPAP requirement shares a strong predictive relationship with their Pcrit and may be used to accurately differentiate OSA patients with mild airway collapsibility from those with moderate-to-severe collapsibility. Although this relationship needs to be confirmed prospectively, our findings may provide clinicians with better understanding of an individual patient's OSA phenotype, which ultimately could assist in determining which patients are most likely to respond to non-CPAP therapies. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  2. The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease.

    Science.gov (United States)

    Martin, J G; Duguet, A; Eidelman, D H

    2000-08-01

    Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass. Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM. Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined.

  3. Stenting of major airway constriction

    International Nuclear Information System (INIS)

    Wu Xiaomei

    2002-01-01

    Objective: To investigate the correlated issues in the stenting treatment of major airway constriction. Methods: Nineteen cases of major airway stenting procedure were studied retrospectively. The clinical choice of stents of different advantages or deficiencies were discussed. The importance of intravenous anesthesia supporting, life-parameters monitoring during the procedures and the prevention of complications were analysed. Results: Under intravenous and local anesthesia, 19 Wallstents had been successively placed and relieved 19 cases of major airway constrictions due to malignant or benign diseases (15 of tumors, 3 of tuberculosis, 1 of tracheomalacia). Intravenous anesthesia and life-parameters monitoring had made the procedures more safe and precise. Conclusions: Major airway stenting is an reliable method for relieving tracheobronchial stenosis; and intravenous anesthesia supporting and life-parameters monitoring guarantee the satisfactions of procedures

  4. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S

    2010-01-01

    Morbidly obese patients present with excess fatty tissue externally on the breast, neck, thoracic wall and abdomen and internally in the mouth, pharynx and abdomen. This excess tissue tends to make access (intubation, tracheostomy) to and patency (during sedation or mask ventilation) of the upper...... in morbidly obese patients and should be followed by actions to counteract atelectasis formation. The decision as to weather to use a rapid sequence induction, an awake intubation or a standard induction with hypnotics should depend on the thorough airway examination and comorbidity and should not be based...... solely on whether morbid obesity is present or not. It is important to ensure sufficient depth of anaesthesia before initiating manipulation of the airway because inadequate anaesthesia depth predisposes to aspiration if airway management becomes difficult. The intubating laryngeal mask airway is more...

  5. Evolutionary trends of the pharyngeal dentition in Cypriniformes (Actinopterygii: Ostariophysi.

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    Emmanuel Pasco-Viel

    Full Text Available BACKGROUND: The fish order Cypriniformes is one of the most diverse ray-finned fish groups in the world with more than 3000 recognized species. Cypriniformes are characterized by a striking distribution of their dentition: namely the absence of oral teeth and presence of pharyngeal teeth on the last gill arch (fifth ceratobranchial. Despite this limited localisation, the diversity of tooth patterns in Cypriniformes is astonishing. Here we provide a further description of this diversity using X-ray microtomography and we map the resulting dental characters on a phylogenetic tree to explore evolutionary trends. RESULTS: We performed a pilot survey of dental formulae and individual tooth shapes in 34 adult species of Cypriniformes by X-ray microtomography (using either conventional X-ray machine, or synchrotron microtomography when necessary or by dissecting. By mapping morphological results in a phylogenetic tree, it emerges that the two super-families Cobitoidea and Cyprinoidea have followed two distinct evolutionary pathways. Furthermore, our analysis supports the hypothesis of a three-row dentition as ancestral for Cyprinoidea and a general trend in tooth row reduction in most derived lineages. Yet, this general scheme must be considered with caution as several events of tooth row gain and loss have occurred during evolutionary history of Cyprinoidea. SIGNIFICANCE: Dentition diversity in Cypriniformes constitutes an excellent model to study the evolution of complex morphological structures. This morphological survey clearly advocates for extending the use of X-ray microtomography to study tooth morphology in Cypriniformes. Yet, our survey also underlines that improved knowledge of Cypriniformes life traits, such as feeding habits, is required as current knowledge is not sufficient to conclude on the link between diet and dental morphology.

  6. Pharyngeal Electrical Stimulation for Treatment of Dysphagia in Subacute Stroke

    Science.gov (United States)

    Scutt, Polly; Love, Jo; Clavé, Pere; Cohen, David; Dziewas, Rainer; Iversen, Helle K.; Ledl, Christian; Ragab, Suzanne; Soda, Hassan; Warusevitane, Anushka; Woisard, Virginie; Hamdy, Shaheen

    2016-01-01

    Background and Purpose— Dysphagia is common after stroke, associated with increased death and dependency, and treatment options are limited. Pharyngeal electric stimulation (PES) is a novel treatment for poststroke dysphagia that has shown promise in 3 pilot randomized controlled trials. Methods— We randomly assigned 162 patients with a recent ischemic or hemorrhagic stroke and dysphagia, defined as a penetration aspiration score (PAS) of ≥3 on video fluoroscopy, to PES or sham treatment given on 3 consecutive days. The primary outcome was swallowing safety, assessed using the PAS, at 2 weeks. Secondary outcomes included dysphagia severity, function, quality of life, and serious adverse events at 6 and 12 weeks. Results— In randomized patients, the mean age was 74 years, male 58%, ischemic stroke 89%, and PAS 4.8. The mean treatment current was 14.8 (7.9) mA and duration 9.9 (1.2) minutes per session. On the basis of previous data, 45 patients (58.4%) randomized to PES seemed to receive suboptimal stimulation. The PAS at 2 weeks, adjusted for baseline, did not differ between the randomized groups: PES 3.7 (2.0) versus sham 3.6 (1.9), P=0.60. Similarly, the secondary outcomes did not differ, including clinical swallowing and functional outcome. No serious adverse device-related events occurred. Conclusions— In patients with subacute stroke and dysphagia, PES was safe but did not improve dysphagia. Undertreatment of patients receiving PES may have contributed to the neutral result. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN25681641. PMID:27165955

  7. A three-microphone acoustic reflection technique using transmitted acoustic waves in the airway.

    Science.gov (United States)

    Fujimoto, Yuki; Huang, Jyongsu; Fukunaga, Toshiharu; Kato, Ryo; Higashino, Mari; Shinomiya, Shohei; Kitadate, Shoko; Takahara, Yutaka; Yamaya, Atsuyo; Saito, Masatoshi; Kobayashi, Makoto; Kojima, Koji; Oikawa, Taku; Nakagawa, Ken; Tsuchihara, Katsuma; Iguchi, Masaharu; Takahashi, Masakatsu; Mizuno, Shiro; Osanai, Kazuhiro; Toga, Hirohisa

    2013-10-15

    The acoustic reflection technique noninvasively measures airway cross-sectional area vs. distance functions and uses a wave tube with a constant cross-sectional area to separate incidental and reflected waves introduced into the mouth or nostril. The accuracy of estimated cross-sectional areas gets worse in the deeper distances due to the nature of marching algorithms, i.e., errors of the estimated areas in the closer distances accumulate to those in the further distances. Here we present a new technique of acoustic reflection from measuring transmitted acoustic waves in the airway with three microphones and without employing a wave tube. Using miniaturized microphones mounted on a catheter, we estimated reflection coefficients among the microphones and separated incidental and reflected waves. A model study showed that the estimated cross-sectional area vs. distance function was coincident with the conventional two-microphone method, and it did not change with altered cross-sectional areas at the microphone position, although the estimated cross-sectional areas are relative values to that at the microphone position. The pharyngeal cross-sectional areas including retropalatal and retroglossal regions and the closing site during sleep was visualized in patients with obstructive sleep apnea. The method can be applicable to larger or smaller bronchi to evaluate the airspace and function in these localized airways.

  8. A hybrid method for airway segmentation and automated measurement of bronchial wall thickness on CT.

    Science.gov (United States)

    Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mansoor, Awais; Udupa, Jayaram K; Mollura, Daniel J

    2015-08-01

    Inflammatory and infectious lung diseases commonly involve bronchial airway structures and morphology, and these abnormalities are often analyzed non-invasively through high resolution computed tomography (CT) scans. Assessing airway wall surfaces and the lumen are of great importance for diagnosing pulmonary diseases. However, obtaining high accuracy from a complete 3-D airway tree structure can be quite challenging. The airway tree structure has spiculated shapes with multiple branches and bifurcation points as opposed to solid single organ or tumor segmentation tasks in other applications, hence, it is complex for manual segmentation as compared with other tasks. For computerized methods, a fundamental challenge in airway tree segmentation is the highly variable intensity levels in the lumen area, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. Moreover, outer wall definition can be difficult due to similar intensities of the airway walls and nearby structures such as vessels. In this paper, we propose a computational framework to accurately quantify airways through (i) a novel hybrid approach for precise segmentation of the lumen, and (ii) two novel methods (a spatially constrained Markov random walk method (pseudo 3-D) and a relative fuzzy connectedness method (3-D)) to estimate the airway wall thickness. We evaluate the performance of our proposed methods in comparison with mostly used algorithms using human chest CT images. Our results demonstrate that, on publicly available data sets and using standard evaluation criteria, the proposed airway segmentation method is accurate and efficient as compared with the state-of-the-art methods, and the airway wall estimation algorithms identified the inner and outer airway surfaces more accurately than the most widely applied methods, namely full width at half maximum and phase congruency. Copyright © 2015. Published by Elsevier B.V.

  9. Empirical validation of Polish guidelines for the management of acute streptococcal pharyngitis in children.

    Science.gov (United States)

    Mazur, Elżbieta; Bochyńska, Ewa; Juda, Marek; Kozioł-Montewka, Maria

    2014-01-01

    Group A Streptococcus (GAS) pharyngitis is currently the only commonly occurring form of acute pharyngitis for which antibiotic therapy is definitely indicated. Polish guidelines advocate the use of modified Centor score (MCS) to assess the probability of GAS pharyngitis. They advise performing throat culture or rapid antigen detection test (RADT) in children with score 2-3 in MCS and treating with antibiotic only those in whom GAS was detected. Negative RADT results should be confirmed by culture. In children with score 4, the guidelines allow to introduce empiric antibiotic therapy. Phenoxymethyl penicillin is recommended as a drug of choice to treat GAS pharyngitis. The aim of our study was to evaluate the accuracy of strategy recommended by Polish guidelines in identifying those children with acute pharyngitis who require antibiotic treatment. Hence, diagnostic values of score 4 in MCS and RADT were assessed using throat culture as a reference standard. Phenoxymethyl penicillin efficacy in GAS eradication and prevention of post-streptococcal complications were estimated as well. Ninety children between 2 and 15 years of age with acute pharyngitis symptoms suggesting GAS etiology (MCS ≥ 2), participated in our study. At the initial visit MCS was evaluated and two throat swabs were collected to perform RADT and culture. In children with GAS pharyngitis treated with penicillin, microbiological cure was assessed by performing two control throat cultures. Next, children were under observation for 3 months. Positive predictive value of score 4 in MCS turned out to be 48.05% (95% CI: 36.5-59.7%). RADT sensitivity, specificity and diagnostic accuracy proved to be 100%, 96%, and 98%, respectively. GAS eradication rate in children treated with penicillin turned out to be 92.5%. No post-streptococcal sequelae occurred in any child in 3-month observation. Empiric antibiotic therapy in children with score 4 in MCS will result in significant overtreatment of those with

  10. Computational Analysis of Pharyngeal Swallowing Mechanics in Patients with Motor Neuron Disease: A Pilot Investigation.

    Science.gov (United States)

    Garand, K L; Schwertner, Ryan; Chen, Amy; Pearson, William G

    2018-04-01

    Swallowing impairment (dysphagia) is a common sequela in patients with motor neuron disease (MND). The purpose of this retrospective, observational pilot investigation was to characterize how pharyngeal swallowing mechanics are impacted in patients with MND using a comparison with healthy, non-dysphagic control group. Computational analysis of swallowing mechanics (CASM) was used to determine covariate biomechanics of pharyngeal swallowing from videofluoroscopic assessment in 15 patients with MND and 15 age- and sex-matched healthy controls. Canonical variant analysis with post hoc discriminate function analysis (DFA) was performed on coordinate data mapping functional muscle groups underlying pharyngeal swallowing. Differences in swallowing mechanics associated with group (MND; control), motor neuron predominance (upper; lower), onset (bulbar; spinal), and swallow task (thin, pudding) were evaluated and visualized. Pharyngeal swallowing mechanics differed significantly in patients with MND compared with healthy controls (D = 2.01, p mechanics by motor neuron predominance (D = 5.03, p mechanics of patients with MND differ from and are more heterogeneous than healthy controls. These findings suggest patients with MND may compensate reductions in pharyngeal shortening and tongue base retraction by extending the head and neck and increasing hyolaryngeal excursion. This work and further CASM investigations will lead to further insights into development and evaluation of targeted clinical treatments designed to prolong safe and efficient swallowing function in patients with MND.

  11. INFLUENCE OF PASSIVE SMOKING ON CONTENT OF NICKEL IN CHILDREN PHARYNGEAL TONSILS

    Directory of Open Access Journals (Sweden)

    Jerzy Kwapuliński

    2010-09-01

    Full Text Available Subject of this study was pharyngeal tonsils which his anatomic location is interesing tissue. They are first tissue which has contact content in air inhalation substances in selective way. Pharyngeal tonsils came from children who lived in Silesia province. Some of these children have been expose to passive smoking. Contains nickel in pharyngeal tonsils was marked by the method of Inductively Coupled Plasma. Geometrical mean of contents of nickel in pharyngeal tonsils from exposed to tobacco smoke girls was 0,75 µg/g, in unexposed girls was 0,67 µg/g, in exposed to tobacco smoke boys was 0,55 µg/g and unexposed boys 0,6 µg/g was observed. The results have verified that sex, living place and exposure to tobacco smoke matter in accumulation nickel in pharyngeal tonsils. The cross-corelation analysis between content of Ni and other metals, found out positive corelation between Ni and Al, Cd, Cu, Pb, Zn, Ca, Mg.

  12. Introducing a Virtual Lesion Model of Dysphagia Resulting from Pharyngeal Sensory Impairment

    Directory of Open Access Journals (Sweden)

    Paul Muhle

    2018-01-01

    Full Text Available Background/Aims: Performing neurophysiological and functional imaging studies in severely affected patients to investigate novel neurostimulation techniques for the treatment of neurogenic dysphagia is difficult. Therefore, basic research needs to be conducted in healthy subjects. Swallowing is a motor function highly dependent on sensory afferent input. Here we propose a virtual peripheral sensory lesion model to mimic pharyngeal sensory impairment, which is known as a major contributor to dysphagia in neurological disease. Methods: In this randomized crossover study on 11 healthy volunteers, cortical activation during pneumatic pharyngeal stimulation was measured applying magnetoencephalography in two separate sessions, with and without pharyngeal surface anesthesia. Results: Stimulation evoked bilateral event-related desynchronization (ERD mainly in the caudolateral pericentral cortex. In comparison to the no-anesthesia condition, topical anesthesia led to a reduction of ERD in beta (13-30 Hz and low gamma (30-60 Hz frequency ranges (p<0.05 in sensory but also motor cortical areas. Conclusions: Withdrawal of sensory afferent information by topical anesthesia leads to reduced response to pneumatic pharyngeal stimulation in a distributed cortical sensorimotor network in healthy subjects. The proposed paradigm may serve to investigate the effect of neuromodulatory treatments specifically on pharyngeal sensory impairment as relevant cause of neurogenic dysphagia.

  13. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

    Directory of Open Access Journals (Sweden)

    Sonia R Rosner

    Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

  14. Upper airway resistance syndrome.

    Science.gov (United States)

    Montserrat, J M; Badia, J R

    1999-03-01

    This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

  15. Bioelectric and Morphological Response of Liquid-Covered Human Airway Epithelial Calu-3 Cell Monolayer to Periodic Deposition of Colloidal 3-Mercaptopropionic-Acid Coated CdSe-CdS/ZnS Core-Multishell Quantum Dots.

    Directory of Open Access Journals (Sweden)

    Aizat Turdalieva

    Full Text Available Lung epithelial cells are extensively exposed to nanoparticles present in the modern urban environment. Nanoparticles, including colloidal quantum dots (QDs, are also considered to be potentially useful carriers for the delivery of drugs into the body. It is therefore important to understand the ways of distribution and the effects of the various types of nanoparticles in the lung epithelium. We use a model system of liquid-covered human airway epithelial Calu-3 cell cultures to study the immediate and long-term effects of repeated deposition of colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs on the lung epithelial cell surface. By live confocal microscope imaging and by QD fluorescence measurements we show that the QD permeation through the mature epithelial monolayers is very limited. At the time of QD deposition, the transepithelial electrical resistance (TEER of the epithelial monolayers transiently decreased, with the decrement being proportional to the QD dose. Repeated QD deposition, once every six days for two months, lead to accumulation of only small amounts of the QDs in the cell monolayer. However, it did not induce any noticeable changes in the long-term TEER and the molecular morphology of the cells. The colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs could therefore be potentially used for the delivery of drugs intended for the surface of the lung epithelia during limited treatment periods.

  16. Teaching the pharyngeal flap and sphincter pharyngoplasty: The sticky note method.

    Science.gov (United States)

    Lee, Jake J; Jabbour, Noel

    2015-11-01

    To demonstrate a cost-effective, quick, and easily reproducible three-dimensional sticky note model to enhance the understanding and conceptualization of the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty. The method involves making specified incisions and rearrangements of readily available components, including disposable clear plastic cups, yellow and pink sticky notes, and white paper. Once assembly is complete, further incisions and remodeling are performed to simulate a pharyngeal flap or sphincter pharyngoplasty. The cost of the materials to make one model was $0.94. Average construction time was less than 10 min. This three-dimensional model is an efficient, interactive, and simple visual aid to teach surgical trainees the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Molecular epidemiology of group A streptococcus from pharyngeal isolates in Auckland, New Zealand, 2013.

    Science.gov (United States)

    Williamson, Deborah A; Moreland, Nicole J; Carter, Philip; Upton, Arlo; Morgan, Julie; Proft, Thomas; Lennon, Diana; Baker, Michael G; Dunbar, Rod; Fraser, John D

    2014-01-24

    To describe the molecular epidemiology of emm types associated with circulating pharyngeal group A streptococcus (GAS) isolates in Auckland, New Zealand. GAS isolates were collected over a 10-day period from a community pathology provider in Auckland. PCR analysis and sequencing of the emm gene was performed at the Institute of Environmental Science and Research. A total of 52 emm types were identified from 278 GAS isolates. The three most common emm types were emm1, emm89 and emm12. Overall, the experimental 30-valent GAS M protein vaccine covered 19 / 52 (37%) of emm types in our study. Our study provides baseline data on the circulating pharyngeal GAS emm types in Auckland. Future clinical and molecular surveillance of GAS pharyngitis is essential in the context of ongoing GAS vaccine development.

  18. Efficacy of Surgical Airway Plasty for Benign Airway Stenosis.

    Science.gov (United States)

    Tsukioka, Takuma; Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

    2016-01-01

    Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh-Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty.

  19. Microbial ecology and adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Yang, Lei; Jelsbak, Lars; Molin, Søren

    2011-01-01

    Chronic infections in the respiratory tracts of cystic fibrosis (CF) patients are important to investigate, both from medical and from fundamental ecological points of view. Cystic fibrosis respiratory tracts can be described as natural environments harbouring persisting microbial communities...... constitute the selective forces that drive the evolution of the microbes after they migrate from the outer environment to human airways. Pseudomonas aeruginosa adapts to the new environment through genetic changes and exhibits a special lifestyle in chronic CF airways. Understanding the persistent...... colonization of microbial pathogens in CF patients in the context of ecology and evolution will expand our knowledge of the pathogenesis of chronic infections and improve therapeutic strategies....

  20. Persistence after treatment of pharyngeal gonococcal infections in patients of the STI clinic, Amsterdam, the Netherlands, 2012-2015: a retrospective cohort study

    NARCIS (Netherlands)

    Hananta, I. Putu Yuda; de Vries, Henry John Christiaan; van Dam, Alje P.; van Rooijen, Martijn Sebastiaan; Soebono, Hardyanto; Schim van der Loeff, Maarten Franciscus

    2017-01-01

    Infection of Neisseria gonorrhoeae in the pharynx (pharyngeal Ng) is associated with gonococcal transmission and development of antimicrobial resistance. We assessed proportion of and determinants for persistence after treatment of pharyngeal Ng. At the STI clinic of Amsterdam, the Netherlands,

  1. Spontaneous pharyngeal Chlamydia trachomatis RNA clearance. A cross-sectional study followed by a cohort study of untreated STI clinic patients in Amsterdam, The Netherlands

    NARCIS (Netherlands)

    van Rooijen, Martijn S.; van der Loeff, Maarten F. Schim; Morré, Servaas A.; van Dam, Alje P.; Speksnijder, Arjen G. C. L.; de Vries, Henry J. C.

    2015-01-01

    Objectives Pharyngeal Chlamydia trachomatis (chlamydia) might contribute to ongoing chlamydia transmission, yet data on spontaneous clearance duration are rare. We examined the prevalence, spontaneous clearance, chlamydial DNA concentration and genotypes of pharyngeal chlamydia among clinic patients

  2. Epidemiology of oral and pharyngeal cancers: A retrospective study in ‎Kermanshah, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zarei

    2016-05-01

    Full Text Available BACKGROUND AND AIM: The aim of this study was to determine the incidence and relative frequency of oral and pharyngeal cancers in Kermanshah, Iran, from March 1993 until March 2006. METHODS: The data used in this epidemiologic study were extracted directly from pathology records registered in 12 (all public and private pathology centers of Kermanshah province during the 13-year study period. The medical data of 13,323 cases of cancer were studied. RESULTS: During the 13-year period of this study, 350 new malignant cases occurred in the oral cavity and pharynx. 247 (70% were men and 103 (30% were women. The mean age for oral and pharyngeal cancers was 57 [standard deviation (SD = 17.09] with male to female ratio 2.39:1. The most common oral and pharyngeal cancers were squamous cell carcinoma (SCC with 283 patients. 211 (74.6% of the patients were men and 72 (25.4% of them were women; the mean age of SCC was 60 (SD = 16 with male to female ratio 2.93:1. The two most common sites of involvement were lips [166 (47.5%] and tongue [25 (7.14%]. The overall incidence rate of oral and pharyngeal cancers was 1.47 per 100000 populations. CONCLUSION: In summary, the incidence risk of oral and pharyngeal cancers in people living in Kermanshah province is similar to the most other provinces of Iran. However, this study showed that the rank of oral and pharyngeal cancers among males (9th most common cancer is low when compared to other regions of Iran and other countries such as India, Australia, and France.

  3. Pharyngeal chemosensitivity in patients with obstructive sleep apnea and healthy subjects.

    Science.gov (United States)

    Heiser, Clemens; Zimmermann, Ingo; Sommer, J Ulrich; Hörmann, Karl; Herr, Raphael M; Stuck, Boris A

    2013-09-01

    Signs of pharyngeal neurodegeneration have been detected in patients with obstructive sleep apnea (OSA). Along with this neurodegeneration, a decreased pharyngeal sensitivity to mechanical stimulation has been described. The decreased sensitivity may play a role in the pathophysiology of this disease. The aim of the study was to investigate the chemosensitivity of the pharyngeal mucosa in patients with OSA compared with controls. Healthy controls and patients with OSA (age: 30-60 years) were included. Testing of oropharyngeal chemosensitivity was performed with subjective intensity ratings of capsaicin (SIR, visual analogue scale 0-10), air puffs (presented with an olfactometer), and stimulation with CO2 at the posterior pharyngeal wall. A 2-point discrimination test at the soft palate, an intensity rating of capsaicin at the tongue, and a nasal lateralization test were performed. Twenty-six patients with OSA and 18 healthy controls were included. No differences were detected in the SIR of capsaicin at the tongue or in the nasal lateralization test. At the pharynx, a decreased sensitivity to capsaicin (OSA: 6.8 ± 2.3; healthy control: 8.6 ± 1.3), air puffs (OSA: 2.8 ± 1.9; healthy control: 4.2 ± 1.6), and stimulation with CO2 (OSA: 1.5 ± 1.7; healthy control: 2.8 ± 1.8) were demonstrated in patients with OSA (all P < 0.05). Two-point discrimination at the soft palate was reduced with statistical significance in the OSA group (OSA: 11.5 ± 5.4 mm; healthy control: 5.0 ± 2.4 mm). The results suggest reduced pharyngeal chemosensitivity in OSA patients in addition to the reduced mechanical pharyngeal sensitivity shown with 2-point discrimination. This demonstrates peripheral neurodegeneration in the context of this disease.

  4. A novel animal model for hyperdynamic airway collapse.

    Science.gov (United States)

    Tsukada, Hisashi; O'Donnell, Carl R; Garland, Robert; Herth, Felix; Decamp, Malcolm; Ernst, Armin

    2010-12-01

    Tracheobronchomalacia (TBM) is increasingly recognized as a condition associated with significant pulmonary morbidity. However, treatment is invasive and complex, and because there is no appropriate animal model, novel diagnostic and treatment strategies are difficult to evaluate. We endeavored to develop a reliable airway model to simulate hyperdynamic airway collapse in humans. Seven 20-kg male sheep were enrolled in this study. Tracheomalacia was created by submucosal resection of > 50% of the circumference of 10 consecutive cervical tracheal cartilage rings through a midline cervical incision. A silicone stent was placed in the trachea to prevent airway collapse during recovery. Tracheal collapsibility was assessed at protocol-specific time points by bronchoscopy and multidetector CT imaging while temporarily removing the stent. Esophageal pressure and flow data were collected to assess flow limitation during spontaneous breathing. All animals tolerated the surgical procedure well and were stented without complications. One sheep died at 2 weeks because of respiratory failure related to stent migration. In all sheep, near-total forced inspiratory airway collapse was observed up to 3 months postprocedure. Esophageal manometry demonstrated flow limitation associated with large negative pleural pressure swings during rapid spontaneous inhalation. Hyperdynamic airway collapse can reliably be induced with this technique. It may serve as a model for evaluation of novel diagnostic and therapeutic strategies for TBM.

  5. On the roles and regulation of chondroitin sulfate and heparan sulfate in zebrafish pharyngeal cartilage morphogenesis

    DEFF Research Database (Denmark)

    Holmborn, Katarina; Habicher, Judith; Kasza, Zsolt

    2012-01-01

    The present study addresses the roles of heparan sulfate (HS) proteoglycans and chondroitin sulfate (CS) proteoglycans in the development of zebrafish pharyngeal cartilage structures. uxs1 and b3gat3 mutants, predicted to have impaired biosynthesis of both HS and CS because of defective formation...... levels of CS than control larvae, whereas morpholino-mediated suppression of csgalnact1/csgalnact2 resulted in increased HS biosynthesis. Thus, the balance of the Extl3 and Csgalnact1/Csgalnact2 proteins influences the HS/CS ratio. A characterization of the pharyngeal cartilage element morphologies...

  6. Lymphogranuloma venereum in an Italian MSM: concurrent pharyngeal and rectal infection.

    Science.gov (United States)

    Foschi, Claudio; Filippini, Andrea; D'Antuono, Antonietta; Compri, Monica; Macca, Francesca; Banzola, Nicoletta; Marangoni, Antonella

    2014-07-01

    An Italian HIV-positive man having sex with men (MSM) attended the STIs Outpatients Clinic of Sant'Orsola Hospital in Bologna complaining of anal pain and constipation. According to patient's sexual history and repertoires, NAAT testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) was performed. Pharyngeal and anal swabs resulted positive for CT DNA detection and the following molecular genotyping identified a L2 serovar, coming to the final diagnosis of pharyngeal and rectal lymphogranuloma venereum (LGV) infection. After an antibiotic therapy with doxycycline 100 mg twice a day for 3 weeks, the patient completely recovered and the test of cure was negative for LGV infection.

  7. Integrated care pathways for airway diseases (AIRWAYS-ICPs)

    DEFF Research Database (Denmark)

    Bousquet, J; Addis, A; Adcock, I

    2014-01-01

    The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy...... and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking...... and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5...

  8. Management of the difficult airway.

    Science.gov (United States)

    Schwartz, D E; Wiener-Kronish, J P

    1991-09-01

    For clinicians involved in airway management, a plan of action for dealing with the difficult airway or a failed intubation should be developed well in advance of encountering a patient in whom intubation is not routine. When difficulty is anticipated, the equipment necessary for performing a difficult intubation should be immediately available. It also is prudent to have a surgeon skilled in performing a tracheotomy and a criothyroidotomy stand by. The intubation should be attempted in the awake state, preferably using the fiberoptic bronchoscope. The more challenging situation is when the difficult airway is confronted unexpectedly. After the first failed attempt at laryngoscopy, head position should be checked and the patient ventilated with oxygen by mask. A smaller styletted tube and possibly a different laryngoscope blade should be selected for a second attempt at intubation. The fiberoptic bronchoscope and other equipment for difficult intubation should be obtained. A second attempt should then be made. If this is unsuccessful, the patient should be reoxygenated, and assistance including a skilled anesthesiologist and surgeon should be summoned. On a third attempt, traction to the tongue can be applied by an assistant, a tube changer could be used to enter the larynx, or one of the other special techniques previously described can be used. If this third attempt fails, it may be helpful to have a physician more experienced in airway management attempt intubation after oxygen has been administered to the patient. If all attempts are unsuccessful, then invasive techniques to secure the airway will have to be performed.

  9. Trends and ethnic disparities in oral and oro-pharyngeal cancers in South Africa, 1992-2001.

    Science.gov (United States)

    Ayo-Yusuf, O A; Lalloo, R; Johnson, N W

    2013-05-01

    To describe trends in the epidemiology of oral and of oro-pharyngeal (OAP) cancers in South Africa for the atest period available. Data were obtained from the South African pathology-based National Cancer Registry. All new cases of OAP cancers diagnosed and confirmed histologically from 1992 to 2001 are included for the ICD-10 sites C00 to C14, excluding those involving the major salivary glands (C07-C08) and the nasopharynx (C11). OAP cancer incidence is reported by demographics (gender, age, race/ethnicity) and the anatomical sites involved. The analysis on anatomical sites was restricted to squamous cell carcinomas. Overall, males had a much higher OAP cancer incidence rate (world age-Standardised incidence rate [ASIR] = 7.01/100 000 per year) than females (ASIR = 1.99). However, among Asian/Indian South Africans, OAP cancer incidence was higher among females (ASIR = 4.60) than among males (ASIR = 3.80). OAP cancer, excluding those involving the lip, was highest among Coloureds (ASIR = 5.72) and lowest among Blacks (ASIR = 3.16). OAP cancer incidence was stable overall, but incidence rates increased significantly among Coloured South Africans over the period under review (p Variations in the incidence of OAP cancers by gender, race/ethnicity and anatomic site indicate a need for culturally-targeted reductions in major risk factors, including promoting tobacco cessation and prevention of risky alcohol use. The implications of the role of the human papillomavirus (HPV) in the prevention of squamous cell carcinomas involving the oro-pharyngeal in South Africa require further investigation.

  10. Clinical review: Management of difficult airways

    Science.gov (United States)

    Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

    2006-01-01

    Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway. PMID:17184555

  11. Clinical review: management of difficult airways.

    Science.gov (United States)

    Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

    2006-01-01

    Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway.

  12. Drug development for airway diseases: looking forward

    NARCIS (Netherlands)

    Holgate, Stephen; Agusti, Alvar; Strieter, Robert M.; Anderson, Gary P.; Fogel, Robert; Bel, Elisabeth; Martin, Thomas R.; Reiss, Theodore F.

    2015-01-01

    Advancing drug development for airway diseases beyond the established mechanisms and symptomatic therapies requires redefining the classifications of airway diseases, considering systemic manifestations, developing new tools and encouraging collaborations

  13. Clinical review: Management of difficult airways

    OpenAIRE

    Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

    2006-01-01

    Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate