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Sample records for human pharyngeal airway

  1. 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.

  2. Assessment of Upper and Lower Pharyngeal Airway Width in Skeletal Class I, II and III Malocclusions

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    Shalu Jain

    2014-01-01

    Full Text Available Introduction: There is a close relationship between the dimensions of airway and the sagittal skeletal malocclusion which makes it reasonable to expect that width of airway is a reflection of determining patency of airway in different skeletal malocclusion groups. So, aim of this study was to assess the upper and lower pharyngeal airway width in skeletal Class I, II and III malocclusion groups and also to evaluate sexual dimorphism in western Uttar Pradesh population. Materials and methods: A sample of 150 subjects in the age group of 18 to 25 years, from Western Uttar Pradesh adult population was selected on the basis of skeletal Class I, II and III malocclusion. Digital lateral cephalograms were taken in natural head position. Nine variables were selected which included four upper and five lower pharyngeal airway variables. Results: Upper and lower pharynx showed statistical significant difference among the skeletal Class I, II and III malocclusion and also between males and females. Conclusion: Wider upper and lower pharyngeal airway width was seen in males than in females in both skeletal Class I as well as Class III malocclusion groups respectively. Skeletal Class III malocclusion subjects had the widest airway width as compared to skeletal Class I malocclusion group. Skeletal Class II malocclusion, airway width was found to be narrowest.

  3. Three-dimensional pharyngeal airway changes in orthodontic patients treated with and without extractions.

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    Stefanovic, N; El, H; Chenin, D L; Glisic, B; Palomo, J M

    2013-05-01

    To evaluate and compare three-dimensional pharyngeal airway changes in orthodontic patients treated with and without extractions. Pharyngeal airway was analyzed for 31 subjects (15 males, 16 females) treated with extractions of four first premolars and 31 age- and gender-matched controls (15 males, 16 females) treated without extractions. The mean age of subjects was 12.97 ± 1.15 years at the beginning and 15.69 ± 1.28 years at the end of treatment. The mean age of controls was 12.86 ± 0.74 years at the beginning and 15.18 ± 0.86 years at the end of treatment. Nasopharyngeal (NP) and oropharyngeal (OP) volumes, area of maximum pharyngeal constriction (AMPC), and upper arch perimeter were measured on T0 and T1 cone beam computed tomography (CBCT) scans. Paired samples t-test was used for analyzing statistical significance of changes (p ≤ 0.05). There were no statistically significant differences in the pharyngeal airway values between the extraction and non-extraction groups at neither T0 nor T1. The extraction group showed a statistically significant increase for NP and OP volumes and AMPC values. Such increase was also noted in the non-extraction group, without statistical significance for AMPC values. The findings suggest that an extraction or non-extraction choice for orthodontic treatment would not affect the pharyngeal airway. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  4. Pharyngitis

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    ... Bacteria that can cause pharyngitis in some cases: Strep throat is caused by group A streptococcus. Less commonly, ... rapid test or throat culture to test for strep throat may be done. Other laboratory tests may be ...

  5. 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 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 palate moved anteriorly, with the greatest movement at its superior point. Significant positive correlations were observed for the posterior and superoposterior airway spaces and 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.

  6. The effect of mandibular setback or two-jaws surgery on pharyngeal airway among different genders.

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    Degerliyurt, K; Ueki, K; Hashiba, Y; Marukawa, K; Simsek, B; Okabe, K; Nakagawa, K; Yamamoto, E

    2009-06-01

    Cephalometric studies show significant gender differences in the size of the pharyngeal airway space. This study aimed to investigate and compare morphologic changes after mandibular setback or two-jaws surgery on the pharyngeal airway in men and women using computed tomography (CT). The sample included 34 women and 13 men diagnosed with Class III skeletal deformities, who had been treated by mandibular setback or bimaxillary surgery (maxillary advancement and mandibular setback). Anteroposterior, lateral and cross-sectional area dimensions of the airway, at the level of soft palate and base of tongue, were measured pre- and postoperatively on CT images. In the mandibular setback group, the anteroposterior and cross-sectional area of the pharyngeal airway at the level of the soft palate and base of tongue were significantly reduced for men or women (Ptwo-jaws surgery group, only midsagittal anteroposterior dimensions at the same levels were significantly decreased for men or women (Ptwo-jaws surgery for the treatment of class III anteroposterior discrepancy were not statistically significant (P>.05). This study suggests that oropharyngeal airway measurements, important for airway patency, do not demonstrate sex dimorphism.

  7. Pharyngeal airway characterization in adolescents related to facial skeletal pattern: a preliminary study.

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    Claudino, Lígia Vieira; Mattos, Claudia Trindade; Ruellas, Antônio Carlos de Oliveira; Sant' Anna, Eduardo Franzotti

    2013-06-01

    The objective of this study was to characterize the volume and the morphology of the pharyngeal airway in adolescent subjects, relating them to their facial skeletal pattern. Fifty-four subjects who had cone-beam computed tomography were divided into 3 groups-skeletal Class I, Class II, and Class III-according to their ANB angles. The volumes of the upper pharyngeal portion and nasopharynx, and the volume and morphology of the lower pharyngeal portion and its subdivisions (velopharynx, oropharynx, and hypopharynx) were assessed with software (version 11.5; Dolphin Imaging & Management Solutions, Chatsworth, Calif). The results were compared with the Kruskal-Wallis and the Dunn multiple comparison tests to identify intergroup differences. Correlations between variables assessed were tested by the Spearman correlation coefficient. Correlations between the logarithms of airway volumes and the ANB angle values were tested as continuous variables with linear regression, considering the sexes as subgroups. The minimum areas in the Class II group (112.9 ± 42.9, 126.9 ± 45.9, and 142.1 ± 83.5 mm(2)) were significantly smaller than in Class III group (186.62 ± 83.2, 234.5 ± 104.9, and 231.1 ± 111.4 mm(2)) for the lower pharyngeal portion, the velopharynx, and the oropharynx, respectively, and significantly smaller than the Class I group for the velopharynx (201.8 ± 94.7 mm(2)). The Class II group had a statistically significant different morphology than did the Class I and Class III groups in the velopharynx. There was a tendency to decreased airway volume with increased ANB angle in the lower pharyngeal portion, velopharynx, and oropharynx. In the upper pharyngeal portion, nasopharynx, and hypopharynx, there seemed to be no association between the airway volume and the skeletal pattern. The Class II subjects had smaller minimum and mean areas (lower pharyngeal portion, velopharynx, and oropharynx) than did the Class III group and significantly less uniform

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

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    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.

  9. Long-term changes in pharyngeal airway dimensions following activator-headgear and fixed appliance treatment.

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    Hänggi, Michael P; Teuscher, Ullrich M; Roos, Malgorzata; Peltomäki, Timo A

    2008-12-01

    The aim of this study was to evaluate changes in the pharyngeal airway in growing children and adolescents and to compare these with a group of children who received activator-headgear Class II treatment. The sample consisted of 64 children (32 males and 32 females), 32 had a combined activator-headgear appliance for at least 9 months (study group) followed by fixed appliance therapy in most patients, while the other half received only minor orthodontic treatment (control group). Lateral cephalograms before treatment (T1, mean age 10.4 years), at the end of active treatment (T2, mean age 14.5 years), and at the long-term follow-up (T3, mean age 22.1 years) were traced and digitized. To reveal the influence of somatic growth, body height measurements were also taken into consideration. A two-sample t-test was applied in order to determine differences between the groups. At T1, the study group had a smaller pharynx length (P = 0.030) and a greater ANB angle (P headgear therapy has the potential to increase pharyngeal airway dimensions, such as the smallest distance between the tongue and the posterior pharyngeal wall or the pharyngeal area. Importantly, this increase seems to be maintained long term, up to 22 years on average in the present study. This benefit may result in a reduced risk of developing long-term impaired respiratory function.

  10. Morphometry of the Palate and Pharyngeal Airway- A Computed Tomographic Study

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    Arvind Kumar Pandey

    2017-10-01

    Full Text Available Background: The morphometry of the palate and pharyngeal airway has a crucial role in the development of disorders like apnea. Therefore the present study aims to explore the shape and dimensions of the palate and the pharyngeal airway. Materials and Methods: The study was carried out on normal sagittal and axial sections of head and neck in 100 CT images. Results: The average length of the hard and soft palates measured 4.49±0.38 and 3.44±0.61cm respectively. The anteroposterior dimension of the soft palate was 0.90±0.33 cm. The velopalatine angle measured 130.23±9.98º. The luminal areas were 4.59±1.81, 2.058±1.09 and 2.99±1.08 cm in naso, oro and laryngo pharynx respectively. The soft palate showed varied shapes which were classified as a straight line, leaf-like, rat-tail, distorted S, crooked and butt like. Conclusion: The present study attempts to provide a normal database to understand the anatomy of the soft palate and pharyngeal airways.

  11. A pilot study for segmentation of pharyngeal and sino-nasal airway subregions by automatic contour initialization.

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    Neelapu, Bala Chakravarthy; Kharbanda, Om Prakash; Sardana, Viren; Gupta, Abhishek; Vasamsetti, Srikanth; Balachandran, Rajiv; Rana, Shailendra Singh; Sardana, Harish Kumar

    2017-11-01

    The objective of the present study is to put forward a novel automatic segmentation algorithm to segment pharyngeal and sino-nasal airway subregions on 3D CBCT imaging datasets. A fully automatic segmentation of sino-nasal and pharyngeal airway subregions was implemented in MATLAB programing environment. The novelty of the algorithm is automatic initialization of contours in upper airway subregions. The algorithm is based on boundary definitions of the human anatomy along with shape constraints with an automatic initialization of contours to develop a complete algorithm which has a potential to enhance utility at clinical level. Post-initialization; five segmentation techniques: Chan-Vese level set (CVL), localized Chan-Vese level set (LCVL), Bhattacharya distance level set (BDL), Grow Cut (GC), and Sparse Field method (SFM) were used to test the robustness of automatic initialization. Precision and F-score were found to be greater than 80% for all the regions with all five segmentation methods. High precision and low recall were observed with BDL and GC techniques indicating an under segmentation. Low precision and high recall values were observed with CVL and SFM methods indicating an over segmentation. A Larger F-score value was observed with SFM method for all the subregions. Minimum F-score value was observed for naso-ethmoidal and sphenoidal air sinus region, whereas a maximum F-score was observed in maxillary air sinuses region. The contour initialization was more accurate for maxillary air sinuses region in comparison with sphenoidal and naso-ethmoid regions. The overall F-score was found to be greater than 80% for all the airway subregions using five segmentation techniques, indicating accurate contour initialization. Robustness of the algorithm needs to be further tested on severely deformed cases and on cases with different races and ethnicity for it to have global acceptance in Katradental radKatraiology workflow.

  12. Three dimensional Cone Beam Computed Tomography Study ofPharyngeal Airway Dimensions in Different Anteroposterior SkeletalClassification Patients

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    2015-07-10

    Thank you to my mother for her countless hours of hard work and sacrifice while educating and raising me. Thank you to my father for providing an...it, especially the tongue . Airway dimensions have been shown to correlate with mandibular size. Muto et al evaluated pharyngeal airway space at the...have been included. For these patients, the anterior boundary of the airway was traced though the soft palate down to the base of the tongue . All

  13. Effects of bodily retraction of mandibular incisors versus mandibular setback surgery on pharyngeal airway space: A comparative study.

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    Keum, Byeong-Tak; Choi, Sung-Hwan; Choi, Yoon Jeong; Baik, Hyoung-Seon; Lee, Kee-Joon

    2017-11-01

    The purpose of this study was to compare the changes induced in the pharyngeal airway space by orthodontic treatment with bodily retraction of the mandibular incisors and mandibular setback surgery without extraction. This retrospective study included 63 adult patients (32 men and 31 women). Thirty-three patients who had been treated via four-bicuspid extraction and bodily retraction of the mandibular incisors (incisor retraction, IR group) were compared with 30 patients who had been treated via mandibular setback surgery (MS group) without extraction. Lateral cephalograms were acquired and analyzed before (T1) and after treatment (T2). The superior pharyngeal airway space did not change significantly in either group during treatment. The middle pharyngeal airway space decreased by 1.15 ± 1.17 mm and 1.25 ± 1.35 mm after treatment in the IR and MS groups, respectively, and the decrease was comparable between the two groups. In the MS group, the inferior pharyngeal airway space (E-IPW) decreased by 0.88 ± 1.67 mm after treatment (p space and the skeletal and dental variables in each group. The middle pharyngeal airway space decreased because of the posterior displacement of the mandibular incisors and/or the mandibular body. The E-IPW decreased only in the MS group because of the posterior displacement of only the mandibular body.

  14. Effects of reverse headgear on pharyngeal airway in patients with different vertical craniofacial features.

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    Baloş Tuncer, Burcu; Ulusoy, Çağrı; Tuncer, Cumhur; Türköz, Çağrı; Kale Varlik, Selin

    2015-01-01

    The aim of this study was to investigate the effects of reverse headgear (RH) on pharyngeal airway morphology in two groups of Class III patients with different vertical craniofacial features in comparison with an untreated Class III group. Seventeen subjects (9 males, 8 females; mean age 11.3 ± 0.98 years) with optimum vertical growth and 17 subjects (10 males, 7 females, mean age 11.5 ± 1.1 years) with a vertical growth pattern treated with a removable intra-oral appliance and a Delaire type facemask were included. An untreated Class III control group of 11 subjects (8 males, 3 females, mean age 9.1 ± 1.1 years) was included to compare the treated groups. The paired t-test for intragroup and one-way ANOVA for intergroup comparisons were performed. The relationships between changes in the craniofacial morphology and airway were assessed by Spearman correlation analysis. The airway dimensions at the adenoid side and soft palate were increased in the treatment groups compared to the control group (p < 0.05). The nasopharyngeal area demonstrated a significant difference in normodivergent and control subjects (p < 0.05). No significant difference was found in the airway morphology due to different vertical features. The effect of RH treatment on the sagittal airway dimensions revealed no significant difference between different vertical craniofacial features in the short term.

  15. Effects of reverse headgear on pharyngeal airway in patients with different vertical craniofacial features

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    Burcu BALOŞ TUNCER

    2015-01-01

    Full Text Available The aim of this study was to investigate the effects of reverse headgear (RH on pharyngeal airway morphology in two groups of Class III patients with different vertical craniofacial features in comparison with an untreated Class III group. Seventeen subjects (9 males, 8 females; mean age 11.3 ± 0.98 years with optimum vertical growth and 17 subjects (10 males, 7 females, mean age 11.5 ± 1.1 years with a vertical growth pattern treated with a removable intra-oral appliance and a Delaire type facemask were included. An untreated Class III control group of 11 subjects (8 males, 3 females, mean age 9.1 ± 1.1 years was included to compare the treated groups. The paired t-test for intragroup and one-way ANOVA for intergroup comparisons were performed. The relationships between changes in the craniofacial morphology and airway were assessed by Spearman correlation analysis. The airway dimensions at the adenoid side and soft palate were increased in the treatment groups compared to the control group (p < 0.05. The nasopharyngeal area demonstrated a significant difference in normodivergent and control subjects (p < 0.05. No significant difference was found in the airway morphology due to different vertical features. The effect of RH treatment on the sagittal airway dimensions revealed no significant difference between different vertical craniofacial features in the short term.

  16. Retrospective study on change in pharyngeal airway space and hyoid bone position after mandibular setback surgery.

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    On, Sung Woon; Han, Min Woo; Hwang, Doo Yeon; Song, Seung Il

    2015-10-01

    The purpose of this study was to evaluate changes in the pharyngeal airway space and hyoid bone position after mandibular setback surgery with bilateral sagittal split ramus osteotomy (BSSRO) and to analyze the correlation between the amount of mandibular setback and the amount of change in pharyngeal airway space or hyoid bone position. From January 2010 to February 2013, a total of 30 patients who were diagnosed with skeletal class III malocclusion and underwent the same surgery (BSSRO) and fixation method in the Division of Oral and Maxillofacial Surgery, Department of Dentistry at the Ajou University School of Medicine (Suwon, Korea) were included in this study. Lateral cephalograms of the 30 patients were assessed preoperatively (T1), immediately postoperatively (T2), and 6 months postoperatively (T3) to investigate the significance of changes by time and the correlation between the amount of mandibular setback and the amount of change in the airway space and hyoid bone position. Three regions of the nasopharynx, oropharynx, and hypopharynx were measured and only the oropharynx showed a statistically significant decrease (Pamount of mandibular setback and the amount of final change in the airway space and hyoid bone position with Pearson's correlation showed no significant correlation. In this study, the oropharynx significantly decreased after mandibular setback surgery, and changes in the surrounding structures were identified through posteroinferior movement of the hyoid bone during long-term follow-up. Therefore, postoperative obstructive sleep apnea should be considered in patients who plan to undergo mandibular setback surgery, and necessary modifications to the treatment plan should also be considered.

  17. Evaluation of hyoid bone position and its correlation with pharyngeal airway space in different types of skeletal malocclusion

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    Nidhin Philip Jose

    2014-01-01

    Full Text Available Introduction: The hyoid bone and its relation with the pharyngeal space in health and disease has been an intriguing subject for years. Aim: This study attempts to evaluate the hyoid bone position and to ascertain any correlations with pharyngeal airway space in skeletal class I, II, and III malocclusions. Materials and Methods: McNamara′s airway analysis was carried out to assess the upper and lower airway widths and Hyoid triangle analysis by Bibby and Preston was carried out to determine the position of the hyoid bone. Conclusion: A positive correlation was found between the lower airway and horizontal distance from the hyoid bone to the retrognathion in class I skeletal pattern with average growth pattern.

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

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    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.

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

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    Sriram, S. Ganapathy; Andrade, Neelam N.

    2014-01-01

    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. PMID:25593419

  20. Three dimensional assessment of the pharyngeal airway in individuals with non-syndromic cleft lip and palate.

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    Tracy Cheung

    Full Text Available INTRODUCTION: Children with cleft lip and palate (CLP are known to have airway problems. Previous studies have shown that individuals with CLP have a 30% reduction in nasal airway size compared to non-cleft controls. No reports have been found on cross-sectional area and volume of the pharyngeal airway in clefts. Introduction of Cone-Beam CT (CBCT and imaging software has facilitated generation of 3D images for assessment of the cross-sectional area and volume of the airway. OBJECTIVE: To assess the pharyngeal airway in individuals with CLP using CBCT by measuring volume and smallest cross-sectional areas and compare with 19 age- and sex-matched non-cleft controls. METHODS: Retrospective study of CBCT data of pre-adolescent individuals (N = 19, Mean age = 10.6, 7 females, 12 males, UCLP = 6, BCLP = 3 from the Center for Craniofacial Anomalies. Volumetric analysis was performed using image segmentation features in CB Works 3.0. Volume and smallest cross-sectional were studied in both groups. Seven measurements were repeated to verify reliability using Pearson correlation coefficient. Volume and cross-sectional area differences were analyzed using paired t-tests. RESULTS: The method was found to be reliable. Individuals with CLP did not exhibit smaller total airway volume and cross sectional area than non-CLP controls. CONCLUSION: 3D imaging using CBCT and CB Works is reliable for assessing airway volume. Previous studies have shown that the nasal airway is restricted in individuals with CLP. In our study, we found that the pharyngeal airway is not compromised in these individuals.

  1. Analysis of pharyngeal airway space and tongue position in individuals with different body types and facial patterns: A cephalometric study

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    Rohit Kulshrestha

    2015-01-01

    Full Text Available Aim: To evaluate if the different body types and facial patterns have any effect on the dimensions of the pharyngeal airway space and tongue position. Materials and Methods: Ninety subjects (age 13-30 years with no history of previous orthodontic treatment, jaw surgeries, or functional jaw orthopedics were taken and divided into different groups based on their body built. They were further subdivided into different groups based on their Frankfort Mandibular Angle. Group I included 30 subjects (15 males, 15 females who were ectomorphic (body mass index [BMI] 25. Lateral cephalograms were traced manually to evaluate the pharyngeal airway passage and tongue position. Results: When the comparison between different facial growth patterns was done, differences in soft palate inclination (P < 0.004 and upper pharyngeal wall - pterygomaxillary (P < 0.012 was found to be statistically significant. A significant difference among different growth patterns was observed for the soft palate inclination between the hypo- and hyper-divergent groups (P < 0.003. No significant differences were seen when a comparison between different facial types (irrespective of growth was done. No significant difference was seen in the position of the tongue in all the groups. Conclusion: Different body types and facial patterns had a significant effect on the dimension of the pharyngeal airway space but no significant effect on the position of the tongue.

  2. Tongue posture improvement and pharyngeal airway enlargement as secondary effects of rapid maxillary expansion: a cone-beam computed tomography study.

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    Iwasaki, Tomonori; Saitoh, Issei; Takemoto, Yoshihiko; Inada, Emi; Kakuno, Eriko; Kanomi, Ryuzo; Hayasaki, Haruaki; Yamasaki, Youichi

    2013-02-01

    Rapid maxillary expansion (RME) is known to improve nasal airway ventilation. Recent evidence suggests that RME is an effective treatment for obstructive sleep apnea in children with maxillary constriction. However, the effect of RME on tongue posture and pharyngeal airway volume in children with nasal airway obstruction is not clear. In this study, we evaluated these effects using cone-beam computed tomography. Twenty-eight treatment subjects (mean age 9.96 ± 1.21 years) who required RME treatment had cone-beam computed tomography images taken before and after RME. Twenty control subjects (mean age 9.68 ± 1.02 years) received regular orthodontic treatment. Nasal airway ventilation was analyzed by using computational fluid dynamics, and intraoral airway (the low tongue space between tongue and palate) and pharyngeal airway volumes were measured. Intraoral airway volume decreased significantly in the RME group from 1212.9 ± 1370.9 mm(3) before RME to 279.7 ± 472.0 mm(3) after RME. Nasal airway ventilation was significantly correlated with intraoral airway volume. The increase of pharyngeal airway volume in the control group (1226.3 ± 1782.5 mm(3)) was only 41% that of the RME group (3015.4 ± 1297.6 mm(3)). In children with nasal obstruction, RME not only reduces nasal obstruction but also raises tongue posture and enlarges the pharyngeal airway. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  3. Effect of Sleeping Position on Upper Airway Patency in Obstructive Sleep Apnea Is Determined by the Pharyngeal Structure Causing Collapse.

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    Marques, Melania; Genta, Pedro R; Sands, Scott A; Azarbazin, Ali; de Melo, Camila; Taranto-Montemurro, Luigi; White, David P; Wellman, Andrew

    2017-03-01

    In some patients, obstructive sleep apnea (OSA) can be resolved with improvement in pharyngeal patency by sleeping lateral rather than supine, possibly as gravitational effects on the tongue are relieved. Here we tested the hypothesis that the improvement in pharyngeal patency depends on the anatomical structure causing collapse, with patients with tongue-related obstruction and epiglottic collapse exhibiting preferential improvements. Twenty-four OSA patients underwent upper airway endoscopy during natural sleep to determine the pharyngeal structure associated with obstruction, with simultaneous recordings of airflow and pharyngeal pressure. Patients were grouped into three categories based on supine endoscopy: Tongue-related obstruction (posteriorly located tongue, N = 10), non-tongue related obstruction (collapse due to the palate or lateral walls, N = 8), and epiglottic collapse (N = 6). Improvement in pharyngeal obstruction was quantified using the change in peak inspiratory airflow and minute ventilation lateral versus supine. Contrary to our hypothesis, patients with tongue-related obstruction showed no improvement in airflow, and the tongue remained posteriorly located while lateral. Patients without tongue involvement showed modest improvement in airflow (peak flow increased 0.07 L/s and ventilation increased 1.5 L/min). Epiglottic collapse was virtually abolished with lateral positioning and ventilation increased by 45% compared to supine position. Improvement in pharyngeal patency with sleeping position is structure specific, with profound improvements seen in patients with epiglottic collapse, modest effects in those without tongue involvement and-unexpectedly-no effect in those with tongue-related obstruction. Our data refute the notion that the tongue falls back into the airway during sleep via gravitational influences.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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...... literature review has been registered in PROSPERO database with following number: CRD42015024567. A systematic literature search performed in PubMed, Embase and Cochrane was carried out in order to evaluate if the effect of human head or tongue posture has an effect on upper airway dimensions and morphology...... in CT, CBCT or MRI. Study quality assessment was performed. Predictor variable was head and tongue posture. Endpoints were numerical values of upper airway dimensions and morphology. RESULTS: Overall 1344 articles (Embase 1063, PubMed 269, and Cochrane 12) resulted in four included publications. Quality...

  6. Human airway smooth muscle

    OpenAIRE

    Jongste, Johan

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less likely, squeezing mucus out of mucous glands and pulling open the alveoli next to the airways1 . Any role of airway smooth muscle is necessarily limited, because an important degree of contraction will l...

  7. CHANGES IN ORO-PHARYNGEAL AIRWAY DIMENSIONS AFTER TREATMENT WITH FUNCTIONAL APPLIANCE IN CLASS II SKELETAL PATTERN.

    Science.gov (United States)

    Ali, Batool; Shaikh, Attiya; Fida, Mubassar

    2015-01-01

    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 apnoea. 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. 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 ≤ 00.5. The upper airway width (p skeletal pattern.

  8. A randomized comparison of pediatric-sized Streamlined Liner of Pharyngeal Airway and Laryngeal Mask Airway-Unique in paralyzed children.

    Science.gov (United States)

    Zhu, Wenxiu; Wei, Xinchuan

    2016-05-01

    The pediatric-sized Streamlined Liner of Pharyngeal Airway (SLIPA) is a new supraglottic airway device for children. The aim of this study was to compare the clinical performance of the pediatric-sized SLIPA with the Laryngeal Mask Airway-Unique in paralyzed children under positive pressure-controlled ventilation (PCV). One hundred children, aged 2 months to 12 years with American Society of Anesthesiologists physical status I-II were enrolled and randomly allocated to the SLIPA group or the Laryngeal Mask Airway-Unique group (50 patients in each group). The primary outcome variable was oropharyngeal leak pressure. Other outcome variables were first insertion success rate, insertion time, minor airway interventions required for successful insertion, intraoperative dislodgement, ventilatory data, and perioperative complications. The insertion characteristics, ventilation data, and perioperative complications were comparable between the two groups. The leak pressure of the SLIPA was significantly higher than that of the Laryngeal Mask Airway-Unique [median (IQR): 25 (22-30) cm H2O vs. 21 (19-26) cm H2O, respectively; mean ± sd: 25.3 ± 4.6 cm H2O vs. 22.6 ± 4.8 cm H2O, respectively; P = 0.006]. The incidence of intraoperative dislodgment was significantly lower in the SLIPA group than in the Laryngeal Mask Airway-Unique group (0 vs. 6 patients, respectively; P = 0.027). In conclusion, both the SLIPA and the Laryngeal Mask Airway-Unique can be used effectively without severe complications in paralyzed children. Additionally, the SLIPA provides a better airway seal and better intraoperative position stability than the Laryngeal Mask Airway-Unique. © 2016 John Wiley & Sons Ltd.

  9. Human airway smooth muscle

    NARCIS (Netherlands)

    J.C. de Jongste (Johan)

    1987-01-01

    textabstractThe function of airway smooth muscle in normal subjects is not evident. Possible physiological roles include maintenance of optimal regional ventilation/perfusion ratios, reduction of anatomic dead space, stabilisation of cartilaginous bronchi, defense against impurities and, less

  10. Comparison of pharyngeal airway volume among different vertical skeletal patterns: a cone-beam computed tomography study.

    Science.gov (United States)

    Celikoglu, Mevlut; Bayram, Mehmet; Sekerci, Ahmet E; Buyuk, Suleyman K; Toy, Ebubekir

    2014-09-01

    To test the null hypothesis that there are no significant differences in pharyngeal airway volumes among adult patients with different vertical skeletal patterns and a clinically normal sagittal skeletal pattern using cone-beam computed tomography (CBCT). The study sample consisted of 100 adult patients (45 men and 55 women; mean age  =  24.0 ± 5.3 years) with a normal sagittal skeletal pattern divided into three groups according to the vertical skeletal patterns: high angle (32 patients: 15 women and 17 men), low angle (34 patients: 14 women and 20 men), and normal angle (34 patients: 16 women and 18 men) groups. Nasopharyngeal, oropharyngeal, and total airway volumes of patients in all vertical groups were calculated. Group differences were analyzed using one-way analysis of variance and post hoc Tukey tests. Nasopharyngeal airway volume in the high-angle group (mean  =  6067.9 ± 1693.9 mm(3)) was significantly lower than that of the low- and normal-angle groups (P skeletal vertical patterns.

  11. Pharyngeal Airway Dimensions and Head Posture in Obstructive Sleep Apnea Patients with and without Morphological Deviations in the Upper Cervical Spine

    Science.gov (United States)

    Petersson, Arne; Berg, Søren; Svanholt, Palle

    2017-01-01

    ABSTRACT Objectives The aim of the study was to analyse differences in pharyngeal airway dimensions and head posture between obstructive sleep apnea patients with and without morphological deviations in the upper cervical spine and to analyse associations between pharyngeal airway dimensions and head posture in the total sample. Material and Methods The sample comprised 53 obstructive sleep apnea (OSA) patients of which 32.1% had upper spine morphological deviations. Accordingly two groups were defined: 17 OSA patients with morphological deviations in the upper spine and 36 without upper spine deviations. Pharyngeal airway dimensions in terms of distances, cross-sectional areas and volume and upper spine morphological deviations were evaluated on cone-beam computed tomography. Head posture was evaluated on two-dimensional generated lateral cephalograms. Differences were analysed and adjusted for age and gender by multiple linear regression analysis. Results OSA patients with upper spine morphological deviations had a significantly more backward and curved neck posture (OPT/HOR, P < 0.01; OPT/CVT, P < 0.05) compared to OSA patients without spine deviations. No significant differences were found in airway dimensions between patients with and without upper spine deviations. In the total group significant associations were found between head posture and pharyngeal airway distances and cross-sectional area at the nasal floor, epiglottis and hyoid bone level (P < 0.05, P < 0.01, P < 0.001). No significant association was found between head posture and airway volume. Conclusions The results may contribute to differentiate obstructive sleep apnea patients and thereby may prove valuable in diagnosis and treatment planning of obstructive sleep apnea patients. PMID:29142656

  12. 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.

  13. Effect of airway surface liquid on the forces on the pharyngeal wall: Experimental fluid-structure interaction study.

    Science.gov (United States)

    Pirnar, Jernej; Širok, Brane; Bombač, Andrej

    2017-10-03

    Obstructive sleep apnoea syndrome (OSAS) is a breathing disorder with a multifactorial etiology. The respiratory epithelium is lined with a thin layer of airway surface liquid preventing interactions between the airflow and epithelium. The effect of the liquid lining in OSAS pathogenesis remains poorly understood despite clinical research. Previous studies have shown that the physical properties of the airway surface liquid or altered stimulation of the airway mechanoreceptors could alleviate or intensify OSAS; however, these studies do not provide a clear physical interpretation. To study the forces transmitted from the airflow to the liquid-lined compliant wall and to discuss the effects of the airway surface liquid properties on the stimulation of the mechanoreceptors, a novel and simplified experimental system mimicking the upper airway fundamental characteristics (i.e., liquid-lined compliant wall and complex unsteady airflow features) was constructed. The fluctuating force on the compliant wall was reduced through a damping mechanism when the liquid film thickness and/or the viscosity were increased. Conversely, the liquid film damping was reduced when the surface tension decreased. Based on the experimental data, empirical correlations were developed to predict the damping potential of the liquid film. In the future, this will enable us to extend the existing computational fluid-structure interaction simulations of airflow in the human upper airway by incorporating the airway surface liquid effect without adopting two-phase flow interface tracking methods. Furthermore, the experimental system developed in this study could be used to investigate the fundamental principles of the complex once/twice-coupled physical phenomena. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Relationship between malocclusion, soft tissue profile, and pharyngeal airways: A cephalometric study

    Directory of Open Access Journals (Sweden)

    Kristina Lopatienė

    2016-01-01

    Conclusions: During critical period of growth and development of the maxillofacial system, the patients with oral functional disturbances should be monitored and treated by a multidisciplinary team consisting of a dentist, an orthodontist, a pediatrician, an ENT specialist, and an allergologist. Cephalometric analysis applied in our study showed that Angle Class II patients with significantly decreased facial convexity angle, increased nasomental, upper lip-chin, and lower lip-chin angles, and upper and lower lips located more proximally to the E line more frequently had constricted airways.

  15. Human immunodeficiency virus and the airway

    African Journals Online (AJOL)

    Analee Milner

    Therefore, it is still of value to recognise and understand the pathology caused by degrees of immune compromise from HIV/AIDS. Ironically, ART may impact on the airway owing to immune reconstitution inflammatory syndrome and lipodystrophy. Keywords: AIDS, ART, airway, head and neck manifestation, HIV, human ...

  16. Pharyngeal fat in obstructive sleep apnea.

    Science.gov (United States)

    Shelton, K E; Woodson, H; Gay, S; Suratt, P M

    1993-08-01

    Although most patients with obstructive sleep apnea (OSA) are obese, it is not known how obesity contributes to airway collapse during sleep. The purpose of this study was to determine whether the volume of adipose tissue adjacent to the pharyngeal airway in humans is related to the degree of OSA. We studied 30 subjects, nine without OSA and 21 with OSA; two subjects were studied before and after weight loss. Adipose tissue was detected with magnetic resonance imaging using T1-weighted spin echo sequences. The volume of adipose tissue adjacent to the upper airway was determined by measuring the volume of all pixels in the intensity range of adipose tissue within the region bounded by the ramus of the mandible, the spine, the anterior border of the soft palate, and the hard palate. Polysomnography was performed with conventional techniques. All subjects had a collection of adipose tissue adjacent to the upper airway; the volume of this adipose tissue correlated with the number of apneas plus hypopneas per hour of sleep (r = 0.59, p lost weight and had fewer apneas and hypopneas had a marked decrease in the pharyngeal adipose tissue volume. We conclude that adipose tissue is deposited adjacent to the pharyngeal airway in patients with OSA and that the volume of this tissue is related to the presence and degree of OSA.

  17. The functional role of the pharyngeal plexus in vocal cord innervation in humans.

    Science.gov (United States)

    Uludag, Mehmet; Aygun, Nurcihan; Isgor, Adnan

    2017-02-01

    Classical understanding of the function of the pharyngeal plexus in humans is that it relies on both motor branches for innervation of the majority of pharyngeal muscles and sensory branches for the pharyngeal wall sensation. To date there has been no reported data on the role of the pharyngeal plexus in vocal cord innervation. The aim of this study is to evaluate whether or not the plexus pharyngeus contributes to the innervation of the vocal cords. One hundred twenty-five sides from 79 patients (59 female, 20 male) undergoing thyroid surgery with intraoperative neuromonitoring were prospectively evaluated. While vocal cord function was evaluated with endotracheal tube surface electrodes, cricothyroid and cricopharyngeal muscle electromyographic recordings were obtained with a pair of needle electrodes. The ipsilateral pharyngeal plexus, external branch of the superior laryngeal nerve, and recurrent laryngeal nerve were stimulated with a monopolar probe at 1 mA. With stimulation of the plexus pharyngeus on 125 operated sides, positive electromyographic waveforms were detected from five ipsilateral vocal cords (accounting for 3.2% of all vocal cords monitored and 6.3% of patients). The mean EMG amplitude of the vocal cords with stimulation of the plexus pharyngeus was 147 ± 35.5 μV (range 110-203). In one case, the long latency time of 19.8 ms correlated with innervation by the glottic closure reflex pathway. The short latencies seen in the other four cases [3.9 ± 1.1 ms (range 3.2-5.5)] correlated with direct innervation. In some cases, the plexus pharyngeus may contribute to vocal cord innervation by reflex or direct innervation patterns in humans.

  18. A comparative study of the pharyngeal airway space, measured with cone beam computed tomography, between patients with different craniofacial morphologies.

    Science.gov (United States)

    Dalmau, Eva; Zamora, Natalia; Tarazona, Beatriz; Gandia, Jose L; Paredes, Vanessa

    2015-10-01

    The present study aims to determine any existing association between airway dimensions, measured with cone beam computed tomography (CBCT), and the different patient craniofacial morphologies. Sixty CBCT (Dental Picasso Master 3D) images, from patients treated at the Orthodontics Master at Valencia University were selected. The program InVivoDental 5.1 was used to visualize sections, analyze three-dimensional images, and perform airway measurements in the three planes of the space. Intra- and interobserver error methods were recorded. After that, measurements at three different levels of the airway (upper, medium, lower) were taken, in both the anteroposterior and transversal directions of the airway space. The area (mm(2)) of the airway space at the three levels was also measured. In the anteroposterior airway measurements, there were differences between the measurements by level. The magnitude of these differences depended on the skeletal pattern of the individual. In the transversal airway measurements and in the area airway measurements, there were no differences according to the skeletal pattern. However, in the transversal direction, measurements in the lower level were significantly higher than in the superior level in all cases. When measuring the area, significantly higher measurements in the upper level were recorded. The homogeneity between medium and lower levels decreased gradually from class I to class III subjects. No statistically significant results were observed that related the anteroposterior and vertical skeletal craniofacial morphology with airway dimensions, although some specific associations have been detected for certain airway levels or for pattern combinations. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  19. 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.

  20. Dynamic Properties of Human Bronchial Airway Tissues

    CERN Document Server

    Wang, Jau-Yi; Pallai, Prathap; Corrigan, Chris J; Lee, Tak H

    2011-01-01

    Young's Modulus and dynamic force moduli were measured on human bronchial airway tissues by compression. A simple and low-cost system for measuring the tensile-strengh of soft bio-materials has been built for this study. The force-distance measurements were undertaken on the dissected bronchial airway walls, cartilages and mucosa from the surgery-removed lungs donated by lung cancer patients with COPD. Young's modulus is estimated from the initial slope of unloading force-displacement curve and the dynamic force moduli (storage and loss) are measured at low frequency (from 3 to 45 Hz). All the samples were preserved in the PBS solution at room temperature and the measurements were perfomed within 4 hours after surgery. Young's modulus of the human bronchial airway walls are fond ranged between 0.17 and 1.65 MPa, ranged between 0.25 to 1.96 MPa for cartilages, and between 0.02 to 0.28 MPa for mucosa. The storage modulus are found varying 0.10 MPa with frequency while the loss modulus are found increasing from ...

  1. No correlation between two-dimensional measurements and three-dimensional configuration of the pharyngeal upper airway space in cone-beam computed tomography.

    Science.gov (United States)

    Abé-Nickler, Marie Dorothée; Pörtner, Samira; Sieg, Peter; Hakim, Samer George

    2017-03-01

    The aim of this study was to evaluate both the 2-dimensional (2D) and 3-dimensional (3D) configuration of the posterior airway space (PAS) in healthy 239 patients using cone-beam computed tomography (CBCT). In particular, we investigated the correlation between the 2D and 3D measurements in view of the potential impact on diagnosis of upper airway obstruction. The pharyngeal airway of each patient was studied at five levels: the level of the posterior nasal spine (PNS), the level of half-height of the PNS and the tip of the soft palate, the level of the tip of the soft palate, the level of the anterior-inferior point of the second vertebra, and at least the level of the top of the epiglottis. At each of these levels, the anterior-posterior dimension as well as the corresponding cross-sectional area was measured. Furthermore we measured the volume of the whole PAS between the first and the last level and compared it with the corresponding 2D values. Differences between genders and age effects were estimated in an analysis of covariance. P values measured distances. Limits of agreement were calculated as 2 ± residual standard deviations. We generated normal 2D and 3D values of the PAS for a normal population. In regard to age, no significant differences were observed. Significant differences were assessed between healthy males and females; however no correlation was observed between the obtained measurements in 2D axial view and the corresponding cross-sectional areas and mean volume in 3D view. In summary, radiologic imaging is a helpful tool to evaluate the airway space in patients with OSAS. However, drawing conclusions from 2D PAS imaging to assess 3D PAS configuration is not reliable, since there is no sufficient correlation between posterior-anterior distances and the corresponding cross-sectional areas. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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

    National Research Council Canada - National Science Library

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

    2009-01-01

    .... 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...

  3. 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...... facing the outside. They were capable of surviving hours of experiment involving continuous superfusion of the bathing medium and changes of osmolarity. A new image analysis technique was developed for measuring the spheroid diameters, giving high time and measurement resolutions. The transepithelial P...

  4. 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

    airway dimensions and morphology, during computed tomography, cone-beam computed tomography or magnetic resonance imaging acquisition. This was the aim of the present literature review study for purposes of valid evidence, which was hypothesized, to be present. MATERIAL AND METHODS: This systematic...... literature review has been registered in PROSPERO database with following number: CRD42015024567. A systematic literature search performed in PubMed, Embase and Cochrane was carried out in order to evaluate if the effect of human head or tongue posture has an effect on upper airway dimensions and morphology...

  5. 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

    literature review has been registered in PROSPERO database with following number: CRD42015024567. A systematic literature search performed in PubMed, Embase and Cochrane was carried out in order to evaluate if the effect of human head or tongue posture has an effect on upper airway dimensions and morphology...... in CT, CBCT or MRI. Study quality assessment was performed. Predictor variable was head and tongue posture. Endpoints were numerical values of upper airway dimensions and morphology. RESULTS: Overall 1344 articles (Embase 1063, PubMed 269, and Cochrane 12) resulted in four included publications. Quality...

  6. Anatomic Optical Coherence Tomography of Upper Airways

    Science.gov (United States)

    Chin Loy, Anthony; Jing, Joseph; Zhang, Jun; Wang, Yong; Elghobashi, Said; Chen, Zhongping; Wong, Brian J. F.

    The upper airway is a complex and intricate system responsible for respiration, phonation, and deglutition. Obstruction of the upper airways afflicts an estimated 12-18 million Americans. Pharyngeal size and shape are important factors in the pathogenesis of airway obstructions. In addition, nocturnal loss in pharyngeal muscular tone combined with high pharyngeal resistance can lead to collapse of the airway and periodic partial or complete upper airway obstruction. Anatomical optical coherence tomography (OCT) has the potential to provide high-speed three-dimensional tomographic images of the airway lumen without the use of ionizing radiation. In this chapter we describe the methods behind endoscopic OCT imaging and processing to generate full three dimensional anatomical models of the human airway which can be used in conjunction with numerical simulation methods to assess areas of airway obstruction. Combining this structural information with flow dynamic simulations, we can better estimate the site and causes of airway obstruction and better select and design surgery for patients with obstructive sleep apnea.

  7. Group A streptococcal surface GAPDH, SDH, recognizes uPAR/CD87 as its receptor on the human pharyngeal cell and mediates bacterial adherence to host cells.

    Science.gov (United States)

    Jin, Hong; Song, Youngmia P; Boel, Gregory; Kochar, Jaspreet; Pancholi, Vijay

    2005-07-01

    Streptococcal surface dehydrogenase (SDH) is a multifunctional, anchorless protein present on the surface of group A Streptococcus (GAS). It plays a regulatory role in GAS-mediated intracellular signaling events in human pharyngeal cells. Using ligand-binding assays, we have identified an approximately 55 kDa protein as an SDH-specific receptor protein on the surface of Detroit human pharyngeal cells. LC-MS/MS analyses identified this SDH-binding pharyngeal cell-surface-exposed membrane-bound protein as uPAR (urokinase plasminogen activator receptor)/CD87. Ligand-binding assays also revealed that only the N-terminal domain (D1) of uPAR bound to SDH. uPAR-D1 more specifically bound to the C-terminal alpha-helix and two immediate flanking regions of the S-loop of the SDH molecule. Site-directed mutagenesis in GAS resulting in SDH with altered C-terminal ends, and the removal of uPAR from pharyngeal cells by phosphatidylinositol-phopsholipase C treatment decreased GAS ability to adhere to pharyngeal cells. When compared to uninfected Detroit pharyngeal cells, GAS-infected pharyngeal cells showed a transient but a significant increase in the expression of uPAR-specific mRNA, and a prolonged recycling process of uPAR on the cell surface. Together, these results indicate that the specific streptococcal surface protein-pharyngeal cell receptor interaction mediated by SDH and uPAR is modulated during GAS infection of human pharyngeal cells. This interaction significantly contributes to bacterial adherence and thus may play a significant role in GAS pathogenesis by regulating intracellular signaling events in pharyngeal cells.

  8. Deposition of graphene nanomaterial aerosols in human upper airways.

    Science.gov (United States)

    Su, Wei-Chung; Ku, Bon Ki; Kulkarni, Pramod; Cheng, Yung Sung

    2016-01-01

    Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

  9. 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 ...

  10. Mast cells in human airways: the culprit?

    Directory of Open Access Journals (Sweden)

    Jonas S. Erjefält

    2014-09-01

    Full Text Available By virtue of their undisputed role in allergy, the study of airway mast cells has focused on nasal and bronchial mast cells and their involvement in allergic rhinitis and asthma. However, recent mechanistic and human studies suggest that peripheral mast cells also have an important role in asthma, as well as chronic obstructive pulmonary disease, respiratory infections and lung fibrosis. Pathogenic roles include immune-modulatory, pro-inflammatory and pro-fibrotic activities. Importantly, mast cells also actively downregulate inflammation and participate in the defence against respiratory infections. Another complicating factor is the notorious mast cell heterogeneity, where each anatomical compartment of the lung harbours site-specific mast cell populations. Alveolar mast cells stand out as they lack the cardinal expression of the high affinity IgE receptor. Supporting the emerging concept of alveolar inflammation in asthma, alveolar mast cells shift to a highly FcϵRI-expressing phenotype in uncontrolled asthma. Site-specific and disease-associated mast cell changes have also recently been described in most other inflammatory conditions of the lung. Thus, in the exploration of new anti-mast cell treatment strategies the search has widened to include the lung periphery and the delicate task of identifying which of the countless potential roles are the critical disease modifying ones in a given clinical situation.

  11. 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.

  12. Analysis of the proteome of human airway epithelial secretions

    Directory of Open Access Journals (Sweden)

    Park Yongsung

    2011-01-01

    Full Text Available Abstract Background Airway surface liquid, often referred to as mucus, is a thin layer of fluid covering the luminal surface that plays an important defensive role against foreign particles and chemicals entering the lungs. Airway mucus contains various macromolecules, the most abundant being mucin glycoproteins, which contribute to its defensive function. Airway epithelial cells cultured in vitro secrete mucins and nonmucin proteins from their apical surface that mimics mucus production in vivo. The current study was undertaken to identify the polypeptide constituents of human airway epithelial cell secretions to gain a better understanding of the protein composition of respiratory mucus. Results Fifty-five proteins were identified in the high molecular weight fraction of apical secretions collected from in vitro cultures of well-differentiated primary human airway epithelial cells and isolated under physiological conditions. Among these were MUC1, MUC4, MUC5B, and MUC16 mucins. By proteomic analysis, the nonmucin proteins could be classified as inflammatory, anti-inflammatory, anti-oxidative, and/or anti-microbial. Conclusions Because the majority of the nonmucin proteins possess molecular weights less than that selected for analysis, it is theoretically possible that they may associate with the high molecular weight and negatively charged mucins to form a highly ordered structural organization that is likely to be important for maintaining the proper defensive function of airway mucus.

  13. Temporal Monitoring of Differentiated Human Airway Epithelial Cells Using Microfluidics.

    Directory of Open Access Journals (Sweden)

    Cornelia Blume

    Full Text Available The airway epithelium is exposed to a variety of harmful agents during breathing and appropriate cellular responses are essential to maintain tissue homeostasis. Recent evidence has highlighted the contribution of epithelial barrier dysfunction in the development of many chronic respiratory diseases. Despite intense research efforts, the responses of the airway barrier to environmental agents are not fully understood, mainly due to lack of suitable in vitro models that recapitulate the complex in vivo situation accurately. Using an interdisciplinary approach, we describe a novel dynamic 3D in vitro model of the airway epithelium, incorporating fully differentiated primary human airway epithelial cells at the air-liquid interface and a basolateral microfluidic supply of nutrients simulating the interstitial flow observed in vivo. Through combination of the microfluidic culture system with an automated fraction collector the kinetics of cellular responses by the airway epithelium to environmental agents can be analysed at the early phases for the first time and with much higher sensitivity compared to common static in vitro models. Following exposure of primary differentiated epithelial cells to pollen we show that CXCL8/IL-8 release is detectable within the first 2h and peaks at 4-6h under microfluidic conditions, a response which was not observed in conventional static culture conditions. Such a microfluidic culture model is likely to have utility for high resolution temporal profiling of toxicological and pharmacological responses of the airway epithelial barrier, as well as for studies of disease mechanisms.

  14. Inhibition of p21 activated kinase (PAK reduces airway responsiveness in vivo and in vitro in murine and human airways.

    Directory of Open Access Journals (Sweden)

    Wyn C Hoover

    Full Text Available The p21-activated protein kinases (Paks have been implicated in the regulation of smooth muscle contractility, but the physiologic effects of Pak activation on airway reactivity in vivo are unknown. A mouse model with a genetic deletion of Pak1 (Pak1(-/- was used to determine the role of Pak in the response of the airways in vivo to challenge with inhaled or intravenous acetylcholine (ACh. Pulmonary resistance was measured in anesthetized mechanically ventilated Pak1(-/- and wild type mice. Pak1(-/- mice exhibited lower airway reactivity to ACh compared with wild type mice. Tracheal segments dissected from Pak1(-/- mice and studied in vitro also exhibited reduced responsiveness to ACh compared with tracheas from wild type mice. Morphometric assessment and pulmonary function analysis revealed no differences in the structure of the airways or lung parenchyma, suggesting that that the reduced airway responsiveness did not result from structural abnormalities in the lungs or airways due to Pak1 deletion. Inhalation of the small molecule synthetic Pak1 inhibitor, IPA3, also significantly reduced in vivo airway responsiveness to ACh and 5-hydroxytryptamine (5-Ht in wild type mice. IPA3 inhibited the contractility of isolated human bronchial tissues to ACh, confirming that this inhibitor is also effective in human airway smooth muscle tissue. The results demonstrate that Pak is a critical component of the contractile activation process in airway smooth muscle, and suggest that Pak inhibition could provide a novel strategy for reducing airway hyperresponsiveness.

  15. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways: e1000424

    National Research Council Canada - National Science Library

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

    2009-01-01

    .... 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°C...

  16. Regional aerosol deposition in human upper airways. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Swift, D.L.

    1997-11-01

    During the award period, a number of studies have been carried out related to the overall objective of the project which is to elucidate important factors which influence the upper airway deposition and dose of particles in the size range 0.5 nm - 10 {mu}m, such as particle size, breathing conditions, age, airway geometry, and mode of breathing. These studies are listed below. (1) A high voltage electrospray system was constructed to generate polydispersed 1-10 {mu}m diameter di-ethylhexyl sebacate aerosol for particle deposition studies in nasal casts and in human subjects. (2) The effect of nostril dimensions, nasal passage geometry, and nasal resistance on particle deposition efficiency in forty healthy, nonsmoking adults at a constant flowrate were studied. (3) The effect of nostril dimensions, nasal passage dimensions and nasal resistance on the percentage of particle deposition in the anterior 3 cm of the nasal passage of spontaneously breathing humans were studied. (4) The region of deposition of monodispersed aerosols were studied using replicate casts. (5) Ultrafine aerosol deposition using simulated breath holding path and natural path was compared. (6) An experimental technique was proposed and tested to measure the oral deposition of inhaled ultrafine particles. (7) We have calculated the total deposition fraction of ultrafine aerosols from 5 to 200 n in the extrathoracic airways and in the lung. (8) The deposition fraction of radon progeny in the head airways was studied using several head airway models.

  17. Computational Flow Modeling of Human Upper Airway Breathing

    Science.gov (United States)

    Mylavarapu, Goutham

    Computational modeling of biological systems have gained a lot of interest in biomedical research, in the recent past. This thesis focuses on the application of computational simulations to study airflow dynamics in human upper respiratory tract. With advancements in medical imaging, patient specific geometries of anatomically accurate respiratory tracts can now be reconstructed from Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans, with better and accurate details than traditional cadaver cast models. Computational studies using these individualized geometrical models have advantages of non-invasiveness, ease, minimum patient interaction, improved accuracy over experimental and clinical studies. Numerical simulations can provide detailed flow fields including velocities, flow rates, airway wall pressure, shear stresses, turbulence in an airway. Interpretation of these physical quantities will enable to develop efficient treatment procedures, medical devices, targeted drug delivery etc. The hypothesis for this research is that computational modeling can predict the outcomes of a surgical intervention or a treatment plan prior to its application and will guide the physician in providing better treatment to the patients. In the current work, three different computational approaches Computational Fluid Dynamics (CFD), Flow-Structure Interaction (FSI) and Particle Flow simulations were used to investigate flow in airway geometries. CFD approach assumes airway wall as rigid, and relatively easy to simulate, compared to the more challenging FSI approach, where interactions of airway wall deformations with flow are also accounted. The CFD methodology using different turbulence models is validated against experimental measurements in an airway phantom. Two case-studies using CFD, to quantify a pre and post-operative airway and another, to perform virtual surgery to determine the best possible surgery in a constricted airway is demonstrated. The unsteady

  18. Airway skills training using a human patient simulator

    African Journals Online (AJOL)

    Thesegan Moodley

    2016-04-11

    Apr 11, 2016 ... Patient simulators are widely employed in educational models ... Sarasota, USA) into our education model. ... Each teaching. Airway skills training using a human patient simulator. Thesegan Moodley* and Dean Gopalan. Discipline of Anaesthesiology and Critical Care, Nelson R Mandela School of ...

  19. Signalment, clinical presentation, concurrent diseases, and diagnostic findings in 28 dogs with dynamic pharyngeal collapse (2008-2013).

    Science.gov (United States)

    Rubin, J A; Holt, D E; Reetz, J A; Clarke, D L

    2015-01-01

    Most information about pharyngeal collapse in dogs is anecdotal and extrapolated from human medicine. A single case report describing dynamic pharyngeal collapse in a cat has been published, but there is no literature describing this disease process in dogs. To describe the signalment, clinical presentation, concurrent disease processes, and imaging findings of a population of client-owned dogs with pharyngeal collapse. Twenty-eight client-owned dogs with pharyngeal collapse. Radiology reports of dogs for which fluoroscopy of the respiratory system was performed were reviewed retrospectively. Patients with a fluoroscopic diagnosis of pharyngeal collapse were included in the study population. Data regarding clinical signs, diagnostic, and pathologic findings were evaluated. Twenty-eight dogs met the inclusion criteria. The median age of affected patients was 6.6 years, whereas median body condition score was 7/9. The most common clinical signs were coughing (n = 20) and stertor (n = 5). In 27 of 28 cases, a concurrent or previously diagnosed cardiopulmonary disorder was detected. The most common concurrent disease processes were mainstem bronchi collapse (n = 18), tracheal collapse (n = 17), and brachycephalic airway syndrome (n = 8). Fluoroscopy identified complete pharyngeal collapse in 20 of 28 dogs. Pharyngeal collapse is a complex disease process that likely is secondary to long-term negative pressure gradients and anatomic and functional abnormalities. Based on the findings of this study, pharyngeal fluoroscopy may be useful diagnostic test in patients with suspected tracheal and mainstem bronchial collapse to identify concurrent pharyngeal collapse. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  20. 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.

  1. Phenotypic Responses of Differentiated Asthmatic Human Airway Epithelial Cultures to Rhinovirus

    OpenAIRE

    Jianwu Bai; Smock, Steven L.; Jackson, George R.; MacIsaac, Kenzie D.; Yongsheng Huang; Courtney Mankus; Jonathan Oldach; Brian Roberts; Yu-Lu Ma; Klappenbach, Joel A.; Crackower, Michael A.; Alves, Stephen E.; Patrick J. Hayden

    2015-01-01

    Objectives Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Methods Air-liquid interface (ALI) human airway epithelial...

  2. Distribution of Major Basic Protein on Human Airway following In Vitro Eosinophil Incubation

    Directory of Open Access Journals (Sweden)

    Ailing Xue

    2010-01-01

    Full Text Available Major basic protein (MBP released from activated eosinophils may influence airway hyperresponsiveness (AHR by either direct effects on airway myocytes or by an indirect effect. In this study, human bronchi, freshly isolated human eosinophils, or MBP purified from human eosinophil granules were incubated for studying eosinophil infiltration and MBP localization. Eosinophils immediately adhered to intact human airway as well as to cultured human airway myocytes and epithelium. Following incubation 18–24 h, eosinophils migrated into the airway media, including the smooth muscle layer, but had no specific recruitment to airway neurons. Eosinophils released significant amounts of MBP within the airway media, including areas comprising the smooth muscle layer. Most deposits of MBP were focally discrete and restricted by immunologic detection to a maximum volume of ∼300 μm3 about the eosinophil. Native MBP applied exogenously was immediately deposited on the surface of the airway, but required at least 1 h to become detected within the media of the airway wall. Tissue MBP infiltration and deposition increased in a time- and concentration-dependent manner. Taken together, these findings suggest that eosinophil-derived cationic proteins may alter airway hyperresponsiveness (AHR in vivo by an effect that is not limited to the bronchial epithelium.

  3. Functional consequences of human airway smooth muscle phenotype plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G J; Bos, I Sophie T; Zaagsma, Johan; Meurs, Herman

    BACKGROUND AND PURPOSE: Airway smooth muscle (ASM) phenotype plasticity, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to increased ASM mass and airway hyper-responsiveness in asthma. Further, increased expression of collagen I

  4. 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

  5. Transduction efficiencies of novel AAV vectors in mouse airway epithelium in vivo and human ciliated airway epithelium in vitro.

    Science.gov (United States)

    Limberis, Maria P; Vandenberghe, Luk H; Zhang, Liqun; Pickles, Raymond J; Wilson, James M

    2009-02-01

    We have characterized the ability of adeno-associated virus (AAV) serotypes 1-9 in addition to nineteen novel vectors isolated from various tissues, to transduce mouse and human ciliated airway epithelium (HAE). Vectors expressing alpha-1-antitrypsin (AAT) and beta-galactosidase were co-instilled into the mouse lung. Of all the vectors tested rh.64R1, AAV5 and AAV6 were the most efficient. The high transduction observed in mouse was reproduced in HAE cell cultures for both rh.64R1 and AAV6 but not for AAV5. Since AAV6 was the most efficient vector in mouse and HAE we also tested the transduction efficiencies of the AAV6 singleton vectors (i.e., AAV6 variants with targeted mutations) in these models. Of these, AAV6.2 transduced mouse airway epithelium and HAE with greater efficiency than all other AAV vectors tested. We demonstrated that AAV6.2 exhibits improved transduction efficiency compared to previously reported AAVs in mouse airways and in culture models of human airway epithelium and that this vector requires further development for preclinical and clinical testing.

  6. 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

  7. Comparative biology of rAAV transduction in ferret, pig and human airway epithelia.

    Science.gov (United States)

    Liu, X; Luo, M; Guo, C; Yan, Z; Wang, Y; Engelhardt, J F

    2007-11-01

    Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. To this end, we have compared the transduction biology of three rAAV serotypes (AAV1, 2 and 5) in human, ferret, pig and mouse-polarized airway epithelia. Our results indicate that apical transduction of ferret and pig airway epithelia with these rAAV serotypes closely mirrors that observed in human epithelia (rAAV1>rAAV2 congruent withrAAV5), while transduction of mouse epithelia was significantly different (rAAV1>rAAV5>rAAV2). Similarly, ferret, pig and human epithelia also shared serotype-specific differences in the polarity (apical vs basolateral) and proteasome dependence of rAAV transduction. Despite these parallels, N-linked sialic acid receptors were required for rAAV1 and rAAV5 transduction of human and mouse airway epithelia, but not ferret or pig airway epithelia. Hence, although the airway tropisms of rAAV serotypes 1, 2 and 5 are conserved better among ferret, pig and human as compared to mouse, viral receptors/co-receptors appear to maintain considerable species diversity.

  8. Prevalence of pharyngeal infection by Neisseria gonorrhoeae among human immunodeficiency virus-positive men who have sex with men in downtown Madrid, 2011.

    Science.gov (United States)

    Jiménez, Esther; Pedrazuela, María García; Pérez, Marta Martínez; de Mosteyrín, Sol Fernández; Arrieta, Juan J; Guerrero, Manuel L Fernández

    2013-11-01

    The prevalence of pharyngeal gonorrhoea in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) is not entirely known. We cultured the pharynx of 264 asymptomatic HIV-positive MSM in downtown Madrid. A questionnaire on sexual and drug use risk behaviours was also administered. Gonococci were isolated in 25 (9.5%). Among the whole study population, 65% had a history of sexual intercourse with two or more partners on a single day and 26% were involved in group sex with other men. Only 29% regularly used condoms in all sexual encounters and 63% used condoms only in insertive anal intercourse. When asked about oral sex, 89% of patients engaged in insertive and/or receptive oral sex and 86% recognized that they did not regularly request the use of condoms when practising "fellatio" on a partner. Cocaine, crystal methamphetamine or alcohol use and a previous history of ≥1 sexually transmitted infection were significantly more common among culture-positive patients. Gonococcal colonization of the pharynx was self-limited in patients that were not treated and re-cultured a mean 18.5 ± 5.2 days after diagnosis. Asymptomatic pharyngeal gonorrhoea is common among HIV-positive MSM and may contribute to the increasing epidemic of gonorrhoea in Madrid.

  9. 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.

  10. 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.

  11. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells.

    Science.gov (United States)

    Huff, Ryan D; Hsu, Alan C-Y; Nichol, Kristy S; Jones, Bernadette; Knight, Darryl A; Wark, Peter A B; Hansbro, Philip M; Hirota, Jeremy A

    2017-01-01

    The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.

  12. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Ryan D Huff

    Full Text Available The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production.Allergen and cigarette smoke mouse models were performed using house dust mite (HDM and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies.HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4 inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells.Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines.

  13. Regulation of xanthine dehydrogensase gene expression and uric acid production in human airway epithelial cells

    Science.gov (United States)

    Huff, Ryan D.; Hsu, Alan C-Y.; Nichol, Kristy S.; Jones, Bernadette; Knight, Darryl A.; Wark, Peter A. B.; Hansbro, Philip M.

    2017-01-01

    Introduction The airway epithelium is a physical and immunological barrier that protects the pulmonary system from inhaled environmental insults. Uric acid has been detected in the respiratory tract and can function as an antioxidant or damage associated molecular pattern. We have demonstrated that human airway epithelial cells are a source of uric acid. Our hypothesis is that uric acid production by airway epithelial cells is induced by environmental stimuli associated with chronic respiratory diseases. We therefore examined how airway epithelial cells regulate uric acid production. Materials and methods Allergen and cigarette smoke mouse models were performed using house dust mite (HDM) and cigarette smoke exposure, respectively, with outcome measurements of lung uric acid levels. Primary human airway epithelial cells isolated from clinically diagnosed patients with asthma and chronic obstructive pulmonary disease (COPD) were grown in submerged cultures and compared to age-matched healthy controls for uric acid release. HBEC-6KT cells, a human airway epithelial cell line, were grown under submerged monolayer conditions for mechanistic and gene expression studies. Results HDM, but not cigarette smoke exposure, stimulated uric acid production in vivo and in vitro. Primary human airway epithelial cells from asthma, but not COPD patients, displayed elevated levels of extracellular uric acid in culture. In HBEC-6KT, production of uric acid was sensitive to the xanthine dehydrogenase (XDH) inhibitor, allopurinol, and the ATP Binding Cassette C4 (ABCC4) inhibitor, MK-571. Lastly, the pro-inflammatory cytokine combination of TNF-α and IFN-γ elevated extracellular uric acid levels and XDH gene expression in HBEC-6KT cells. Conclusions Our results suggest that the active production of uric acid from human airway epithelial cells may be intrinsically altered in asthma and be further induced by pro-inflammatory cytokines. PMID:28863172

  14. 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.

  15. 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...... amino acid substitutions at amino acids 112 and 158. The objective of this study was to assess whether the human apoE alleles modify airway responses to repeated nasal HDM challenges. Mice expressing the human apoE e2 (huApoE2), e3 (huApoE3), or e4 (huApoE4) alleles received nasal HDM challenges......, and airway responses were compared with mice expressing the endogenous murine apoE gene (muApoE). huApoE3 mice displayed significant reductions in AHR, mucous cell metaplasia, and airway inflammation compared with muApoE mice. The attenuated severity of airway inflammation in huApoE3 mice was associated...

  16. Human neutrophil elastase degrades SPLUNC1 and impairs airway epithelial defense against bacteria.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Acute exacerbations of chronic obstructive pulmonary disease (AECOPD are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare. One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi] infection. However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood. As neutrophilic inflammation including increased release of human neutrophil elastase (HNE is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1.Recombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE. To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells. The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi. We found that: (1 HNE directly increased NTHi load in human airway epithelial cells; (2 HNE degraded human SPLUNC1 protein; (3 Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4 NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5 SPLUNC1 was reduced in lungs of COPD patients.Our findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD.

  17. 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.

  18. Excitatory and inhibitory actions of isoprostanes in human and canine airway smooth muscle.

    Science.gov (United States)

    Janssen, L J; Premji, M; Netherton, S; Catalli, A; Cox, G; Keshavjee, S; Crankshaw, D J

    2000-11-01

    Isoprostanes are generated nonenzymatically during free radical-mediated lipid peroxidation, and are used clinically and experimentally as markers of oxidative stress. However, their biological effects are poorly understood. We examined the effects of seven different 8-isoprostanes in human and canine airway smooth muscles. In large order airways (carina) of the human, several isoprostanes evoked powerful contractions, with 8-iso-prostaglandin (PG) E(2), 8-iso-PGF(1 alpha), and 8-iso-PGF(2 alpha) being the most efficacious (and with logEC(50) values of 7.0, 5.9, and 6.2 microM, respectively). These contractions were sensitive to the prostanoid TP receptor antagonist ICI 192,605 (0.1-1 microM), but not the EP prostanoid receptor antagonist AH-6809 (50 microM), or the leukotriene receptor antagonists monteleukast or ICI 198,615 (both 1 microM). Qualitatively similar results were obtained in small order human airways (<2 mm o.d.), except that the isoprostanes were generally slightly less potent. None of the isoprostanes had any marked excitatory effect in canine airways. In carbachol-preconstricted tissues (pretreated with ICI 192,605 to block any potential contraction), several isoprostanes completely relaxed canine airways: 8-iso-PGE(1), 8-iso-PGE(2), and 8-iso-PGF(3 alpha) were the most potent, with logIC(50) values of 6.9, 6.9, and 5.7, respectively. Only 8-iso-PGF(3 alpha) relaxed human airways (logIC(50) = 4.9). Our results show that several 8-isoprostanes are highly biologically active in human and canine airways, evoking both excitatory and/or inhibitory effects, and that these effects are compound, species, and tissue dependent.

  19. 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.

  20. [Symptomatic therapy of pharyngeal pathology].

    Science.gov (United States)

    Turovskiĭ, A B; Kondrashina, V V

    2013-01-01

    The objective of the present work was to describe the current approaches to symptomatic therapy of pharyngeal diseases. The data on the principal pathogens responsible for pharyngeal pathology are presented in conjunction with the specific features of differential treatment of pharyngeal diseases taking into consideration the concrete causative factor. The possibility of using Strepsils pills for resorption is discussed.

  1. Biological Differences in rAAV Transduction of Airway Epithelia in Humans and in Old World Non-human Primates.

    Science.gov (United States)

    Liu, Xiaoming; Luo, Meihui; Trygg, Cyndi; Yan, Ziying; Lei-Butters, Diana C M; Smith, Carolina I; Fischer, Anne C; Munson, Keith; Guggino, William B; Bunnell, Bruce A; Engelhardt, John F

    2007-12-01

    Non-human primates (NHPs) are considered to be among the most relevant animal models for pre-clinical testing of human therapies, on the basis of their close evolutionary relatedness to humans in terms of organ cell biology and physiology. In this study, we sought to investigate whether NHP models accurately reflect the effectiveness of recombinant adeno-associated virus (rAAV)-mediated gene delivery to the airway in humans. In order to do this, we utilized an identical model system of differentiated airway epithelia from Indian Rhesus monkeys and from humans, cultured at an air-liquid interface (ALI). In addition to assessing the biology of rAAV-mediated transduction for three serotypes, we characterized the bioelectric properties as a reference for biological similarities and differences between the cell cultures from the two species. Our results demonstrate that airway epithelia from NHPs and humans have very similar Na(+) and Cl(-) transport properties. In contrast, rAAV transduction of airway epithelia of NHPs demonstrated significant differences to those in humans with regard to the efficiency of apical and/or basal transduction with three rAAV serotypes (AAV1, AAV2, AAV5). These findings suggest that the IndianRhesusmonkey may not be the best model for preclinical testing of rAAV-mediated gene therapy to the airway in humans.

  2. 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....

  3. 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.

  4. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Science.gov (United States)

    Bai, Jianwu; Smock, Steven L; Jackson, George R; MacIsaac, Kenzie D; Huang, Yongsheng; Mankus, Courtney; Oldach, Jonathan; Roberts, Brian; Ma, Yu-Lu; Klappenbach, Joel A; Crackower, Michael A; Alves, Stephen E; Hayden, Patrick J

    2015-01-01

    Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively. ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1). ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  5. Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.

    Directory of Open Access Journals (Sweden)

    Jianwu Bai

    Full Text Available Human airway epithelial cells are the principal target of human rhinovirus (HRV, a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1 to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2 to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model.Air-liquid interface (ALI human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively.ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3, and novel ones that were identified for the first time in this study (e.g. CCRL1.ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.

  6. [A method for the primary culture of fibroblasts isolated from human airway granulation tissues].

    Science.gov (United States)

    Chen, Nan; Zhang, Jie; Xu, Min; Wang, Yu-ling; Pei, Ying-hua

    2013-04-01

    To establish a feasible method to culture primary fibroblasts isolated from human airway granulation tissues, and therefore to provide experimental data for the investigation of the pathogenesis of benign airway stenosis. The granulation tissues were collected from 6 patients during routine bronchoscopy at our department of Beijing Tiantan Hospital from April to June 2011. Primary fibroblasts were obtained by culturing the explanted tissues. Cell growth was observed under inverted microscope. All of these 6 primary cultures were successful. Fibroblast-like cells were observed to migrate from the tissue pieces 3 d after inoculation. After 9-11 d of culture, cells reached to 90% confluence and could be sub-cultured. After passage, the cells were still in a typical elongated spindle-shape and grew well. The cells could be sub-cultured further when they formed a monolayer. Explant culture is a reliable method for culturing primary fibroblasts from human airway granulation tissues.

  7. Page 1 Modelling aerodynamic Sound in the human airways 10 dB ...

    Indian Academy of Sciences (India)

    Modelling aerodynamic Sound in the human airways. 10 dB/div (A) bond Centre frequency. Figure 6. Examples of 1/3 octave band power spectra of the microphone output for 5 mm thick obstacle in the wake-side of the vocal cord jet. The figures of group A are for the obstacle 51 mm downstream of the nozzle exit with the.

  8. Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line

    Directory of Open Access Journals (Sweden)

    Philipp Gierok

    2016-11-01

    Full Text Available The Gram positive opportunistic human pathogen Staphylococcus aureus induces a variety of diseases including pneumonia. S. aureus is the second most isolated pathogen in cystic fibrosis patients and accounts for a large proportion of nosocomial pneumonia. Inside the lung, the human airway epithelium is the first line in defence with regard to microbial recognition and clearance as well as regulation of the immune response. The metabolic host response is, however, yet unknown. To address the question of whether the infection alters the metabolome and metabolic activity of airway epithelial cells, we used a metabolomics approach. The nutrition uptake by the human airway epithelial cell line A549 was monitored over time by proton magnetic resonance spectroscopy (1H-NMR and the intracellular metabolic fingerprints were investigated by gas chromatography and high performance liquid chromatography (GC-MS and (HPLC-MS. To test the metabolic activity of the host cells, glutamine analogues and labelled precursors were applied after the infection. We found that A549 cells restrict uptake of essential nutrients from the medium after S. aureus infection. Moreover, the infection led to a shutdown of the purine and pyrimidine synthesis in the A549 host cell, whereas other metabolic routes such as the hexosamine biosynthesis pathway remained active. In summary, our data show that the infection with S. aureus negatively affects growth, alters the metabolic composition and specifically impacts the de novo nucleotide biosynthesis in this human airway epithelial cell model.

  9. Human neutrophil defensins and secretory leukocyte proteinase inhibitor in squamous metaplastic epithelium of bronchial airways.

    NARCIS (Netherlands)

    Aarbiou, J.; Schadewijk, A. van; Stolk, J.; Sont, J.K.; Boer, W.I.; Rabe, K.F.; Krieken, J.H.J.M. van; Mauad, T.; Hiemstra, P.S.

    2004-01-01

    OBJECTIVE: The aim of this study was to analyze a possible contribution of human neutrophil defensins and secretory leukocyte proteinase inhibitor (SLPI) to the induction of airway epithelial changes such as squamous cell metaplasia. MATERIALS AND METHODS: The presence of these molecules and the

  10. 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

  11. Unique Biologic Properties of Recombinant AAV1 Transduction in Polarized Human Airway Epithelia

    National Research Council Canada - National Science Library

    Ziying Yan; Diana C. M. Lei-Butters; Xiaoming Liu; Yulong Zhang; Liang Zhang; Meihui Luo; Roman Zak; John F. Engelhardt

    2006-01-01

    .... In the present study, we sought to compare the biologic properties of rAAV2/1, rAAV2/2, and rAAV2/5 transduction in polarized human airway epithelia using viruses purified by a newly developed common...

  12. 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...

  13. 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.

  14. Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Qun Wu

    Full Text Available Human rhinovirus (HRV is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5 effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I and IFN-β promoter stimulator 1 (IPS-1, two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

  15. 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

  16. 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.

  17. Human Metapneumovirus Attachment Protein Contributes to Neutrophil Recruitment into the Airways of Infected Mice

    Directory of Open Access Journals (Sweden)

    Nagarjuna R. Cheemarla

    2017-10-01

    Full Text Available Human Metapneumovirus (HMPV is a leading respiratory pathogen that causes lower respiratory tract infections worldwide. Acute HMPV infection induces an exacerbated inflammatory neutrophilic response leading to bronchiolitis and pneumonia. However, the mechanism by which the virus regulates neutrophil infiltration into the airways still remains unexplored. In this work, we used an experimental mouse model of HMPV infection to demonstrate that the attachment (G protein of HMPV contributes to the recruitment of neutrophils into the airways and modulate the production of neutrophil chemoattractants and Type I IFN responses, specifically IFN-α. These findings provide the first evidence that the HMPV G protein contributes to the in vivo neutrophilic response to HMPV infection and furthers our understanding on virus induced inflammatory responses in the airways.

  18. Premature infants have impaired airway antiviral IFNγ responses to human metapneumovirus compared to respiratory syncytial virus.

    Science.gov (United States)

    Pancham, Krishna; Perez, Geovanny F; Huseni, Shehlanoor; Jain, Amisha; Kurdi, Bassem; Rodriguez-Martinez, Carlos E; Preciado, Diego; Rose, Mary C; Nino, Gustavo

    2015-10-01

    It is unknown why human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) cause severe respiratory infection in children, particularly in premature infants. Our aim was to investigate if there are defective airway antiviral responses to these viruses in young children with history of prematurity. Nasal airway secretions were collected from 140 children ≤ 3 y old without detectable virus (n = 80) or with PCR-confirmed HMPV or RSV infection (n = 60). Nasal protein levels of IFNγ, CCL5/RANTES, IL-10, IL-4, and IL-17 were determined using a multiplex magnetic bead immunoassay. Full-term children with HMPV and RSV infection had increased levels of nasal airway IFNγ, CCL5, and IL-10 along with an elevation in Th1 (IFNγ)/Th2 (IL-4) ratios, which is expected during antiviral responses. In contrast, HMPV-infected premature children (respiratory disease in children with history of prematurity.

  19. Human Rhinovirus Infection of Epithelial Cells Modulates Airway Smooth Muscle Migration.

    Science.gov (United States)

    Shariff, Sami; Shelfoon, Christopher; Holden, Neil S; Traves, Suzanne L; Wiehler, Shahina; Kooi, Cora; Proud, David; Leigh, Richard

    2017-06-01

    Airway remodeling, a characteristic feature of asthma, begins in early life. Recurrent human rhinovirus (HRV) infections are a potential inciting stimulus for remodeling. One component of airway remodeling is an increase in airway smooth muscle cell (ASMC) mass with a greater proximity of the ASMCs to the airway epithelium. We asked whether human bronchial epithelial cells infected with HRV produced mediators that are chemotactic for ASMCs. ASMC migration was investigated using the modified Boyden Chamber and the xCELLigence Real-Time Cell Analyzer (ACEA Biosciences Inc., San Diego, CA). Multiplex bead analysis was used to measure HRV-induced epithelial chemokine release. The chemotactic effects of CCL5, CXCL8, and CXCL10 were also examined. Supernatants from HRV-infected epithelial cells caused ASMC chemotaxis. Pretreatment of ASMCs with pertussis toxin abrogated chemotaxis, as did treatment with formoterol, forskolin, or 8-bromo-cAMP. CCL5, CXCL8, and CXCL10 were the most up-regulated chemokines produced by HRV-infected airway epithelial cells. When recombinant CCL5, CXCL8, and CXCL10 were used at levels found in epithelial supernatants, they induced ASMC chemotaxis similar to that seen with epithelial cell supernatants. When examined individually, CCL5 was the most effective chemokine in causing ASMC migration, and treatment of supernatant from HRV-infected epithelial cells with anti-CCL5 antibodies significantly attenuated ASMC migration. These findings suggest that HRV-induced CCL5 can induce ASMC chemotaxis and thus may contribute to the pathogenesis of airway remodeling in patients with asthma.

  20. Smoking-mediated up-regulation of GAD67 expression in the human airway epithelium.

    Science.gov (United States)

    Wang, Guoqing; Wang, Rui; Ferris, Barbara; Salit, Jacqueline; Strulovici-Barel, Yael; Hackett, Neil R; Crystal, Ronald G

    2010-10-29

    The production of gamma-amino butyric acid (GABA) is dependent on glutamate decarboxylases (GAD65 and GAD67), the enzymes that catalyze the decarboxylation of glutamate to GABA. Based on studies suggesting a role of the airway epithelial GABAergic system in asthma-related mucus overproduction, we hypothesized that cigarette smoking, another disorder associated with increased mucus production, may modulate GABAergic system-related gene expression levels in the airway epithelium. We assessed expression of the GABAergic system in human airway epithelium obtained using bronchoscopy to sample the epithelium and microarrays to evaluate gene expression. RT-PCR was used to confirm gene expression of GABAergic system gene in large and small airway epithelium from heathy nonsmokers and healthy smokers. The differences in the GABAergic system gene was further confirmed by TaqMan, immunohistochemistry and Western analysis. The data demonstrate there is a complete GABAergic system expressed in the large and small human airway epithelium, including glutamate decarboxylase, GABA receptors, transporters and catabolism enzymes. Interestingly, of the entire GABAergic system, smoking modified only the expression of GAD67, with marked up-regulation of GAD67 gene expression in both large (4.1-fold increase, p smoking. In the context that GAD67 is the rate limiting enzyme in GABA synthesis, the correlation of GAD67 gene expression with MUC5AC expressions suggests that the up-regulation of airway epithelium expression of GAD67 may contribute to the increase in mucus production observed in association with cigarette smoking. NCT00224198; NCT00224185.

  1. Apical Localization of Zinc Transporter ZnT4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Chiara Murgia

    2011-10-01

    Full Text Available The apical cytoplasm of airway epithelium (AE contains abundant labile zinc (Zn ions that are involved in the protection of AE from oxidants and inhaled noxious substances. A major question is how dietary Zn traffics to this compartment. In rat airways, in vivo selenite autometallographic (Se-AMG-electron microscopy revealed labile Zn-selenium nanocrystals in structures resembling secretory vesicles in the apical cytoplasm. This observation was consistent with the starry-sky Zinquin fluorescence staining of labile Zn ions confined to the same region. The vesicular Zn transporter ZnT4 was likewise prominent in both the apical and basal parts of the epithelium both in rodent and human AE, although the apical pools were more obvious. Expression of ZnT4 mRNA was unaffected by changes in the extracellular Zn concentration. However, levels increased 3-fold during growth of cells in air liquid interface cultures and decreased sharply in the presence of retinoic acid. When comparing nasal versus bronchial human AE cells, there were significant positive correlations between levels of ZnT4 from the same subject, suggesting that nasal brushings may allow monitoring of airway Zn transporter expression. Finally, there were marked losses of both basally-located ZnT4 protein and labile Zn in the bronchial epithelium of mice with allergic airway inflammation. This study is the first to describe co-localization of zinc vesicles with the specific zinc transporter ZnT4 in airway epithelium and loss of ZnT4 protein in inflamed airways. Direct evidence that ZnT4 regulates Zn levels in the epithelium still needs to be provided. We speculate that ZnT4 is an important regulator of zinc ion accumulation in secretory apical vesicles and that the loss of labile Zn and ZnT4 in airway inflammation contributes to AE vulnerability in diseases such as asthma.

  2. High mobility group box 1-induced epithelial mesenchymal transition in human airway epithelial cells.

    Science.gov (United States)

    Chen, Yu-Ching; Statt, Sarah; Wu, Reen; Chang, Hao-Teng; Liao, Jiunn-Wang; Wang, Chien-Neng; Shyu, Woei-Cherng; Lee, Chen-Chen

    2016-01-07

    Epithelial-mesenchymal transition (EMT) is implicated in bronchial remodeling and loss of lung function in chronic inflammatory airway diseases. Previous studies showed the involvement of the high mobility group box 1 (HMGB1) protein in the pathology of chronic pulmonary inflammatory diseases. However, the role of HMGB1 in EMT of human airway epithelial cells is still unclear. In this study, we used RNA sequencing to show that HMGB1 treatment regulated EMT-related gene expression in human primary-airway epithelial cells. The top five upregulated genes were SNAI2, FGFBP1, VIM, SPARC (osteonectin), and SERPINE1, while the downregulated genes included OCLN, TJP1 (ZO-1), FZD7, CDH1 (E-cadherin), and LAMA5. We found that HMGB1 induced downregulation of E-cadherin and ZO-1, and upregulation of vimentin mRNA transcription and protein translation in a dose-dependent manner. Additionally, we observed that HMGB1 induced AKT phosphorylation, resulting in GSK3β inactivation, cytoplasmic accumulation, and nuclear translocation of β-catenin to induce EMT in human airway epithelial cells. Treatment with PI3K inhibitor (LY294006) and β-catenin shRNA reversed HMGB1-induced EMT. Moreover, HMGB1 induced expression of receptor for advanced glycation products (RAGE), but not that of Toll-like receptor (TLR) 2 or TLR4, and RAGE shRNA inhibited HMGB1-induced EMT in human airway epithelial cells. In conclusion, we found that HMGB1 induced EMT through RAGE and the PI3K/AKT/GSK3β/β-catenin signaling pathway.

  3. Effect of High Glucose on MUC5B expression in Human Airway Epithelial Cells.

    Science.gov (United States)

    Ye, Sang Baik; Choi, Yoon Seok; Choi, Yo Han; Bae, Chang Hoon; Kim, Yong-Woon; Park, So-Young; Song, Si-Youn; Kim, Yong-Dae

    2017-03-01

    Excessive production of mucus results in plugging of the airway tract, which can increase morbidity and mortality in affected patients. In patients with diabetes, inflammatory airway disease appears with more frequent relapse and longer duration of symptoms. However, the effects of high glucose (HG) on the secretion of mucin in inflammatory respiratory diseases are not clear. Therefore, this study was conducted in order to investigate the effect and the brief signaling pathway of HG on MUC5B expression in human airway epithelial cells. The effect and signaling pathway of HG on MUC5B expression were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA. HG increased MUC5B expression and epidermal growth factor receptor (EGFR) expression, and activated the phosphorylation of EGFR and p38 mitogen-activated protein kinase (MAPK). Pretreatment with EGFR inhibitor significantly attenuated the HG-induced phosphorylation of p38 MAPK, and pretreatments with p38 inhibitor or EGFR inhibitor significantly attenuated HG-induced MUC5B expression. In addition, knockdown of p38 MAPK by p38 MAPK siRNA significantly blocked HG-induced MUC5B expression. These findings suggest that HG induces MUC5B expression via the sequential activations of the EGFR/p38 MAPK signaling pathway in human airway epithelial cells.

  4. Replication of human tracheobronchial hollow airway models using a selective laser sintering rapid prototyping technique.

    Science.gov (United States)

    Clinkenbeard, Rodney E; Johnson, David L; Parthasarathy, Ramkumar; Altan, M Cengiz; Tan, Kah-Hoe; Park, Seok-Min; Crawford, Richard H

    2002-01-01

    Exposures to toxic or pathogenic aerosols are known to produce adverse health effects. The nature and severity of these effects often are governed in large part by the location and amount of aerosol deposition within the respiratory tract. Morphologically detailed replica hollow lung airway casts are widely used in aerosol deposition research; however, techniques are not currently available that allow replicate deposition studies in identical morphologically detailed casts produced from a common reference anatomy. This project developed a technique for the precision manufacture of morphologically detailed human tracheobronchial airway models based on high-resolution anatomical imaging data. Detailed physical models were produced using the selective laser sintering (SLS) rapid prototyping process. Input to the SLS process was a three-dimensional computer model developed by boundary-based two-dimension to three-dimension conversion of anatomical images from the original National Institutes of Health/National Library of Medicine Visible Human male data set. The SLS process produced identical replicate models that corresponded exactly to the anatomical section images, within the limits of the measurement. At least five airway generations were achievable, corresponding to airways less than 2 mm in diameter. It is anticipated that rapid prototyping manufacture of respiratory tract structures based on reference anatomies such as the Visible Male and Visible Female may provide "gold standard" models for inhaled aerosol deposition studies. Adaptations of the models to represent various disease states may be readily achieved, thereby promoting exploration of pharmaceutical research on targeted drug delivery via inhaled aerosols.

  5. Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation.

    Science.gov (United States)

    Taranto-Montemurro, Luigi; Sands, Scott A; Edwards, Bradley A; Azarbarzin, Ali; Marques, Melania; de Melo, Camila; Eckert, Danny J; White, David P; Wellman, Andrew

    2016-11-01

    We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea-hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V'0,passive) and active (V'0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced active Pcrit (median (interquartile range) -5.2 (4.3) cmH2O on desipramine versus -1.9 (2.7) cmH2O on placebo; p=0.049) but not passive Pcrit (-2.2 (3.4) versus -0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined as V'0,active-V'0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation. Copyright ©ERS 2016.

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

    Science.gov (United States)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning; Wang, Jingjing; Wang, Zailiang; Yan, Xiaopei; Wang, Yanli; Xie, Weiping; Wang, Hong

    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 (KATP) channels have been identified in ASMCs. Mount evidence has suggested that KATP channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K(+) channels triggers K(+) efflux, which leading to membrane hyperpolarization, preventing Ca(2+)entry through closing voltage-operated Ca(2+) channels. Intracellular Ca(2+) is the most important regulator of muscle contraction, cell proliferation and migration. K(+) efflux decreases Ca(2+) influx, which consequently influences ASMCs proliferation and migration. As a KATP 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(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 KATP channel antagonist. These findings provide a strong evidence to support that Ipt antagonize the proliferating and migrating effects of PDGF-BB on

  7. Unique biologic properties of recombinant AAV1 transduction in polarized human airway epithelia.

    Science.gov (United States)

    Yan, Ziying; Lei-Butters, Diana C M; Liu, Xiaoming; Zhang, Yulong; Zhang, Liang; Luo, Meihui; Zak, Roman; Engelhardt, John F

    2006-10-06

    The choice of adeno-associated virus serotypes for clinical applications is influenced by the animal model and model system used to evaluate various serotypes. In the present study, we sought to compare the biologic properties of rAAV2/1, rAAV2/2, and rAAV2/5 transduction in polarized human airway epithelia using viruses purified by a newly developed common column chromatography method. Results demonstrated that apical transduction of human airway epithelia with rAAV2/1 was 100-fold more efficient than rAAV2/2 and rAAV2/5. This transduction profile in human airway epithelia (rAAV2/1 > rAAV2/2 = rAAV2/5) was significantly different from that seen following nasal administration of these vectors to mouse lung (rAAV2/5 > rAAV2/1 > rAAV2/2), emphasizing differences in transduction of these serotypes between these two species. In stark contrast to rAAV2/2 and rAAV2/5, rAAV2/1 transduced both the apical and basolateral membrane of human airway epithelia with similar efficiency. However, the overall level of transduction across serotypes did not correlate with vector internalization. We hypothesized that differences in post-entry processing of these serotypes might influence the efficiency of apical transduction. To this end, we tested the effectiveness of proteasome inhibitors to augment nuclear translocation and gene expression from the three serotypes. Augmentation of rAAV2/1 apical transduction of human polarized airway epithelia was 10-fold lower than that for rAAV2/2 and rAAV2/5. Cellular fractionation studies demonstrated that proteasome inhibitors more significantly enhanced rAAV2/2 and rAAV2/5 translocation to the nucleus than rAAV2/1. These results demonstrate that AAV1 transduction biology in human airway epithelia differs from that of AAV2 and AAV5 by virtue of altered ubiquitin/proteasome sensitivities that influence nuclear translocation.

  8. 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.

  9. Respiratory syncytial virus can infect basal cells and alter human airway epithelial differentiation.

    Directory of Open Access Journals (Sweden)

    B David Persson

    Full Text Available Respiratory syncytial virus (RSV is a major cause of morbidity and mortality worldwide, causing severe respiratory illness in infants and immune compromised patients. The ciliated cells of the human airway epithelium have been considered to be the exclusive target of RSV, although recent data have suggested that basal cells, the progenitors for the conducting airway epithelium, may also become infected in vivo. Using either mechanical or chemical injury models, we have demonstrated a robust RSV infection of p63+ basal cells in air-liquid interface (ALI cultures of human bronchial epithelial cells. In addition, proliferating basal cells in 2D culture were also susceptible to RSV infection. We therefore tested the hypothesis that RSV infection of this progenitor cell would influence the differentiation status of the airway epithelium. RSV infection of basal cells on the day of seeding (MOI≤0.0001, resulted in the formation of an epithelium that showed a profound loss of ciliated cells and gain of secretory cells as assessed by acetylated α-tubulin and MUC5AC/MUC5B immunostaining, respectively. The mechanism driving the switch in epithelial phenotype is in part driven by the induced type I and type III interferon response that we demonstrate is triggered early following RSV infection. Neutralization of this response attenuates the RSV-induced loss of ciliated cells. Together, these data show that through infection of proliferating airway basal cells, RSV has the potential to influence the cellular composition of the airway epithelium. The resulting phenotype might be expected to contribute towards both the severity of acute infection, as well as to the longer-term consequences of viral exacerbations in patients with pre-existing respiratory diseases.

  10. 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.

  11. FOXJ1 Prevents Cilia Growth Inhibition by Cigarette Smoke in Human Airway Epithelium In Vitro

    Science.gov (United States)

    Brekman, Angelika; Walters, Matthew S.; Tilley, Ann E.

    2014-01-01

    Airway epithelium ciliated cells play a central role in clearing the lung of inhaled pathogens and xenobiotics, and cilia length and coordinated beating are important for airway clearance. Based on in vivo studies showing that the airway epithelium of healthy smokers has shorter cilia than that of healthy nonsmokers, we investigated the mechanisms involved in cigarette smoke–mediated inhibition of ciliogenesis by assessing normal human airway basal cell differentiation in air–liquid interface (ALI) cultures in the presence of nontoxic concentrations of cigarette smoke extract (CSE). Measurements of cilia length from Day 28 ALI cultures demonstrated that CSE exposure was associated with shorter cilia (P cilia length observed in vivo. This phenotype correlated with a broad CSE-mediated suppression of genes involved in cilia-related transcriptional regulation, intraflagellar transport, cilia motility, structural integrity, and basal body development but not of control genes or epithelial barrier integrity. The CSE-mediated inhibition of cilia growth could be prevented by lentivirus-mediated overexpression of FOXJ1, the major cilia-related transcription factor, which led to partial reversal of expression of cilia-related genes suppressed by CSE. Together, the data suggest that components of cigarette smoke are responsible for a broad suppression of genes involved in cilia growth, but, by stimulating ciliogenesis with the transcription factor FOXJ1, it may be possible to maintain close to normal cilia length despite the stress of cigarette smoking. PMID:24828273

  12. Human Airway Epithelial Cells Direct Significant Rhinovirus Replication in Monocytic Cells by Enhancing ICAM1 Expression.

    Science.gov (United States)

    Zhou, Xu; Zhu, Lingxiang; Lizarraga, Rosa; Chen, Yin

    2017-08-01

    Human rhinovirus (RV) is the major cause of common cold, and it also plays a significant role in asthma and asthma exacerbation. The airway epithelium is the primary site of RV infection and production. In contrast, monocytic cells (e.g., monocytes and macrophages) are believed to be nonpermissive for RV replication. Instead, RV has been shown to modulate inflammatory gene expressions in these cells via a replication-independent mechanism. In the study presented here, replication of RV16 (a major-group RV) was found to be significantly enhanced in monocytes when it was cocultivated with airway epithelial cells. This effect appeared to be mediated by secretory components from epithelial cells, which stimulated RV16 replication and significantly elevated the expression of a number of proinflammatory cytokines. The lack of such an effect on RV1A, a minor-group RV that enters the cell by a different receptor, suggests that intercellular adhesion molecule 1 (ICAM1), the receptor for major-group RVs, may be involved. Indeed, conditioned media from epithelial cells significantly increased ICAM1 expression in monocytes. Consistently, ICAM1 overexpression and ICAM1 knockdown enhanced and blocked RV production, respectively, confirming the role of ICAM1 in this process. Thus, this is the first report demonstrating that airway epithelial cells direct significant RV16 replication in monocytic cells via an ICAM1-dependent mechanism. This finding will open a new avenue for the study of RV infection in airway disease and its exacerbation.

  13. Interleukin-13–Induced Mucous Metaplasia Increases Susceptibility of Human Airway Epithelium to Rhinovirus Infection

    Science.gov (United States)

    Lachowicz-Scroggins, Marrah E.; Boushey, Homer A.; Finkbeiner, Walter E.; Widdicombe, Jonathan H.

    2010-01-01

    Infection of airway epithelium by rhinovirus is the most common cause of asthma exacerbations. Even in mild asthma, airway epithelium exhibits mucous metaplasia, which increases with increasing severity of the disease. We previously showed that squamous cultures of human airway epithelium manifest rhinoviral infection at levels many times higher than in well-differentiated cultures of a mucociliary phenotype. Here we tested the hypothesis that mucous metaplasia is also associated with increased levels of rhinoviral infection. Mucous metaplasia was induced with IL-13, which doubled the numbers of goblet cells. In both control (mucociliary) and IL-13– treated (mucous metaplastic) cultures, goblet cells were preferentially infected by rhinovirus. IL-13 doubled the numbers of infected cells by increasing the numbers of infected goblet cells. Furthermore, IL-13 increased both the maturity of goblet cells and the probability that a goblet cell would be infected. The infection of cells other than goblet cells was unaltered by IL-13. Treatment with IL-13 did not alter the levels of rhinovirus receptor ICAM-1, nor did the proliferative effects of IL-13 enhance infection, because rhinovirus did not colocalize with dividing cells. However, the induction of mucous metaplasia caused changes in the apical membrane structure, notably a marked decrease in overall ciliation, and an increase in the overall flatness of the apical surface. We conclude that mucous metaplasia in asthma increases the susceptibility of airway epithelium to infection by rhinovirus because of changes in the overall architecture of the apical surface. PMID:20081054

  14. Mechanisms used to restore ventilation after partial upper airway collapse during sleep in humans.

    Science.gov (United States)

    Jordan, Amy S; Wellman, Andrew; Heinzer, Raphael C; Lo, Yu-Lun; Schory, Karen; Dover, Louise; Gautam, Shiva; Malhotra, Atul; White, David P

    2007-10-01

    Most patients with obstructive sleep apnoea (OSA) can restore airflow after an obstructive respiratory event without arousal at least some of the time. The mechanisms that enable this ventilatory recovery are unclear but probably include increased upper airway dilator muscle activity and/or changes in respiratory timing. The aims of this study were to compare the ability to recover ventilation and the mechanisms of compensation following a sudden reduction of continuous positive airway pressure (CPAP) in subjects with and without OSA. Ten obese patients with OSA (mean (SD) apnoea-hypopnoea index 62.6 (12.4) events/h) and 15 healthy non-obese non-snorers were instrumented with intramuscular genioglossus electrodes and a mask/pneumotachograph which was connected to a modified CPAP device that could deliver either continuous positive or negative pressure. During stable non-rapid eye movement sleep the CPAP was repeatedly reduced 2-10 cm H2O below the level required to eliminate flow limitation and was held at this level for 5 min or until arousal from sleep occurred. During reduced CPAP the increases in genioglossus activity (311.5 (49.4)% of baseline in subjects with OSA and 315.4 (76.2)% of baseline in non-snorers, p = 0.9) and duty cycle (123.8 (3.9)% of baseline in subjects with OSA and 118.2 (2.8)% of baseline in non-snorers, p = 0.4) were similar in both groups, yet patients with OSA could restore ventilation without cortical arousal less often than non-snorers (54.1% vs 65.7% of pressure drops, p = 0.04). When ventilatory recovery did not occur, genioglossus muscle and respiratory timing changes still occurred but these did not yield adequate pharyngeal patency/ventilation. Compensatory mechanisms (increased genioglossus muscle activity and/or duty cycle) often restore ventilation during sleep but may be less effective in obese patients with OSA than in non-snorers.

  15. Novel flow cytometry approach to identify bronchial epithelial cells from healthy human airways

    OpenAIRE

    Danay Maestre-Batlle; Pena, Olga M.; Hirota, Jeremy A.; Evelyn Gunawan; Rider, Christopher F.; Darren Sutherland; Alexis, Neil E.; Chris Carlsten

    2017-01-01

    Sampling various compartments within the lower airways to examine human bronchial epithelial cells (HBEC) is essential for understanding numerous lung diseases. Conventional methods to identify HBEC in bronchoalveolar lavage (BAL) and wash (BW) have throughput limitations in terms of efficiency and ensuring adequate cell numbers for quantification. Flow cytometry can provide high-throughput quantification of cell number and function in BAL and BW samples, while requiring low cell numbers. To ...

  16. 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 ...

  17. Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia.

    Science.gov (United States)

    Yamada, Takahiro; Takemura, Yoshizumi; Niisato, Naomi; Mitsuyama, Etsuko; Iwasaki, Yoshinobu; Marunaka, Yoshinori

    2009-03-13

    We report the effects of new N-acylated ambroxol derivatives (TEI-588a, TEI-588b, TEI-589a, TEI-589b, TEI-602a and TEI-602b: a, aromatic amine-acylated derivative; b, aliphatic amine-acylated derivative) induced from ambroxol (a mucolytic agent to treat human lung diseases) on Cl(-) secretion in human submucosal serous Calu-3 cells under a Na(+)/K(+)/2Cl(-) cotransporter-1 (NKCC1)-mediated hyper-secreting condition. TEI-589a, TEI-589b and TEI-602a diminished hyper-secretion of Cl(-) by diminishing the activity of NKCC1 without blockade of apical Cl(-) channel (TEI-589a>TEI-602a>TEI-589b), while any other tested compounds including ambroxol had no effects on Cl(-) secretion. These indicate that the inhibitory action of an aromatic amine-acylated derivative on Cl(-) secretion is stronger that that of an aliphatic amine-acylated derivative, and that 3-(2,5-dimethyl)furoyl group has a strong action in inhibition of Cl(-) secretion than cyclopropanoyl group. We here indicate that TEI-589a, TEI-589b and TEI-602a reduce hyper-secretion to an appropriate level in the airway, providing a possibility that the compound can be an effective drug in airway obstructive diseases including COPD by reducing the airway resistance under a hyper-secreting condition.

  18. Dexamethasone and N-acetyl-cysteine attenuate Pseudomonas aeruginosa-induced mucus expression in human airways.

    Science.gov (United States)

    Sprenger, Lisa; Goldmann, Torsten; Vollmer, Ekkehard; Steffen, Armin; Wollenberg, Barbara; Zabel, Peter; Hauber, Hans-Peter

    2011-04-01

    Infection with Pseudomonas aeruginosa (PA) induces mucus hypersecretion in airways. Therapeutic options to attenuate excessive mucus expression are sparse. To investigate the effect of steroids and N-acetyl-cysteine (NAC) on PA-induced mucus expression. Calu-3 cells and explanted human mucosa from the upper airways were stimulated with either PA, lipopolysaccharide from alginate producing PA (smooth, sPA-LPS) or non-alginate producing PA (rough, rPA-LPS). Dexamethasone (DEX) and NAC were added in different concentrations. Expression of mucin (MUC5AC) gene and mucin protein expression was quantified using PAS (periodic acids Schiff) staining and real time PCR. PA, sPA-LPS or rPA-LPS significantly induced mucin protein and MUC5AC gene expression in Calu-3 cells and explanted mucosal tissue (P NAC significantly decreased PA-, sPA-LPS- and rPA-LPS-induced mucin protein expression both in vitro and ex vivo (P 0.05). Our data show that both an anti-inflammatory drug (DEX) and an anti-oxidative agent (NAC) can attenuate PA-induced mucus expression in human airways. These results support the use of steroids and NAC in clinical practice to treat PA-induced mucus hypersecretion. Copyright © 2010 Elsevier Ltd. All rights reserved.

  19. 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.

  20. Comparative biology of rAAV transduction in ferret, pig and human airway epithelia

    OpenAIRE

    Liu, X.; Luo, M.; Guo, C.; Yan, Z.; Wang, Y.; Engelhardt, JF

    2007-01-01

    Differences between rodent and human airway cell biology have made it difficult to translate recombinant adeno-associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig models for CF become available, knowledge about host cell/vector interactions in these species will become increasingly important for testing potential gene therapies. To this end, we have compared the transduction biology of three rAAV serotypes (AAV1, 2 and 5) in human, ferre...

  1. Nitric oxide gas phase release in human small airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Suresh Vinod

    2009-01-01

    Full Text Available Abstract Background Asthma is a chronic airway inflammatory disease characterized by an imbalance in both Th1 and Th2 cytokines. Exhaled nitric oxide (NO is elevated in asthma, and is a potentially useful non-invasive marker of airway inflammation. However, the origin and underlying mechanisms of intersubject variability of exhaled NO are not yet fully understood. We have previously described NO gas phase release from normal human bronchial epithelial cells (NHBEs, tracheal origin. However, smaller airways are the major site of morbidity in asthma. We hypothesized that IL-13 or cytomix (IL-1β, TNF-α, and IFN-γ stimulation of differentiated small airway epithelial cells (SAECs, generation 10–12 and A549 cells (model cell line of alveolar type II cells in culture would enhance NO gas phase release. Methods Confluent monolayers of SAECs and A549 cells were cultured in Transwell plates and SAECs were allowed to differentiate into ciliated and mucus producing cells at an air-liquid interface. The cells were then stimulated with IL-13 (10 ng/mL or cytomix (10 ng/mL for each cytokine. Gas phase NO release in the headspace air over the cells was measured for 48 hours using a chemiluminescence analyzer. Results In contrast to our previous result in NHBE, baseline NO release from SAECs and A549 is negligible. However, NO release is significantly increased by cytomix (0.51 ± 0.18 and 0.29 ± 0.20 pl.s-1.cm-2, respectively reaching a peak at approximately 10 hours. iNOS protein expression increases in a consistent pattern both temporally and in magnitude. In contrast, IL-13 only modestly increases NO release in SAECs reaching a peak (0.06 ± 0.03 pl.s-1.cm-2 more slowly (30 to 48 hours, and does not alter NO release in A549 cells. Conclusion We conclude that the airway epithelium is a probable source of NO in the exhaled breath, and intersubject variability may be due, in part, to variability in the type (Th1 vs Th2 and location (large vs small airway

  2. 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.

  3. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro

    OpenAIRE

    Benam, Kambez H; Villenave, Remi; Lucchesi, Carolina; Varone, Antonio; Hubeau, Cedric; Lee, Hyun-Hee; Alves, Stephen E; Salmon, Michael; Ferrante, Thomas Charles; Weaver, James C.; Bahinski, Anthony; Hamilton, Geraldine A; Ingber, Donald Elliot

    2015-01-01

    Here we describe development of a human ‘lung small airway-on-a-chip’ containing a differentiated, mucociliary, bronchiolar epithelium and an underlying microvascular endothelium that experiences fluid flow, which enables analysis of organ-level lung pathophysiology in vitro. Exposure of the epithelium to IL-13 reconstitutes the goblet cell hyperplasia, cytokine hypersecretion and decreased ciliary function of asthmatics. Small airway chips lined by epithelial cells from chronic obstructive p...

  4. 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.

  5. 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.

  6. Flow in the human upper airway: work of breathing and the compliant soft palate and tongue

    Science.gov (United States)

    Jermy, Mark; Adams, Cletus; Aplin, Jonathan; Buchajczyk, Marcin; van Hove, Sibylle; Kabaliuk, Natalia; Geoghegan, Patrick; Cater, John

    2016-11-01

    The human upper airway (nasal cavity, pharynx and trachea) filters, heats and humidifies inspired air. Its pressure drop affects the work of breathing (WOB, energy expended to inspire and expire) to a degree which varies from person to person, and which is altered by breathing therapy devices. We report experimental studies using 3D printed models of the upper airway based on CT scans of single individuals (adult and paediatric), and average geometries based on PCA analysis of 150 individuals. Particle Image Velocimetry (PIV), gas concentration and pressure measurements, coupled with CFD simulation. These reveal the details of the washout of CO2 rich exhaled gas, the direction-dependent time-varying pressure drop, and the effect of high-flow nasal therapy (HFNT) on these phenomena. A 1D multi-compartment model is used to estimate the work of breathing. For the first time, soft (compliant) elements have been included in the model airways and show that the assumption of rigid tissue is acceptable for unassisted breathing, but unrealistic for therapy-assisted flows.

  7. Staphylococcus aureus hemolysin A disrupts cell-matrix adhesions in human airway epithelial cells.

    Science.gov (United States)

    Hermann, Ina; Räth, Susann; Ziesemer, Sabine; Volksdorf, Thomas; Dress, Regine J; Gutjahr, Melanie; Müller, Christian; Beule, Achim G; Hildebrandt, Jan-Peter

    2015-01-01

    Treatment of primary or immortalized human airway epithelial cells (16HBE14o-, S9) or alveolar cancer cells (A549) with recombinant hemolysin A (rHla), a major virulence-associated factor of Staphylococcus aureus, induces alterations in cell shape and formation of paracellular gaps in the cell layer. Semiquantitative Western blotting using extracts of freshly isolated airway tissue (nasal epithelium) or 16HBE14o- model cells revealed that phosphorylation levels of focal adhesion kinase (Fak) and paxillin were altered upon treatment of tissue or cells with rHla. Immune fluorescence analyses showed that rHla treatment of 16HBE14o- cells results in losses of vinculin and paxillin from focal contacts and a net reduction in the number of focal contacts. The actin cytoskeleton was strongly remodeled. We concluded that treatment of cells with rHla activates Fak signaling, which accelerates focal contact turnover and prevents newly formed focal contacts (focal complexes) from maturation to focal adhesions. The inability of rHla-treated cells to form stable focal adhesions may be one factor that contributes to gap formation in the cell layer. In vivo, such changes may disturb the defensive barrier function of the airway epithelium and may facilitate lung infections by S. aureus.

  8. Airways, vasculature, and interstitial tissue: anatomically informed computational modeling of human lungs for virtual clinical trials

    Science.gov (United States)

    Abadi, Ehsan; Sturgeon, Gregory M.; Agasthya, Greeshma; Harrawood, Brian; Hoeschen, Christoph; Kapadia, Anuj; Segars, W. P.; Samei, Ehsan

    2017-03-01

    This study aimed to model virtual human lung phantoms including both non-parenchymal and parenchymal structures. Initial branches of the non-parenchymal structures (airways, arteries, and veins) were segmented from anatomical data in each lobe separately. A volume-filling branching algorithm was utilized to grow the higher generations of the airways and vessels to the level of terminal branches. The diameters of the airways and vessels were estimated using established relationships between flow rates and diameters. The parenchyma was modeled based on secondary pulmonary lobule units. Polyhedral shapes with variable sizes were modeled, and the borders were assigned to interlobular septa. A heterogeneous background was added inside these units using a non-parametric texture synthesis algorithm which was informed by a high-resolution CT lung specimen dataset. A voxelized based CT simulator was developed to create synthetic helical CT images of the phantom with different pitch values. Results showed the progressive degradation in depiction of lung details with increased pitch. Overall, the enhanced lung models combined with the XCAT phantoms prove to provide a powerful toolset to perform virtual clinical trials in the context of thoracic imaging. Such trials, not practical using clinical datasets or simplistic phantoms, can quantitatively evaluate and optimize advanced imaging techniques towards patient-based care.

  9. One-step immortalization of primary human airway epithelial cells capable of oncogenic transformation.

    Science.gov (United States)

    Smith, Jordan L; Lee, Liam C; Read, Abigail; Li, Qiuning; Yu, Bing; Lee, Chih-Shia; Luo, Ji

    2016-01-01

    The ability to transform normal human cells into cancer cells with the introduction of defined genetic alterations is a valuable method for understanding the mechanisms of oncogenesis. Easy establishment of immortalized but non-transformed human cells from various tissues would facilitate these genetic analyses. We report here a simple, one-step immortalization method that involves retroviral vector mediated co-expression of the human telomerase protein and a shRNA targeting the CDKN2A gene locus. We demonstrate that this method could successfully immortalize human small airway epithelial cells while maintaining their chromosomal stability. We further showed that these cells retain p53 activity and can be transformed by the KRAS oncogene. Our method simplifies the immortalization process and is broadly applicable for establishing immortalized epithelial cell lines from primary human tissues for cancer research.

  10. 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.

  11. RNA-Seq quantification of the human small airway epithelium transcriptome

    Directory of Open Access Journals (Sweden)

    Hackett Neil R

    2012-02-01

    Full Text Available Abstract Background The small airway epithelium (SAE, the cell population that covers the human airway surface from the 6th generation of airway branching to the alveoli, is the major site of lung disease caused by smoking. The focus of this study is to provide quantitative assessment of the SAE transcriptome in the resting state and in response to chronic cigarette smoking using massive parallel mRNA sequencing (RNA-Seq. Results The data demonstrate that 48% of SAE expressed genes are ubiquitous, shared with many tissues, with 52% enriched in this cell population. The most highly expressed gene, SCGB1A1, is characteristic of Clara cells, the cell type unique to the human SAE. Among other genes expressed by the SAE are those related to Clara cell differentiation, secretory mucosal defense, and mucociliary differentiation. The high sensitivity of RNA-Seq permitted quantification of gene expression related to infrequent cell populations such as neuroendocrine cells and epithelial stem/progenitor cells. Quantification of the absolute smoking-induced changes in SAE gene expression revealed that, compared to ubiquitous genes, more SAE-enriched genes responded to smoking with up-regulation, and those with the highest basal expression levels showed most dramatic changes. Smoking had no effect on SAE gene splicing, but was associated with a shift in molecular pattern from Clara cell-associated towards the mucus-secreting cell differentiation pathway with multiple features of cancer-associated molecular phenotype. Conclusions These observations provide insights into the unique biology of human SAE by providing quantit-ative assessment of the global transcriptome under physiological conditions and in response to the stress of chronic cigarette smoking.

  12. Human leukocyte antigen-G expression in differentiated human airway epithelial cells: lack of modulation by Th2-associated cytokines

    Directory of Open Access Journals (Sweden)

    White Steven R

    2013-01-01

    Full Text Available Abstract Background Human leukocyte antigen (HLA-G is a nonclassical class I antigen with immunomodulatory roles including up-regulation of suppressor T regulatory lymphocytes. HLA-G was recently identified as an asthma susceptibility gene, and expression of a soluble isoform, HLA-G5, has been demonstrated in human airway epithelium. Increased presence of HLA-G5 has been demonstrated in bronchoalveolar lavage fluid recovered from patients with mild asthma; this suggests a role for this isoform in modulating airway inflammation though the mechanisms by which this occurs is unclear. Airway inflammation associated with Th2 cytokines such as IL-4 and IL-13 is a principal feature of asthma, but whether these cytokines elicit expression of HLA-G is not known. Methods We examined gene and protein expression of both soluble (G5 and membrane-bound (G1 HLA-G isoforms in primary differentiated human airway epithelial cells collected from normal lungs and grown in air-liquid interface culture. Cells were treated with up to 10 ng/ml of either IL-4, IL-5, or IL-13, or 100 ng/ml of the immunomodulatory cytokine IL-10, or 10,000 U/ml of the Th1-associated cytokine interferon-beta, for 24 hr, after which RNA was isolated for evaluation by quantitative PCR and protein was collected for Western blot analysis. Results HLA-G5 but not G1 was present in dAEC as demonstrated by quantitative PCR, western blot and confocal microscopy. Neither G5 nor G1 expression was increased by the Th2-associated cytokines IL-4, IL-5 or IL-13 over 24 hr, nor after treatment with IL-10, but was increased 4.5 ± 1.4 fold after treatment with 10,000 U/ml interferon-beta. Conclusions These data demonstrate the constitutive expression of a T lymphocyte regulatory molecule in differentiated human airway epithelial cells that is not modulated by Th2-associated cytokines.

  13. Airflow Shape Is Associated With the Pharyngeal Structure Causing OSA.

    Science.gov (United States)

    Genta, Pedro R; Sands, Scott A; Butler, James P; Loring, Stephen H; Katz, Eliot S; Demko, B Gail; Kezirian, Eric J; White, David P; Wellman, Andrew

    2017-09-01

    OSA results from the collapse of different pharyngeal structures (soft palate, tongue, lateral walls, and epiglottis). The structure involved in collapse has been shown to impact non-CPAP OSA treatment. Different inspiratory airflow shapes are also observed among patients with OSA. We hypothesized that inspiratory flow shape reflects the underlying pharyngeal structure involved in airway collapse. Subjects with OSA were studied with a pediatric endoscope and simultaneous nasal flow and pharyngeal pressure recordings during natural sleep. The mechanism causing collapse was classified as tongue-related, isolated palatal, lateral walls, or epiglottis. Flow shape was classified according to the degree of negative effort dependence (NED), defined as the percent reduction in inspiratory flow from peak to plateau. Thirty-one subjects with OSA (mean apnea-hypopnea index score ± SD, 54 ± 27 events/h) who were 50 ± 9 years of age were studied. NED was associated with the structure causing collapse (P < .001). Tongue-related obstruction (n = 13) was associated with a small amount of NED (median, 19; interquartile range [IQR], 14%-25%). Moderate NED was found among subjects with isolated palatal collapse (median, 45; IQR, 39%-52%; n = 8) and lateral wall collapse (median, 50; IQR, 44%-64%; n = 8). The epiglottis was associated with severe NED (median, 89; IQR, 78%-91%) and abrupt discontinuities in inspiratory flow (n = 9). Inspiratory flow shape is influenced by the pharyngeal structure causing collapse. Flow shape analysis may be used as a noninvasive tool to help determine the pharyngeal structure causing collapse. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  14. Human and equipment resources for difficult airway management, airway education programs, and capnometry use in Japanese emergency departments: a nationwide cross-sectional study.

    Science.gov (United States)

    Ono, Yuko; Tanigawa, Koichi; Shinohara, Kazuaki; Yano, Tetsuhiro; Sorimachi, Kotaro; Inokuchi, Ryota; Shimada, Jiro

    2017-09-13

    Although human and equipment resources, proper training, and the verification of endotracheal intubation are vital elements of difficult airway management (DAM), their availability in Japanese emergency departments (EDs) has not been determined. How ED type and patient volume affect DAM preparation is also unclear. We conducted the present survey to address this knowledge gaps. This nationwide cross-sectional study was conducted from April to September 2016. All EDs received a mailed questionnaire regarding their DAM resources, airway training methods, and capnometry use for tube placement. Outcome measures were the availability of: (1) 24-h in-house back-up; (2) key DAM resources, including a supraglottic airway device (SGA), a dedicated DAM cart, surgical airway devices, and neuromuscular blocking agents; (3) anesthesiology rotation as part of an airway training program; and (4) the routine use of capnometry to verify tube placement. EDs were classified as academic, tertiary, high-volume (upper quartile of annual ambulance visits), and urban. Of the 530 EDs, 324 (61.1%) returned completed questionnaires. The availability of in-house back-up coverage, surgical airway devices, and neuromuscular blocking agents was 69.4, 95.7, and 68.5%, respectively. SGAs and dedicated DAM carts were present in 51.5 and 49.7% of the EDs. The rates of routine capnometry use (47.8%) and the availability of an anesthesiology rotation (38.6%) were low. The availability of 24-h back-up coverage was significantly higher in academic EDs and tertiary EDs in both the crude and adjusted analysis. Similarly, neuromuscular blocking agents were more likely to be present in academic EDs, high-volume EDs, and tertiary EDs; and the rate of routine use of capnometry was significantly higher in tertiary EDs in both the crude and adjusted analysis. In Japanese EDs, the rates of both the availability of SGAs and DAM carts and the use of routine capnometry to confirm tube placement were approximately

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

    Directory of Open Access Journals (Sweden)

    Ming-Wei Chang

    2013-12-01

    Full Text Available 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.

  16. 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.

  17. Pharyngitis and sore throat: A review

    African Journals Online (AJOL)

    Jane

    2011-07-06

    1993). Clinical scoring system in the evaluation of adult pharyngitis. Arch. Otolaryngol Head Neck Surg. 119: 288-291. Stillerman M, Bernstein SH (1961). Streptococcal pharyngitis. Evaluation of clinical syndromes in diagnosis.

  18. Quantitative Proteomic Analysis of Human Airway Cilia Identifies Previously Uncharacterized Proteins of High Abundance.

    Science.gov (United States)

    Blackburn, Kevin; Bustamante-Marin, Ximena; Yin, Weining; Goshe, Michael B; Ostrowski, Lawrence E

    2017-04-07

    Cilia are essential to many diverse cellular processes. Although many major axonemal components have been identified and studied, how they interact to form a functional axoneme is not completely understood. To further our understanding of the protein composition of human airway cilia, we performed a semiquantitative analysis of ciliary axonemes using label-free LC/MSE, which identified over 400 proteins with high confidence. Tubulins were the most abundant proteins identified, with evidence of 20 different isoforms obtained. Twelve different isoforms of axonemal dynein heavy chain were also identified. Absolute quantification of the nontubulin components demonstrated a greater than 75-fold range of protein abundance (RSPH9;1850 fmol vs CCDC103;24 fmol), adding another level of complexity to axonemal structure. Of the identified proteins, ∼70% are known axonemal proteins. In addition, many previously uncharacterized proteins were identified. Unexpectedly, several of these, including ERICH3, C1orf87, and CCDC181, were present at high relative abundance in the cilia. RT-PCR analysis and immunoblotting confirmed cilia-specific expression for eight uncharacterized proteins, and fluorescence microscopy demonstrated unique axonemal localizations. These studies have provided the first quantitative analysis of the ciliary proteome and have identified and characterized several previously unknown proteins as major constituents of human airway cilia.

  19. Novel flow cytometry approach to identify bronchial epithelial cells from healthy human airways.

    Science.gov (United States)

    Maestre-Batlle, Danay; Pena, Olga M; Hirota, Jeremy A; Gunawan, Evelyn; Rider, Christopher F; Sutherland, Darren; Alexis, Neil E; Carlsten, Chris

    2017-02-06

    Sampling various compartments within the lower airways to examine human bronchial epithelial cells (HBEC) is essential for understanding numerous lung diseases. Conventional methods to identify HBEC in bronchoalveolar lavage (BAL) and wash (BW) have throughput limitations in terms of efficiency and ensuring adequate cell numbers for quantification. Flow cytometry can provide high-throughput quantification of cell number and function in BAL and BW samples, while requiring low cell numbers. To date, a flow cytometric method to identify HBEC recovered from lower human airway samples is unavailable. In this study we present a flow cytometric method identifying HBEC as CD45 negative, EpCAM/pan-cytokeratin (pan-CK) double-positive population after excluding debris, doublets and dead cells from the analysis. For validation, the HBEC panel was applied to primary HBEC resulting in 98.6% of live cells. In healthy volunteers, HBEC recovered from BAL (2.3% of live cells), BW (32.5%) and bronchial brushing samples (88.9%) correlated significantly (p = 0.0001) with the manual microscopy counts with an overall Pearson correlation of 0.96 across the three sample types. We therefore have developed, validated, and applied a flow cytometric method that will be useful to interrogate the role of the respiratory epithelium in multiple lung diseases.

  20. Generation of novel AAV variants by directed evolution for improved CFTR delivery to human ciliated airway epithelium.

    Science.gov (United States)

    Li, Wuping; Zhang, Liqun; Johnson, Jarrod S; Zhijian, Wu; Grieger, Joshua C; Ping-Jie, Xiao; Drouin, Lauren M; Agbandje-McKenna, Mavis; Pickles, Raymond J; Samulski, R Jude

    2009-12-01

    Recombinant adeno-associated virus (AAV) vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been used to deliver CFTR to the airway epithelium of cystic fibrosis (CF) patients. However, no significant CFTR function has been demonstrated likely due to low transduction efficiencies of the AAV vectors. To improve AAV transduction efficiency for human airway epithelium (HAE), we generated a chimeric AAV library and performed directed evolution of AAV on an in vitro model of human ciliated airway epithelium. Two independent and novel AAV variants were identified that contained capsid components from AAV-1, AAV-6, and/or AAV-9. The transduction efficiencies of the two novel AAV variants for human ciliated airway epithelium were three times higher than that for AAV-6. The novel variants were then used to deliver CFTR to ciliated airway epithelium from CF patients. Here we show that our novel AAV variants, but not the parental, AAV provide sufficient CFTR delivery to correct the chloride ion transport defect to ~25% levels measured in non-CF cells. These results suggest that directed evolution of AAV on relevant in vitro models will enable further improvements in CFTR gene transfer efficiency and the development of an efficacious and safe gene transfer vector for CF lung disease.

  1. Tracing molecular and structural changes upon mucolysis with N-acetyl cysteine in human airway mucus.

    Science.gov (United States)

    Vukosavljevic, Branko; Murgia, Xabier; Schwarzkopf, Konrad; Schaefer, Ulrich F; Lehr, Claus-Michael; Windbergs, Maike

    2017-11-30

    The conducting airways of the human lungs are lined by mucus, which lubricates the lung epithelium and provides a first-line protection against airborne threats. As a novel approach for visualization of the human mucus microstructure, we applied confocal Raman microscopy as a label-free and chemically selective technique. We were successfully able to chemically resolve the pulmonary surfactant from the mucus matrix and show its spatial distribution, as well as to visualize the structural changes within the freeze-dried mucus mesh upon chemical mucolysis. Subsequently, we performed rheological measurements before and after mucolysis and correlated morphology and chemical structure of the mucus with its rheological characteristics. These results do not only enrich the knowledge about the mucus microstructure, but can also, significantly contribute to rational development of future lung therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Wnt/β-catenin signaling modulates human airway sensitization induced by β2-adrenoceptor stimulation.

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    Christophe Faisy

    Full Text Available BACKGROUND: Regular use of β2-agonists may enhance non-specific airway responsiveness. The wingless/integrated (Wnt signaling pathways are responsible for several cellular processes, including airway inflammation and remodeling while cAMP-PKA cascade can activate the Wnt signaling. We aimed to investigate whether the Wnt signaling pathways are involved in the bronchial hyperresponsiveness induced by prolonged exposure to β2-adrenoceptor agonists in human isolated airways. METHODS: Bronchi were surgically removed from 44 thoracic surgery patients. After preparation, bronchial rings and primary cultures of bronchial epithelial cells were incubated with fenoterol (0.1 µM, 15 hours, 37 °C, a β2-agonist with high intrinsic efficacy. The effects of inhibitors/blockers of Wnt signaling on the fenoterol-induced airway sensitization were examined and the impact of fenoterol exposure on the mRNA expression of genes interacting with Wnt signaling or cAMP-PKA cascade was assessed in complete bronchi and in cultured epithelial cells. RESULTS: Compared to paired controls, fenoterol-sensitization was abolished by inhibition/blockage of the Wnt/β-catenin signaling, especially the cell-surface LRP5/6 co-receptors or Fzd receptors (1 µM SFRP1 or 1 µM DKK1 and the nuclear recruitment of TCF/LEF transcriptions factors (0.3 µM FH535. Wnt proteins secretion did not seem to be involved in the fenoterol-induced sensitization since the mRNA expression of Wnt remained low after fenoterol exposure and the inactivator of Wnt secretion (1 µM IWP2 had no effect on the fenoterol-sensitization. Fenoterol exposure did not change the mRNA expression of genes regulating Wnt signaling or cAMP-PKA cascade. CONCLUSIONS: Collectively, our pharmacological investigations indicate that fenoterol-sensitization is modulated by the inhibition/blockage of canonical Wnt/β-catenin pathway, suggesting a phenomenon of biased agonism in connection with the β2-adrenoceptor stimulation

  3. Oscillatory Flow in the Human Airways from the Mouth through Several Bronchial Generations

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    Banko, Andrew; Coletti, Filippo; Elkins, Chris; Eaton, John

    2014-11-01

    The time-varying flow is studied experimentally in an anatomically accurate model of the human airways from the mouth through the fourth to eighth generation of the bronchi. 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 Re = 4200 and the Womersley number is α = 7. This represents a regime of moderate exertion. Integral parameters are defined to quantify the degree of velocity profile non-uniformity (which correlates with axial dispersion) and secondary flow strength (which correlates with lateral dispersion). It is found that the streamwise momentum flux and secondary flow strength increase and decrease in proportion throughout most of the breathing cycle. On the other hand, the strength of secondary flows during the 10% of the breathing cycle surrounding flow reversal remains approximately half of that at peak inspiration while the streamwise momentum flux goes to zero. The strong and persistent secondary flows have important implications for dispersion of scalar or particulate contaminants in the lungs.

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

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    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

  5. Interleukin-1beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells.

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    Billington, C K; Pascual, R M; Hawkins, M L; Penn, R B; Hall, I P

    2001-05-01

    Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been reported to cause beta2 adrenergic receptor hyporesponsiveness in human airway smooth muscle (HASM) via cellular secretion of interleukin (IL)-1beta. We studied the effects of IL-1beta and RV on cyclic adenosine monophosphate (cAMP) production in HASM cells. Chronic incubation with IL-1beta or RV caused a significant increase (approximately 3- and approximately 2-fold, respectively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensitization of adenylyl cyclase (AC). The observed augmentation of FSK-stimulated cAMP formation by IL-1beta was completely abrogated by pretreatment with an IL-1 receptor antagonist or cycloheximide, demonstrating that the effect is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein synthesis is required. In contrast, RV-induced AC sensitization was not mediated via the IL-1R1 but was observed to be protein kinase C-dependent. We suggest that the sensitization of AC observed after exposure to IL-1beta or RV infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.

  6. Pseudomonas Pyocyanin Increases Interleukin-8 Expression by Human Airway Epithelial Cells

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    Denning, Gerene M.; Wollenweber, Laura A.; Railsback, Michelle A.; Cox, Charles D.; Stoll, Lynn L.; Britigan, Bradley E.

    1998-01-01

    Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1α. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n-acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen-activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed in Pseudomonas-associated lung disease. PMID:9826354

  7. Upper airway collapsibility is associated with obesity and hyoid position.

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    Genta, Pedro R; Schorr, Fabiola; Eckert, Danny J; Gebrim, Eloisa; Kayamori, Fabiane; Moriya, Henrique T; Malhotra, Atul; Lorenzi-Filho, Geraldo

    2014-10-01

    Upper airway anatomy plays a major role in obstructive sleep apnea (OSA) pathogenesis. An inferiorly displaced hyoid as measured by the mandibular plane to hyoid distance (MPH) has been consistently associated with OSA. The hyoid is also a common landmark for pharyngeal length, upper airway volume, and tongue base. Tongue dimensions, pharyngeal length, and obesity are associated with OSA severity, although the link between these anatomical variables and pharyngeal collapsibility is less well known. We hypothesized that obesity as measured by body mass index (BMI), neck and waist circumferences, and variables associated with hyoid position (pharyngeal length, upper airway volume, and tongue dimensions) would be associated with passive pharyngeal critical closing pressure (Pcrit). Cross-sectional. Academic hospital. 34 Japanese-Brazilian males age 21 to 70 y. N/A. We performed computed tomography scans of the upper airway, overnight polysomnography, and Pcrit measurements in all subjects. On average, subjects were overweight (BMI = 28 ± 4 kg/m(2)) and OSA was moderately severe (apnea-hypopnea index = 29 [13-51], range 1-90 events/h). Factor analysis identified two factors among the studied variables: obesity (extracted from BMI, neck and waist circumferences) and hyoid position (MPH, pharyngeal length, tongue length, tongue volume, and upper airway volume). Both obesity and hyoid position correlated with Pcrit (r = 0.470 and 0.630, respectively) (P obesity and hyoid position. Tongue dimensions, pharyngeal length, and the mandibular plane to hyoid distance are associated with obesity variables. These findings provide novel insight into the potential factors mediating upper airway collapse in obstructive sleep apnea. © 2014 Associated Professional Sleep Societies, LLC.

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

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    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.

  9. Chemokine release from human rhinovirus-infected airway epithelial cells promotes fibroblast migration.

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    Shelfoon, Christopher; Shariff, Sami; Traves, Suzanne L; Kooi, Cora; Leigh, Richard; Proud, David

    2016-07-01

    Thickening of the lamina reticularis, a feature of remodeling in the asthmatic airways, is now known to be present in young children who wheeze. Human rhinovirus (HRV) infection is a common trigger for childhood wheezing, which is a risk factor for subsequent asthma development. We hypothesized that HRV-infected epithelial cells release chemoattractants to recruit fibroblasts that could potentially contribute to thickening of the lamina reticularis. We sought to investigate whether conditioned medium from HRV-infected epithelial cells can trigger directed migration of fibroblasts. Human bronchial epithelial cells were exposed to medium alone or infected with HRV-16. Conditioned medium from both conditions were tested as chemoattractants for human bronchial fibroblasts in the xCELLigence cell migration apparatus. HRV-conditioned medium was chemotactic for fibroblasts. Treatment of fibroblasts with pertussis toxin, an inhibitor of Gαi-coupled receptors, prevented their migration. Production of epithelial chemoattractants required HRV replication. Multiplex analysis of epithelial supernatants identified CXCL10, CXCL8, and CCL5 as Gαi-coupled receptor agonists of potential interest. Subsequent analysis confirmed that fibroblasts express CXCR3 and CXCR1 receptors and that CXCL10 and, to a lesser extent, CXCL8, but not CCL5, are major contributors to fibroblast migration caused by HRV-conditioned medium. CXCL10 and CXCL8 produced from HRV-infected epithelial cells are chemotactic for fibroblasts. This raises the possibility that repeated HRV infections in childhood could contribute to the initiation and progression of airway remodeling in asthmatic patients by recruiting fibroblasts that produce matrix proteins and thicken the lamina reticularis. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  10. Control of Neurotransmission by NaV1.7 in Human, Guinea Pig, and Mouse Airway Parasympathetic Nerves.

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    Kocmalova, Michaela; Kollarik, Marian; Canning, Brendan J; Ru, Fei; Adam Herbstsomer, R; Meeker, Sonya; Fonquerna, Silvia; Aparici, Monica; Miralpeix, Montserrat; Chi, Xian Xuan; Li, Baolin; Wilenkin, Ben; McDermott, Jeff; Nisenbaum, Eric; Krajewski, Jeffrey L; Undem, Bradley J

    2017-04-01

    Little is known about the neuronal voltage-gated sodium channels (NaVs) that control neurotransmission in the parasympathetic nervous system. We evaluated the expression of the α subunits of each of the nine NaVs in human, guinea pig, and mouse airway parasympathetic ganglia. We combined this information with a pharmacological analysis of selective NaV blockers on parasympathetic contractions of isolated airway smooth muscle. As would be expected from previous studies, tetrodotoxin potently blocked the parasympathetic responses in the airways of each species. Gene expression analysis showed that that NaV 1.7 was virtually the only tetrodotoxin-sensitive NaV1 gene expressed in guinea pig and human airway parasympathetic ganglia, where mouse ganglia expressed NaV1.1, 1.3, and 1.7. Using selective pharmacological blockers supported the gene expression results, showing that blocking NaV1.7 alone can abolish the responses in guinea pig and human bronchi, but not in mouse airways. To block the responses in mouse airways requires that NaV1.7 along with NaV1.1 and/or NaV1.3 is blocked. These results may suggest novel indications for NaV1.7-blocking drugs, in which there is an overactive parasympathetic drive, such as in asthma. The data also raise the potential concern of antiparasympathetic side effects for systemic NaV1.7 blockers. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers

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    Wang Guoqing

    2012-06-01

    Full Text Available Abstract Background Mucus hypersecretion contributes to the morbidity and mortality of smoking-related lung diseases, especially chronic obstructive pulmonary disease (COPD, which starts in the small airways. Despite progress in animal studies, the genes and their expression pattern involved in mucus production and secretion in human airway epithelium are not well understood. We hypothesized that comparison of the transcriptomes of the small airway epithelium of individuals that express high vs low levels of MUC5AC, the major macromolecular component of airway mucus, could be used as a probe to identify the genes related to human small airway mucus production/secretion. Methods Flexible bronchoscopy and brushing were used to obtain small airway epithelium (10th to 12th order bronchi from healthy nonsmokers (n=60 and healthy smokers (n=72. Affymetrix HG-U133 plus 2.0 microarrays were used to assess gene expression. Massive parallel sequencing (RNA-Seq was used to verify gene expression of small airway epithelium from 5 nonsmokers and 6 smokers. Results MUC5AC expression varied 31-fold among the healthy nonsmokers. Genome-wide comparison between healthy nonsmokers (n = 60 grouped as “high MUC5AC expressors” vs “low MUC5AC expressors” identified 528 genes significantly up-regulated and 15 genes significantly down-regulated in the high vs low expressors. This strategy identified both mucus production and secretion related genes under control of a network composed of multiple transcription factors. Based on the literature, genes in the up-regulated list were used to identify a 73 “MUC5AC-associated core gene” list with 9 categories: mucus component; mucus-producing cell differentiation-related transcription factor; mucus-producing cell differentiation-related pathway or mediator; post-translational modification of mucin; vesicle transport; endoplasmic reticulum stress-related; secretory granule-associated; mucus secretion

  12. INCREASED IL-8 AND IL-6 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO CARBON ULTRAFINE PARTICLES

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    INCREASED IL-6 AND IL-8 EXPRESSION IN HUMAN AIRWAY EPITHELIAL CELLS EXPOSED TO CARBON ULTRAFINE PARTICLES.R Silbajoris1, A G Lenz2, I Jaspers3, J M Samet1. 1NHEERL, USEPA, RTP, NC, USA; 2GSF-Institute for Inhalation Biology, Neuherberg, Germany; 3 CEMLB, UNC-CH, Chapel Hill, ...

  13. Pharyngeal Satellite Cells Undergo Myogenesis Under Basal Conditions and Are Required for Pharyngeal Muscle Maintenance.

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    Randolph, Matthew E; Phillips, Brittany L; Choo, Hyo-Jung; Vest, Katherine E; Vera, Yandery; Pavlath, Grace K

    2015-12-01

    The pharyngeal muscles of the nasal, oral, and laryngeal pharynxes are required for swallowing. Pharyngeal muscles are preferentially affected in some muscular dystrophies yet spared in others. Muscle stem cells, called satellite cells, may be critical factors in the development of pharyngeal muscle disorders; however, very little is known about pharyngeal satellite cells (PSC) and their role in pharyngeal muscles. We show that PSC are distinct from the commonly studied hindlimb satellite cells both transcriptionally and biologically. Under basal conditions PSC proliferate, progress through myogenesis, and fuse with pharyngeal myofibers. Furthermore, PSC exhibit biologic differences dependent on anatomic location in the pharynx. Importantly, PSC are required to maintain myofiber size and myonuclear number in pharyngeal myofibers. Together, these results demonstrate that PSC are critical for pharyngeal muscle maintenance and suggest that satellite cell impairment could contribute to pharyngeal muscle pathology associated with various muscular dystrophies and aging. © 2015 AlphaMed Press.

  14. Towards a clinical implementation of μOCT instrument for in vivo imaging of human airways

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    Leung, Hui Min; Cui, Dongyao; Ford, Timothy N.; Hyun, Daryl; Dong, Jing; Yin, Biwei; Birket, Susan E.; Solomon, George M.; Liu, Linbo; Rowe, Steven M.; Tearney, Guillermo J.

    2017-03-01

    High resolution micro-optical coherence tomography (µOCT) technology has been demonstrated to be useful for imaging respiratory epithelial functional microanatomy relevant to the study of pulmonary diseases such as cystic fibrosis and COPD. We previously reported the use of a benchtop μOCT imaging technology to image several relevant respiratory epithelial functional microanatomy at 40 fps and at lateral and axial resolutions of 2 and 1.3μm, respectively. We now present the development of a portable μOCT imaging system with comparable optical and imaging performance, which enables the μOCT technology to be translated to the clinic for in vivo imaging of human airways.

  15. Collective motion of motile cilia: from human airways to model systems

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

    Mammalian airways are a fantastic playground of nonlinear phenomena, from the function of individual active filaments, to the emerging collective behaviour, to the rheology of the mucus solution surrounding cilia. We have been investigating the fundamental physics of this system through a variety of model system approaches, both experimental and computational. In the last year we have started measurements on living human cells, observing cilia shape during beating, and measuring speed and coherence of the collective dynamics. We report on significant differences in the collective motion in ciliated cell carpets from a variety of diseases, and we attempt to reconcile the collective dynamical phenotypes to the properties of individual filaments and the mechanics of the environment.

  16. Monitoring the state of the human airways by analysis of respiratory sound

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    Hardin, J. C.; Patterson, J. L. Jr

    1979-01-01

    A mechanism whereby sound is generated by the motion of vortices in the human lung is described. This mechanism is believed to be responsible for most of the sound which is generated both on inspiration and expiration in normal lungs. Mathematical expressions for the frequencies of sound generated, which depend only upon the axial flow velocity and diameters of the bronchi, are derived. This theory allows the location within the bronchial tree from which particular sounds emanate to be determined. Redistribution of pulmonary blood volume following transition from Earth gravity to the weightless state probably alters the caliber of certain airways and doubtless alters sound transmission properties of the lung. We believe that these changes can be monitored effectively and non-invasively by spectral analysis of pulmonary sound.

  17. Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway epithelial cells.

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    Kistemaker, Loes E M; Hiemstra, Pieter S; Bos, I Sophie T; Bouwman, Susanne; van den Berge, Maarten; Hylkema, Machteld N; Meurs, Herman; Kerstjens, Huib A M; Gosens, Reinoud

    2015-07-01

    It has been shown that acetylcholine is both a neurotransmitter and acts as a local mediator, produced by airway cells including epithelial cells. In vivo studies have demonstrated an indirect role for acetylcholine in epithelial cell differentiation. Here, we aimed to investigate direct effects of endogenous non-neuronal acetylcholine on epithelial cell differentiation. Human airway epithelial cells from healthy donors were cultured at an air-liquid interface (ALI). Cells were exposed to the muscarinic antagonist tiotropium (10 nM), interleukin (IL)-13 (1, 2 and 5 ng/mL), or a combination of IL-13 and tiotropium, during or after differentiation at the ALI. Human airway epithelial cells expressed all components of the non-neuronal cholinergic system, suggesting acetylcholine production. Tiotropium had no effects on epithelial cell differentiation after air exposure. Differentiation into goblet cells was barely induced after air exposure. Therefore, IL-13 (1 ng/mL) was used to induce goblet cell metaplasia. IL-13 induced MUC5AC-positive cells (5-fold) and goblet cells (14-fold), as assessed by histochemistry, and MUC5AC gene expression (105-fold). These effects were partly prevented by tiotropium (47-92%). Goblet cell metaplasia was induced by IL-13 in a dose-dependent manner, which was inhibited by tiotropium. In addition, tiotropium reversed goblet cell metaplasia induced by 2 weeks of IL-13 exposure. IL-13 decreased forkhead box protein A2 (FoxA2) expression (1.6-fold) and increased FoxA3 (3.6-fold) and SAM-pointed domain-containing ETS transcription factor (SPDEF) (5.2-fold) expression. Tiotropium prevented the effects on FoxA2 and FoxA3, but not on SPDEF. We demonstrate that tiotropium has no effects on epithelial cell differentiation after air exposure, but inhibits and reverses IL-13-induced goblet cell metaplasia, possibly via FoxA2 and FoxA3. This indicates that non-neuronal acetylcholine contributes to goblet cell differentiation by a direct effect

  18. Regulation of high glucose-mediated mucin expression by matrix metalloproteinase-9 in human airway epithelial cells.

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    Yu, Hongmei; Yang, Juan; Xiao, Qian; Lü, Yang; Zhou, Xiangdong; Xia, Li; Nie, Daijing

    2015-04-10

    Mucus hypersecretion is the key manifestation in patients with chronic inflammatory airway diseases and mucin 5AC (MUC5AC) is a major component of airway mucus. Matrix metalloproteinases (MMP)-9, have been found to be involved in the pathogenesis of inflammatory airway diseases. Hyperglycemia has been shown to be an independent risk factor for respiratory infections. We hypothesize that high glucose (HG)-regulates MMP-9 production and MMP-9 activity through nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS) cascades pathways, leading to mucin production in human airway epithelial cells (16HBE). We show that HG increases MMP-9 production, MMP-9 activity and MUC5AC expression. These effects are prevented by small interfering RNA (siRNA) for MMP-9, indicating that HG-induced mucin production is MMP-9-dependent. HG activates MMP-9 production, MMP-9 activity and MUC5AC overproduction, which is inhibited by nPG, DMSO and DPI (inhibitors of ROS and NADPH), suggesting that HG-activated mucin synthesis is mediated by NADPH/ROS in 16HBE cells. These observations demonstrate an important role for MMP-9 activated by NADPH/ROS signaling pathways in regulating HG-induced MUC5AC expression. These findings may bring new insights into the molecular pathogenesis of the infections related to diabetes mellitus and lead to novel therapeutic intervention for mucin overproduction in chronic inflammatory airway diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke.

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    Berman, Reena; Jiang, Di; Wu, Qun; Chu, Hong Wei

    2016-01-01

    Human rhinovirus (HRV) infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS) increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether α1-antitrypsin (A1AT) reduces HRV-16 infection in CS-exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air-liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS) with or without HRV-16 (5×10(4) 50% Tissue Culture Infective Dose [TCID50]/transwell) infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-λ1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection.

  20. α1-Antitrypsin reduces rhinovirus infection in primary human airway epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Berman R

    2016-06-01

    Full Text Available Reena Berman, Di Jiang, Qun Wu, Hong Wei Chu Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: Human rhinovirus (HRV infections target airway epithelium and are the leading cause of acute exacerbations of COPD. Cigarette smoke (CS increases the severity of viral infections, but there is no effective therapy for HRV infection. We determined whether α1-antitrypsin (A1AT reduces HRV-16 infection in CS-exposed primary human airway epithelial cells. Brushed bronchial epithelial cells from normal subjects and patients diagnosed with COPD were cultured at air–liquid interface to induce mucociliary differentiation. These cells were treated with A1AT or bovine serum albumin for 2 hours and then exposed to air or whole cigarette smoke (WCS with or without HRV-16 (5×104 50% Tissue Culture Infective Dose [TCID50]/transwell infection for 24 hours. WCS exposure significantly increased viral load by an average of fivefold and decreased the expression of antiviral genes interferon-λ1, OAS1, and MX1. When A1AT was added to WCS-exposed cells, viral load significantly decreased by an average of 29-fold. HRV-16 infection significantly increased HRV-16 receptor intercellular adhesion molecule-1 messenger RNA expression in air-exposed cells, which was decreased by A1AT. A1AT-mediated reduction of viral load was not accompanied by increased epithelial antiviral gene expression or by inhibiting the activity of 3C protease involved in viral replication or maturation. Our findings demonstrate that A1AT treatment prevents a WCS-induced increase in viral load and for the first time suggest a therapeutic effect of A1AT on HRV infection. Keywords: α1-antitrypsin, rhinovirus, COPD, cigarette smoke, ICAM-1

  1. CADM1 is a key receptor mediating human mast cell adhesion to human lung fibroblasts and airway smooth muscle cells.

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    Elena P Moiseeva

    Full Text Available Mast cells (MCs play a central role in the development of many diseases including asthma and pulmonary fibrosis. Interactions of human lung mast cells (HLMCs with human airway smooth muscle cells (HASMCs are partially dependent on adhesion mediated by cell adhesion molecule-1 (CADM1, but the adhesion mechanism through which HLMCs interact with human lung fibroblasts (HLFs is not known. CADM1 is expressed as several isoforms (SP4, SP1, SP6 in HLMCs, with SP4 dominant. These isoforms differentially regulate HLMC homotypic adhesion and survival.In this study we have investigated the role of CADM1 isoforms in the adhesion of HLMCs and HMC-1 cells to primary HASMCs and HLFs.CADM1 overexpression or downregulation was achieved using adenoviral delivery of CADM1 short hairpin RNAs or isoform-specific cDNAs respectively.Downregulation of CADM1 attenuated both HLMC and HMC-1 adhesion to both primary HASMCs and HLFs. Overexpression of either SP1 or SP4 isoforms did not alter MC adhesion to HASMCs, whereas overexpression of SP4, but not SP1, significantly increased both HMC-1 cell and HLMC adhesion to HLFs. The expression level of CADM1 SP4 strongly predicted the extent of MC adhesion; linear regression indicated that CADM1 accounts for up to 67% and 32% of adhesion to HLFs for HMC-1 cells and HLMCs, respectively. HLFs supported HLMC proliferation and survival through a CADM1-dependent mechanism. With respect to CADM1 counter-receptor expression, HLFs expressed both CADM1 and nectin-3, whereas HASMCs expressed only nectin-3.Collectively these data indicate that the CADM1 SP4 isoform is a key receptor mediating human MC adhesion to HASMCs and HLFs. The differential expression of CADM1 counter-receptors on HLFs compared to HASMCs may allow the specific targeting of either HLMC-HLF or HLMC-HASMC interactions in the lung parenchyma and airways.

  2. CADM1 Is a Key Receptor Mediating Human Mast Cell Adhesion to Human Lung Fibroblasts and Airway Smooth Muscle Cells

    Science.gov (United States)

    Moiseeva, Elena P.; Roach, Katy M.; Leyland, Mark L.; Bradding, Peter

    2013-01-01

    Background Mast cells (MCs) play a central role in the development of many diseases including asthma and pulmonary fibrosis. Interactions of human lung mast cells (HLMCs) with human airway smooth muscle cells (HASMCs) are partially dependent on adhesion mediated by cell adhesion molecule-1 (CADM1), but the adhesion mechanism through which HLMCs interact with human lung fibroblasts (HLFs) is not known. CADM1 is expressed as several isoforms (SP4, SP1, SP6) in HLMCs, with SP4 dominant. These isoforms differentially regulate HLMC homotypic adhesion and survival. Objective In this study we have investigated the role of CADM1 isoforms in the adhesion of HLMCs and HMC-1 cells to primary HASMCs and HLFs. Methods CADM1 overexpression or downregulation was achieved using adenoviral delivery of CADM1 short hairpin RNAs or isoform-specific cDNAs respectively. Results Downregulation of CADM1 attenuated both HLMC and HMC-1 adhesion to both primary HASMCs and HLFs. Overexpression of either SP1 or SP4 isoforms did not alter MC adhesion to HASMCs, whereas overexpression of SP4, but not SP1, significantly increased both HMC-1 cell and HLMC adhesion to HLFs. The expression level of CADM1 SP4 strongly predicted the extent of MC adhesion; linear regression indicated that CADM1 accounts for up to 67% and 32% of adhesion to HLFs for HMC-1 cells and HLMCs, respectively. HLFs supported HLMC proliferation and survival through a CADM1-dependent mechanism. With respect to CADM1 counter-receptor expression, HLFs expressed both CADM1 and nectin-3, whereas HASMCs expressed only nectin-3. Conclusion and Clinical Relevance Collectively these data indicate that the CADM1 SP4 isoform is a key receptor mediating human MC adhesion to HASMCs and HLFs. The differential expression of CADM1 counter-receptors on HLFs compared to HASMCs may allow the specific targeting of either HLMC-HLF or HLMC-HASMC interactions in the lung parenchyma and airways. PMID:23620770

  3. 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

  4. 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

    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...

  5. Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.

    Directory of Open Access Journals (Sweden)

    Saskia Scholz

    2017-06-01

    Full Text Available Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs, including monocytes and dendritic cells (DCs, orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS. Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.

  6. Dung biomass smoke activates inflammatory signaling pathways in human small airway epithelial cells.

    Science.gov (United States)

    McCarthy, Claire E; Duffney, Parker F; Gelein, Robert; Thatcher, Thomas H; Elder, Alison; Phipps, Richard P; Sime, Patricia J

    2016-12-01

    Animal dung is a biomass fuel burned by vulnerable populations who cannot afford cleaner sources of energy, such as wood and gas, for cooking and heating their homes. Exposure to biomass smoke is the leading environmental risk for mortality, with over 4,000,000 deaths each year worldwide attributed to indoor air pollution from biomass smoke. Biomass smoke inhalation is epidemiologically associated with pulmonary diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and respiratory infections, especially in low and middle-income countries. Yet, few studies have examined the mechanisms of dung biomass smoke-induced inflammatory responses in human lung cells. Here, we tested the hypothesis that dung biomass smoke causes inflammatory responses in human lung cells through signaling pathways involved in acute and chronic lung inflammation. Primary human small airway epithelial cells (SAECs) were exposed to dung smoke at the air-liquid interface using a newly developed, automated, and reproducible dung biomass smoke generation system. The examination of inflammatory signaling showed that dung biomass smoke increased the production of several proinflammatory cytokines and enzymes in SAECs through activation of the activator protein (AP)-1 and arylhydrocarbon receptor (AhR) but not nuclear factor-κB (NF-κB) pathways. We propose that the inflammatory responses of lung cells exposed to dung biomass smoke contribute to the development of respiratory diseases. Copyright © 2016 the American Physiological Society.

  7. 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

  8. 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

  9. [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.

  10. 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.

  11. Dynamics of heat, water, and soluble gas exchange in the human airways: 1. A model study.

    Science.gov (United States)

    Tsu, M E; Babb, A L; Ralph, D D; Hlastala, M P

    1988-01-01

    In order to provide a means for analysis of heat, water, and soluble gas exchange with the airways during tidal ventilation, a one dimensional theoretical model describing heat and water exchange in the respiratory airways has been extended to include soluble gas exchange with the airway mucosa and water exchange with the mucous layer lining the airways. Not only do heat, water, and gas exchange occur simultaneously, but they also interact. Heating and cooling of the airway surface and mucous lining affects both evaporative water and soluble gas exchange. Water evaporation provides a major source of heat exchange. The model-predicted mean airway temperature profiles agree well with literature data for both oral and nasal breathing validating that part of the model. With model parameters giving the best fit to experimental data, the model shows: (a) substantial heat recovery in the upper airways, (b) minimal respiratory heat and water loss, and (c) low average mucous temperatures and maximal increases in mucous thickness. For resting breathing of room air, heat and water conservation appear to be more important than conditioning efficiency. End-tidal expired partial pressures of very soluble gases eliminated by the lungs are predicted to be lower than the alveolar partial pressures due to the absorption of the expired gases by the airway mucosa. The model may be usable for design of experiments to examine mechanisms associated with the local hydration and dehydration dynamics of the mucosal surface, control of bronchial perfusion, triggering of asthma, mucociliary clearance and deposition of inhaled pollutant gases.

  12. Effect of airway inflammation on short-latency reflex inhibition to inspiratory loading in human scalene muscles.

    Science.gov (United States)

    Murray, Nicholas P S; McKenzie, David K; Gandevia, Simon C; Butler, Jane E

    2012-04-30

    The short-latency reflex inhibition of human inspiratory muscles produced by loading is prolonged in asthma and obstructive sleep apnoea, both diseases involving airway and systemic inflammation. Both diseases also involve repetitive inspiratory loading. Although airway mucosal afferents are not critical components of the normal reflex arc, during airway inflammation, prolongation of the reflex may be caused by altered mucosal afferent sensitivity, or altered central processing of their inputs. We hypothesised that acute viral airway inflammation would replicate the reflex abnormality. The reflex was tested in 9 subjects with a "common cold" during both the acute infection and when well. Surface electrodes recorded electromyographic (EMG) activity bilaterally from scalene muscles. Latencies of the inhibitory response (IR) did not differ significantly (IR peak 67 vs 70 ms (p=0.12), and IR offset 87 vs 90 ms (p=0.23), between the inflamed and well conditions, respectively). There was no difference in any measure of the size of the reflex inhibition. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. 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...

  14. 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.

  15. DNS and PIV Measurements of the Flow in a Model of the Human Upper Airway

    Science.gov (United States)

    Wang, Yong; Oren, Liran; Gutmark, Epharim; Elghobashi, Said; University of California, Irvine Collaboration; Univ. of Cincinnati, Cincinnati Collaboration

    2014-11-01

    The flow in the human upper airway (HUA) is 3D, unsteady, undergoes transition from laminar to turbulent, and reverses its main direction about every two seconds. In order to enhance the understanding of the flow properties, both numerical and experimental studies are needed. In the present study, DNS results of the flow in a patient-specific model of HUA are compared with experimental data. The DNS solver uses the lattice Boltzmann method which was validated for some canonical laminar and turbulent flows The experimental model was constructed from transparent silicone using a mold prepared by 3D printing. Velocity measurements were performed via high speed particle image velocimetry (HSPIV). The refractive index of the fluid used in the HUA experimental model matched the refractive index of the silicone. Both inspiration and expiration cases with several flow rates in the HUA are studied. The DNS velocity fields at several cross section planes are compared with the HSPIV measurements. The computed pressure and vorticity distributions will be also presented. NIH Heart Lung and Blood Inst.-Grant HL105215.

  16. Steady Flow in Subject-Specific Human Airways from Mouth to Sixth Bronchial Generation

    Science.gov (United States)

    Banko, Andrew; Coletti, Filippo; Schiavazzi, Daniele; Elkins, Christopher; Eaton, John

    2013-11-01

    Understanding the complex flow topology within the human lung is critical to assess gas exchange and particle transport as they relate to the development and treatment of respiratory diseases. While idealized airway models have been investigated extensively, only limited information is available for anatomically accurate geometries. We have measured the full three-dimensional, mean velocity field from the mouth to the sixth bronchial generation in a patient-specific geometry at steady inspiration. Magnetic resonance velocimetry is used to measure the flow of water at realistic Reynolds number in a 3D-printed model derived from the CT scan of a healthy subject. The canonical laryngeal jet is observed; however, its structure is altered by an upstream jet behind the tongue, which is not discussed in the literature. Regions of separation in the supraglottic space are found to generate streamwise vortices. The resulting swirl persists to the first bifurcation and modifies the vorticity distribution in the main bronchi relative to that of a symmetric bifurcation with uniform inlet conditions. An integral momentum distortion parameter is calculated along several complete bronchial paths to assess the impact of branching angle and generation length on the flow field.

  17. Phase-contrast helium-3 MRI of aerosol deposition in human airways.

    Science.gov (United States)

    Sarracanie, Mathieu; Grebenkov, Denis; Sandeau, Julien; Coulibaly, Soulé; Martin, Andrew R; Hill, Kyle; Pérez Sánchez, José Manuel; Fodil, Redouane; Martin, Lionel; Durand, Emmanuel; Caillibotte, Georges; Isabey, Daniel; Darrasse, Luc; Bittoun, Jacques; Maître, Xavier

    2015-02-01

    One of the key challenges in the study of health-related aerosols is predicting and monitoring sites of particle deposition in the respiratory tract. The potential health risks of ambient exposure to environmental or workplace aerosols and the beneficial effects of medical aerosols are strongly influenced by the site of aerosol deposition along the respiratory tract. Nuclear medicine is the only current modality that combines quantification and regional localization of aerosol deposition, and this technique remains limited by its spatial and temporal resolutions and by patient exposure to radiation. Recent work in MRI has shed light on techniques to quantify micro-sized magnetic particles in living bodies by the measurement of associated static magnetic field variations. With regard to lung MRI, hyperpolarized helium-3 may be used as a tracer gas to compensate for the lack of MR signal in the airways, so as to allow assessment of pulmonary function and morphology. The extrathoracic region of the human respiratory system plays a critical role in determining aerosol deposition patterns, as it acts as a filter upstream from the lungs. In the present work, aerosol deposition in a mouth-throat phantom was measured using helium-3 MRI and compared with single-photon emission computed tomography. By providing high sensitivity with high spatial and temporal resolutions, phase-contrast helium-3 MRI offers new insights for the study of particle transport and deposition. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Spatial and temporal traction response in human airway smooth muscle cells

    Science.gov (United States)

    Tolic-Norrelykke, Iva Marija; Butler, James P.; Chen, Jianxin; Wang, Ning

    2002-01-01

    Tractions that cells exert on their substrates are essential in cell spreading, migration, and contraction. These tractions can be determined by plating the cells on a flexible gel and measuring the deformation of the gel by using fluorescent beads embedded just below the surface of the gel. In this article we describe the image correlation method (ICM) optimized for determining the displacement field of the gel under a contracting cell. For the calculation of the traction field from the displacement field we use the recently developed method of Fourier transform traction cytometry (FTTC). The ICM and FTTC methods are applied to human airway smooth muscle cells during stimulation with the contractile agonist histamine or the relaxing agonist isoproterenol. The overall intensity of the cell contraction (the median traction magnitude, the energy transferred from the cell to the gel, and the net contractile moment) increased after activation with histamine, and decreased after treatment with isoproterenol. Cells exhibited regional differences in the time course of traction during the treatment. Both temporal evolution and magnitude of traction increase induced by histamine varied markedly among different cell protrusions, whereas the nuclear region showed the smallest response. These results suggest that intracellular mediators of cell adhesion and contraction respond to contractile stimuli with different rates and intensities in different regions of the cell.

  19. 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.

  20. Morphological and functional properties of the conducting human airways investigated by in vivo CT and in vitro MRI.

    Science.gov (United States)

    Van de Moortele, Tristan; Wendt, Christine H; Coletti, Filippo

    2017-11-02

    The accurate representation of the human airway anatomy is crucial for understanding and modeling the structure-function relationship in both healthy and diseased lungs. The present knowledge in this area is based on morphometric studies of excised lung casts, partially complemented by in vivo studies in which computed tomography (CT) was used on a small number of subjects. In the present study, we analyze CT scans of a cohort of healthy subjects and obtain comprehensive morphometric information down to the seventh generation of bronchial branching, including airway diameter, length, branching angle, and rotation angle. While some of the geometrical parameters (such as the child-to-parent branch diameter ratio) are found to be in line with accepted values, for others (such as the branch length-to-diameter ratio) our findings challenge the common assumptions. We also evaluate several metrics of self-similarity, including the fractal dimension of the airway tree. Additionally, we use phase-contrast magnetic resonance imaging (MRI) to obtain the volumetric flow field in the 3D printed airway model of one of the subjects during steady inhalation. This is used to relate structural and functional parameters and, in particular, to close the power-law relationship between branch flow rate and diameter. The diameter exponent is found to be significantly lower than in the usually assumed Poiseuille regime, which we attribute to the strong secondary (i.e. transverse) velocity component. The strength of the secondary velocity with respect to the axial component exceeds the levels found in idealized airway models, and persists within the first seven generations. Copyright © 2017, Journal of Applied Physiology.

  1. Diesel exhaust augments allergen-induced lower airway inflammation in allergic individuals: a controlled human exposure study.

    Science.gov (United States)

    Carlsten, Chris; Blomberg, Anders; Pui, Mandy; Sandstrom, Thomas; Wong, Sze Wing; Alexis, Neil; Hirota, Jeremy

    2016-01-01

    Traffic-related air pollution has been shown to augment allergy and airway disease. However, the enhancement of allergenic effects by diesel exhaust in particular is unproven in vivo in the human lung, and underlying details of this apparent synergy are poorly understood. To test the hypothesis that a 2 h inhalation of diesel exhaust augments lower airway inflammation and immune cell activation following segmental allergen challenge in atopic subjects. 18 blinded atopic volunteers were exposed to filtered air or 300 µg PM(2.5)/m(3) of diesel exhaust in random fashion. 1 h post-exposure, diluent-controlled segmental allergen challenge was performed; 2 days later, samples from the challenged segments were obtained by bronchoscopic lavage. Samples were analysed for markers and modifiers of allergic inflammation (eosinophils, Th2 cytokines) and adaptive immune cell activation. Mixed effects models with ordinal contrasts compared effects of single and combined exposures on these end points. Diesel exhaust augmented the allergen-induced increase in airway eosinophils, interleukin 5 (IL-5) and eosinophil cationic protein (ECP) and the GSTT1 null genotype was significantly associated with the augmented IL-5 response. Diesel exhaust alone also augmented markers of non-allergic inflammation and monocyte chemotactic protein (MCP)-1 and suppressed activity of macrophages and myeloid dendritic cells. Inhalation of diesel exhaust at environmentally relevant concentrations augments allergen-induced allergic inflammation in the lower airways of atopic individuals and the GSTT1 genotype enhances this response. Allergic individuals are a susceptible population to the deleterious airway effects of diesel exhaust. NCT01792232. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. 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.

  3. Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium.

    Directory of Open Access Journals (Sweden)

    Guadalupe Ayora-Talavera

    2009-11-01

    Full Text Available The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary "dead end." We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.

  4. 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.

  5. 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.

  6. Mechanisms of GM-CSF increase by diesel exhaust particles in human airway epithelial cells.

    Science.gov (United States)

    Boland, S; Bonvallot, V; Fournier, T; Baeza-Squiban, A; Aubier, M; Marano, F

    2000-01-01

    We have previously shown that exposure to diesel exhaust particles (DEPs) stimulates human airway epithelial cells to secrete the inflammatory cytokines interleukin-8, interleukin-1beta, and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in allergic diseases. In the present paper, we studied the mechanisms underlying the increase in GM-CSF release elicited by DEPs using the human bronchial epithelial cell line 16HBE14o-. RT-PCR analysis has shown an increase in GM-CSF mRNA levels after DEP treatments. Comparison of the effects of DEPs, extracted DEPs, or extracts of DEPs has shown that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and not to the metals present on the DEP surface because the metal chelator desferrioxamine had no inhibitory effect. Furthermore, radical scavengers inhibited the DEP-induced GM-CSF release, showing involvement of reactive oxygen species in this response. Moreover genistein, a tyrosine kinase inhibitor, abrogated the effects of DEPs on GM-CSF release, whereas protein kinase (PK) C, PKA, cyclooxygenase, or lipoxygenase inhibitors had no effect. PD-98059, an inhibitor of mitogen-activated protein kinase, diminished the effects of DEPs, whereas SB-203580, an inhibitor of p38 mitogen-activated protein kinase, had a lower effect, and DEPs did actually increase the active, phosphorylated form of the extracellular signal-regulated kinase as shown by Western blotting. In addition, cytochalasin D, which inhibits the phagocytosis of DEPs, reduced the increase in GM-CSF release after DEP treatment. Together, these data suggest that the increase in GM-CSF release is mainly due to the adsorbed organic compounds and that the effect of native DEPs requires endocytosis of the particles. Reactive oxygen species and tyrosine kinase(s) may be involved in the DEP-triggered signaling of the GM-CSF response.

  7. Cortactin mediates elevated shear stress-induced mucin hypersecretion via actin polymerization in human airway epithelial cells.

    Science.gov (United States)

    Liu, Chunyi; Li, Qi; Zhou, Xiangdong; Kolosov, Victor P; Perelman, Juliy M

    2013-12-01

    Mucus hypersecretion is a remarkable pathophysiological manifestation in airway obstructive diseases. These diseases are usually accompanied with elevated shear stress due to bronchoconstriction. Previous studies have reported that shear stress induces mucin5AC (MUC5AC) secretion via actin polymerization in cultured nasal epithelial cells. Furthermore, it is well known that cortactin, an actin binding protein, is a central mediator of actin polymerization. Therefore, we hypothesized that cortactin participates in MUC5AC hypersecretion induced by elevated shear stress via actin polymerization in cultured human airway epithelial cells. Compared with the relevant control groups, Src phosphorylation, cortactin phosphorylation, actin polymerization and MUC5AC secretion were significantly increased after exposure to elevated shear stress. Similar effects were found when pretreating the cells with jasplakinolide, and transfecting with wild-type cortactin. However, these effects were significantly attenuated by pretreating with Src inhibitor, cytochalasin D or transfecting cells with the specific small interfering RNA of cortactin. Collectively, these results suggest that elevated shear stress induces MUC5AC hypersecretion via tyrosine-phosphorylated cortactin-associated actin polymerization in cultured human airway epithelial cells. Copyright © 2013. Published by Elsevier Ltd.

  8. 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.

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

    Science.gov (United States)

    Shaikh, Nooreen; Johnson, Malcolm; Hall, David A; Chung, Kian Fan; Riley, John H; Worsley, Sally; Bhavsar, Pankaj K

    2017-01-01

    Intracellular mechanisms of action of umeclidinium (UMEC), a long-acting muscarinic receptor antagonist, and vilanterol (VI), a long-acting β 2 -adrenoceptor (β 2 R) agonist, were investigated in target cells: human airway smooth-muscle cells (ASMCs). 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 ([Ca 2+ ] i ) using a fluorescence assay, and regulator of G-protein signaling 2 (RGS2) messenger RNA using real-time quantitative polymerase chain reaction. 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. β 2 R 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 [Ca 2+ ] i , which was attenuated with UMEC pretreatment. Reduction of MCh-induced [Ca 2+ ] i release was greater with UMEC + VI versus UMEC. UMEC enhanced VI-induced RGS2 messenger RNA expression. These data indicate that UMEC reverses cholinergic inhibition of VI-induced cAMP production, and is a more potent muscarinic receptor antagonist when in combination with VI versus either alone.

  10. Velo-pharyngeal dysfunction: Evaluation and management.

    Science.gov (United States)

    Marsh, Jeffrey L

    2009-10-01

    Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD) may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention.

  11. Velo-pharyngeal dysfunction: Evaluation and management

    Directory of Open Access Journals (Sweden)

    Marsh Jeffrey

    2009-10-01

    Full Text Available Separation of the nasal and oral cavities by dynamic closure of the velo-pharyngeal port is necessary for normal speech and swallowing. Velo-pharyngeal dysfunction (VPD may either follow repair of a cleft palate or be independent of clefting. While the diagnosis of VPD is made by audiologic perceptual evaluation of speech, identification of the mechanism of the dysfunction requires instrumental visualization of the velo-pharyngeal port during specific speech tasks. Matching the specific intervention for management of VPD with the type of dysfunction, i.e. differential management for differential diagnosis, maximizes the result while minimizing the morbidity of the intervention.

  12. Cleavage of the SARS coronavirus spike glycoprotein by airway proteases enhances virus entry into human bronchial epithelial cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yiu-Wing Kam

    Full Text Available BACKGROUND: Entry of enveloped viruses into host cells requires the activation of viral envelope glycoproteins through cleavage by either intracellular or extracellular proteases. In order to gain insight into the molecular basis of protease cleavage and its impact on the efficiency of viral entry, we investigated the susceptibility of a recombinant native full-length S-protein trimer (triSpike of the severe acute respiratory syndrome coronavirus (SARS-CoV to cleavage by various airway proteases. METHODOLOGY/PRINCIPAL FINDINGS: PURIFIED TRISPIKE PROTEINS WERE READILY CLEAVED IN VITRO BY THREE DIFFERENT AIRWAY PROTEASES: trypsin, plasmin and TMPRSS11a. High Performance Liquid Chromatography (HPLC and amino acid sequencing analyses identified two arginine residues (R667 and R797 as potential protease cleavage site(s. The effect of protease-dependent enhancement of SARS-CoV infection was demonstrated with ACE2 expressing human bronchial epithelial cells 16HBE. Airway proteases regulate the infectivity of SARS-CoV in a fashion dependent on previous receptor binding. The role of arginine residues was further shown with mutant constructs (R667A, R797A or R797AR667A. Mutation of R667 or R797 did not affect the expression of S-protein but resulted in a differential efficacy of pseudotyping into SARS-CoVpp. The R667A SARS-CoVpp mutant exhibited a lack of virus entry enhancement following protease treatment. CONCLUSIONS/SIGNIFICANCE: These results suggest that SARS S-protein is susceptible to airway protease cleavage and, furthermore, that protease mediated enhancement of virus entry depends on specific conformation of SARS S-protein upon ACE2 binding. These data have direct implications for the cell entry mechanism of SARS-CoV along the respiratory system and, furthermore expand the possibility of identifying potential therapeutic agents against SARS-CoV.

  13. Arsenic Alters ATP-Dependent Ca2+ Signaling in Human Airway Epithelial Cell Wound Response

    Science.gov (United States)

    Sherwood, Cara L.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

    2011-01-01

    Arsenic is a natural metalloid toxicant that is associated with occupational inhalation injury and contaminates drinking water worldwide. Both inhalation of arsenic and consumption of arsenic-tainted water are correlated with malignant and nonmalignant lung diseases. Despite strong links between arsenic and respiratory illness, underlying cell responses to arsenic remain unclear. We hypothesized that arsenic may elicit some of its detrimental effects on the airway through limitation of innate immune function and, specifically, through alteration of paracrine ATP (purinergic) Ca2+ signaling in the airway epithelium. We examined the effects of acute (24 h) exposure with environmentally relevant levels of arsenic (i.e., arsenic reduces purinergic Ca2+ signaling in a dose-dependent manner and results in a reshaping of the Ca2+ signaling response to localized wounds. We next examined arsenic effects on two purinergic receptor types: the metabotropic P2Y and ionotropic P2X receptors. Arsenic inhibited both P2Y- and P2X-mediated Ca2+ signaling responses to ATP. Both inhaled and ingested arsenic can rapidly reach the airway epithelium where purinergic signaling is essential in innate immune functions (e.g., ciliary beat, salt and water transport, bactericide production, and wound repair). Arsenic-induced compromise of such airway defense mechanisms may be an underlying contributor to chronic lung disease. PMID:21357385

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

    DEFF Research Database (Denmark)

    Pedersen, Søren Damkiær

    environments. The model system used for these investigations has been long-term chronic airway infections in Cystic fibrosis (CF) patients caused by the opportunistic pathogen Pseudomonas aeruginosa. Using a systems biology approach, we have monitored the adaptive development of the clinically important P...

  15. 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

    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...

  16. Tiotropium attenuates IL-13-induced goblet cell metaplasia of human airway epithelial cells

    NARCIS (Netherlands)

    Kistemaker, Loes E. M.; Hiemstra, Pieter S.; Bos, I. Sophie T.; Bouwman, Susanne; van den Berge, Maarten; Hylkema, Machteld N.; Meurs, Herman; Kerstjens, Huib A. M.; Gosens, Reinoud

    BACKGROUND: It has been shown that acetylcholine is both a neurotransmitter and acts as a local mediator, produced by airway cells including epithelial cells. In vivo studies have demonstrated an indirect role for acetylcholine in epithelial cell differentiation. Here, we aimed to investigate direct

  17. Optical coherence tomography for identification and quantification of human airway wall layers

    NARCIS (Netherlands)

    d'Hooghe, Julia N. S.; Goorsenberg, Annika W. M.; de Bruin, Daniel M.; Roelofs, Joris J. T. H.; Annema, Jouke T.; Bonta, Peter I.

    2017-01-01

    High-resolution computed tomography has limitations in the assessment of airway wall layers and related remodeling in obstructive lung diseases. Near infrared-based optical coherence tomography (OCT) is a novel imaging technique that combined with bronchoscopy generates highly detailed images of the

  18. Maximal airway narrowing in humans in vivo. Histamine compared with methacholine

    NARCIS (Netherlands)

    Sterk, P. J.; Timmers, M. C.; Dijkman, J. H.

    1986-01-01

    Maximal airway narrowing to inhaled nonsensitizing stimuli is limited to a mild degree in nonasthmatic and mildly asthmatic subjects. We investigated whether this limitation is due to a nonspecific inhibitory mechanism (with regard to the agonist) by comparing the maximal response plateaus of

  19. 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

  20. 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.

  1. Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

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    Devi Rajan

    Full Text Available Infections with human rhinovirus (HRV are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences

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

    Science.gov (United States)

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

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. 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...

  4. Distinct Transduction Difference Between Adeno-Associated Virus Type 1 and Type 6 Vectors in Human Polarized Airway Epithelia

    OpenAIRE

    Yan, Ziying; Lei-Butters, Diana Chi Man; Keiser, Nicholas W; Engelhardt, John F.

    2012-01-01

    Of the many biologically isolated AAV serotypes, AAV1 and AAV6 share the highest degree of sequence homology, with only six different capsid residues. We compared the transduction efficiencies of rAAV1 and rAAV6 in primary polarized human airway epithelia (HAE) and found significant differences in their abilities to transduce epithelia from the apical and basolateral membranes. rAAV1 transduction was ~10-fold higher than rAAV6 following apical infection, while rAAV6 transduction was ~10-fold ...

  5. 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

  6. Cell-to-Cell Contact and Nectin-4 Govern Spread of Measles Virus from Primary Human Myeloid Cells to Primary Human Airway Epithelial Cells

    Science.gov (United States)

    Singh, Brajesh K.; Li, Ni; Mark, Anna C.; Mateo, Mathieu; Cattaneo, Roberto

    2016-01-01

    ABSTRACT Measles is a highly contagious, acute viral illness. Immune cells within the airways are likely first targets of infection, and these cells traffic measles virus (MeV) to lymph nodes for amplification and subsequent systemic dissemination. Infected immune cells are thought to return MeV to the airways; however, the mechanisms responsible for virus transfer to pulmonary epithelial cells are poorly understood. To investigate this process, we collected blood from human donors and generated primary myeloid cells, specifically, monocyte-derived macrophages (MDMs) and dendritic cells (DCs). MDMs and DCs were infected with MeV and then applied to primary cultures of well-differentiated airway epithelial cells from human donors (HAE). Consistent with previous results obtained with free virus, infected MDMs or DCs were incapable of transferring MeV to HAE when applied to the apical surface. Likewise, infected MDMs or DCs applied to the basolateral surface of HAE grown on small-pore (0.4-μm) support membranes did not transfer virus. In contrast, infected MDMs and DCs applied to the basolateral surface of HAE grown on large-pore (3.0-μm) membranes successfully transferred MeV. Confocal microscopy demonstrated that MDMs and DCs are capable of penetrating large-pore membranes but not small-pore membranes. Further, by using a nectin-4 blocking antibody or recombinant MeV unable to enter cells through nectin-4, we demonstrated formally that transfer from immune cells to HAE occurs in a nectin-4-dependent manner. Thus, both infected MDMs and DCs rely on cell-to-cell contacts and nectin-4 to efficiently deliver MeV to the basolateral surface of HAE. IMPORTANCE Measles virus spreads rapidly and efficiently in human airway epithelial cells. This rapid spread is based on cell-to-cell contact rather than on particle release and reentry. Here we posit that MeV transfer from infected immune cells to epithelial cells also occurs by cell-to-cell contact rather than through cell

  7. A novel role of protein tyrosine kinase2 in mediating chloride secretion in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Lihua Liang

    Full Text Available Ca(2+ activated Cl(- channels (CaCC are up-regulated in cystic fibrosis (CF airway surface epithelia. The presence and functional properties of CaCC make it a possible therapeutic target to compensate for the deficiency of Cl(- secretion in CF epithelia. CaCC is activated by an increase in cytosolic Ca(2+, which not only activates epithelial CaCCs, but also inhibits epithelial Na(+ hyperabsorption, which may also be beneficial in CF. Our previous study has shown that spiperone, a known antipsychotic drug, activates CaCCs and stimulates Cl(- secretion in polarized human non-CF and CF airway epithelial cell monolayers in vitro, and in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR knockout mice in vivo. Spiperone activates CaCC not by acting in its well-known role as an antagonist of either 5-HT2 or D2 receptors, but through a protein tyrosine kinase-coupled phospholipase C-dependent pathway. Moreover, spiperone independently activates CFTR through a novel mechanism. Herein, we performed a mass spectrometry analysis and identified the signaling molecule that mediates the spiperone effect in activating chloride secretion through CaCC and CFTR. Proline-rich tyrosine kinase 2 (PYK2 is a non-receptor protein tyrosine kinase, which belongs to the focal adhesion kinase family. The inhibition of PYK2 notably reduced the ability of spiperone to increase intracellular Ca(2+ and Cl(- secretion. In conclusion, we have identified the tyrosine kinase, PYK2, as the modulator, which plays a crucial role in the activation of CaCC and CFTR by spiperone. The identification of this novel role of PYK2 reveals a new signaling pathway in human airway epithelial cells.

  8. 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.

  9. A bottom-up approach for labeling of human airway trees

    DEFF Research Database (Denmark)

    2011-01-01

    In this paper, an airway labeling algorithm that allows for gaps between the labeled branches is introduced. A bottom-up approach for arriving to an optimal set of branches and their associated labels is used in the proposed method. A K nearest neighbor based appearance model is used to different...... with simulated errors, such as missing branches and having falsely detected branches, where we showed that such errors have little or no effect on the proposed method....

  10. 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.

  11. 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

  12. Inhibition of human airway sensitization by a novel monoclonal anti-IgE antibody, 17-9.

    Science.gov (United States)

    Rabe, K F; Watson, N; Dent, G; Morton, B E; Wagner, K; Magnussen, H; Heusser, C H

    1998-05-01

    We investigated the effect of a novel mouse IgG2b nonanaphylactogenic anti-human IgE antibody, 17-9, on allergen and histamine responses in passively sensitized human airways in vitro to determine the specific contribution of IgE to the sensitization process. Bronchial rings were sensitized with serum containing high levels of allergen-specific IgE (Dermatophagoides farinae), or with a hapten-specific chimeric humanized IgE (JW8). There was a concentration-dependent contraction of serum-sensitized bronchial rings to D. farinae (517 +/- 188 mg tension at 10 U/ml, n = 8) that was not observed in nonsensitized controls. This response was practically abolished when tissues were sensitized in the presence of 100 microg/ml anti-IgE antibody 17-9 (54 +/- 20 mg). In tissues sensitized with the anti-NIP IgE, JW8, there was a concentration-dependent contraction to the specific antigen NIP-BSA (560 +/- 154 mg at 0.3 microg/ml, n = 5) that was not observed in nonsensitized control subjects and that was substantially inhibited when 17-9 was present in the sensitization buffer (124 +/- 109 mg). The inhibition with 17-9 was specific, as pretreatment with a non-IgE-specific IgG2b antibody did not affect allergen responses. Potency and maximal contractions to histamine in serum-sensitized tissues were significantly elevated compared with nonsensitized controls; this was not affected by the presence of 17-9 during sensitization (pEC50 = 5.1 +/- 0.2 versus 5.0 +/- 0.3 in tissues sensitized in the absence of 17-9). In tissues sensitized with JW8 there was no significant increase in responsiveness to histamine. We conclude that allergen responses in sensitized human airways are dependent on IgE levels in the sensitizing serum while nonspecific (hyper)responsiveness depends on serum factors other than IgE. Nonanaphylactogenic anti-human IgE antibodies effectively inhibit allergen responses of human airways in vitro but may not affect other factors inducing hyperresponsiveness.

  13. 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

  14. Ezrin/Exocyst complex regulates mucin 5AC secretion induced by neutrophil elastase in human airway epithelial cells.

    Science.gov (United States)

    Li, Qi; Li, Na; Liu, Chun-Yi; Xu, Rui; Kolosov, Victor P; Perelman, Juliy M; Zhou, Xiang-Dong

    2015-01-01

    Increased mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in mucin 5AC (MUC5AC) secretion after neutrophil elastase (NE) attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes. © 2015 S. Karger AG, Basel.

  15. Ezrin/Exocyst Complex Regulates Mucin 5AC Secretion Induced by Neutrophil Elastase in Human Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Qi Li

    2015-01-01

    Full Text Available Background/Aim: Increased mucin secretion is a characteristic feature of many chronic airway diseases, particularly during periods of exacerbation; however, the exact mechanism of mucin secretion remains unclear. Ezrin, which is a specific marker of apical membranes, is predominantly concentrated in exocyst-rich cell surface structures, crosslinking the actin cytoskeleton with the plasma membrane. In the present study, we examined whether Ezrin is involved in mucin 5AC (MUC5AC secretion after neutrophil elastase (NE attack, and we investigated the role of the exocyst complex docking protein Sec3 in this process. Methods: NE was used as a stimulator in a 16HBE14o- cell culture model. The expression and location of Ezrin and Sec3 were investigated, and the interaction between Ezrin and Sec3 in 16HBE14o-cells was assayed after treatment with NE, Ezrin siRNA, Sec3 siRNA, neomycin or PIP2-Ab. Results: We found that Ezrin was highly expressed in the bronchi of humans with chronic airway diseases. NE induced robust MUC5AC protein secretion. The Ezrin siRNA, Sec3 siRNA, and neomycin treatments led to impaired MUC5AC secretion in cells. Both Ezrin and Sec3 were recruited primarily to the cytoplasmic membrane after NE stimulation, and the neomycin and PIP2-Ab treatments abrogated this effect. Immunoprecipitation analysis revealed that Ezrin and Sec3 combined to form complexes; however, these complexes could not be detected in Ezrin∆1-333 mutant-transfected cells, even when PIP2 was added. Conclusions: These results demonstrate that Ezrin/Sec3 complexes are essential for MUC5AC secretion in NE-stimulated airway epithelial cells and that PIP2 is of critical importance in the formation of these complexes.

  16. Biomechanical properties of the human upper airway and their effect on its behavior during breathing and in obstructive sleep apnea.

    Science.gov (United States)

    Bilston, Lynne E; Gandevia, Simon C

    2014-02-01

    The upper airway is a complex, multifunctional, dynamic neuromechanical system. Its patency during breathing requires moment-to-moment coordination of neural and mechanical behavior and varies with posture. Failure to continuously recruit and coordinate dilator muscles to counterbalance the forces that act to close the airway results in hypopneas or apneas. Repeated failures lead to obstructive sleep apnea (OSA). Obesity and anatomical variations, such as retrognathia, increase the likelihood of upper airway collapse by altering the passive mechanical behavior of the upper airway. This behavior depends on the mechanical properties of each upper airway tissue in isolation, their geometrical arrangements, and their physiological interactions. Recent measurements of respiratory-related deformation of the airway wall have shown that there are different patterns of airway soft tissue movement during the respiratory cycle. In OSA patients, airway dilation appears less coordinated compared with that in healthy subjects (matched for body mass index). Intrinsic mechanical properties of airway tissues are altered in OSA patients, but the factors underlying these changes have yet to be elucidated. How neural drive to the airway dilators relates to the biomechanical behavior of the upper airway (movement and stiffness) is still poorly understood. Recent studies have highlighted that the biomechanical behavior of the upper airway cannot be simply predicted from electromyographic activity (electromyogram) of its muscles.

  17. Role of caveolin-1 in p42/p44 MAP kinase activation and proliferation of human airway smooth muscle

    NARCIS (Netherlands)

    Gosens, Reinoud; Stelmack, Gerald L; Dueck, Gordon; McNeill, Karol D; Yamasaki, Akira; Gerthoffer, William T; Unruh, Helmut; Gounni, Abdelilah Soussi; Zaagsma, Johan; Halayko, Andrew J

    2006-01-01

    Chronic airways diseases, including asthma, are associated with an increased airway smooth muscle (ASM) mass, which may contribute to chronic airway hyperresponsiveness. Increased muscle mass is due, in part, to increased ASM proliferation, although the precise molecular mechanisms for this response

  18. 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.

  19. Pharyngeal Packing during Rhinoplasty: Advantages and Disadvantages.

    Science.gov (United States)

    Razavi, Majid; Taghavi Gilani, Mehryar; Bameshki, Ali Reza; Behdani, Reza; Khadivi, Ehsan; Bakhshaee, Mahdi

    2015-11-01

    Controversy remains as to the advantages and disadvantages of pharyngeal packing during septorhinoplasty. Our study investigated the effect of pharyngeal packing on postoperative nausea and vomiting and sore throat following this type of surgery or septorhinoplasty. This clinical trial was performed on 90 American Society of Anesthesiologists (ASA) I or II patients who were candidates for septorhinoplasty. They were randomly divided into two groups. Patients in the study group had received pharyngeal packing while those in the control group had not. The incidence of nausea and vomiting and sore throat based on the visual analog scale (VAS) was evaluated postoperatively in the recovery room as well as at 2, 6 and 24 hours. The incidence of postoperative nausea and vomiting (PONV) was 12.3%, with no significant difference between the study and control groups. Sore throat was reported in 50.5% of cases overall (56.8% on pack group and 44.4% on control). Although the severity of pain was higher in the study group at all times, the incidence in the two groups did not differ significantly. The use of pharyngeal packing has no effect in reducing the incidence of nausea and vomiting and sore throat after surgery. Given that induced hypotension is used as the routine method of anesthesia in septorhinoplasty surgery, with a low incidence of hemorrhage and a high risk of unintended retention of pharyngeal packing, its routine use is not recommended for this procedure.

  20. Pharyngeal Swallowing Mechanics Secondary to Hemispheric Stroke.

    Science.gov (United States)

    May, Nelson H; Pisegna, Jessica M; Marchina, Sarah; Langmore, Susan E; Kumar, Sandeep; Pearson, William G

    2017-05-01

    Computational analysis of swallowing mechanics (CASM) is a method that utilizes multivariate shape change analysis to uncover covariant elements of pharyngeal swallowing mechanics associated with impairment using videofluoroscopic swallowing studies. The goals of this preliminary study were to (1) characterize swallowing mechanics underlying stroke-related dysphagia, (2) decipher the impact of left and right hemispheric strokes on pharyngeal swallowing mechanics, and (3) determine pharyngeal swallowing mechanics associated with penetration-aspiration status. Videofluoroscopic swallowing studies of 18 dysphagic patients with hemispheric infarcts and age- and gender-matched controls were selected from well-controlled data sets. Patient data including laterality and penetration-aspiration status were collected. Coordinates mapping muscle group action during swallowing were collected from videos. Multivariate morphometric analyses of coordinates associated with stroke, affected hemisphere, and penetration-aspiration status were performed. Pharyngeal swallowing mechanics differed significantly in the following comparisons: stroke versus controls (D = 2.19, P mechanics associated with each comparison were visualized using eigenvectors. Whereas current literature focuses on timing changes in stroke-related dysphagia, these data suggest that mechanical changes are also functionally important. Pharyngeal swallowing mechanics differed by the affected hemisphere and the penetration-aspiration status. CASM can be used to identify patient-specific swallowing impairment associated with stroke injury that could help guide rehabilitation strategies to improve swallowing outcomes. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. Sensory regulation of swallowing and airway protection: a role for the internal superior laryngeal nerve in humans

    Science.gov (United States)

    Jafari, Samah; Prince, Rebecca A; Kim, Daniel Y; Paydarfar, David

    2003-01-01

    During swallowing, the airway is protected from aspiration of ingested material by brief closure of the larynx and cessation of breathing. Mechanoreceptors innervated by the internal branch of the superior laryngeal nerve (ISLN) are activated by swallowing, and connect to central neurones that generate swallowing, laryngeal closure and respiratory rhythm. This study was designed to evaluate the hypothesis that the ISLN afferent signal is necessary for normal deglutition and airway protection in humans. In 21 healthy adults, we recorded submental electromyograms, videofluoroscopic images of the upper airway, oronasal airflow and respiratory inductance plethysmography. In six subjects we also recorded pressures in the hypopharynx and upper oesophagus. We analysed swallows that followed a brief infusion (4–5 ml) of liquid barium onto the tongue, or a sip (1–18 ml) from a cup. In 16 subjects, the ISLN was anaesthetised by transcutaneous injection of bupivacaine into the paraglottic compartment. Saline injections using the identical procedure were performed in six subjects. Endoscopy was used to evaluate upper airway anatomy, to confirm ISLN anaesthesia, and to visualise vocal cord movement and laryngeal closure. Comparisons of swallowing and breathing were made within subjects (anaesthetic or saline injection vs. control, i.e. no injection) and between subjects (anaesthetic injection vs. saline injection). In the non-anaesthetised condition (saline injection, 174 swallows in six subjects; no injection, 522 swallows in 20 subjects), laryngeal penetration during swallowing was rare (1.4 %) and tracheal aspiration was never observed. During ISLN anaesthesia (16 subjects, 396 swallows), all subjects experienced effortful swallowing and an illusory globus sensation in the throat, and 15 subjects exhibited penetration of fluid into the larynx during swallowing. The incidence of laryngeal penetration in the anaesthetised condition was 43 % (P deglutition, especially for

  2. 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. PMID:22363778

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear ...

  4. 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.

  5. 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.

  6. Asian sand dust increases MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK in human airway epithelial cells.

    Science.gov (United States)

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

    2015-01-01

    Asian sand dust (ASD) is a natural phenomenon and originates from the deserts of China and is known to contain various chemical and biomolecular components that enhance airway inflammation. The overproduction of airway mucins is an important pathologic finding in inflammatory airway diseases. However, the mechanism of ASD on mucin production of airway epithelial cells has not been elucidated. To investigate the effect and signaling pathway of ASD on mucin expressions in human airway epithelial cells. In the NCI-H292 cells and the primary cultures of human nasal epithelial cells, the effect and signaling pathway of ASD on MUC8 and MUC5B expressions were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). ASD increased MUC8 and MUC5B expressions and activated the phosphorylations of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK). U0126 (ERK1/2 MAPK inhibitor) and SB203580 (p38 MAPK inhibitor) inhibited ASD-induced MUC8 and MUC5B expressions. In addition, knockdowns of ERK2 and p38 MAPK by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Toll-like receptor 4 (TLR4) mRNA expression was increased after treatment with ASD. Knockdown of TLR4 by siRNA blocked ASD-induced MUC8 and MUC5B mRNA expressions. Furthermore, the phosphorylations of ERK1/2 and p38 MAPK were blocked by knockdown of TLR4. These results show that ASD induces MUC8 and MUC5B expressions via TLR4-dependent ERK2 and p38 MAPK signaling pathway in human airway epithelial cells.

  7. Role for TAK1 in cigarette smoke-induced proinflammatory signaling and IL-8 release by human airway smooth muscle cells

    NARCIS (Netherlands)

    Pera, Tonio; Atmaj, Claudia; van der Vegt, Marieke; Halayko, Andrew J.; Zaagsma, Johan; Meurs, Herman

    Pera T, Atmaj C, van der Vegt M, Halayko AJ, Zaagsma J, Meurs H. Role for TAK1 in cigarette smoke-induced proinflammatory signaling and IL-8 release by human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 303: L272-L278, 2012. First published April 20, 2012;

  8. Techniques in human airway inflammation : Differences in plastic-embedded and snap-frozen sections for CD3, CD4, and CD8 immunostaining of bronchial biopsy specimens

    NARCIS (Netherlands)

    tenHacken, NHT; Aleva, RM; Rutgers, B; Kraan, J; vanGoor, H; Postma, DS; Timens, W

    1997-01-01

    Today, the quantification of inflammatory cells in human airway biopsies might be facilitated by better morphologic resolution provided by special resin (plastic)-embedding techniques. The present study compares the numbers of CD3-, CD4-, and CD8-positive cells in glycolmethacrylate-embedded versus

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

    OpenAIRE

    O'Halloran, Ken D.; Lewis, Philip; Fiona B Mcdonald

    2016-01-01

    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...

  10. Simulation of the human airways using virtual topology tools and meshing optimization.

    Science.gov (United States)

    Fernández-Tena, A; Marcos, A C; Agujetas, R; Ferrera, C

    2017-11-05

    A method is proposed to improve the quality of the three-dimensional airway geometric models using a commercial software, checking the number of elements, meshing time, and aspect ratio and skewness parameters. The use of real and virtual topologies combined with patch-conforming and patch-independent meshing algorithms results in four different models being the best solution the combination of virtual topology and patch-independent algorithm, due to an excellent aspect ratio and skewness of the elements, and minimum meshing time. The result is a reduction in the computational time required for both meshing and simulation due to a smaller number of cells. The use of virtual topologies combined with patch-independent meshing algorithms could be extended in bioengineering because the geometries handling is similar to this case. The method is applied to a healthy person using their computed tomography images. The resulting numerical models are able to simulate correctly a forced spirometry.

  11. 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

    -A and SP-D in the first three samplings were also analyzed by enzyme-linked immunosorbent assay. Results: In nasal mucosal biopsies, SP-A, -B, -C and -D were all demonstrated in the serous acini of the submucosal glands and in the surface epithelium. SP-D was detected in nasal brush biopsies, whereas...... the other SPs were absent. Moreover, SP-A, -B, -C and -D were absent in nasal lavage and mucus. Conclusion: SP-A, -B, -C and -D exert their protective effect in the ductal epithelium of the submucosal glands rather than in nasal secretions and mucus. Further studies are required to clarify the functions...... of these proteins in nasal secretory pathways for understanding upper airway diseases. © 2014 S. Karger AG, Basel....

  12. 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.

  13. 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.

  14. 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.

  15. Graphic representation of pharyngeal wall motion during swallow: technical note.

    Science.gov (United States)

    Ekberg, O; Borgstrom, P S

    1989-01-01

    Movements of the pharyngeal wall were measured at 12 transverse levels, on consecutive cineradiograms obtained during swallowing of thin, liquid barium, in a single nondysphagic volunteer. By graphic representation of these measurements on the IBM personal computer, it was possible to analyze in detail pharyngeal motor activity in terms of displacement of the pharyngeal wall. The contraction created a fairly steep narrowing of the lumen. The peristaltic wave was more difficult to analyze. Movements of the pharyngeal wall in posteroanterior projection gave good information about the constrictors. Although this technique has several inherent methodologic difficulties, its use may expand our knowledge of pharyngeal peristalsis.

  16. 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

  17. Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells.

    Science.gov (United States)

    Goodale, Britton C; Rayack, Erica J; Stanton, Bruce A

    2017-09-15

    Arsenic contamination of drinking water and food threatens the health of hundreds of millions of people worldwide by increasing the risk of numerous diseases. Arsenic exposure has been associated with infectious lung disease in epidemiological studies, but it is not yet understood how ingestion of low levels of arsenic increases susceptibility to bacterial infection. Accordingly, the goal of this study was to examine the effect of arsenic on gene expression in primary human bronchial epithelial (HBE) cells and to determine if arsenic altered epithelial cell responses to Pseudomonas aeruginosa, an opportunistic pathogen. Bronchial epithelial cells line the airway surface, providing a physical barrier and serving critical roles in antimicrobial defense and signaling to professional immune cells. We used RNA-seq to define the transcriptional response of HBE cells to Pseudomonas aeruginosa, and investigated how arsenic affected HBE gene networks in the presence and absence of the bacterial challenge. Environmentally relevant levels of arsenic significantly changed the expression of genes involved in cellular redox homeostasis and host defense to bacterial infection, and decreased genes that code for secreted antimicrobial factors such as lysozyme. Using pathway analysis, we identified Sox4 and Nrf2-regulated gene networks that are predicted to mediate the arsenic-induced decrease in lysozyme secretion. In addition, we demonstrated that arsenic decreased lysozyme in the airway surface liquid, resulting in reduced lysis of Microccocus luteus. Thus, arsenic alters the expression of genes and proteins in innate host defense pathways, thereby decreasing the ability of the lung epithelium to fight bacterial infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dapsone inhibits IL-8 secretion from human bronchial epithelial cells stimulated with lipopolysaccharide and resolves airway inflammation in the ferret.

    Science.gov (United States)

    Kanoh, Soichiro; Tanabe, Tsuyoshi; Rubin, Bruce K

    2011-10-01

    IL-8 is an important activator and chemoattractant for neutrophils that is produced by normal human bronchial epithelial (NHBE) cells through mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) p65 pathways. Dapsone, a synthetic sulfone, is widely used to treat chronic neutrophil dermatoses. We investigated the effects of dapsone on polarized IL-8 secretion from lipopolysaccharide (LPS)-stimulated NHBE cells and further evaluated its ability to decrease LPS-induced inflammation in the ferret airway. NHBE cells were grown at air-liquid interface (ALI) to ciliated differentiation. Baseline and endotoxin (LPS)-stimulated IL-8 secretion was measured by enzyme-linked immunosorbent assay at air and basal sides with and without dapsone. Western blotting was used to determine signaling pathways. In vivo, ferrets were exposed to intratracheal LPS over a period of 5 days. Once inflammation was established, oral or nebulized dapsone was administered for 5 days. Intraepithelial neutrophil accumulation was analyzed histologically, and mucociliary transport was measured on the excised trachea. Dapsone, 1 μg/mL, did not influence unstimulated (basal) IL-8 secretion. Apical LPS stimulation induced both apical and basolateral IL-8, but basolateral LPS increased only basolateral IL-8. Dapsone inhibited polarized IL-8 secretion from ALI-conditioned cells. Dapsone also decreased LPS-induced IL-8 mRNA level. LPS led to phosphorylation of extracellular signal-regulated kinase 1/2, but not p38 MAPK or c-Jun NH(2)-terminal kinase. LPS also induced NF-κB p65 phosphorylation, an effect that was inhibited by dapsone. Both oral and aerosol dapsone decreased LPS-induced intraepithelial neutrophil accumulation, but only treatment with aerosol dapsone restored mucociliary transport to normal. Dapsone, given either systemically or as an aerosol, may be useful in treating neutrophilic airway inflammation.

  19. MiR-21 modulates human airway smooth muscle cell proliferation and migration in asthma through regulation of PTEN expression.

    Science.gov (United States)

    Liu, Yun; Yang, Kunzheng; Shi, Hongyang; Xu, Jing; Zhang, Dexin; Wu, Yuanyuan; Zhou, Shuru; Sun, Xiuzhen

    2015-01-01

    Asthma is characterized by airway remodeling arising from an increase in airway smooth muscle (ASM) mass. This increase is regulated in part by ASM cell proliferation and migration. MicroRNA (miR)-21 also plays a role in asthma, but the molecular mechanisms underlying its effects are not completely understood. This study investigated the effects and mechanism of miR-21 on the human ASM (HASM) cell proliferation and migration. HASM cells were transduced with a miR-21 vector, and the expression of miR-21 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effect of the miR-21 on HASM cell proliferation and migration was analyzed by CCK8 and transwell assay. The expression level of PTEN (phosphatase and tensin homolog deleted on chromosome 10) in HASM cells was assessed by qRT-PCR and Western blot analysis. Meanwhile, the activity of PTEN was measured by PTEN malachite green assay kit. Lentivirus-mediated miR-21 overexpression markedly enhanced the proliferation and migration of HASM cells (P migration. We demonstrated that miR-21 overexpression significantly reduced the expression of PTEN (P migration. Furthermore, we found that overexpression of PTEN led to a decrease of HASM cell proliferation and migration. MiR-21 mediated HASM cell proliferation and migration through activation of the phosphoinositide 3-kinase pathway. This study provides the first in vitro evidence that overexpression of miR-21 in HASM cells can trigger cell proliferation and migration, and the effects of miR-21 depend on the level of PTEN.

  20. 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.

  1. 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.

  2. 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)....

  3. 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

  4. 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.

  5. 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.

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

    Science.gov (United States)

    Francois, Lissa; Tyagi, Rachanna; Hegyi, Thomas; Santolaya-Forgas, Joaquin

    2014-01-01

    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. PMID:25452890

  7. 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.

  8. Assays for in vitro monitoring of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cell migration.

    Science.gov (United States)

    Goncharova, Elena A; Goncharov, Dmitry A; Krymskaya, Vera P

    2006-01-01

    Migration of human pulmonary vascular smooth muscle (VSM) cells contributes to vascular remodeling in pulmonary arterial hypertension and atherosclerosis. Evidence also indicates that, in part, migration of airway smooth muscle (ASM) cells may contribute to airway remodeling associated with asthma. Here we describe migration of VSM and ASM cells in vitro using Transwell or Boyden chamber assays. Because dissecting signaling mechanisms regulating cell migration requires molecular approaches, our protocol also describes how to assess migration of transfected VSM and ASM cells. Transwell or Boyden chamber assays can be completed in approximately 8 h and include plating of serum-deprived VSM or ASM cell suspension on membrane precoated with collagen, migration of cells toward chemotactic gradient and visual (Transwell) or digital (Boyden chamber) analysis of membrane. Although the Transwell assay is easy, the Boyden chamber assay requires hands-on experience; however, both assays are reliable cell-based approaches providing valuable information on how chemotactic and inflammatory factors modulate VSM and ASM migration.

  9. Rhythmic Pressure Waves Induce Mucin5AC Expression via an EGFR-Mediated Signaling Pathway in Human Airway Epithelial Cells

    Science.gov (United States)

    Liu, Chunyi; Li, Qi; Kolosov, Victor P.; Perelman, Juliy M.

    2013-01-01

    Rhythmic pressure waves (RPW), mimicking the mechanical forces generated during normal breathing, play a key role in airway surface liquid (ASL) homeostasis. As a major component of ASL, we speculated that the mucin5AC (MUC5AC) expression must also be regulated by RPW. However, fewer researches have focused on this question. Therefore, our aim was to test the effect and mechanism of RPW on MUC5AC expression in cultured human bronchial epithelial cells. Compared with the relevant controls, the transcriptional level of MUC5AC and the protein expressions of MUC5AC, the phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-related kinase (p-ERK), and phospho-Akt (p-Akt) were all significantly increased after mechanical stimulation. However, this effect could be significantly attenuated by transfecting with EGFR-siRNA. Similarly, pretreating with the inhibitor of ERK or phosphatidylinositol 3-kinases (PI3K)/Akt separately or jointly also significantly reduced MUC5AC expression. Collectively, these results indicate that RPW modulate MUC5AC expression via the EGFR-PI3K-Akt/ERK-signaling pathway in human bronchial epithelial cells. PMID:23768102

  10. sup 125 I-albumin may not be used as a tracer of absorption across the human nasal airway bassiers

    Energy Technology Data Exchange (ETDEWEB)

    Greiff, L.; Pipkorn, U. (Lund Univ. Hospital (Sweden). Dept. of Oto-Rhino-Laryngology); Wollmer, P. (Lund Univ. Hospital (Sweden). Dept. of Clinical Physiology); Persson, C.G.A. (Lund Univ. Hospital (Sweden). Dept. of Clinical Pharmacology)

    1991-01-01

    This study set out to examine the effects of histamine on airway absorption of macromolecules. By employment of a novel 'nasal pool' technique instillates containing {sup 125}I-albumin with or without histamine, were kept for 15 min on human nasal mucosa. Unaffected by the presence of histamine, this instillations produced significant levels of plasma radioactivity, increasing for 60 min. However, gel-filtration data showed that only 30% of the plasma radioactivity was still bound to albumin. Incubation experiments indicated that radioiodine did not dissociate from albumin in nasal liquids nor in the blood. Further experiments involved oral ingestion of the entire nasal instillate. Prompts gastrointestinal absorption of radioactivity occurred, giving rise to plasma levels about two orders of magnitude higher than those recorded after the nasal applications. Moreover, only 25% of the plasma radioactivity was now bound to albumin. It must be considered unavoidable that a small portion (<1%) of the nasal instillate is swallowed. Hence, the plasma radioactivity detected in this study may largely, reflect gastrointestinal break-down of {sup 125}I-albumin and subsequent absorption of radioiodine. We conclude that {sup 125}I-albumin may not be employed in studies addressing macromolecular absorption across the human nasal mucosa and that previous work and conclusions based on nasal absorption of {sup 125}I-albumin are invalid. (au).

  11. Delayed Airway Obstruction after Internal Jugular Venous Catheterization in a Patient with Anticoagulant Therapy

    Directory of Open Access Journals (Sweden)

    Pei-Ju Wu

    2011-01-01

    Full Text Available Delayed onset of neck hematoma following central venous catheterization without arterial puncture is uncommon. Herein, we present a patient who developed a delayed neck hematoma after repeated attempts at right internal jugular venous puncture and subsequent enoxaparin administration. Progressive airway obstruction occurred on the third day after surgery. Ultrasound examination revealed diffuse hematoma of the right neck, and fibreoptic examination of the airway revealed pharyngeal edema. After emergent surgical removal of the hematoma, the patient was extubated uneventfully.

  12. The impact of low-frequency, low-force cyclic stretching of human bronchi on airway responsiveness.

    Science.gov (United States)

    Le Guen, Morgan; Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Brollo, Marion; Longchampt, Elisabeth; Kleinmann, Philippe; Devillier, Philippe; Faisy, Christophe

    2016-11-14

    In vivo, the airways are constantly subjected to oscillatory strain (due to tidal breathing during spontaneous respiration) and (in the event of mechanical ventilation) positive pressure. This exposure is especially problematic for the cartilage-free bronchial tree. The effects of cyclic stretching (other than high-force stretching) have not been extensively characterized. Hence, the objective of the present study was to investigate the functional and transcriptional response of human bronchi to repetitive mechanical stress caused by low-frequency, low-force cyclic stretching. After preparation and equilibration in an organ bath, human bronchial rings from 66 thoracic surgery patients were stretched in 1-min cycles of elongation and relaxation over a 60-min period. For each segment, the maximal tension corresponded to 80% of the reference contraction (the response to 3 mM acetylcholine). The impact of cyclic stretching (relative to non-stretched controls) was examined by performing functional assessments (epithelium removal and incubation with sodium channel agonists/antagonists or inhibitors of intracellular pathways), biochemical assays of the organ bath fluid (for detecting the release of pro-inflammatory cytokines), and RT-PCR assays of RNA isolated from tissue samples. The application of low-force cyclic stretching to human bronchial rings for 60 min resulted in an immediate, significant increase in bronchial basal tone, relative to non-cyclic stretching (4.24 ± 0.16 g vs. 3.28 ± 0.12 g, respectively; p stretching up-regulated the early mRNA expression of MMP9 only, and was not associated with changes in organ bath levels of pro-inflammatory mediators. Low-frequency, low-force cyclic stretching of whole human bronchi induced a myogenic response rather than activation of the pro-inflammatory signaling pathways mediated by mechanotransduction.

  13. Dietary Indicators of Oral and Pharyngeal Cancer

    OpenAIRE

    LA VECCHIA, CARLO; NEGRI, EVA; D'AVANZO, BARBARA; BOYLE, PETER; FRANCESCHI, SILVIA

    2017-01-01

    The relationship between frequency of consumption of a selected number of indicator foods and oral and oropharyngeal cancer risk was analysed in a case-control study conducted in Northern Italy on 105 cases of oral and pharyngeal cancer and 1169 controls in hospital for acute, non-neoplastic or digestive diseases. Besides significant and strong direct associations with tobacco (relative risk, RR = 11.0 for current versus never smokers) and alcohol (RR = 5.8 for upper versus lower consumption ...

  14. Dietary factors in oral and pharyngeal cancer.

    Science.gov (United States)

    McLaughlin, J K; Gridley, G; Block, G; Winn, D M; Preston-Martin, S; Schoenberg, J B; Greenberg, R S; Stemhagen, A; Austin, D F; Ershow, A G

    1988-10-05

    A population-based case-control study of oral and pharyngeal cancer conducted in four areas of the United States provided information on a number of risk factors, including diet. Interviews were obtained from 871 oral cancer patients and 979 controls among whites, frequency matched for age and sex. Consumption frequency of 61 food items was assessed in the questionnaire; attention was given to foods that are sources of vitamins A and C and carotene. The major finding was an inverse relationship between fruit intake and risk of oral and pharyngeal cancer; individuals in the highest quartile of intake had about half the risk of those in the lowest quartile. Vitamin C, carotene, or fiber in fruit did not appear to account completely for this relationship, since these nutrients in vegetables did not provide similar protection. This finding suggests the influence of other constituents in fruits, although it is possible that cooking vegetables may have a nutrient-diminishing effect. Dietary intake of other nutrients, such as the B vitamins, vitamin E, folate, and iron, showed no consistent relationship to risk of oral and pharyngeal cancer. Coffee or other hot beverage consumption did not increase risk; intake of nitrite-containing meats or cooking practices, such as smoking, pickling, or charcoal grilling, also did not increase risk. All analyses were adjusted for the effects of tobacco and alcohol, strong risk factors for oral and pharyngeal cancer. Dietary findings among the few subjects who did not use tobacco or alcohol were similar to those for all subjects.

  15. Effect of static vs. dynamic imaging on particle transport in CT-based numerical models of human central airways.

    Science.gov (United States)

    Miyawaki, Shinjiro; Hoffman, Eric A; Lin, Ching-Long

    2016-10-01

    Advances in quantitative computed tomography (CT) has provided methods to assess the detailed structure of the pulmonary airways and parenchyma, providing the means of applying computational fluid dynamics-based modeling to better understand subject-specific differences in structure-to-function relationships. Most of the previous numerical studies, seeking to predict patterns of inhaled particle deposition, have considered airway geometry and regional ventilation derived from static images. Because geometric alterations of the airway and parenchyma associated with regional ventilation may greatly affect particle transport, we have sought to investigate the effect of rigid vs. deforming airways, linear vs. nonlinear airway deformations, and step-wise static vs. dynamic imaging on particle deposition with varying numbers of intermediate lung volume increments. Airway geometry and regional ventilation at different time points were defined by four-dimensional (space and time) dynamic or static CT images. Laminar, transitional, and turbulent air flows were reproduced with a three-dimensional eddy-resolving computational fluid dynamics model. Finally, trajectories of particles were computed with the Lagrangian tracking algorithm. The results demonstrated that static-imaging-based models can contribute 7% uncertainty to overall particle distribution and deposition primarily due to regional flow rate (ventilation) differences as opposed to geometric alterations. The effect of rigid vs. deforming airways on serial distribution of particles over generations was significantly smaller than reported in a previous study that used the symmetric Weibel geometric model with smaller flow rate. Rigid vs. deforming airways were also shown to affect parallel particle distribution over lobes by 8% and the differences associated with use of static vs. dynamic imaging was 18%. These differences demonstrate that estimates derived from static vs. dynamic imaging can significantly affect the

  16. Directional Secretory Response of Double Stranded RNA-Induced Thymic Stromal Lymphopoetin (TSLP) and CCL11/Eotaxin-1 in Human Asthmatic Airways

    OpenAIRE

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

    2014-01-01

    BACKGROUND: 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. METHODS: Primary human bronchial epithelial cells (HBEC) from c...

  17. 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

  18. Modeling of inertial deposition in scaled models of rat and human nasal airways: Towards in vitro regional dosimetry in small animals

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Jinxiang; Kim, JongWon; Si, Xiuhua A.; Corley, Richard A.; Zhou, Yue

    2016-09-01

    Rodents are routinely used in inhalation toxicology tests as human surrogates. However, in vitro dosimetry tests in rodent casts are still scarce due to small rodent airways and in vitro tests to quantify sub-regional dosimetry are still impractical. We hypothesized that for inertial particles whose deposition is dominated by airflow convection (Reynolds number) and particle inertia (Stokes number), the deposition should be similar among airway replicas of different scales if their Reynolds and Stokes numbers are kept the same. In this study, we aimed to (1) numerically test the hypothesis in three airway geometries: a USP induction port, a human nose model, and a Sprague-Dawley rat nose model, and (2) find the range of applicability of this hypothesis. Five variants of the USP and human nose models and three variants of the rat nose model were tested. Inhalation rates and particle sizes were scaled to match the Reynolds number and Stokes numbers. A low-Reynolds-number k–ω model was used to resolve the airflow and a Lagrangian tracking algorithm was used to simulate the particle transport and deposition. Statistical analysis of predicted doses was conducted using ANOVA. For normal inhalation rates and particle dia- meters ranging from 0.5 to 24 mm, the deposition differences between the life-size and scaled models are insignificant for all airway geometries considered (i.e., human nose, USP, and rat nose). Furthermore, the deposition patterns and exit particle profiles also look similar among scaled models. However, deposition rates and patterns start to deviate if inhalation rates are too low, or particle sizes are too large. For the rat nose, the threshold velocity was found to be 0.71 m/s and the threshold Froude number to be 50. Results of this study provide a theoretical foundation for sub-regional in vitro dosimetry tests in small animals and for interpretation of data from inter-species or intra-species with varying body sizes.

  19. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model

    National Research Council Canada - National Science Library

    Tracey L. Bonfield; Mary Koloze; Donald P. Lennon; Brandon Zuchowski; Sung Eun Yang; Arnold I. Caplan

    2010-01-01

    .... host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases...

  20. 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.

  1. Distinct transduction difference between adeno-associated virus type 1 and type 6 vectors in human polarized airway epithelia.

    Science.gov (United States)

    Yan, Z; Lei-Butters, D C M; Keiser, N W; Engelhardt, J F

    2013-03-01

    Of the many biologically isolated adeno-associated virus (AAV) serotypes, AAV1 and AAV6 share the highest degree of sequence homology, with only six different capsid residues. We compared the transduction efficiencies of rAAV1 and rAAV6 in primary polarized human airway epithelia and found significant differences in their abilities to transduce epithelia from the apical and basolateral membranes. rAAV1 transduction was ~10-fold higher than rAAV6 following apical infection, whereas rAAV6 transduction was ~10-fold higher than rAAV1 following basolateral infection. Furthermore, rAAV6 demonstrated significant polarity of transduction (100-fold; basolateral » apical), whereas rAAV1 transduced from both membranes with equal efficiency. To evaluate capsid residues responsible for the observed serotype differences, we mutated the six divergent amino acids either alone or in combination. Results from these studies demonstrated that capsid residues 418 and 531 most significantly controlled membrane polarity differences in transduction between serotypes, with the rAAV6-D418E/K531E mutant demonstrating decreased (~10-fold) basolateral transduction and the rAAV1-E418D/E531K mutant demonstrating a transduction polarity identical to rAAV6-WT (wild type). However, none of the rAAV6 mutants obtained apical transduction efficiencies of rAAV1-WT, suggesting that all six divergent capsid residues in AAV1 act in concert to improve apical transduction of HAE.

  2. Use of sensitive, broad-spectrum molecular assays and human airway epithelium cultures for detection of respiratory pathogens.

    Directory of Open Access Journals (Sweden)

    Krzysztof Pyrc

    Full Text Available Rapid and accurate detection and identification of viruses causing respiratory tract infections is important for patient care and disease control. Despite the fact that several assays are available, identification of an etiological agent is not possible in ~30% of patients suffering from respiratory tract diseases. Therefore, the aim of the current study was to develop a diagnostic set for the detection of respiratory viruses with sensitivity as low as 1-10 copies per reaction. Evaluation of the assay using a training clinical sample set showed that viral nucleic acids were identified in ~76% of cases. To improve assay performance and facilitate the identification of novel species or emerging strains, cultures of fully differentiated human airway epithelium were used to pre-amplify infectious viruses. This additional step resulted in the detection of pathogens in all samples tested. Based on these results it can be hypothesized that the lack of an etiological agent in some clinical samples, both reported previously and observed in the present study, may result not only from the presence of unknown viral species, but also from imperfections in the detection methods used.

  3. 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

  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. [Involvement of MAPKs and NF-kappaB pathways in Pseudomonas pyocyanin-induced interleukin-8 expression by human airway epithelial cells].

    Science.gov (United States)

    Feng, Yan; Wang, Fang; Li, Xiang; Wang, Bo-yao; Wu, Qi

    2005-02-01

    To investigate the molecular mechanisms of signaling transduction by which Pseudomonas pyocyanin induces IL-8 expression in human airway epithelial cells, A549 and SPC-A-1 cells were challenged with P. aeruginosa conditioned medium or pyocyanin. Chemokine interleukin-8 (IL-8) release from the challenged cells was measured by ELISA, and Western blot was performed to analyze the degradation of IkappaB-alpha and the phosphorylation of MAPKs (mitogen-activated protein kinases) in the extracts from cells stimulated with pyocyanin. Both of P. aeruginosa conditioned medium and pyocyanin remarkably increased IL-8 expression by human airway epithelial cells. Degradation of IkappaB-alpha was found shortly after A549 cells were stimulated with pyocyanin. Western hybridization analysis also demonstrated that pyocyanin caused phosphorylation of MAPKs including ERK1/2, p38 and JNK in A549 cells. Pretreatment of A549 cells with U0126 (10 micromol/L), a selective inhibitor of MEK1/2 (ERK1/2 kinase) or with SB203580 (10 micromol/L), a specific inhibitor of p38 MAPK, diminished the pyocyanin-induced IL-8 production. These findings suggest that Pseudomonas pyocyanin can increase IL-8 expression by human airway epithelial cells through MAPKs signaling pathways and the activation of NF-kappaB is also involved in this process.

  6. Pharyngeal sense organs drive robust sugar consumption in Drosophila

    OpenAIRE

    LeDue, Emily E; Chen, Yu-Chieh; Jung, Aera Y; Dahanukar, Anupama; Gordon, Michael D

    2015-01-01

    The fly pharyngeal sense organs lie at the transition between external and internal nutrient sensing mechanisms. Here, we investigate the function of pharyngeal sweet gustatory receptor neurons (GRNs), demonstrating that they express a subset of the nine previously identified sweet receptors and respond to stimulation with a panel of sweet compounds. We show that pox-neuro (poxn) mutants lacking taste function in the legs and labial palps have intact pharyngeal sweet taste, which is both nece...

  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. Absorption of 51Cr EDTA across the human nasal airway barriers in the presence of topical histamine.

    Science.gov (United States)

    Greiff, L; Wollmer, P; Pipkorn, U; Persson, C G

    1991-01-01

    Whether histamine, a mediator that causes exudation, affects the airway absorption of luminal solutes has been examined in a study of eight healthy volunteers. Fluid containing the absorption tracer chromium-51 labelled EDTA was instilled into one nasal cavity for 15 minutes, with a nasal pool-device (total volume 14 ml). The airway absorption of 51Cr EDTA determined by urinary recovery of radioactivity corresponded to 0.095 (SE 0.023) ml of the instillate in the absence of histamine. When histamine was added to the nasal instillate at a concentration of 2.0 mg/ml, which is known to produce substantial exudation of plasma into the airway lumen, the absorption of 51Cr EDTA was unchanged (0.093 (0.025) ml of the instillate). Separate experiments excluded the possibility that any swallowed portion of 51Cr EDTA could have contributed significantly to the amount absorbed. The present data agree with previous observations in guinea pig tracheobronchial airways, where histamine and other exudative agents did not increase the mucosal absorption of solutes from the airway lumen. These data suggest that the potent protein systems of blood plasma can transverse the endothelial-epithelial linings and operate on the surface of the airway mucosa without compromising its integrity as a barrier to luminal material. PMID:1948790

  9. Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of human airway epithelial cells.

    Science.gov (United States)

    Liu, Yao-Zhong; Zhang, Lei; Roy-Engel, Astrid M; Saito, Shigeki; Lasky, Joseph A; Wang, Guangdi; Wang, He

    2017-02-20

    The health impacts of the BP oil spill are yet to be further revealed as the toxicological effects of oil products and dispersants on human respiratory system may be latent and complex, and hence difficult to study and follow up. Here we performed RNA-seq analyses of a system of human airway epithelial cells treated with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were used to help break up the oil spill. Based on the RNA-seq data, we then systemically analyzed the transcriptomic perturbations of the cells at the KEGG pathway level using two pathway-based analysis tools, GAGE (generally applicable gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results suggested a pattern of change towards carcinogenesis for the treated cells marked by upregulation of ribosomal biosynthesis (hsa03008) (p=1.97E-13), protein processing (hsa04141) (p=4.09E-7), Wnt signaling (hsa04310) (p=6.76E-3), neurotrophin signaling (hsa04722) (p=7.73E-3) and insulin signaling (hsa04910) (p=1.16E-2) pathways under the dispersant Corexit 9527 treatment, as identified by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co-expression changes for several KEGG cancer pathways, including small cell lung cancer pathway (hsa05222, p=9.99E-5), under various treatments of oil/dispersant, especially the mixture of oil and Corexit 9527. Overall, our results suggested carcinogenic effects of dispersants (in particular Corexit 9527) and their mixtures with the BP crude oil, and provided further support for more stringent safety precautions and regulations for operations involving long-term respiratory exposure to oil and dispersants. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Development of a model for human and rat airway particle deposition: implications for risk assessment

    NARCIS (Netherlands)

    Cassee FR; Freijer JI; Subramaniam R; Asghararian B; Miller FJ; Bree L van; Rombout PJA; LEO

    2000-01-01

    Particulate matter is a collective term for very small-suspended particulates in ambient air that cannot be observed by the human eye. They are also referred to as PM10, particles with an aerodynamic diameter smaller than 10 um. The chemical composition of PM10 is complex and varies from day to day

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

    Science.gov (United States)

    Exposure to oxidant air pollution is associated with Increased respiratory morbiditses 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 pri...

  12. Influence of pharyngeal flap surgery on nasality and nasalance scores of nasal sounds production in individuals with cleft lip and palate.

    Science.gov (United States)

    Fukushiro, Ana Paula; Ferlin, Flávia; Yamashita, Renata Paciello; Trindade, Inge Elly Kiemle

    2015-01-01

    To verify the influence of pharyngeal flap surgery on the management of velopharyngeal insufficiency on nasality and speech nasalance on nasal sound production in individuals with cleft lip and palate. Prospective study in 159 individuals with repaired cleft palate ± lip, of both genders, aged 6 to 57 years old. All the participants presented residual velopharyngeal insufficiency and were submitted to pharyngeal flap surgery. Perceptual speech evaluation and nasometric assessment were performed before and after (14 months on average) the pharyngeal flap surgery. Hyponasality was rated as absent or present, and nasalance scores were determined by means of nasometer using nasal stimuli, with a cutoff score of 43% used as the lowest limit of normality. Nasality and nasalance were compared before and after surgery (p < 0.05). On the basis of correlation between both the methods used, perceptual hyponasality was observed in 14% of the individuals, whereas nasalance scores indicating hyponasality (< 43%) were obtained in 25% of the patients after surgery. Pharyngeal flap surgery influenced the production of nasal sounds, causing hyponasality in a significant proportion of individuals. The presence of this speech symptom can also be an indicator of upper airway obstruction caused by pharyngeal flap, which should be investigated objectively and prudently postoperatively.

  13. Hag Mediates Adherence of Moraxella catarrhalis to Ciliated Human Airway Cells▿ §

    OpenAIRE

    Balder, Rachel; Krunkosky, Thomas M; Nguyen, Chi Q.; Feezel, Lacey; Lafontaine, Eric R.

    2009-01-01

    Moraxella catarrhalis is a human pathogen causing otitis media in infants and respiratory infections in adults, particularly patients with chronic obstructive pulmonary disease. The surface protein Hag (also designated MID) has previously been shown to be a key adherence factor for several epithelial cell lines relevant to pathogenesis by M. catarrhalis, including NCIH292 lung cells, middle ear cells, and A549 type II pneumocytes. In this study, we demonstrate that Hag mediates adherence to a...

  14. Hag mediates adherence of Moraxella catarrhalis to ciliated human airway cells.

    Science.gov (United States)

    Balder, Rachel; Krunkosky, Thomas M; Nguyen, Chi Q; Feezel, Lacey; Lafontaine, Eric R

    2009-10-01

    Moraxella catarrhalis is a human pathogen causing otitis media in infants and respiratory infections in adults, particularly patients with chronic obstructive pulmonary disease. The surface protein Hag (also designated MID) has previously been shown to be a key adherence factor for several epithelial cell lines relevant to pathogenesis by M. catarrhalis, including NCIH292 lung cells, middle ear cells, and A549 type II pneumocytes. In this study, we demonstrate that Hag mediates adherence to air-liquid interface cultures of normal human bronchial epithelium (NHBE) exhibiting mucociliary activity. Immunofluorescent staining and laser scanning confocal microscopy experiments demonstrated that the M. catarrhalis wild-type isolates O35E, O12E, TTA37, V1171, and McGHS1 bind principally to ciliated NHBE cells and that their corresponding hag mutant strains no longer associate with cilia. The hag gene product of M. catarrhalis isolate O35E was expressed in the heterologous genetic background of a nonadherent Haemophilus influenzae strain, and quantitative assays revealed that the adherence of these recombinant bacteria to NHBE cultures was increased 27-fold. These experiments conclusively demonstrate that the hag gene product is responsible for the previously unidentified tropism of M. catarrhalis for ciliated NHBE cells.

  15. Respiratory Syncytial Virus Uses CX3CR1 as a Receptor on Primary Human Airway Epithelial Cultures.

    Directory of Open Access Journals (Sweden)

    Sara M Johnson

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of lower respiratory disease in infants, but no vaccine or effective therapy is available. The initiation of RSV infection of immortalized cells is largely dependent on cell surface heparan sulfate (HS, a receptor for the RSV attachment (G glycoprotein in immortalized cells. However, RSV infects the ciliated cells in primary well differentiated human airway epithelial (HAE cultures via the apical surface, but HS is not detectable on this surface. Here we show that soluble HS inhibits infection of immortalized cells, but not HAE cultures, confirming that HS is not the receptor on HAE cultures. Conversely, a "non-neutralizing" monoclonal antibody against the G protein that does not block RSV infection of immortalized cells, does inhibit infection of HAE cultures. This antibody was previously shown to block the interaction between the G protein and the chemokine receptor CX3CR1 and we have mapped the binding site for this antibody to the CX3C motif and its surrounding region in the G protein. We show that CX3CR1 is present on the apical surface of ciliated cells in HAE cultures and especially on the cilia. RSV infection of HAE cultures is reduced by an antibody against CX3CR1 and by mutations in the G protein CX3C motif. Additionally, mice lacking CX3CR1 are less susceptible to RSV infection. These findings demonstrate that RSV uses CX3CR1 as a cellular receptor on HAE cultures and highlight the importance of using a physiologically relevant model to study virus entry and antibody neutralization.

  16. 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.

  17. Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia.

    Science.gov (United States)

    Hasegawa, Isao; Niisato, Naomi; Iwasaki, Yoshinobu; Marunaka, Yoshinori

    2006-05-05

    Ambroxol is often used as a mucolytic agent in various lung diseases. However, it is unclear how ambroxol acts on bronchial epithelial cells. To clarify the action of ambroxol, we studied the effects of ambroxol on the ion transport in human Calu-3 cells, a human submucosal serous cell line, measuring the transepithelial short-circuit current and conductance across monolayers of Calu-3 cells. Ambroxol of 100 microM diminished the terbutaline (a beta2-adrenergic agonist)-stimulated Cl-/HCO3(-)-dependent secretion without any decreases in the conductance of cystic fibrosis transmembrane conductance regulator (CFTR) channel locating on the apical membrane. On the other hand, under the basal (unstimulated) condition ambroxol increased the Cl(-)-dependent secretion with no significant change in the apical CFTR channel conductance and decreased the HCO3- secretion associated with a decrease in the apical CFTR channel conductance. Ambroxol had no major action on the epithelial Na+ channel (ENaC) or the ENaC-mediated Na+ absorption. These results indicate that in Calu-3 cells: (1) under the basal (unstimulated) condition ambroxol increases Cl- secretion by stimulating the entry step of Cl- and decreases HCO3- secretion by diminishing the activity of the CFTR channel and/or the Na+/HCO3(-)-dependent cotransporter, (2) under the adrenergic agonist-stimulated condition, ambroxol decreases Cl- secretion by acting on the Cl-/HCO3- exchanger, and (3) ambroxol has a more powerful action than the adrenergic agonist on the Cl-/HCO3- exchanger, leading fluid secretion to a moderately stimulated level from a hyper-stimulated level.

  18. 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.

  19. Pharyngeal reconstruction after total laryngectomy: options in a ...

    African Journals Online (AJOL)

    (62.5%) patients accepted to undergo total laryngectomy. Pharyngeal reconstructive methods carried out were: direct mucosal closure using the residual mucosa in 12 patients, full Skin thickness skin graft in three cases and musculo-cutaneous (pectoralis major) flap in one case. Pharyngeal stenosis was the commonest ...

  20. Assessment of difficult laryngoscopy by electronically measured maxillo-pharyngeal angle on lateral cervical radiograph: A prospective study

    Directory of Open Access Journals (Sweden)

    Gupta Kumkum

    2010-01-01

    Full Text Available Background: Difficult airway continued to be a major cause of anesthesia-related morbidity and mortality. Successful airway management depends on direct laryngoscopy and tracheal intubation. Difficult laryngoscopy is a resultant of incomplete structural arrangements during the process of head positioning. Through clinical history,examination of the patients along with craniofacial indices alerts the anesthetist for difficult laryngoscopy. But it does not predict all causes of difficult laryngoscopy during pre-anesthetic evaluation. The maxillo-pharyngeal angle, an upper airway anatomical balance, was proposed for better understanding the pathophysiology of difficult laryngoscopy. In our study we have assess difficult laryngoscopy by electronically measuring maxillo-pharyngeal angles on a lateral cervical radiograph. This angle is normally greater than 100 o . Less than 90 o angle suggests either impossible or difficult direct laryngoscopy when all known craniofacial indices were within the normal range. Cervical radiographic assessment is a simple, economical, and non-invasive predictive method for difficult laryngoscopy. It should be used routinely along with other indices as pre-anesthetic airway assessment criteria to predict the difficult laryngoscopy. Context: Difficulties with airway management continue to be a major cause of anesthesia-related morbidity, mortality, and litigation. Pre-operative assessment of difficult laryngoscopy by the simple and non-invasive radiological method can help to prevent them. Aims: To assess the difficult laryngoscopy pre operatively by a simple and non invasive radiological method by electronically measuring maxillo-pharyngeal angle on a lateral cervical radiograph and it′s correlation with Cormack and Lehane grading. Settings and Design: This is a controlled, nonrandomized, prospective, cohort observation study. Patients and Methods: The 157 adult consented patients of ASA grade I to III of either sex

  1. Assessment of difficult laryngoscopy by electronically measured maxillo-pharyngeal angle on lateral cervical radiograph: A prospective study.

    Science.gov (United States)

    Gupta, Kumkum; Gupta, Prashant K

    2010-09-01

    Difficult airway continued to be a major cause of anesthesia-related morbidity and mortality. Successful airway management depends on direct laryngoscopy and tracheal intubation. Difficult laryngoscopy is a resultant of incomplete structural arrangements during the process of head positioning. Through clinical history, examination of the patients along with craniofacial indices alerts the anesthetist for difficult laryngoscopy. But it does not predict all causes of difficult laryngoscopy during pre-anesthetic evaluation. The maxillo-pharyngeal angle, an upper airway anatomical balance, was proposed for better understanding the pathophysiology of difficult laryngoscopy. In our study we have assess difficult laryngoscopy by electronically measuring maxillo-pharyngeal angles on a lateral cervical radiograph. This angle is normally greater than 100°. Less than 90° angle suggests either impossible or difficult direct laryngoscopy when all known craniofacial indices were within the normal range. Cervical radiographic assessment is a simple, economical, and non-invasive predictive method for difficult laryngoscopy. It should be used routinely along with other indices as pre-anesthetic airway assessment criteria to predict the difficult laryngoscopy. Difficulties with airway management continue to be a major cause of anesthesia-related morbidity, mortality, and litigation. Pre-operative assessment of difficult laryngoscopy by the simple and non-invasive radiological method can help to prevent them. To assess the difficult laryngoscopy pre operatively by a simple and non invasive radiological method by electronically measuring maxillo-pharyngeal angle on a lateral cervical radiograph and it's correlation with Cormack and Lehane grading. This is a controlled, nonrandomized, prospective, cohort observation study. The 157 adult consented patients of ASA grade I to III of either sex, scheduled for elective surgery under general anesthesia with endo-tracheal intubation, were

  2. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012.

    Science.gov (United States)

    Shield, Kevin D; Ferlay, Jacques; Jemal, Ahmedin; Sankaranarayanan, Rengaswamy; Chaturvedi, Anil K; Bray, Freddie; Soerjomataram, Isabelle

    2017-01-01

    By using data from the International Agency for Research on Cancer publication Cancer Incidence in 5 Continents and GLOBOCAN, this report provides the first consolidated global estimation of the subsite distribution of new cases of lip, oral cavity, and pharyngeal cancers by country, sex, and age for the year 2012. Major geographically based, sex-based, and age-based variations in the incidence of lip, oral cavity, and pharyngeal cancers by subsite were observed. Lip cancers were highly frequent in Australia (associated with solar radiation) and in central and eastern Europe (associated with tobacco smoking). Cancers of the oral cavity and hypopharynx were highly common in south-central Asia, especially in India (associated with smokeless tobacco, bidi, and betel-quid use). Rates of oropharyngeal cancers were elevated in northern America and Europe, notably in Hungary, Slovakia, Germany, and France and were associated with alcohol use, tobacco smoking, and human papillomavirus infection. Nasopharyngeal cancers were most common in northern Africa and eastern/southeast Asia, indicative of genetic susceptibility combined with Epstein-Barr virus infection and early life carcinogenic exposures (nitrosamines and salted foods). The global incidence of lip, oral cavity, and pharyngeal cancers of 529,500, corresponding to 3.8% of all cancer cases, is predicted to rise by 62% to 856,000 cases by 2035 because of changes in demographics. Given the rising incidence of lip, oral cavity, and pharyngeal cancers and the variations in incidence by subsites across world regions and countries, there is a need for local, tailored approaches to prevention, screening, and treatment interventions that will optimally reduce the lip, oral cavity, and pharyngeal cancer burden in future decades. CA Cancer J Clin 2017;67:51-64. © 2016 American Cancer Society. © 2016 American Cancer Society.

  3. Dietary indicators of oral and pharyngeal cancer.

    Science.gov (United States)

    La Vecchia, C; Negri, E; D'Avanzo, B; Boyle, P; Franceschi, S

    1991-03-01

    The relationship between frequency of consumption of a selected number of indicator foods and oral and oropharyngeal cancer risk was analysed in a case-control study conducted in Northern Italy on 105 cases of oral and pharyngeal cancer and 1169 controls in hospital for acute, non-neoplastic or digestive diseases. Besides significant and strong direct associations with tobacco (relative risk, RR = 11.0 for current versus never smokers) and alcohol (RR = 5.8 for upper versus lower consumption tertile), consumption of six food items (milk, meat, cheese, carrots, green vegetables and fruit) were inversely and significantly related to oral and pharyngeal cancer risk. The strongest protection was apparently related to frequent fruit consumption, with RRs of 0.8 and 0.2 in the two highest tertiles. Allowance for major potential confounding factors, including tobacco, alcohol and social class indicators explained only part of the dietary correlates observed. The two items remaining significant after multivariate analysis were fruit (RR = 0.3 for the upper tertile) and alcohol (RR = 3.8 for the upper tertile). The associations observed may simply reflect a generally poorer nutritional status in the cases, although the observation that fruit consumption appears to be a particularly important protective factor against oropharyngeal cancer is of potential interest, in terms of aetiological clues and preventive implications.

  4. Brd4 is essential for IL-1β-induced inflammation in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Younis M Khan

    Full Text Available Chronic inflammation and oxidative stress are key features of chronic obstructive pulmonary disease (COPD. Oxidative stress enhances COPD inflammation under the control of the pro-inflammatory redox-sensitive transcription factor nuclear factor-kappaB (NF-κB. Histone acetylation plays a critical role in chronic inflammation and bromodomain and extra terminal (BET proteins act as "readers" of acetylated histones. Therefore, we examined the role of BET proteins in particular Brd2 and Brd4 and their inhibitors (JQ1 and PFI-1 in oxidative stress- enhanced inflammation in human bronchial epithelial cells.Human primary epithelial (NHBE cells and BEAS-2B cell lines were stimulated with IL-1β (inflammatory stimulus in the presence or absence of H2O2 (oxidative stress and the effect of pre-treatment with bromodomain inhibitors (JQ1 and PFI-1 was investigated. Pro-inflammatory mediators (CXCL8 and IL-6 were measured by ELISA and transcripts by RT-PCR. H3 and H4 acetylation and recruitment of p65 and Brd4 to the native IL-8 and IL-6 promoters was investigated using chromatin immunoprecipitation (ChIP. The impact of Brd2 and Brd4 siRNA knockdown on inflammatory mediators was also investigated.H2O2 enhanced IL1β-induced IL-6 and CXCL8 expression in NHBE and BEAS-2B cells whereas H2O2 alone did not have any affect. H3 acetylation at the IL-6 and IL-8 promoters was associated with recruitment of p65 and Brd4 proteins. Although p65 acetylation was increased this was not directly targeted by Brd4. The BET inhibitors JQ1 and PFI-1 significantly reduced IL-6 and CXCL8 expression whereas no effect was seen with the inactive enantiomer JQ1(-. Brd4, but not Brd2, knockdown markedly reduced IL-6 and CXCL8 release. JQ1 also inhibited p65 and Brd4 recruitment to the IL-6 and IL-8 promoters.Oxidative stress enhanced IL1β-induced IL-6 and CXCL8 expression was significantly reduced by Brd4 inhibition. Brd4 plays an important role in the regulation of inflammatory genes

  5. Pharyngeal transit in patients with chronic progressive external ophthalmoplegia.

    Science.gov (United States)

    Domenis, Danielle Ramos; Granzotti, Raphaela B; Sobreira, Claudia Ferreira; Dantas, Roberto Oliveira

    2015-01-01

    A common presentation of mitochondrial myopathies is chronic progressive external ophthalmoplegia (CPEO). Dysphagia is a complaint in about 50% of cases. This investigation evaluated pharyngeal transit in patients with CPEO. Videofluoroscopic swallowing evaluation was performed with paste, liquid and solid boluses in 14 patients with CPEO and in 16 normal volunteers. There was no difference between patients and volunteers in the duration of pharyngeal swallowing events with the liquid bolus. Compared to control participants, patients with CPEO had significantly shorter duration of pharyngeal transit for paste and solid boluses, of pharyngeal clearance for paste bolus, and of upper oesophageal sphincter transit for paste and solid boluses. Spontaneous multiple swallows and effortful swallows were performed by patients but not by the volunteers. It was concluded that patients with CPEO have shorter pharyngeal transit duration of paste and solid boluses than normal volunteers, which may be a consequence of a spontaneous smaller bolus volume in each swallow and/or effortful swallows.

  6. 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

  7. 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 ... Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy ...

  8. 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 ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Twitter YouTube Instagram Email DONATE Breadcrumb Navigation Home Life With CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your ... for fitting ACTs into daily life Airway Clearance Techniques | Webcast To learn more about how you can ...

  11. Cephalometric evaluation of the airway space and head posture in children with normal and atypical deglutition: correlations study.

    Science.gov (United States)

    Almiro, Jose Machado Junior; Crespo, Agrício N

    2013-11-01

    Head posture has been related to pharyngeal space, especially in the syndrome of obstructive sleep apnea (OSA) in adults. However no studies were found that evaluated the possible correlation between head posture and pharyngeal airway space measured in children with atypical swallowing. The purpose of this study was to evaluate the possible correction between head posture and the measurement of pharyngeal space on radiographs of children who were in the period of mixed dentition who demonstrated atypical swallowing and in children with normal deglutition. A retrospective clinical study, using cephalometric analysis of lateral radiographs to obtain measures of the antero-posterior dimension of the pharyngeal airway space (PAS) and the angle formed between the base of the skull and the odontoid process (CC1) between two groups: the 55 radiographs experimental group (with atypical swallowing) and 55 radiographs of the control group (normal swallowing). The Spearman Coefficient of Correlation was used to evaluate the possible relationship between PAS and CC1 was used. Results indicated a positive correlation between measures of CC1 and PAS (r = 0357) only in the control group (normal swallowing). There is positive correlation between head posture and measure pharyngeal airway space (PAS) in the group of normal swallowing. This correlation was not observed in the experimental group (atypical swallowing).

  12. Comparison of reliability of lateral cephalogram and computed tomography for assessment of airway space.

    Science.gov (United States)

    Kaur, S; Rai, S; Kaur, M

    2014-01-01

    The oropharyngeal (OP) and nasopharyngeal structures seems to play roles in the development of the dentofacial complex. Soft palate as a part of nasopharyngeal and OP apparatus has an important role in phonation, deglutition and respiration. The aim of this study was to find whether any correlation exists between the three types of malocclusion and airway space using lateral cephalogram and computed tomography (CT) and to compare its reliability. To obtain important information on the morphology of the soft palate on lateral cephalogram and to determine its etiopathogenesis in obstructive sleep apnea (OSA). Lateral cephalogram of 45 subjects were used to measure the pharyngeal airway. The subjects were divided into three groups (each group included 15 subjects) according to ANB angle: Class I (ANB angle 2-4°), Class II (ANB angle > 4°), Class III (ANB angle ≤ 2°). The result showed a significant reduction in pharyngeal airway in ANB Class II. Type I soft palate, leaf-shape was found in maximum subjects. The volume of airway size showed higher statistical significance with the greater coefficient of variation on CT in relation to corresponding cephalometric airway area. The sagittal skeletal pattern is a contributory factor in variations in the upper airway dimensions. The measurements acquired from both the modalities are reliable and reproducible, but CT gives the better assessment of cross-sectional dimensions of airway space. Morphology of the soft palate can be used as references for etiological research of OSA.

  13. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice.

    Science.gov (United States)

    Cruz, Fernanda F; Borg, Zachary D; Goodwin, Meagan; Sokocevic, Dino; Wagner, Darcy E; Coffey, Amy; Antunes, Mariana; Robinson, Kristen L; Mitsialis, S Alex; Kourembanas, Stella; Thane, Kristen; Hoffman, Andrew M; McKenna, David H; Rocco, Patricia R M; Weiss, Daniel J

    2015-11-01

    An increasing number of studies demonstrate that administration of either conditioned media (CM) or extracellular vesicles (EVs) released by mesenchymal stromal cells (MSCs) derived from bone marrow and other sources are as effective as the MSCs themselves in mitigating inflammation and injury. The goal of the current study was to determine whether xenogeneic administration of CM or EVs from human bone marrow-derived MSCs would be effective in a model of mixed Th2/Th17, neutrophilic-mediated allergic airway inflammation, reflective of severe refractory asthma, induced by repeated mucosal exposure to Aspergillus hyphal extract (AHE) in immunocompetent C57Bl/6 mice. Systemic administration of both CM and EVs isolated from human and murine MSCs, but not human lung fibroblasts, at the onset of antigen challenge in previously sensitized mice significantly ameliorated the AHE-provoked increases in airway hyperreactivity (AHR), lung inflammation, and the antigen-specific CD4 T-cell Th2 and Th17 phenotype. Notably, both CM and EVs from human MSCs (hMSCs) were generally more potent than those from mouse MSCs (mMSCs) in most of the outcome measures. The weak cross-linking agent 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride was found to inhibit release of both soluble mediators and EVs, fully negating effects of systemically administered hMSCs but only partly inhibited the ameliorating effects of mMSCs. These results demonstrate potent xenogeneic effects of CM and EVs from hMSCs in an immunocompetent mouse model of allergic airway inflammation and they also show differences in mechanisms of action of hMSCs versus mMSCs to mitigate AHR and lung inflammation in this model. There is a growing experience demonstrating benefit of mesenchymal stromal cell (MSC)-based cell therapies in preclinical models of asthma. In the current study, conditioned media (CM) and, in particular, the extracellular vesicle fraction obtained from the CM were as potent as the MSCs

  14. Effects of lung disease on the three-dimensional structure and air flow pattern in the human airway tree

    Science.gov (United States)

    van de Moortele, Tristan; Nemes, Andras; Wendt, Christine; Coletti, Filippo

    2016-11-01

    The morphological features of the airway tree directly affect the air flow features during breathing, which determines the gas exchange and inhaled particle transport. Lung disease, Chronic Obstructive Pulmonary Disease (COPD) in this study, affects the structural features of the lungs, which in turn negatively affects the air flow through the airways. Here bronchial tree air volume geometries are segmented from Computed Tomography (CT) scans of healthy and diseased subjects. Geometrical analysis of the airway centerlines and corresponding cross-sectional areas provide insight into the specific effects of COPD on the airway structure. These geometries are also used to 3D print anatomically accurate, patient specific flow models. Three-component, three-dimensional velocity fields within these models are acquired using Magnetic Resonance Imaging (MRI). The three-dimensional flow fields provide insight into the change in flow patterns and features. Additionally, particle trajectories are determined using the velocity fields, to identify the fate of therapeutic and harmful inhaled aerosols. Correlation between disease-specific and patient-specific anatomical features with dysfunctional airflow patterns can be achieved by combining geometrical and flow analysis.

  15. Distinct microRNA Expression in Human Airway Cells of Asthmatic Donors Identifies a Novel Asthma-associated Gene

    Science.gov (United States)

    Airway inflammation is the hallmark of asthma and suggests a dysregulation of homeostatic mechanisms. MicroRNAs (miRNAs) are key regulators of gene expression, necessary for the proper function of cellular processes. Here, we tested the hypothesis that differences between healthy...

  16. Positron emission tomography studies of human airways using an inhaled beta-adrenoceptor antagonist, S-11C-CGP 12388

    NARCIS (Netherlands)

    Van Waarde, Aren; Maas, Bram; Doze, Petra; Slart, Riemer H.; Frijlink, Henderik W.; Vaalburg, Willem; Elsinga, Philippus

    2005-01-01

    Objectives: Positron emission tomography (PET) scanning may provide information on changes in the density and affinity of airway beta-adrenoceptors in lung diseases. However, the injection of a radiolabeled P-blocker results in a pulmonary PET signal that reflects the binding of the ligand in the

  17. The glutathione-S-transferase Mu 1 null genotype modulates ozone-induced airway inflammation in humans*

    Science.gov (United States)

    Background: The Glutathione-S-Transferase Mu 1 null genotype has been reported to be a risk factor for acute respiratory disease associated with increases in ambient air ozone. Ozone is known to cause an immediate decrease in lung function and increased airway inflammation. Howev...

  18. Particle deposition in a realistic geometry of the human conducting airways: Effects of inlet velocity profile, inhalation flowrate and electrostatic charge

    DEFF Research Database (Denmark)

    Koullapis, P. G.; Kassinos, S. C.; Bivolarova, Mariya Petrova

    2016-01-01

    , we use Large Eddy Simulations (LES) to investigate the deposition of inhaled aerosol particles with diameters of dp=0.1,0.5,1,2.5,5dp=0.1,0.5,1,2.5,5 and 10μm (particle density of 1200 kg/m3). We use a reconstructed geometry of the human airways obtained via computed tomography and assess the effects......-regions of our reconstructed geometry. Although there was a relatively small impact of inhalation flowrate on the deposition of charged particles for sizes dp

  19. Once-Daily Amoxicillin for Pharyngitis

    Science.gov (United States)

    Andrews, Megan; Condren, Michelle

    2010-01-01

    A once-daily antibiotic regimen for group A β-hemolytic streptococcal pharyngitis (GABHS) could improve compliance and be effective in the prevention of rheumatic fever, a dangerous complication of untreated or poorly treated GABHS. Amoxicillin is ideal for once-daily dosing due to its low cost. Azithromycin, cefadroxil, ceftibuten, cefixime and extended release amoxicillin are also FDA approved to treat GABHS once daily; however, even when taken for short courses, these antibiotics are more expensive compared with a oncedaily dosing of conventional amoxicillin for 10 days. The American Heart Association recently recommended once-daily amoxicillin dosing when treating GABHS, and amoxicillin has been proven to be effective when dosed once daily, with no obvious disadvantage compared with twice-daily dosing or with conventional penicillin treatment 3 to 4 times daily. PMID:22477812

  20. 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.

  1. Modulation of Human Airway Barrier Functions during Burkholderia thailandensis and Francisella tularensis Infection Running Title: Airway Barrier Functions during Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Cornelia Blume

    2016-08-01

    Full Text Available The bronchial epithelium provides protection against pathogens from the inhaled environment through the formation of a highly-regulated barrier. In order to understand the pulmonary diseases melioidosis and tularemia caused by Burkholderia thailandensis and Fransicella tularensis, respectively, the barrier function of the human bronchial epithelium were analysed. Polarised 16HBE14o- or differentiated primary human bronchial epithelial cells (BECs were exposed to increasing multiplicities of infection (MOI of B. thailandensis or F. tularensis Live Vaccine Strain and barrier responses monitored over 24–72 h. Challenge of polarized BECs with either bacterial species caused an MOI- and time-dependent increase in ionic permeability, disruption of tight junctions, and bacterial passage from the apical to the basolateral compartment. B. thailandensis was found to be more invasive than F. tularensis. Both bacterial species induced an MOI-dependent increase in TNF-α release. An increase in ionic permeability and TNF-α release was induced by B. thailandensis in differentiated BECs. Pretreatment of polarised BECs with the corticosteroid fluticasone propionate reduced bacterial-dependent increases in ionic permeability, bacterial passage, and TNF-α release. TNF blocking antibody Enbrel® reduced bacterial passage only. BEC barrier properties are disrupted during respiratory bacterial infections and targeting with corticosteroids or anti-TNF compounds may represent a therapeutic option.

  2. Alternaria Fungus Induces the Production of GM-CSF, Interleukin-6 and Interleukin-8 and Calcium Signaling in Human Airway Epithelium through Protease-Activated Receptor 2

    Science.gov (United States)

    Matsuwaki, Yoshinori; Wada, Kota; White, Thomas; Moriyama, Hiroshi; Kita, Hirohito

    2012-01-01

    Rationale Recent studies suggest that host immune responses to environmental fungi may play an important role in the development of allergic diseases, such as human asthma. Epithelium is considered an active participant in allergic inflammation. We previously reported that aspartate protease from Alternaria induces the activation and degranulation of human eosinophils that are mediated through protease-activated receptor 2 (PAR-2). However, our current knowledge on the innate immune responses of epithelium to environmental fungi is very limited. We investigated the responses of epithelium to fungi and the mechanisms of these responses. Methods Human airway epithelial cell line BEAS-2B and Calu-3 (both from American Type Culture Collection) were incubated with PAR-2 peptides and extracts of various fungi. The cellular responses, including GM-CSF, interleukin (IL)-6, IL-8, eotaxin, eotaxin-2 and RANTES production as well as increases in intracellular calcium concentration ([Ca2+]i), were examined. To characterize the proteases involved in these responses, protease inhibitors such as pepstatin A and alkalo-thermophilic Bacillus inhibitor (ATBI), HIV protease inhibitors and 4-amidinophenylmethanesulfonyl fluoride hydrochloride were used. To investigate the role of PAR-2, PAR-2-agonistic and PAR-2-antagonistic peptides were used. Results PAR-2-activating peptide, but not the control peptide, induced GM-CSF, IL-6 and IL-8 production; these cellular responses were accompanied by a quick and marked increase in [Ca2+]i. Among 7 common environmental fungi, only Alternaria induced GM-CSF, IL-6 and IL-8 production and increased [Ca2+]i response. Both cytokine production and increased [Ca2+]i were significantly inhibited by PAR-2 antagonist peptide and by aspartate protease inhibitors (pepstatin A, ritonavir, nelfinavir and ATBI), but not by the PAR-2 control peptide or by other protease inhibitors. Conclusions Aspartate proteases from Alternaria induce cytokine production and

  3. Synergistic up-regulation of CXCL10 by virus and IFN γ in human airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Karen L Oslund

    Full Text Available Airway epithelial cells are the first line of defense against viral infections and are instrumental in coordinating the inflammatory response. In this study, we demonstrate the synergistic stimulation of CXCL10 mRNA and protein, a key chemokine responsible for the early immune response to viral infection, following treatment of airway epithelial cells with IFN γ and influenza virus. The synergism also occurred when the cells were treated with IFN γ and a viral replication mimicker (dsRNA both in vitro and in vivo. Despite the requirement of type I interferon (IFNAR signaling in dsRNA-induced CXCL10, the synergism was independent of the IFNAR pathway since it wasn't affected by the addition of a neutralizing IFNAR antibody or the complete lack of IFNAR expression. Furthermore, the same synergistic effect was also observed when a CXCL10 promoter reporter was examined. Although the responsive promoter region contains both ISRE and NFκB sites, western blot analysis indicated that the combined treatment of IFN γ and dsRNA significantly augmented NFκB but not STAT1 activation as compared to the single treatment. Therefore, we conclude that IFN γ and dsRNA act in concert to potentiate CXCL10 expression in airway epithelial cells via an NFκB-dependent but IFNAR-STAT independent pathway and it is at least partly regulated at the transcriptional level.

  4. 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.

  5. Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures.

    Science.gov (United States)

    Corry, Jacqueline; Johnson, Sara M; Cornwell, Jessica; Peeples, Mark E

    2015-11-18

    All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines. Worldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein are less infectious

  6. Preventing Cleavage of the Respiratory Syncytial Virus Attachment Protein in Vero Cells Rescues the Infectivity of Progeny Virus for Primary Human Airway Cultures

    Science.gov (United States)

    Corry, Jacqueline; Johnson, Sara M.; Cornwell, Jessica

    2015-01-01

    ABSTRACT All live attenuated respiratory syncytial virus (RSV) vaccines that have advanced to clinical trials have been produced in Vero cells. The attachment (G) glycoprotein in virions produced in these cells is smaller than that produced in other immortalized cells due to cleavage. These virions are 5-fold less infectious for primary well-differentiated human airway epithelial (HAE) cell cultures. Because HAE cells are isolated directly from human airways, Vero cell-grown vaccine virus would very likely be similarly inefficient at initiating infection of the nasal epithelium following vaccination, and therefore, a larger inoculum would be required for effective vaccination. We hypothesized that Vero cell-derived virus containing an intact G protein would be more infectious for HAE cell cultures. Using protease inhibitors with increasing specificity, we identified cathepsin L to be the protease responsible for cleavage. Our evidence suggests that cleavage occurs in the late endosome or lysosome during endocytic recycling. Cathepsin L activity was 100-fold greater in Vero cells than in HeLa cells. In addition, cathepsin L was able to cleave the G protein in Vero cell-grown virions but not in HeLa cell-grown virions, suggesting a difference in G-protein posttranslational modification in the two cell lines. We identified by mutagenesis amino acids important for cleavage, and these amino acids included a likely cathepsin L cleavage site. Virus containing a modified, noncleavable G protein produced in Vero cells was 5-fold more infectious for HAE cells in culture, confirming our hypothesis and indicating the value of including such a mutation in future live attenuated RSV vaccines. IMPORTANCE Worldwide, RSV is the second leading infectious cause of infant death, but no vaccine is available. Experimental live attenuated RSV vaccines are grown in Vero cells, but during production the virion attachment (G) glycoprotein is cleaved. Virions containing a cleaved G protein

  7. Pharyngeal-Cervical-Brachial Variant of Guillain-Barre Syndrome

    OpenAIRE

    J Gordon Millichap; John J Millichap

    2014-01-01

    Investigators from National University Hospital, Singapore, review the clinical features of 13 cases of pharyngeal-cervical-brachial (PCB) variant of Guillain-Barre syndrome (GBS) and outline new diagnostic criteria.

  8. Protein kinase A and the exchange protein directly activated by cAMP (Epac) modulate phenotype plasticity in human airway smooth muscle

    NARCIS (Netherlands)

    Roscioni, Sara S.; Prins, Alwin G.; Elzinga, Carolina R. S.; Menzen, Mark H.; Dekkers, Bart G. J.; Halayko, Andrew J.; Meurs, Herman; Maarsingh, Harm; Schmidt, Martina

    2011-01-01

    BACKGROUND AND PURPOSE Platelet-derived growth factor (PDGF) modulates the airway smooth muscle (ASM) 'contractile' phenotype to a more 'proliferative' phenotype, resulting in increased proliferation and reduced contractility. Such phenotypic modulation may contribute to airway remodelling in

  9. Update on the management of acute pharyngitis in children

    OpenAIRE

    Galli Luisa; Bonsignori Francesca; Chiappini Elena; Regoli Marta; de Martino Maurizio

    2011-01-01

    Abstract Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting dis...

  10. Numerical simulations of aerosol delivery to the human lung with an idealized laryngeal model, image-based airway model, and automatic meshing algorithm.

    Science.gov (United States)

    Miyawaki, Shinjiro; Hoffman, Eric A; Lin, Ching-Long

    2017-04-22

    The authors proposed a new method to automatically mesh computed tomography (CT)-based three-dimensional human airway geometry for computational fluid dynamics (CFD)-based simulations of pulmonary gas-flow and aerosol delivery. Traditional methods to construct and mesh realistic geometry were time-consuming, because they were done manually using image-processing and mesh-generating programs. Furthermore, most of CT thoracic image data sets do not include the upper airway structures. To overcome these issues, the proposed method consists of CFD grid-size distribution, an automatic meshing algorithm, and the addition of a laryngeal model along with turbulent velocity inflow boundary condition attached to the proximal end of the trachea. The method is based on our previously developed geometric model with irregular centerlines and cross-sections fitted to CT segmented airway surfaces, dubbed the "fitted-surface model." The new method utilizes anatomical information obtained from the one-dimensional tree, e.g., skeleton connectivity and branch diameters, to efficiently generate optimal CFD mesh, automatically impose boundary conditions, and systematically reduce simulation results. The aerosol deposition predicted by the proposed method agreed well with the prediction by a traditional CT-based model, and the laryngeal model generated a realistic level of turbulence in the trachea. Furthermore, the computational time was reduced by factor of two without losing accuracy by using the proposed grid-size distribution. The new method is well suited for branch-by-branch analyses of gas-flow and aerosol distribution in multiple subjects due to embedded anatomical information.

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

    Science.gov (United States)

    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

    2015-12-15

    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 (Rt) were measured. Immediately after exposure to 25 ppm both flavorings reduced Na+ transport,without affecting Cl- transport or Na+,K+-pump activity. Rt 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.

  12. Epidemiology of group A streptococcal pharyngitis & impetigo: a cross-sectional & follow up study in a rural community of northern India.

    Science.gov (United States)

    Kumar, R; Vohra, H; Chakraborty, A; Sharma, Y P; Bandhopadhya, S; Dhanda, V; Sagar, V; Sharma, M; Shah, B; Ganguly, N K

    2009-12-01

    Group A streptococcus (GAS) causes a wide array of human diseases. Epidemiological picture of streptococcal infection in India is not complete. Hence, disease burden due to GAS in 5-15 yr old school children in northern India was studied and emm typing of GAS isolates was carried out to help in designing prevention strategies. A cross-sectional survey was carried out among 4249 school children (5-15 yr) from Raipur Rani Block of Panchkula district in Haryana during 2000-2002; 334 children were followed up fortnightly for one year. Standard clinical and microbiological procedures were used for collection of swabs from throat and skin and confirmation of GAS and its emm types. Of the 4249 children studied, 658 (15.5%) had pharyngitis; 579 of them could be swabbed, of which 2.8 per cent had GAS. From 3591 children without pharyngitis, 3385 who could be swabbed, GAS was found in 1.3 per cent of them. Impetigo was rare (0.7%), but 7.1 per cent (2/28) children had GAS. In the followup study, 17.4 per cent (776/4447 child-contacts) had pharyngitis, 761 could be swabbed and 2.4 per cent had GAS; among those without pharyngitis, 2016 swabs could be taken and GAS was found in 1.3 per cent; whereas only 2.6 per cent (2/75) of skin sores had GAS. Three children had GAS pharyngitis twice during follow up. Fourteen different GAS emm types were found. emm 71, 77 and 81 constituted 69 per cent of the pharyngeal isolates. GAS pharyngitis and impetigo were more common in winters and summers respectively. In north India, pharyngitis was more common than impetigo. Most prevalent emm types of GAS in this region differ from those included in M protein-based vaccines.

  13. Differential effects of cigarette smoke on oxidative stress and proinflammatory cytokine release in primary human airway epithelial cells and in a variety of transformed alveolar epithelial cells

    Directory of Open Access Journals (Sweden)

    Rahman Irfan

    2006-10-01

    Full Text Available Abstract Background Cigarette smoke mediated oxidative stress and inflammatory events in the airway and alveolar epithelium are important processes in the pathogenesis of smoking related pulmonary diseases. Previously, individual cell lines were used to assess the oxidative and proinflammatory effects of cigarette smoke with confounding results. In this study, a panel of human and rodent transformed epithelial cell lines were used to determine the effects of cigarette smoke extract (CSE on oxidative stress markers, cell toxicity and proinflammatory cytokine release and compared the effects with that of primary human small airway epithelial cells (SAEC. Methods Primary human SAEC, transformed human (A549, H1299, H441, and rodent (murine MLE-15, rat L2 alveolar epithelial cells were treated with different concentrations of CSE (0.2–10% ranging from 20 min to 24 hr. Cytotoxicity was assessed by lactate dehydrogenase release assay, trypan blue exclusion method and double staining with acridine orange and ethidium bromide. Glutathione concentration was measured by enzymatic recycling assay and 4-hydroxy-2-nonenal levels by using lipid peroxidation assay kit. The levels of proinflammatory cytokines (e.g. IL-8 and IL-6 were measured by ELISA. Nuclear translocation of the transcription factor, NF-κB was assessed by immunocytochemistry and immunoblotting. Results Cigarette smoke extract dose-dependently depleted glutathione concentration, increased 4-hydroxy-2-nonenal (4-HNE levels, and caused necrosis in the transformed cell lines as well as in SAEC. None of the transformed cell lines showed any significant release of cytokines in response to CSE. CSE, however, induced IL-8 and IL-6 release in primary cell lines in a dose-dependent manner, which was associated with the nuclear translocation of NF-κB in SAEC. Conclusion This study suggests that primary, but not transformed, lung epithelial cells are an appropriate model to study the inflammatory

  14. 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.

  15. Aerobic cloacal and pharyngeal bacterial flora in six species of free-living birds.

    Science.gov (United States)

    Stenkat, J; Krautwald-Junghanns, M-E; Schmitz Ornés, A; Eilers, A; Schmidt, V

    2014-12-01

    The purpose of this study was to investigate the culturable aerobic pharyngeal and cloacal bacterial flora of free-living birds, to determine the physiological bacterial microbiota, to identify possible interactions between feeding behaviour and the composition of the pharyngeal and cloacal microflora and to investigate the occurrence of pathogenic bacteria. Cloacal and pharyngeal swabs of 167 free-living birds, including water rails (Rallus aquaticus), spotted crakes (Porzana porzana), mute swans (Cygnus olor), barn swallows (Hirundo rustica), reed warblers (Acrocephalus scirpaceus) and black cormorants (Phalacrocorax carbo) from Germany, were cultured to determine the prevalence of aerobic bacteria. Statistical analysis of bacterial findings and feeding behaviour was performed. A widespread soil and water bacteria were isolated, which are expected to be present in the habitat and food. However, some potentially avian- and human-pathogenic bacteria, such as Aeromonas hydrophila, Elizabethkingia meningoseptica, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli, were also recovered. Free-living birds of the examined species harbour several environmental bacteria, which could be facultative pathogenic. Prevalence of bacteria in healthy free-living birds of the species included in this survey is influenced by environmental and alimentary factors. © 2014 The Society for Applied Microbiology.

  16. Onyx embolization of dural arteriovenous fistulas of the cavernous sinus through the superior pharyngeal branch of the ascending pharyngeal artery

    OpenAIRE

    Pero, Guglielmo; Quilici, Luca; Piano, Mariangela; Valvassori, Luca; Boccardi, Edoardo

    2014-01-01

    We report three cases of dural arteriovenous fistula (DAVF) of the cavernous sinus treated by Onyx injection through the superior pharyngeal branch of the ascending pharyngeal artery. The treatment of choice of DAVFs of the cavernous sinus is endovascular, and it is preferentially done via transvenous occlusion of the cavernous sinus. The cavernous sinus can be reached through either the inferior petrosal sinus or the superior ophthalmic vein. When these venous routes are occluded, the first ...

  17. Effect of acute ozone induced airway inflammation on human sympathetic nerve traffic: a randomized, placebo controlled, crossover study.

    Directory of Open Access Journals (Sweden)

    Jens Tank

    Full Text Available BACKGROUND: Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22-47 years, who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59±2, ozone 60±2 bpm, blood pressure (clean air: 121±3/71±2 mmHg; ozone: 121±2/71±2 mmHg, cardiac output (clean air: 7.42±0.29 mmHg; ozone: 7.98±0.60 l/min, and plasma norepinephrine levels (clean air: 213±21 pg/ml; ozone: 202±16 pg/ml, were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 23±2, ozone: 23±2 bursts/min. Maximum MSNA obtained at the end of apnea (air: 44±4, ozone: 48±4 bursts/min and during the phase II of the Valsalva maneuver (air: 64±5, ozone: 57±6 bursts/min was similar. CONCLUSIONS/SIGNIFICANCE: Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic

  18. Changes in upper airway width associated with Class II treatments (headgear vs activator) and different growth patterns.

    Science.gov (United States)

    Godt, Arnim; Koos, Bernd; Hagen, Hanno; Göz, Gernot

    2011-05-01

    To investigate the upper airways for anteroposterior width against different growth patterns and for alterations during various Class II treatments. Cephalograms from three treatment groups (headgear, activator, and bite-jumping appliance) were evaluated by a single investigator at baseline and at the end of orthodontic treatment. Cephalograms were used to determine upper airway width at different levels in the anteroposterior plane. Patients in the headgear group were additionally divided into six subsets on the basis of y-axis values to assess the influence of different growth patterns. Small increases in pharyngeal width were noted at all vertical level segments, both at baseline and during orthodontic treatments. No significant differences in these small increases were noted across various treatment modalities and growth patterns. Upper airway changes did not significantly vary with the different treatment modalities investigated in the present study. Nevertheless, reductions in pharyngeal width potentially triggering or exacerbating obstructive sleep apnea syndrome (OSAS) are always possible in the headgear phase.

  19. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography.

    Science.gov (United States)

    Agarwal, Anirudh; Marwah, Nikhil

    2016-01-01

    The aim of our study is to use cone beam computed tomography (CBCT) to assess the dimensional changes in the nasopharyngeal soft-tissue characteristics in children of Indian origin with repaired cleft lip and palate (CLP) and to compare the results with patients with ideal occlusion. A sample of 20 children (10 girls, 10 boys) with repaired CLP was selected. Cone beam computed tomography scans were taken to measure the nasopharyngeal airway changes in terms of linear measurements and sagittal cross-sectional areas. Error analysis was performed to prevent systematic or random errors. Independent means t-tests and Pearson correlation analysis were used to evaluate sex differences and the correlations among the variables. Nasopharyngeal soft-tissue characteristics were different in the control and the study groups. Subjects with repaired CLP had lesser lower aerial width, lower adenoidal width and lower airway width. The upper airway width was also significantly lesser. The retropalatal and the total airway area were significantly greater in the control group. The narrow pharyngeal airway in patients with CLP might result in functional impairment of breathing in patients. Further investigations are necessary to clarify the relationship between pharyngeal structure and airway function in patients with CLP. How to cite this article: Agarwal A, Marwah N. Assessment of the Airway Characteristics in Children with Cleft Lip and Palate using Cone Beam Computed Tomography. Int J Clin Pediatr Dent 2016;9(1):5-9.

  20. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... of treatment options. Airway Clearance Active Cycle of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of ... Pulmonary Exacerbations Clinical Care Guidelines SCREENING & TREATING DEPRESSION & ANXIETY GUIDELINES Clinician Resources As a clinician, you’re ...

  1. Emergency airway puncture

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003017.htm Emergency airway puncture To use the sharing features on this page, please enable JavaScript. Emergency airway puncture is the placement of a hollow ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Consider Regarding a Lung Transplant Medications Antibiotics Bronchodilators Mucus Thinners Nebulizer Care at Home Vascular Access Devices ... them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance ...

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    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 ...

  4. Exposure to PM2.5 induces aberrant activation of NF-κB in human airway epithelial cells by downregulating miR-331 expression.

    Science.gov (United States)

    Song, Lei; Li, Dan; Li, Xiaoping; Ma, Lianjun; Bai, Xiaoxue; Wen, Zhongmei; Zhang, Xiufang; Chen, Dong; Peng, Liping

    2017-03-01

    Exposure to particulate matter (PM) with an aerodynamic diameter≤2.5μm (PM2.5) induces reactive oxygen species (ROS) and pro-inflammatory cytokine production, leading to airway epithelial injury. However, the mechanisms underlying the toxicity of PM2.5 have not been clarified. Here, we show that exposure to PM2.5 induces sustained activation of the nuclear factor kappa B (NF-κB) signaling in human airway epithelial Beas-2B (B2B) cells. In addition, PM2.5 exposure significantly decreased miR-331 expression in B2B cells, which was abrogated by inhibition of ROS or phosphoinositide 3-kinase (PI3K)/Akt pathway. Induction of miR-331 overexpression attenuated the PM2.5 exposure-induced NF-kBp65 nuclear translocation, IL-6 and IL-8 expression in B2B cells. Furthermore, miR-331 targeted the inhibitor of NF-κB kinase beta (IKK-β) by down-regulating the IKK-β-regulated luciferase activity in HEK293 cells. Moreover, induction of miR-331 over-expression inhibited IKK-β expression while induction of IKK-β over-expression prevented the inhibition of miR-331 on the PM2.5 exposure-induced NF-kBp65 nuclear translocation, IL-6 and IL-8 expression in B2B cells. Therefore, PM2.5 exposure decreased miR-331 expression via the ROS/PI3K/Akt pathway, resulting in an increase in the IKK-β expression and sustained NF-κB activation in human airway epithelial cells. Our findings may provide new insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure and aid in design of new therapeutic strategies to prevent PM2.5-induced toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Disruption of CXCR4 signaling in pharyngeal neural crest cells causes DiGeorge syndrome-like malformations.

    Science.gov (United States)

    Escot, Sophie; Blavet, Cédrine; Faure, Emilie; Zaffran, Stéphane; Duband, Jean-Loup; Fournier-Thibault, Claire

    2016-02-15

    DiGeorge syndrome (DGS) is a congenital disease causing cardiac outflow tract anomalies, craniofacial dysmorphogenesis, thymus hypoplasia, and mental disorders. It results from defective development of neural crest cells (NCs) that colonize the pharyngeal arches and contribute to lower jaw, neck and heart tissues. Although TBX1 has been identified as the main gene accounting for the defects observed in human patients and mouse models, the molecular mechanisms underlying DGS etiology are poorly identified. The recent demonstrations that the SDF1/CXCR4 axis is implicated in NC chemotactic guidance and impaired in cortical interneurons of mouse DGS models prompted us to search for genetic interactions between Tbx1, Sdf1 (Cxcl12) and Cxcr4 in pharyngeal NCs and to investigate the effect of altering CXCR4 signaling on the ontogeny of their derivatives, which are affected in DGS. Here, we provide evidence that Cxcr4 and Sdf1 are genetically downstream of Tbx1 during pharyngeal NC development and that reduction of CXCR4 signaling causes misrouting of pharyngeal NCs in chick and dramatic morphological alterations in the mandibular skeleton, thymus and cranial sensory ganglia. Our results therefore support the possibility of a pivotal role for the SDF1/CXCR4 axis in DGS etiology. © 2016. Published by The Company of Biologists Ltd.

  6. Serotonin is required for pharyngeal arch morphogenesis in zebrafish

    Directory of Open Access Journals (Sweden)

    Saleh Bashammakh

    2014-12-01

    Full Text Available Serotonin (5-HT is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2, the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expressions. Tph2-deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest (NC cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of NC-derived tissues.

  7. Towards the modeling of mucus draining from human lung: role of airways deformation on air-mucus interaction.

    Directory of Open Access Journals (Sweden)

    Benjamin eMauroy

    2015-08-01

    Full Text Available Chest physiotherapy is an empirical technique used to help secretions to get out of the lung whenever stagnation occurs. Although commonly used, little is known about the inner mechanisms of chest physiotherapy and controversies about its use are coming out regularly. Thus, a scientific validation of chest physiotherapy is needed to evaluate its effects on secretions.We setup a quasi-static numerical model of chest physiotherapy based on thorax and lung physiology and on their respective biophysics. We modeled the lung with an idealized deformable symmetric bifurcating tree. Bronchi and their inner fluids mechanics are assumed axisymmetric. Static data from the literature is used to build a model for the lung's mechanics. Secretions motion is the consequence of the shear constraints apply by the air flow. The input of the model is the pressure on the chest wall at each time, and the output is the bronchi geometry and air and secretions properties. In the limit of our model, we mimicked manual and mechanical chest physiotherapy techniques. We show that for secretions to move, air flow has to be high enough to overcome secretion resistance to motion. Moreover, the higher the pressure or the quicker it is applied, the higher is the air flow and thus the mobilization of secretions. However, pressures too high are efficient up to a point where airways compressions prevents air flow to increase any further. Generally, the first effects of manipulations is a decrease of the airway tree hydrodynamic resistance, thus improving ventilation even if secretions do not get out of the lungs. Also, some secretions might be pushed deeper into the lungs; this effect is stronger for high pressures and for mechanical chest physiotherapy. Finally, we propose and tested two adimensional numbers that depend on lung properties and that allow to measure the efficiency and comfort of a manipulation.

  8. Dynamic upper airway collapse observed from sleep MRI: BMI-matched severe and mild OSA patients.

    Science.gov (United States)

    Huon, Leh-Kiong; Liu, Stanley Yung-Chuan; Shih, Tiffany Ting-Fang; Chen, Yunn-Jy; Lo, Men-Tzung; Wang, Pa-Chun

    2016-11-01

    Dynamic magnetic resonance imaging (MRI) allows real-time characterization of upper airway collapse in sleeping subjects with obstructive sleep apnea (OSA). The aim of our study was to use sleep MRI to compare differences in upper airway collapse sites between BMI-matched subjects with mild OSA and severe OSA. This is a prospective, nested case-control study using dynamic sleep MRI to compare 15 severe OSA subjects (AHI >40) and 15 mild OSA (AHI BMI. Upper airway imaging was performed on sleeping subjects in a 3.0 T MRI scanner. Sleep MRI movies were used by blinded reviewers to identify retropalatal (RP), retroglossal (RG), and lateral pharyngeal wall (LPW) airway collapse. Mean AHI in the severe OSA group was 70.3 ± 23 events/h, and in the mild group was 7.8 ± 1 events/h (p BMI-matched mild OSA patients.

  9. 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...

  10. Dual Oxidase 2 (Duox2) Regulates Pannexin 1-mediated ATP Release in Primary Human Airway Epithelial Cells via Changes in Intracellular pH and Not H2O2 Production.

    Science.gov (United States)

    Krick, Stefanie; Wang, Junjie; St-Pierre, Melissa; Gonzalez, Carlos; Dahl, Gerhard; Salathe, Matthias

    2016-03-18

    Human airway epithelial cells express pannexin 1 (Panx1) channels to release ATP, which regulates mucociliary clearance. Airway inflammation causes mucociliary dysfunction. Exposure of primary human airway epithelial cell cultures to IFN-γ for 48 h did not alter Panx1 protein expression but significantly decreased ATP release in response to hypotonic stress. The IFN-γ-induced functional down-regulation of Panx1 was due to the up-regulation of dual oxidase 2 (Duox2). Duox2 suppression by siRNA led to an increase in ATP release in control cells and restoration of ATP release in cells treated with IFN-γ. Both effects were reduced by the pannexin inhibitor probenecid. Duox2 up-regulation stoichiometrically increases H2O2 and proton production. H2O2 inhibited Panx1 function temporarily by formation of disulfide bonds at the thiol group of its terminal cysteine. Long-term exposure to H2O2, however, had no inhibitory effect. To assess the role of cellular acidification upon IFN-γ treatment, fully differentiated airway epithelial cells were exposed to ammonium chloride to alkalinize the cytosol. This led to a 2-fold increase in ATP release in cells treated with IFN-γ that was also inhibited by probenecid. Duox2 knockdown also partially corrected IFN-γ-mediated acidification. The direct correlation between intracellular pH and Panx1 open probability was shown in oocytes. Therefore, airway epithelial cells release less ATP in response to hypotonic stress in an inflammatory environment (IFN-γ exposure). Decreased Panx1 function is a response to cell acidification mediated by IFN-γ-induced up-regulation of Duox2, representing a novel mechanism for mucociliary dysfunction in inflammatory airway diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Development of an in vitro model assay system for the evaluation of the effects of toxic chemicals on human airways. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, J.L.; Filbert, M.G.

    1994-03-01

    The ability of the anticholinesterase agent soman to contract human bronchi was examined. Soman (1-2 uM) had variable effects on human bronchi that had not been stimulated with an electric field stimulator (EFS). In bronchi continuously stimulated by EFS (0.5 Hz, 1 ms, 12 V), soman produced contractions in all tissues examined (12 preparations from 9 humans). In tissues stimulated by EFS, the beta-adrenoreceptor agonist isoproterenol produced relaxations that were greater in magnitude than the contractions produced by soman. The duration of the isoproterenol induced relaxations was variable. Of 12 preparations studied, 3 showed no reversal of the relaxation within 120 min, 6 showed a slow reversal with a reversal time of 106 + or - 6 min and 3 showed rapid reversal with a 50% reversal time of 14 min. In the latter group the duration of the relaxation produced by isoproterenol was doubled (28 + or - 2 min) by the M2 muscarinic receptor antagonist AFDX 116 (10 uM). These results show that the isolated human bronchus is a useful model for studying the effects of toxic chemical agents such as soman on the airways. The data obtained with isoproterenol suggest that beta-2 agonists may be useful adjuncts for treating the effects of anticholinesterase agents.

  12. Assays for in vitro monitoring of proliferation of human airway smooth muscle (ASM) and human pulmonary arterial vascular smooth muscle (VSM) cells.

    Science.gov (United States)

    Goncharova, Elena A; Lim, Poay; Goncharov, Dmitry A; Eszterhas, Andrew; Panettieri, Reynold A; Krymskaya, Vera P

    2006-01-01

    Vascular and airway remodeling, which are characterized by airway smooth muscle (ASM) and pulmonary arterial vascular smooth muscle (VSM) proliferation, contribute to the pathology of asthma, pulmonary hypertension, restenosis and atherosclerosis. To evaluate the proliferation of VSM and ASM cells in response to mitogens, we perform a [3H]thymidine incorporation assay. The proliferation protocol takes approximately 48 h and includes stimulating cells synchronized in G0/G1 phase of the cell cycle with agonists, labeling cells with [3H]thymidine and examining levels of [3H]thymidine incorporation by scintillation counting. Although using radiolabeled [3H]thymidine incorporation is a limitation, the greatest benefit of the assay is providing reliable and statistically significant data.

  13. A three‐dimensional placoderm (stem‐group gnathostome) pharyngeal skeleton and its implications for primitive gnathostome pharyngeal architecture

    Science.gov (United States)

    Friedman, Matt; Jerve, Anna; Atwood, Robert C.

    2017-01-01

    Abstract The pharyngeal skeleton is a key vertebrate anatomical system in debates on the origin of jaws and gnathostome (jawed vertebrate) feeding. Furthermore, it offers considerable potential as a source of phylogenetic data. Well‐preserved examples of pharyngeal skeletons from stem‐group gnathostomes remain poorly known. Here, we describe an articulated, nearly complete pharyngeal skeleton in an Early Devonian placoderm fish, Paraplesiobatis heinrichsi Broili, from Hunsrück Slate of Germany. Using synchrotron light tomography, we resolve and reconstruct the three‐dimensional gill arch architecture of Paraplesiobatis and compare it with other gnathostomes. The preserved pharyngeal skeleton comprises elements of the hyoid arch (probable ceratohyal) and a series of branchial arches. Limited resolution in the tomography scan causes some uncertainty in interpreting the exact number of arches preserved. However, at least four branchial arches are present. The final and penultimate arches are connected as in osteichthyans. A single median basihyal is present as in chondrichthyans. No dorsal (epibranchial or pharyngobranchial) elements are observed. The structure of the pharyngeal skeleton of Paraplesiobatis agrees well with Pseudopetalichthys from the same deposit, allowing an alternative interpretation of the latter taxon. The phylogenetic significance of Paraplesiobatis is considered. A median basihyal is likely an ancestral gnathostome character, probably with some connection to both the hyoid and the first branchial arch pair. Unpaired basibranchial bones may be independently derived in chondrichthyans and osteichthyans. PMID:28543631

  14. The fibrinogen-binding M1 protein reduces pharyngeal cell adherence and colonization phenotypes of M1T1 group A Streptococcus.

    Science.gov (United States)

    Anderson, Ericka L; Cole, Jason N; Olson, Joshua; Ryba, Bryan; Ghosh, Partho; Nizet, Victor

    2014-02-07

    Group A Streptococcus (GAS) is a leading human pathogen producing a diverse array of infections from simple pharyngitis ("strep throat") to invasive conditions, including necrotizing fasciitis and toxic shock syndrome. The surface-anchored GAS M1 protein is a classical virulence factor that promotes phagocyte resistance and exaggerated inflammation by binding host fibrinogen (Fg) to form supramolecular networks. In this study, we used a virulent WT M1T1 GAS strain and its isogenic M1-deficient mutant to examine the role of M1-Fg binding in a proximal step in GAS infection-interaction with the pharyngeal epithelium. Expression of the M1 protein reduced GAS adherence to human pharyngeal keratinocytes by 2-fold, and this difference was increased to 4-fold in the presence of Fg. In stationary phase, surface M1 protein cleavage by the GAS cysteine protease SpeB eliminated Fg binding and relieved its inhibitory effect on GAS pharyngeal cell adherence. In a mouse model of GAS colonization of nasal-associated lymphoid tissue, M1 protein expression was associated with an average 6-fold decreased GAS recovery in isogenic strain competition assays. Thus, GAS M1 protein-Fg binding reduces GAS pharyngeal cell adherence and colonization in a fashion that is counterbalanced by SpeB. Inactivation of SpeB during the shift to invasive GAS disease allows M1-Fg binding, increasing pathogen phagocyte resistance and proinflammatory activities.

  15. Nasopharyngeal Airway Volume for Different GOSLON Scores in Patients With Unilateral Cleft Lip and Palate.

    Science.gov (United States)

    Olmez Gurlen, S; Aras, I; Dogan, S

    2015-09-01

    The aim of this study is to evaluate the nasopharyngeal airway volumes of patients with unilateral cleft lip and palate (UCLP) with different GOSLON scores. The study sample consisted of 34 patients with UCLP and 20 controls with no cleft history. In the UCLP group, three experienced examiners used the GOSLON Yardstick to rate dental arch relationships, and the sample was divided into three groups as GOSLON 2 (G2) (n = 13), GOSLON 3 (G3) (n = 10), and GOSLON 4 (G4) (n = 11). Airway volumes were constructed using three-dimensional computed tomography data and divided into four compartments named the nasal airway, and superior, middle, and inferior pharyngeal airways. No statistically significant difference was detected among G2, G3, and G4 between the constitutive airway departments of the nasopharyngeal region. However, nasal airway volumes were significantly higher in the control group when compared with the UCLP group. Although there was no correlation among the investigated parameters, it is also a fact that airway capacities display a great variability among patients when investigated three dimensionally. Although the severity of GOSLON scores might predetermine the extent of which the airways are affected from the cleft, a larger sample size is needed in future studies.

  16. 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.

  17. Escherichia coli-derived and Staphylococcus aureus-derived extracellular vesicles induce MUC5AC expression via extracellular signal related kinase 1/2 and p38 mitogen-activated protein kinase in human airway epithelial cells.

    Science.gov (United States)

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

    2017-01-01

    Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) release extracellular vesicles (EVs). E. coli-derived and S. aureus-derived EVs are associated with neutrophilic respiratory inflammation. In neutrophilic respiratory inflammation of human, expression of mucin is increased in airway epithelial cells and is associated with increased morbidity and mortality of the affected patients. However, no study on the effects of EVs on expression of mucin genes has been reported in airway epithelial cells. Therefore, this study was conducted in order to examine the effects and the brief signaling pathways of E. coli-derived and S. aureus-derived EVs on MUC5AC expression in human airway epithelial cells. In mucin-producing human NCI-H292 airway epithelial cells and primary cultures of normal nasal epithelial cells, the effects and signaling pathways of E. coli-derived and S. aureus-derived EVs on MUC5AC expression were examined using reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, enzyme immunoassay, and immunoblot analysis with several specific inhibitors and small interfering RNA (siRNA). E. coli-derived and S. aureus-derived EVs induced MUC5AC expression. E. coli-derived and S. aureus-derived EVs significantly activated phosphorylation of extracellular signal related kinase 1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) and p38 MAPK. ERK1/2 MAPK inhibitor, p38 MAPK inhibitor, ERK1/2 MAPK siRNA, and p38 MAPK siRNA significantly blocked E. coli-derived and S. aureus-derived EVs induced MUC5AC messenger RNA (mRNA) expression. The results of this study suggest that E. coli-derived and S. aureus-derived EVs induced MUC5AC expression via ERK1/2 and p38 MAPK signaling pathways in human airway epithelial cells. © 2016 ARS-AAOA, LLC.

  18. The impact of oil spill to lung health – insights from an RNA-seq study of human airway epithelial cells

    Science.gov (United States)

    Liu, Yao-Zhong; Roy-Engel, Astrid M; Baddoo, Melody C; Flemington, Erik K; Wang, Guangdi; Wang, He

    2015-01-01

    The Deepwater Horizon oil spill (BP oil spill) in the Gulf of Mexico was a unique disaster event, where a huge amount of oil spilled from the sea bed and a large volume of dispersants were applied to clean the spill. The operation lasted for almost three months and involved >50,000 workers. The potential health hazards to these workers may be significant as previous research suggested an association of persistent respiratory symptoms with exposure to oil and oil dispersants. To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527 and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil-dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527 + oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of gene sets involved in angiogenesis and immune responses and downregulation of gene sets involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil or Corexit 9500 + oil mixture. Interestingly, these key molecular signatures coincide with important pathological features observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggests significant health impacts of the recent BP oil spill to those

  19. Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Émilie Maillé

    2017-11-01

    Full Text Available The function of cystic fibrosis transmembrane conductance regulator (CFTR channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1ΔlasR or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1ΔlasR had no impact. Importantly, treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of P. aeruginosa in infected patients.

  20. Quorum Sensing Down-Regulation Counteracts the Negative Impact of Pseudomonas aeruginosa on CFTR Channel Expression, Function and Rescue in Human Airway Epithelial Cells.

    Science.gov (United States)

    Maillé, Émilie; Ruffin, Manon; Adam, Damien; Messaoud, Hatem; Lafayette, Shantelle L; McKay, Geoffrey; Nguyen, Dao; Brochiero, Emmanuelle

    2017-01-01

    The function of cystic fibrosis transmembrane conductance regulator (CFTR) channels is crucial in human airways. However unfortunately, chronic Pseudomonas aeruginosa infection has been shown to impair CFTR proteins in non-CF airway epithelial cells (AEC) and to alter the efficiency of new treatments with CFTR modulators designed to correct the basic CFTR default in AEC from cystic fibrosis (CF) patients carrying the F508del mutation. Our aim was first to compare the effect of laboratory strains, clinical isolates, engineered and natural mutants to determine the role of the LasR quorum sensing system in CFTR impairment, and second, to test the efficiency of a quorum sensing inhibitor to counteract the deleterious impact of P. aeruginosa both on wt-CFTR and on the rescue of F508del-CFTR by correctors. We first report that exoproducts from either the laboratory PAO1 strain or a clinical ≪Early≫ isolate (from an early stage of infection) altered CFTR expression, localization and function in AEC expressing wt-CFTR. Genetic inactivation of the quorum-sensing LasR in PAO1 (PAO1ΔlasR) or in a natural clinical mutant (≪Late≫ CF-adapted clinical isolate) abolished wt-CFTR impairment. PAO1 exoproducts also dampened F508del-CFTR rescue by VRT-325 or Vx-809 correctors in CF cells, whereas PAO1ΔlasR had no impact. Importantly, treatment of P. aeruginosa cultures with a quorum sensing inhibitor (HDMF) prevented the negative effect of P. aeruginosa exoproducts on wt-CFTR and preserved CFTR rescue by correctors in CF AEC. These findings indicate that LasR-interfering strategies could be of benefits to counteract the deleterious effect of P. aeruginosa in infected patients.

  1. Effects of transient receptor potential canonical 1 (TRPC1) on the mechanical stretch-induced expression of airway remodeling-associated factors in human bronchial epithelioid cells.

    Science.gov (United States)

    Yu, Qian; Li, Minchao

    2017-01-25

    Research has shown that mechanical stress stimulation can cause airway remodeling. We investigate the effects of mechanical stretch on the expression of the airway remodeling-associated factors interleukin-13 (IL-13) and matrix metalloprotein-9 (MMP-9) and signaling pathways in human bronchial epithelioid (16HBE) cells under mechanical stretch. A Flexcell FX-4000 Tension System with a flexible substrate was applied to stretch 16HBE cells at a 15% elongation amplitude and 1Hz frequency, with stretching for 0.5h, 1h, 1.5h and 2h. The experimental group with higher IL-13, MMP-9, and TRPC1 expression and higher Ca(2+) levels was selected for performing intervention experiment. These cells were pretreated with the transient receptor potential canonical 1 (TRPC1) channel antagonist SKF96365 and TRPC1-specific siRNA, and then mechanical stretch was applied. Our results provided evidences that mechanical pressure significantly increased IL-13, MMP-9, and TRPC1 protein and mRNA expression levels and intracellular Ca(2+) fluorescence intensity at 4 time points compared with the control group. The peak IL-13, MMP-9, and TRPC1 expression levels were observed at 0.5h after exposure to mechanical pressure. IL-13 and MMP-9 expression levels and Ca(2+) fluorescence intensity in the stretch+SKF96365 group and in the stretch+TRPC1 siRNA group were significantly lower than those were in the mechanical stretch group. By incubating the cells with the intracellular calcium chelator BAPTA-AM, the expression of IL-13 and MMP9 was significantly decreased, and the expression level of TRPC1 remained unchanged. These observations suggest that mechanical stretch may induce an influx of Ca(2+) and up-regulation of IL-13 and MMP-9 expression in 16HBE cells via activation of TRPC1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Novel diagnostic device for oral and pharyngeal examinations of children: folding-scope for the oral and pharyngeal cavities.

    Science.gov (United States)

    Tsunoda, Koichi; Sekimoto, Sotaro; Tsunoda, Atsunobu

    2010-12-02

    Although children may dislike and/or resist oral and pharyngeal examination with a tongue depressor, they enjoy lollipops on sticks, eating with spoons, forks, and chopsticks, and brushing their teeth. Many reports have noted this apparent contradiction, since paediatric patients are often treated after toothbrushes or chopsticks penetrate the pharyngeal wall. We therefore developed a novel device to observe the inside of the mouth without using a flashlight, tongue depressor or head mirror. We previously developed the AWS for tracheal intubation through the mouth for anaesthesia and emergency situations, along with a new device to observe the inside of the oral cavity simultaneously. We have developed a new attachment to the AWS for observations inside the oral cavity and pharynx. Our newly developed oral and pharyngeal examination system is a useful tool for diagnostic examinations and may also enable treatment without causing discomfort or distress to patients and their families.

  4. Glucose depletion in the airway surface liquid is essential for sterility of the airways.

    Directory of Open Access Journals (Sweden)

    Alejandro A Pezzulo

    2011-01-01

    Full Text Available Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources--including glucose--in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.

  5. 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......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize...... the interior and exterior airway wall surface in three dimensions, and branches were matched in consecutive scans by image registration. Emphysema was defined as attenuation Emphysema limits were set at

  6. 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.

  7. Pharyngeal related non-lexical vowels in Sephardic Modern Hebrew

    NARCIS (Netherlands)

    Pariente, I.

    2010-01-01

    This paper examines non-lexical vowels in Sephardic Modern Hebrew. It is argued that two kinds of vowel, which are triggered by the pharyngeal consonants, should be identified: (a) true epenthetic vowels that emerge on the surface to repair illicit (marked) syllable structures. (b) "Echo-vowels"

  8. Histological study of the pharyngeal pad of the african catfish ...

    African Journals Online (AJOL)

    The pharyngeal pad located dorsally on the oro-pharynx was processed for light microscopy. The epithelium was of stratified mucous type containing taste buds, club cells and teeth. The micromorphology revealed the co-localization of teeth and taste bud. Developing, erupting and erupted teeth were also seen. The thin ...

  9. Bacterial isolates of tonsillitis and pharyngitis in a paediatric casualty ...

    African Journals Online (AJOL)

    BHS and S. aureus showed 100% sensitivity to cefuroxine, azithromycin, ceftazidine and genticin. All the isolates had little or no sensitivity to ampicillin and cotrimoxazole. BHS is a significant cause of pharyngitis and tonsillitis in our environment and therefore poses a potential danger of rheumatic fever and rheumatic heart ...

  10. Group A Streptococcus pharyngitis among schoolchildren in Mbulu ...

    African Journals Online (AJOL)

    Streptococcal pharyngitis continues to be one of the most common childhood illnesses throughout the world. Recent evidence indicates an increased incidence of group A Streptococcal (GAS) infections, which is a significant cause of mortality and morbidity on the global scale. The objective of this study was to determine ...

  11. Pharyngitis and sore throat: A review | Somro | African Journal of ...

    African Journals Online (AJOL)

    Pharyngitis is a sore throat caused by inflammation of the back of the throat. It is one of the most common reasons for visits to family physicians. Throat may be scratchy and swallowing can be painful. Usually, a sore throat is the sign of another illness, such as a cold or the flu. In this review article, epidemiology, national ...

  12. 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:...

  13. 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 ...

  14. Placoderm fishes, pharyngeal denticles, and the vertebrate dentition.

    Science.gov (United States)

    Johanson, Zerina; Smith, Moya M

    2003-09-01

    The correlation of the origin of teeth with jaws in vertebrate history has recently been challenged with an alternative to the canonical view of teeth deriving from separate skin denticles. This alternative proposes that organized denticle whorls on the pharyngeal (gill) arches in the fossil jawless fish Loganellia are precursors to tooth families developing from a dental lamina along the jaw, such as those occurring in sharks, acanthodians, and bony fishes. This not only indicates that homologs of tooth families were present, but also illustrates that they possessed the relevant developmental controls, prior to the evolution of jaws. However, in the Placodermi, a phylogenetically basal group of jawed fishes, the state of pharyngeal denticles is poorly known, tooth whorls are absent, and the presence of teeth homologous to those in extant jawed fishes (Chondrichthyes + Osteichthyes) is controversial. Thus, placoderms would seem to provide little evidence for the early evolution of dentitions, or of denticle whorls, or tooth families, at the base of the clade of jawed fishes. However, organized denticles do occur at the rear of the placoderm gill chamber, but are associated with the postbranchial lamina of the anterior trunkshield, assumed to be part of the dermal cover. Significantly, these denticles have a different organization and morphology relative to the external dermal trunkshield tubercles. We propose that they represent a denticulate part of the visceral skeleton, under the influence of pharyngeal patterning controls comparable to those for pharyngeal denticles in other jawed vertebrates and Loganellia. Copyright 2003 Wiley-Liss, Inc.

  15. Postoperative upper airway problems

    African Journals Online (AJOL)

    QuickSilver

    2003-06-09

    Jun 9, 2003 ... PATHOLOGICAL CHANGES. The site of most applied force is different when comparing inser- tion of an ETT to a LMA (2). With the LMA, the main force is exerted at the end of the soft palate and the pharyngeal wall di- rectly behind, whereas with the ETT, it is the hard palate and the entrance to the trachea ...

  16. [Pharyngeal ulcer in patients with acquired immune deficiency syndrome].

    Science.gov (United States)

    Fang, Gaoli; Zhang, Luo; Wang, Chengshuo; Xiao, Jiang; Fu, Qian; Zhao, Hongxin

    2014-02-01

    To understand the high incidence of pharyngeal ulcer in patients with acquired immune deficiency syndrome (AIDS). By analyzing the clinical features in AIDS patients with pharyngeal ulcer, this study provided reference for clinicians. Twenty AIDS patients with pharyngeal ulcer were retrospectively analysed to explore its clinical features and mechanism, and to explore the feasible therapeutic methods. The patients generally had severe sore throat and dysphagia for 7 days to 8 months, resulting in significant weight loss. Common therapeutical method does not work. The ulcers developed mainly at vestibule of pharynx (10 cases), tonsil (3 cases), epiglottis (3 cases) and pyriform sinus (2 cases). Ulcer types included major aphthous ulcer (MaAU, 14 cases), fungal ulcer (2 cases), herpes zoster (1 case), ulcer secondary to drug eruption(1 case ), and lymphoma(2 cases). The disease course was long with CD4(+) T lymphocytes decreased significantly. Treatment was given with highly active antiretroviral therapy (HARRT), regulation of immune function, analgesic, anti-inflammatory and anti fungal. Treatment lasted from 2 weeks to 3 months, ulcer healed in 13 cases; 1 patient lost to follow-up, 6 patients dead. The manifestation of pharyngeal ulcer in AIDS patients has its particularity. It is often associated with a variety of opportunistic infection and tumors. Local treatment is preferred. HAART therapy and systemic comprehensive treatment play more important and effective role. Pharyngeal ulcer persists for a long time, complicated with fever, diarrhea and other symptoms. The history of blood transfusion, injection drug use or unsafe sexual behavior may predict HIV infection.

  17. Engineering Airway Epithelium

    Directory of Open Access Journals (Sweden)

    John P. Soleas

    2012-01-01

    Full Text Available Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990. In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium.

  18. 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.

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

    Science.gov (United States)

    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. PMID:25389533

  20. 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.

  1. 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.

  2. 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.

  3. Pyocyanin and its precursor phenazine-1-carboxylic acid increase IL-8 and intercellular adhesion molecule-1 expression in human airway epithelial cells by oxidant-dependent mechanisms.

    Science.gov (United States)

    Look, Dwight C; Stoll, Lynn L; Romig, Sara A; Humlicek, Alicia; Britigan, Bradley E; Denning, Gerene M

    2005-09-15

    Pseudomonas aeruginosa secretes numerous factors that alter host cell function and may contribute to disease pathogenesis. Among recognized virulence factors is the redox-active phenazine pyocyanin. We have recently demonstrated that the precursor for pyocyanin, phenazine-1-carboxylic acid (PCA), increases oxidant formation and alters gene expression in human airway epithelial cells. We report in this work that PCA and pyocyanin increase expression of ICAM-1 both in vivo and in vitro. Moreover, phenazines enhanced cytokine-dependent increases in IL-8 and ICAM-1. Antioxidant intervention studies indicated both similarities and differences between PCA and pyocyanin. The thiol antioxidant N-acetyl cysteine, extracellular catalase, and inducible NO synthase inhibitors inhibited ICAM-1 and IL-8 increases in response to both phenazines. However, pyocyanin was significantly more sensitive to N-acetylcysteine inhibition. Interestingly, hydroxyl radical scavengers inhibited the response to pyocyanin, but not to PCA. These studies suggest that P. aeruginosa phenazines coordinately up-regulate chemokines (IL-8) and adhesion molecules (ICAM-1) by mechanisms that are, at least in part, oxidant dependent. However, results indicate that the mechanisms by which PCA and pyocyanin exert their effects are not identical, and not all antioxidant interventions are equally effective in inhibiting phenazine-mediated proinflammatory effects.

  4. Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells.

    Science.gov (United States)

    Below, Sabine; Konkel, Anne; Zeeck, Cathrin; Müller, Christian; Kohler, Christian; Engelmann, Susanne; Hildebrandt, Jan-Peter

    2009-03-01

    Part of the innate defense of bronchial epithelia against bacterial colonization is regulated secretion of salt, water, and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos on treatment with Staphylococcus aureus culture supernatants from the stationary growth phase [optical density (OD)(540 nm) = 10] or with recombinant S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating that the bacterial products activated the entire signaling cascade that coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10 supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10 supernatant was sensitive to PD-98059, while that induced by Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus interaction of bacterial factors with airway epithelial cells may be highly cell type specific.

  5. Obstetric airway management

    African Journals Online (AJOL)

    high rate of general anaesthesia (30% of emergency, and 8% of elective, Caesarean sections), readily available senior cover ... better training and preparation, earlier identification of the difficult airway, and potentially increased regional .... in high-volume theatres. References. 1. Preston R, Jee R. Obstetric airway ...

  6. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that they can do on their ... (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  7. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low......-dose CT for a period of 5 years (table 1). Images were reconstructed both with high contrast resolution (3 mm, kernel C) for emphysema analysis and with high spatial resolution (1 mm, kernel D) for airway analysis. Images were analysed by in-house developed software designed to segment lungs and localize......-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...

  8. Establishment of a tumour-stroma airway model (OncoCilAir) to accelerate the development of human therapies against lung cancer.

    Science.gov (United States)

    Mas, Christophe; Boda, Bernadett; Caul Futy, Mireille; Huang, Song; Wisniewski, Ludovic; Constant, Samuel

    2016-10-01

    This paper highlights the work for which OncoTheis, a Swiss biotechnology company, engaged in the development of innovative bioengineered tissues and organoids for cancer research, was co-awarded the 2015 Lush Science Prize. Noting that the use of animal models failed to lead to the design of effective treatments for cancer, OncoTheis has opted to develop in vitro models based exclusively on human cells. The company currently focuses on lung cancer, which is the leading cause of cancer-related deaths worldwide, with more than one million deaths per year. To address this public health concern, we developed OncoCilAir™, a new 3-D model that mimics in vitro the progression of the disease as it happens in patients. In this system, bronchial and lung tumour cells obtained from discarded surgical tissue are cocultured in a Petri dish to reconstitute a fragment of the human lung. After appropriate differentiation, the culture closely reproduces malignant pulmonary nodules invading a small piece of functional airway tissue. As OncoCilAir includes both healthy and cancerous tissues, it can be used to test tumour-killing activity and the adverse effects of chemotherapies and other anti-cancer drugs. Moreover, a single culture can be maintained for up to three months, which permits studies of longer-term effects, including the assessment of drug resistance and tumour recurrence. OncoCilAir heralds a new generation of integrated in vitro models, which is expected to increase the quality of preclinical research while replacing animal testing. 2016 FRAME.

  9. 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...

  10. Atomized human amniotic mesenchymal stromal cells for direct delivery to the airway for treatment of lung injury

    NARCIS (Netherlands)

    Kim, Sally Yunsun; Burgess, Janette K.; Wang, Yiwei; Kable, Eleanor P. W.; Weiss, Daniel J.; Chan, Hak-Kim; Chrzanowski, Wojciech

    2016-01-01

    Background: Current treatment regimens for inhalation injury are mainly supportive and rely on self-regeneration processes for recovery. Cell therapy with mesenchymal stromal cells (MSCs) is increasingly being investigated for the treatment of inhalation injury. Human amniotic MSCs (hAMSCs) were

  11. The Role of Lipid Hydroperoxides in Ozone-Induced Increases in Glutathione Redox Potential in Human Airway Epithelial Cells

    Science.gov (United States)

    Human exposure to tropospheric ozone pollution is of global public health concern. Exposure to ozone induces functional decrements and inflammatory responses in the respiratory tract that are thought to occur through oxidative mechanisms. While it is known that ozone oxidizes p...

  12. A single amino acid in the HA of pH1N1 2009 influenza virus affects cell tropism in human airway epithelium, but not transmission in ferrets.

    Directory of Open Access Journals (Sweden)

    Neeltje van Doremalen

    Full Text Available The first pandemic of the 21(st century, pandemic H1N1 2009 (pH1N1 2009, emerged from a swine-origin source. Although human infections with swine-origin influenza have been reported previously, none went on to cause a pandemic or indeed any sustained human transmission. In previous pandemics, specific residues in the receptor binding site of the haemagglutinin (HA protein of influenza have been associated with the ability of the virus to transmit between humans. In the present study we investigated the effect of residue 227 in HA on cell tropism and transmission of pH1N1 2009. In pH1N1 2009 and recent seasonal H1N1 viruses this residue is glutamic acid, whereas in swine influenza it is alanine. Using human airway epithelium, we show a differential cell tropism of pH1N1 2009 compared to pH1N1 2009 E227A and swine influenza suggesting this residue may alter the sialic acid conformer binding preference of the HA. Furthermore, both pH1N1 2009 E227A and swine influenza multi-cycle viral growth was found to be attenuated in comparison to pH1N1 2009 in human airway epithelium. However this altered tropism and viral growth in human airway epithelium did not abrogate respiratory droplet transmission of pH1N1 2009 E227A in ferrets. Thus, acquisition of E at residue 227 was not solely responsible for the ability of pH1N1 2009 to transmit between humans.

  13. [Recommendations for management of acute pharyngitis in adults].

    Science.gov (United States)

    Cots, Josep M; Alós, Juan-Ignacio; Bárcena, Mario; Boleda, Xavier; Cañada, José L; Gómez, Niceto; Mendoza, Ana; Vilaseca, Isabel; Llor, Carles

    2016-11-01

    Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  14. Recommendations for management of acute pharyngitis in adults.

    Science.gov (United States)

    Cots, Josep M; Alós, Juan-Ignacio; Bárcena, Mario; Boleda, Xavier; Cañada, José L; Gómez, Niceto; Mendoza, Ana; Vilaseca, Isabel; Llor, Carles

    2015-01-01

    Acute pharyngitis in adults is one of the most common infectious diseases seen in general practitioners' consultations. Viral aetiology is the most common. Among bacterial causes, the main agent is Streptococcus pyogenes or group A β-haemolytic streptococcus (GABHS), which causes 5%-30% of the episodes. In the diagnostic process, clinical assessment scales can help clinicians to better predict suspected bacterial aetiology by selecting patients who should undergo a rapid antigen detection test. If these techniques are not performed, an overdiagnosis of streptococcal pharyngitis often occurs, resulting in unnecessary prescriptions of antibiotics, most of which are broad spectrum. Consequently, management algorithms that include the use of predictive clinical rules and rapid tests have been set up. The aim of the treatment is speeding up symptom resolution, reducing the contagious time span and preventing local suppurative and non-suppurative complications. Penicillin and amoxicillin are the antibiotics of choice for the treatment of pharyngitis. The association of amoxicillin and clavulanate is not indicated as the initial treatment of acute infection. Neither are macrolides indicated as first-line therapy; they should be reserved for patients allergic to penicillin. The appropriate diagnosis of bacterial pharyngitis and proper use of antibiotics based on the scientific evidence available are crucial. Using management algorithms can be helpful in identifying and screening the cases that do not require antibiotic therapy. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

  15. 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

  16. 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.

  17. 3D Reconstruction of the Human Airway Mucosa In Vitro as an Experimental Model to Study NTHi Infections

    Science.gov (United States)

    Marrazzo, Pasquale; Maccari, Silvia; Taddei, Annarita; Bevan, Luke; Telford, John; Soriani, Marco; Pezzicoli, Alfredo

    2016-01-01

    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. PMID:27101006

  18. 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.

  19. Airway distensibility in Chronic Obstructive Airway Disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    on the airway distensibility, defined as the ratio of relative change in lumen diameter to the relative change in total lung volume (TLV) divided by predicted total lung capacity (pTLC) . Methods – We included 1900 participants from the Danish Lung Cancer Screening Trial (DLCST); all randomized to annual low...

  20. Nitrogen Dioxide Exposure and Airway Responsiveness in Individuals with Asthma

    Science.gov (United States)

    Controlled human exposure studies evaluating the effect of inhaled NO2 on the inherent responsiveness of the airways to challenge by bronchoconstricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway r...

  1. Surfactant in airway disease.

    Science.gov (United States)

    Enhorning, Goran

    2008-04-01

    Beta(2)-adrenergic agonists cause a release of pulmonary surfactant into lung airways. The surfactant phospholipids maintain the patency of the conducting airways, but this function is inhibited by plasma proteins entering an inflamed airway. The physical behavior of the surfactant can be studied with a pulsating bubble surfactometer and a capillary surfactometer. Calf lung surfactant extract was found to be inhibited by plasma proteins and by a lowering of temperature. Severe breathing difficulties and malfunctioning surfactant developed in BALB/c mice inhaling ozone or infected with respiratory syncytial virus, mainly as a result of proteins invading the airways. Patients with asthma were challenged with allergens in an area of one lung. BAL fluid (BALF) from such an area contained a surfactant that functioned poorly (ie, an inability to maintain airway openness) compared with BALF from the other lung or from the lungs of healthy volunteers. When proteins in the BALF were removed, surfactant performance clearly improved. Eosinophils, so prominent in asthmatic patients, synthesize the enzyme lysophospholipase, which, together with the enzyme phospholipase A(2), catalyzes the hydrolysis of the main component of the surfactant, phosphatidylcholine. Such hydrolysis incapacitates the ability of the surfactant to maintain airway patency. The treatment of asthma with beta(2)-adrenergic agonists and steroids will have a valuable effect on the surfactant system. It will cause a release of fresh surfactant into terminal airways. Surfactant can also be nebulized and inhaled, which has been shown to be an effective treatment.

  2. A systematic study on the influence of the main ingredients of an ivy leaves dry extract on the β2-adrenergic responsiveness of human airway smooth muscle cells.

    Science.gov (United States)

    Greunke, Christian; Hage-Hülsmann, Anne; Sorkalla, Thomas; Keksel, Nelli; Häberlein, Felix; Häberlein, Hanns

    2015-04-01

    The bronchospasmolytic and secretolytic effects of ivy leaves dry extracts can be explained by an increased β2-adrenergic responsiveness of the bronchi. Recently, it was shown that α-hederin inhibits the internalization of β2-adrenergic receptors (ß2AR) under stimulating conditions. α-Hederin pretreated alveolar type II cells and human airway smooth muscle cells revealed an increased ß2AR binding and an elevated intracellular cAMP level, respectively. In order to identify whether additional compounds also mediate an increased β2-adrenergic responsiveness, we examined the ingredients of an ivy leaves dry extract (EA 575) protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, 3,4-, 3,5- and 4,5-dicaffeoylquinic acid, hederacoside B, and β-hederin. Within all the tested substances, only β-hederin inhibited the internalization of GFP-tagged ß2AR in stably transfected HEK293 cells. Using fluorescence correlation spectroscopy β-hederin (1 μM, 24 h) pretreated HASM cells showed a statistically significant increase in the ß2AR binding from 33.0 ± 8.9% to 44.1 ± 11.5% which was distributed with 36.0 ± 9.5% for τbound1 and 8.1 ± 2.6% for τbound2, respectively (n = 8, p dry extract on HASM cells it was possible to identify β-hederin as further component presumably responsible for the β2-mimetic effects. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Real time analysis of β2-adrenoceptor-mediated signaling kinetics in Human Primary Airway Smooth Muscle Cells reveals both ligand and dose dependent differences

    Directory of Open Access Journals (Sweden)

    Hall Ian P

    2011-07-01

    Full Text Available Abstract Background β2-adrenoceptor agonists elicit bronchodilator responses by binding to β2-adrenoceptors on airway smooth muscle (ASM. In vivo, the time between drug administration and clinically relevant bronchodilation varies significantly depending on the agonist used. Our aim was to utilise a fluorescent cyclic AMP reporter probe to study the temporal profile of β2-adrenoceptor-mediated signaling induced by isoproterenol and a range of clinically relevant agonists in human primary ASM (hASM cells by using a modified Epac protein fused to CFP and a variant of YFP. Methods Cells were imaged in real time using a spinning disk confocal system which allowed rapid and direct quantification of emission ratio imaging following direct addition of β2-adrenoceptor agonists (isoproterenol, salbutamol, salmeterol, indacaterol and formoterol into the extracellular buffer. For pharmacological comparison a radiolabeling assay for whole cell cyclic AMP formation was used. Results Temporal analysis revealed that in hASM cells the β2-adrenoceptor agonists studied did not vary significantly in the onset of initiation. However, once a response was initiated, significant differences were observed in the rate of this response with indacaterol and isoproterenol inducing a significantly faster response than salmeterol. Contrary to expectation, reducing the concentration of isoproterenol resulted in a significantly faster initiation of response. Conclusions We conclude that confocal imaging of the Epac-based probe is a powerful tool to explore β2-adrenoceptor signaling in primary cells. The ability to analyse the kinetics of clinically used β2-adrenoceptor agonists in real time and at a single cell level gives an insight into their possible kinetics once they have reached ASM cells in vivo.

  4. NGS meta data analysis for identification of SNP and INDEL patterns in human airway transcriptome: A preliminary indicator for lung cancer

    Directory of Open Access Journals (Sweden)

    Sathya B.

    2015-03-01

    Full Text Available High-throughput sequencing of RNA (RNA-Seq was developed primarily to analyze global gene expression in different tissues. It is also an efficient way to discover coding SNPs and when multiple individuals with different genetic backgrounds were used, RNA-Seq is very effective for the identification of SNPs. The objective of this study was to perform SNP and INDEL discoveries in human airway transcriptome of healthy never smokers, healthy current smokers, smokers without lung cancer and smokers with lung cancer. By preliminary comparative analysis of these four data sets, it is expected to get SNP and INDEL patterns responsible for lung cancer. A total of 85,028 SNPs and 5738 INDELs in healthy never smokers, 32,671 SNPs and 1561 INDELs in healthy current smokers, 50,205 SNPs and 3008 INDELs in smokers without lung cancer and 51,299 SNPs and 3138 INDELs in smokers with lung cancer were identified. The analysis of the SNPs and INDELs in genes that were reported earlier as differentially expressed was also performed. It has been found that a smoking person has SNPs at position 62,186,542 and 62,190,293 in SCGB1A1 gene and 180,017,251, 180,017,252, and 180,017,597 in SCGB3A1 gene and INDELs at position 35,871,168 in NFKBIA gene and 180,017,797 in SCGB3A1 gene. The SNPs identified in this study provides a resource for genetic studies in smokers and shall contribute to the development of a personalized medicine. This study is only a preliminary kind and more vigorous data analysis and wet lab validation are required.

  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. Cervical Spine Motion During Airway Management Using Two Manual In-line Immobilization Techniques: A Human Simulator Model Study.

    Science.gov (United States)

    De Jesus, Clarines Rosa; García Peña, Barbara M; Lozano, Juan Manuel; Maniaci, Vincenzo

    2015-09-01

    The aim of this study is to evaluate cervical spine motion using 2 manual inline immobilization techniques with the use of a human simulator model. Medical students, pediatric and family practice residents, and pediatric emergency medicine fellows were recruited to maintain cervical manual in line immobilization above the head of the bed and across the chest of a human simulator while orotracheal intubation was performed. Participants were then instructed on appropriate holding techniques after the initial session took place. Orotracheal intubation followed. A tilt sensor measured time to intubation and cervical extension and rotation angle. Seventy-one subjects participated in a total of 284 successful orotracheal intubations. No change in cervical spine movement or time to intubation was observed when using 2 different inline manual immobilization techniques with no training. However, a statistically significant difference with assistants above the head versus across the chest was observed after training in: extension 2.1° (95% confidence interval [95% CI], 1.15 to 3.00; P < 0.0001); rotation 0.7° (95% CI, 0.26 to 1.19; P = 0.003) and intubation time of -1.9 seconds (95% CI, -3.45 to -0.13; P = 0.035) after training. Cervical spine movement did not change when maintaining cervical spine immobilization from above the head versus across the chest before training. There was a statistically significant change in extension and rotation when assistants were above the head and in time to intubation when assistants were across the chest after training. The clinical significance of these results is unclear.

  7. Unusual pharyngeal pain caused by acute coronary syndrome: a report of three cases

    Directory of Open Access Journals (Sweden)

    Takashi Anzai

    2017-01-01

    Full Text Available Most patients complaining of pharyngeal pain have an upper respiratory tract infection or other local explanation for their pain. Here we show 3 rare cases of patients visiting our Otorhinolaryngology Department who had an initial symptom of pharyngeal pain caused by acute coronary syndrome (ACS. An electrocardiogram and a cardiac biomarker test are recommended to exclude ACS with atypical presentation in cases without pharyngolaryngeal findings comparable to pharyngeal pain.

  8. CT demonstration of pharyngeal narrowing in adult obstructive sleep apnea

    Energy Technology Data Exchange (ETDEWEB)

    Bohlman, M.E. (Johns Hopkins Univ. School of Medicine, Baltimore, MD); Haponik, E.F.; Smith, P.L.; Allen, R.P.; Bleecker, E.R.; Goldman, S.M.

    1983-03-01

    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.

  9. A stem-deuterostome origin of the vertebrate pharyngeal transcriptional network

    Science.gov (United States)

    Gillis, J. Andrew; Fritzenwanker, Jens H.; Lowe, Christopher J.

    2012-01-01

    Hemichordate worms possess ciliated gills on their trunk, and the homology of these structures with the pharyngeal gill slits of chordates has long been a topic of debate in the fields of evolutionary biology and comparative anatomy. Here, we show conservation of transcription factor expression between the developing pharyngeal gill pores of the hemichordate Saccoglossus kowalevskii and the pharyngeal gill slit precursors (i.e. pharyngeal endodermal outpockets) of vertebrates. Transcription factors that are expressed in the pharyngeal endoderm, ectoderm and mesenchyme of vertebrates are expressed exclusively in the pharyngeal endoderm of S. kowalevskii. The pharyngeal arches and tongue bars of S. kowalevskii lack Tbx1-expressing mesoderm, and are supported solely by an acellular collagenous endoskeleton and by compartments of the trunk coelom. Our findings suggest that hemichordate and vertebrate gills are homologous as simple endodermal outpockets from the foregut, and that much vertebrate pharyngeal complexity arose coincident with the incorporation of cranial paraxial mesoderm and neural crest-derived mesenchyme within pharyngeal arches along the chordate and vertebrate stems, respectively. PMID:21676974

  10. Airway Clearance Techniques (ACTs)

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    Full Text Available ... decisions about your health care. CF Genetics: The Basics CF Mutations Video Series CFTR2 Personalized Medicine Types ... of Breathing Technique Airway Clearance Techniques Autogenic Drainage Basics of Lung Care Chest Physical Therapy Coughing and ...

  11. Airway Clearance Techniques (ACTs)

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    Full Text Available ... and Resources Bioinformatics Tools for CF CFTR Antibodies Distribution Program CFTR Assays CFFT Biorepository CFTR Chemical Compound ... huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how ...

  12. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Guidelines Bone Disease in CF Clinical Care Guidelines Cystic Fibrosis-Related Diabetes Clinical Care Guidelines Liver Disease Clinical Care Guidelines Respiratory Care Guidelines CF Airway ...

  13. 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 ...

  14. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Medications Antibiotics Bronchodilators 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 ...

  15. Emergency airway puncture - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100113.htm Emergency airway puncture - series—Normal anatomy To use the ... 2016 Updated by: Jacob L. Heller, MD, MHA, Emergency Medicine, Virginia Mason Medical Center, Seattle, WA. Also ...

  16. Airway Clearance Techniques (ACTs)

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

  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: NACFC 2017 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 ... Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory Comments Congressional Cystic Fibrosis Caucus Our Policy Agenda Policy ... for airway clearance. Facebook Twitter Email More Related Content Medications Autogenic Drainage Positive Expiratory Pressure High-Frequency ...

  19. Airway Clearance Techniques (ACTs)

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    Full Text Available ... GI Care Guidelines Antioxidants Clinical Care Guidelines Enteral Tube Feeding Clinical Care Guidelines Nutrition in Children and ... clear your airways. Most are easy to do. Infants and toddlers will need help from a parent ...

  20. 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 ...

  1. Airway Clearance Techniques (ACTs)

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    Full Text Available ... Medications Antibiotics Bronchodilators 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 ...

  2. 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 Health Clinical Care Guidelines ...

  3. Airway Clearance Techniques (ACTs)

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    Full Text Available ... a Family Parenting as an Adult With CF Treatments & 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 ( ...

  4. 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 ...

  5. 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 ... 20814 301-951-4422 800-344-4823 (toll free) We will not rest until we find a ...

  6. Blockage of upper airway

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    ... obstruction - acute upper Images Throat anatomy Choking Respiratory system References Cukor J, Manno M. Pediatric respiratory emergencies: upper airway obstruction and infections. In: Marx J, ed. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier ...

  7. 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 ... Clearance Active Cycle of Breathing Technique (ACBT) Airway Clearance Techniques ( ...

  8. Molecular genetic and biochemical responses in human airway epithelial cell cultures exposed to titanium nanoparticles in vitro.

    Science.gov (United States)

    Aydın, Elanur; Türkez, Hasan; Hacımüftüoğlu, Fazıl; Tatar, Abdulgani; Geyikoğlu, Fatime

    2017-07-01

    Titanium nanoparticles (NPs) have very wide application areas such as paint, cosmetics, pharmaceuticals, and biomedical applications. And, to translate these nanomaterials to the clinic and industrial domains, their safety needs to be verified, particularly in terms of genotoxicity and cytotoxicity. Therefore, in this study, we aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium (as titanium carbide, titanium carbo-nitride, titanium (II) oxide, titanium (III) oxide, titanium (IV) oxide, titanium nitride, titanium silicon oxide) NPs in human alveolar epithelial (HPAEpiC) and pharynx (HPPC) cell lines in vitro since inhalation is an important pathway for exposure to these NPs. HPAEpiC and HPPC cells were treated with titanium (0-100 µg/mL), NPs for 24 and 48 h, and then cytotoxicity was detected by, [3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide] (MTT), uptake of neutral red (NR) and lactate dehydrogenase (LDH) release assays, while genotoxicity was also analyzed by cDNA array - RT-PCR assay. According to the results of MTT, NR and LDH assays, all tested NPs induced cytotoxicity on both HPAEpiC and HPPC cells in a time- and dose-dependent manner. Determining and analyzing the gene expression profiles of HPAEpiC and HPPC cells, titanium NPs showed more changes in genes related to DNA damage or repair, oxidative stress, and apoptosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2056-2064, 2017. © 2017 Wiley Periodicals, Inc.

  9. Toward the modeling of mucus draining from the human lung: role of the geometry of the airway tree

    Science.gov (United States)

    Mauroy, Benjamin; Fausser, Christian; Pelca, Dominique; Merckx, Jacques; Flaud, Patrice

    2011-10-01

    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.

  10. Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma.

    Science.gov (United States)

    Larose, Marie-Chantal; Chakir, Jamila; Archambault, Anne-Sophie; Joubert, Philippe; Provost, Véronique; Laviolette, Michel; Flamand, Nicolas

    2015-10-01

    High pulmonary eosinophil counts are associated with asthma symptoms and severity. Bronchial epithelial cells (BECs) produce CC chemokines, notably CCL26 (eotaxin-3), which recruits and activates eosinophils from asthmatic patients. This suggests that CCL26 production by BECs might be involved in persistent eosinophilia in patients with severe asthma despite treatment with high corticosteroid doses. We sought to determine whether CCL26 levels correlate with eosinophilia and asthma severity. Human CC chemokine expression was assessed by means of quantitative PCR or a quantitative PCR array in vehicle- or IL-13-treated BECs. CCL26 was quantitated by means of ELISA. Immunohistochemistry analyses of CCL26 and major basic protein were done on bronchial biopsy specimens. IL-13 selectively induced CCL26 expression by BECs. This increase was time-dependent and more prominent in BECs from patients with severe eosinophilic asthma. CCL26 levels measured in supernatants of IL-13-stimulated BECs also increased with asthma severity as follows: patients with severe eosinophilic asthma > patients with mild asthma ≈ healthy subjects. Immunohistochemistry analyses of bronchial biopsy specimens confirmed increased levels of CCL26 in the epithelium of patients with mild and those with severe eosinophilic asthma. Tissue eosinophil counts did not correlate with CCL26 staining. However, sputum CCL26 levels significantly correlated with sputum eosinophil counts (P asthma severity. They also suggest a role for CCL26 in the sustained inflammation observed in patients with severe eosinophilic asthma and reveal CCL26 as a potential target for treating patients with eosinophilic asthma that are refractory to classic therapies. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Passive movement of human soft palate during respiration: A simulation of 3D fluid/structure interaction.

    Science.gov (United States)

    Zhu, Jian Hua; Lee, Heow Pueh; Lim, Kian Meng; Lee, Shu Jin; Teo, Li San Lynette; Wang, De Yun

    2012-07-26

    This study reconstructed a three dimensional fluid/structure interaction (FSI) model to investigate the compliance of human soft palate during calm respiration. Magnetic resonance imaging scans of a healthy male subject were obtained for model reconstruction of the upper airway and the soft palate. The fluid domain consists of nasal cavity, nasopharynx and oropharynx. The airflow in upper airway was assumed as laminar and incompressible. The soft palate was assumed as linear elastic. The interface between airway and soft palate was the FSI interface. Sinusoidal variation of velocity magnitude was applied at the oropharynx corresponding to ventilation rate of 7.5L/min. Simulations of fluid model in upper airway, FSI models with palatal Young's modulus of 7539Pa and 3000Pa were carried out for two cycles of respiration. The results showed that the integrated shear forces over the FSI interface were much smaller than integrated pressure forces in all the three directions (axial, coronal and sagittal). The total integrated force in sagittal direction was much smaller than that of coronal and axial directions. The soft palate was almost static during inspiration but moved towards the posterior pharyngeal wall during expiration. In conclusion, the displacement of human soft palate during respiration was mainly driven by air pressure around the surface of the soft palate with minimal contribution of shear stress of the upper airway flow. Despite inspirational negative pressure, expiratory posterior movement of soft palate could be another factor for the induction of airway collapse. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. 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.

  13. Clinical Scoring Value for Diagnosis of Streptococcal Pharyngitis

    Directory of Open Access Journals (Sweden)

    N.M. Noori

    2011-07-01

    Full Text Available Introduction & Objective: β- hemolytic group A streptococcus is the most common cause of acute bacterial pharyngitis in children.Due to the high incidence of this disease and it's difficult diagnosis , we decided to compare clinical scoring and throat cultures for diagnosis of streptococcal pharyngitis. Materials & Methods: This cross-sectional analytic study was done on 3-16 year old patients reffered to pediatric clinic with complaint of sore throat. After taking history and physical examination, scoring was done based on clinical findings.The patients with chronic disease or those who received antibiotics or other drugs were eliminated from the study. Analysis was performed using SPSS. Score for each patient was calculated and compared with the result of throat cultures. Sensitivity, specificity, positive and negative predictive values for each clinical finding were determined. Results: 315 patients out of 350 patients with complaint of sore throat referred to the clinic had fever of whom 51.1% had positive throat culture with 51.1% sensitivity and 77% specifity (p<0.01. 127 patients had pharyngeal petechia of whom 67% had positive throat culture with 66.9% sensitivity and 73.5% specifity (p<0.002. 105 children had pharyngeal exudates of whom 65.7% had positive throat culture with 65.7% sensitivity and 58.3% specifity (p<0.001. Anterior cervical lymphadenopathy was detected in 293 patients of whom 53.24% had positive throat culture with 53.2% sensitivity and 73.8% specifity (p<0.002. 182 patients had no signs of upper respiratory infection, among them 65.9% had positive throat culture with 65.9% sensitivity and 70.4% specifity (p<0.001. 130 patients had sore throat, 66.3% of them had positive throat culture with 62.3% sensitivity and 59% specifity (p<0.001. 310 patients had pharyngeal erythema of which 51.6% had positive throat culture with 57.5% sensitivity and 22.7% specifity (p<0.02. 99 children had gastrointestinal signs, 66.14% had

  14. Genome Analysis of Streptococcus pyogenes Associated with Pharyngitis and Skin Infections

    Science.gov (United States)

    Ibrahim, Joe; Eisen, Jonathan A.; Jospin, Guillaume; Coil, David A.; Khazen, Georges

    2016-01-01

    Streptococcus pyogenes is a very important human pathogen, commonly associated with skin or throat infections but can also cause life-threatening situations including sepsis, streptococcal toxic shock syndrome, and necrotizing fasciitis. Various studies involving typing and molecular characterization of S. pyogenes have been published to date; however next-generation sequencing (NGS) studies provide a comprehensive collection of an organism’s genetic variation. In this study, the genomes of nine S. pyogenes isolates associated with pharyngitis and skin infection were sequenced and studied for the presence of virulence genes, resistance elements, prophages, genomic recombination, and other genomic features. Additionally, a comparative phylogenetic analysis of the isolates with global clones highlighted their possible evolutionary lineage and their site of infection. The genomes were found to also house a multitude of features including gene regulation systems, virulence factors and antimicrobial resistance mechanisms. PMID:27977735

  15. 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 u...

  16. Histamine affects interleukin-4, interleukin-5, and interferon-gamma production by human T cell clones from the airways and blood

    NARCIS (Netherlands)

    Krouwels, F. H.; Hol, B. E.; Lutter, R.; Bruinier, B.; Bast, A.; Jansen, H. M.; Out, T. A.

    1998-01-01

    High levels of histamine can be found in the airways of asthma patients. This study describes the effects of histamine on anti-CD3-induced production of IL-4, IL-5, and IFN-gamma by T cell clones from subjects with allergic asthma and healthy subjects. T cell clones were obtained from

  17. Angiotensin II induces hypertrophy of human airway smooth muscle cells: expression of transcription factors and transforming growth factor-beta1

    NARCIS (Netherlands)

    S. McKay (Sue); J.C. de Jongste (Johan); P.R. Saxena (Pramod Ranjan); H.S. Sharma (Hari)

    1998-01-01

    textabstractIncreased smooth muscle mass due to hyperplasia and hypertrophy of airway smooth muscle (ASM) cells is a common feature in asthma. Angiotensin II (Ang II), a potent vasoconstrictor and mitogen for a wide variety of cells, has recently been implicated in

  18. Trans-oral robotic cleft surgery (TORCS) for palate and posterior pharyngeal wall reconstruction: A feasibility study.

    Science.gov (United States)

    Khan, Khurram; Dobbs, Tom; Swan, Marc C; Weinstein, Gregory S; Goodacre, Tim E E

    2016-01-01

    Robot-assisted surgery has become increasingly routine, replacing open and laparoscopic techniques in certain domains, with recent extension to head and neck surgery through trans-oral access. Some advantages of the robot-assisted surgery include the ability to access confined spaces, enhanced dexterity instrumentation with intuitive movement, motion scaling, tremor elimination and three-dimensional (3D) endoscopic viewing with true depth perception. The aim of this study was to investigate the technical feasibility of trans-oral robotic cleft surgery (TORCS) to access the posterior pharyngeal wall and palate for potential use in the cleft population. All possible permutations of patient and robotic instrument configurations were used with the daVinci Si Surgical System® (Intuitive Surgical, USA) 0° and 30° 3D endoscopes and 8-mm training instruments to determine the optimal visualization and surgical access to the palate and posterior pharynx in a paediatric airway manikin, and to simulate posterior pharyngeal wall surgery. A full robot-assisted cadaveric Hynes pharyngoplasty was performed using 5-mm training instruments. Experiments were recorded with still and video photography. TORCS is technically feasible in the paediatric cleft population. We predict a short learning curve due to the intuitive instrumentation, easier dissection and the potential to limit secondary insult compared with traditional surgery, as well as improved ergonomics for the operating surgeon. The as-yet unreported use of robotic-assisted cleft palate surgery may considerably enhance a surgeon's ability to perform difficult procedures of the palate and posterior pharynx in selected patients with limited access as well as lay the foundation for potential novel techniques. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  19. Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.

    Science.gov (United States)

    Lesseur, Corina; Diergaarde, Brenda; Olshan, Andrew F; Wünsch-Filho, Victor; Ness, Andrew R; Liu, Geoffrey; Lacko, Martin; Eluf-Neto, José; Franceschi, Silvia; Lagiou, Pagona; Macfarlane, Gary J; Richiardi, Lorenzo; Boccia, Stefania; Polesel, Jerry; Kjaerheim, Kristina; Zaridze, David; Johansson, Mattias; Menezes, Ana M; Curado, Maria Paula; Robinson, Max; Ahrens, Wolfgang; Canova, Cristina; Znaor, Ariana; Castellsagué, Xavier; Conway, David I; Holcátová, Ivana; Mates, Dana; Vilensky, Marta; Healy, Claire M; Szeszenia-Dąbrowska, Neonila; Fabiánová, Eleonóra; Lissowska, Jolanta; Grandis, Jennifer R; Weissler, Mark C; Tajara, Eloiza H; Nunes, Fabio D; de Carvalho, Marcos B; Thomas, Steve; Hung, Rayjean J; Peters, Wilbert H M; Herrero, Rolando; Cadoni, Gabriella; Bueno-de-Mesquita, H Bas; Steffen, Annika; Agudo, Antonio; Shangina, Oxana; Xiao, Xiangjun; Gaborieau, Valérie; Chabrier, Amélie; Anantharaman, Devasena; Boffetta, Paolo; Amos, Christopher I; McKay, James D; Brennan, Paul

    2016-12-01

    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.

  20. 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.

  1. Upper airway asymmetry in velo-cardio-facial syndrome.

    Science.gov (United States)

    Chegar, Burke E; Tatum, Sherard A; Marrinan, Eileen; Shprintzen, Robert J

    2006-08-01

    Various forms of asymmetry have been recognized as a feature of velo-cardio-facial syndrome (VCFS). This study was implemented to determine the frequency of anatomic and functional asymmetry of the velum, pharynx and larynx in children with VCFS. Individuals with VCFS underwent prospective, blinded analysis by an expert panel who assessed the velum, pharynx and larynx with multi-view videofluoroscopy (MVF) and nasopharyngolaryngoscopy (NPL). The VCFS group was compared to an age-matched group of normal individuals. Eight different parameters were assessed in both groups for functional and anatomic symmetry including: velar elevation, adenoid size, posterior pharyngeal wall size, carotid pulsations, epiglottis size and shape, arytenoid size, true vocal cord size and true vocal cord motion. One hundred and twenty-one subjects with VCFS and 20 normal individuals underwent examination. Children with VCFS showed significantly more asymmetry compared to the normal group (69% versus 20%, P=0.01) with greatest differences seen with palatal motion, posterior pharyngeal wall size and epiglottis shape. On average, subjects with VCFS had three asymmetric parameters versus one parameter in the normal group. Asymmetric development of the pharynx and larynx in children with VCFS appears to be a distinct clinical feature of this syndrome. This finding may provide an important diagnostic clue for patients presenting with subtle features of the 22q11.2 microdeletion. These developmental abnormalities may increase the risk of speech impairment, aspiration and airway obstruction in affected individuals.

  2. 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.

  3. Normal saline solution nasal-pharyngeal irrigation improves chronic cough associated with allergic rhinitis.

    Science.gov (United States)

    Lin, Lin; Chen, Zhongchun; Cao, Yitan; Sun, Guangbin

    2017-03-01

    Upper airway inflammation is one of the most commonly identified causes of chronic cough, although the underlying mechanism is not clear. This study compared normal saline solution nasal-pharyngeal irrigation (NSNPI) and fluticasone propionate nasal spray (FPNS) treatment for chronic cough associated with allergic rhinitis (AR). Patients with suspected AR to house-dust mite were enrolled, and the symptom of cough was assessed by a cough symptom score and the Leicester Cough Questionnaire, and cough response to capsaicin was evaluated. AR was assessed by using the visual analog scale (VAS) and the Mini Juniper Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). Mediators, including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein from nasal lavage fluid (NLF) were examined. The patients were treated with NSNPI (the NSNPI group) or FPNS (the FPNS group) for 30 days, after which they were reassessed. Forty-five of 50 patients completed this study. The scores of the cough symptom and the Leicester Cough Questionnaire, and the capsaicin cough threshold all improved statistically after NSNPI but did not change after FPNS. There were statistically significant changes in the evaluations of the MiniRQLQ and the mediators, including histamine and leukotriene C4, in the NLF in the NSNPI group. However, significant changes were found in the assessments of VAS, MiniRQLQ, and all above mediators including histamine, leukotriene C4, and prostaglandin D2, and the major basic protein in the NLF of the FPNS group. Furthermore, the assessments of VAS and all the mediators were reduced more in the FPNS group compared with those in the NSNPI group. The patients with suspected AR to house-dust mite reported a better relief of the cough symptom after 30 days of treatment with NSNPI compared with that after nasal corticosteroid.

  4. 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

    BACKGROUND AND OBJECTIVE: Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma......, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). METHODS: Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response......-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...

  5. 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

  6. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation.

    Science.gov (United States)

    Ravasi, Saula; Citro, Simona; Viviani, Barbara; Capra, Valérie; Rovati, G Enrico

    2006-03-22

    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. 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. 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. Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF-R through the intervention of PI3K and ROS. While PI3K

  7. Somnofluoroscopy, computed tomography, and cephalometry in the assessment of the airway in obstructive sleep apnoea.

    Science.gov (United States)

    Pepin, J L; Ferretti, G; Veale, D; Romand, P; Coulomb, M; Brambilla, C; Lévy, P A

    1992-01-01

    BACKGROUND: Assessments of the upper airways in patients with the obstructive sleep apnoea syndrome are usually carried out on awake patients who are upright. The dynamics of the airway in a patient who is asleep and lying down may be different. METHODS: Somnofluoroscopy, computed tomography of the upper airway, and cephalometry were carried out in 11 patients with the obstructive sleep apnoea syndrome (10 male; mean (SD) age 53 (10) years) to examine the airway while they were awake and asleep. RESULTS: At somnofluoroscopy 10 patients were in stage 2 sleep and only one in REM sleep. At least five obstructive events were visualised by lateral fluoroscopy in each patient. Imaging allowed observation of the dynamics of airway collapse, which began in the oropharynx in all cases, progressing to the hypopharynx in 10 cases and to the laryngopharynx in five. At fluoroscopy the soft palate was seen to hook up during airway occlusion in 10 patients, thereby increasing its cross sectional area. It was then sucked down into the hypopharynx. Somnofluoroscopic and cephalometric findings agreed, eight of the 10 patients with hypopharyngeal collapse shown by somnofluoroscopy having an inferiorly placed hyoid bone according to cephalometry (distance from the mandibular plane to the hyoid bone (MP-H distance) increased); the one patient with no hypopharyngeal collapse had a normal MP-H. By contrast, six of the 11 patients had a normal or supranormal hypopharyngeal cross sectional area of the airway on the computed tomogram. CONCLUSIONS: Somnofluoroscopy allows examination of the dynamics of airway closure in this disorder and shows the important role of the soft palate in acting as a plug in the oropharynx. Dynamic studies are required to determine the pattern of pharyngeal obstruction in obstructive sleep apnoea. Images PMID:1519190

  8. Familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome.

    Science.gov (United States)

    Adachi, Masao; Watanabe, Aika; Nishiyama, Atsushi; Oyazato, Yoshinobu; Kamioka, Ichiro; Murase, Masanori; Ishida, Akihito; Sakai, Hidemasa; Nishikomori, Ryuta; Heike, Toshio

    2011-01-01

    We report three familial cases of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, including a pair of monozygotic twins and their mother. It suggests that periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome may have a certain monogenetic background. Copyright © 2011 Mosby, Inc. All rights reserved.

  9. Colds, flu and coughing: Over-the-counter products for pharyngitis ...

    African Journals Online (AJOL)

    Pharyngotonsillitis is an inflammatory condition of the pharyngeal wall. Respiratory viruses are the major causes of pharyngitis, while bacteria account for 5-30% of cases. Once treatment of the underlying aetiology is considered and addressed, management of pharyngotonsillitis focuses on providing symptomatic relief.

  10. Benign Lymphoid Hyperplasia of the Tongue Base Causing Upper Airway Obstruction

    Directory of Open Access Journals (Sweden)

    Noah B. Sands

    2011-01-01

    Full Text Available Severe benign lymphoid hyperplasia (LH is unusual in the head and neck region, but the diagnosis of LH is of clinical importance as it may be confused with malignant lymphoma, both on clinical examination and pathologically. While the etiology is poorly understood, a number of previous theories exist, which are included here in the context of a literature review. In this paper we present a case of severe pharyngeal lymphoid hyperplasia causing airway obstruction and requiring tracheotomy and subsequent surgical debulking.

  11. Oropharyngeal approach as a surgical alternative for cervical lymphatic malformation with airway compression.

    Science.gov (United States)

    Díaz-Manzano, José Antonio; Pelegrín-Hernández, Juan Pablo; Mínguez-Merlos, Nieves; Cegarra-Navarro, María Francisca

    2014-07-01

    Cervical lymphatic malformation is an infrequent benign congenital malformation of the lymphatic system, whose rapid growing capacity can compromise the airway. Here we present a 3-month-old male with severe respiratory impairment showing pharyngeal, cervical and mediastinal lymphatic malformation. Transoral surgery maintaining the mucosa allowed removal of numerous cystic lumps occupying the whole pharynx up to the pyriform sinus, surrounding the common carotid artery. Postsurgical MRI showed that the pharynx portion of the lymphatic malformation had disappeared. We conclude that the oropharyngeal approach is an alternative to the classical external surgery involving upper respiratory tract compression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. 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

  13. Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome.

    Science.gov (United States)

    Ali, Nora S; Sartori-Valinotti, Julio C; Bruce, Alison J

    2016-01-01

    Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, the most common periodic disorder of childhood, presents with the cardinal symptoms of periodic fever, aphthous stomatitis, pharyngitis, and adenitis typically before age 5. This review presents the recent literature on PFAPA and summarizes key findings in the pathogenesis, evaluation, and treatment of the disease. Theories surrounding the pathogenesis of PFAPA include a faulty innate immunologic response in conjunction with dysregulated T-cell activation. A potential genetic link is also under consideration. Mediterranean fever (MEFV) gene variants have been implicated and appear to modify disease severity. In individuals with the heterozygous variant, PFAPA episodes are milder and shorter in duration. Diagnostic criteria include the traditional clinical signs, in addition to the following biomarkers: elevated C-reactive protein in the absence of elevated procalcitonin, vitamin D, CD64, mean corpuscular volume, and other nonspecific inflammatory mediators in the absence of an infectious explanation for fever. Treatment of PFAPA includes tonsillectomy, a single dose of corticosteroids, and, most recently, interleukin 1 blockers such as anakinra, rilonacept, and canakinumab. Tonsillectomy remains the only permanent treatment modality. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Update on the management of acute pharyngitis in children

    Directory of Open Access Journals (Sweden)

    Galli Luisa

    2011-01-01

    Full Text Available Abstract Streptococcal pharyngitis is a very common pathology in paediatric age all over the world. Nevertheless there isn't a joint agreement on the management of this condition. Some authors recommend to perform a microbiological investigation in suspected bacterial cases in order to treat the confirmed cases with antibiotics so to prevent suppurative complications and acute rheumatic fever. Differently, other authors consider pharyngitis, even streptococcal one, a benign, self-limiting disease. Consequently they wouldn't routinely perform microbiological tests and, pointing to a judicious use of antibiotics, they would reserve antimicrobial treatment to well-selected cases. It has been calculated that the number of patients needed to treat to prevent one complication after upper respiratory tract infections (including sore throat, was over 4000. Even the use of the Centor score, in order to evaluate the risk of streptococcal infection, is under debate and the interpretation of the test results may vary considerably. Penicillin is considered all over the world as first line treatment, but oral amoxicillin is also accepted and, due to its better palatability, can be a suitable option. Macrolides should be reserved to the rare cases of proved allergy to β-lactams. Cephalosporins can be used in patients allergic to penicillin (with the exception of type I hypersensibility and have been also proposed to treat the relapses.

  15. Observation the swallowing mechanism in elderly patients with pharyngeal dysphagia

    Directory of Open Access Journals (Sweden)

    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.

  16. 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

  17. Numerical analysis of extensional flow through the pharyngeal duct

    Science.gov (United States)

    Preciado-Méndez, M.; Salinas-Vázquez, M.; Vicente, W.; Brito-de la Fuente, E.; Ascanio, G.

    2017-01-01

    The flow through the pharynx from the glossopalatal junction (GPJ) to the upper esophageal sphincter (UES) has been numerically investigated with a non-Newtonian fluid obeying the power-law with similar rheological indices to a contrast medium used in videofluroscopy. For that purpose, a three-dimensional model of the transport of food bolus along the pharynx has been proposed using the immersed boundaries method, which allow representing the shape of the pharynx using Cartesian grids. The pharyngeal wall has been considered to be an elastic membrane. Flow fields in terms of the axial velocity, pressure, shear rate and strain rate were obtained. Results show that the highest velocity concentrates in the central stream as the fluid enters into the pharynx. In addition, as the flow quits the pharynx, a recirculation zone appears inside the cavity, resulting in low velocity zone, which increases with the coefficient of elasticity. A strong dependence on the coefficient of elasticity was observed on the pressure fields; so that as such a coefficient increases, the pressure in the pharyngeal wall will increase. It has been also observed that the bolus head travels faster than the bolus tail, which indicates that the bolus is not only subjected to shear but also to elongation. Results from this work can be further used for a rheological characterization (shear and extension) of oral nutritional supplements for patients suffering from swallowing disorders.

  18. 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

  19. 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

  20. Airway structural components drive airway smooth muscle remodeling in asthma

    NARCIS (Netherlands)

    Dekkers, Bart G J; Maarsingh, Harm; Meurs, Herman; Gosens, Reinoud

    2009-01-01

    Chronic asthma is an inflammatory airways disease characterized by pathological changes in the airway smooth muscle (ASM) bundle that contribute to airway obstruction and hyperresponsiveness. Remodeling of the ASM is associated with an increased smooth muscle mass, involving components of cellular

  1. Inter-airway structural heterogeneity interacts with dynamic heterogeneity to determine lung function and flow patterns in both asthmatic and control simulated lungs.

    Science.gov (United States)

    Donovan, G M

    2017-12-21

    Asthma is a disease involving both airway remodelling (e.g. thickening of the airway wall) and acute, reversible airway narrowing driven by airway smooth muscle contraction. Both of these processes are known to be heterogeneous, and in this study we consider a new theoretical model which considers the interactions of both mechanisms: structural heterogeneity (variation in airway remodelling) and dynamic heterogeneity (emergent variation in airway narrowing and flow). By integrating both types of inter-airway heterogeneity in a full human lung geometry, we are able to draw several insights regarding the mechanisms underlying observed ventilation heterogeneity. We show that: (1) bimodal ventilation distributions are driven by paradoxical contraction/dilation patterns for airways of all sizes; (2) structural heterogeneity differences between asthmatic and control subjects significantly influences resulting lung function, and observed ventilation heterogeneity patterns; and (3) individual airway dilation probabilities are uncorrelated with prior airway remodelling of that airway. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Compensatory responses to upper airway obstruction in obese apneic men and women.

    Science.gov (United States)

    Chin, Chien-Hung; Kirkness, Jason P; Patil, Susheel P; McGinley, Brian M; Smith, Philip L; Schwartz, Alan R; Schneider, Hartmut

    2012-02-01

    Defective structural and neural upper airway properties both play a pivotal role in the pathogenesis of obstructive sleep apnea. A more favorable structural upper airway property [pharyngeal critical pressure under hypotonic conditions (passive Pcrit)] has been documented for women. However, the role of sex-related modulation in compensatory responses to upper airway obstruction (UAO), independent of the passive Pcrit, remains unclear. Obese apneic men and women underwent a standard polysomnography and physiological sleep studies to determine sleep apnea severity, passive Pcrit, and compensatory airflow and respiratory timing responses to prolonged periods of UAO. Sixty-two apneic men and women, pairwise matched by passive Pcrit, exhibited similar sleep apnea disease severity during rapid eye movement (REM) sleep, but women had markedly less severe disease during non-REM (NREM) sleep. By further matching men and women by body mass index and age (n = 24), we found that the lower NREM disease susceptibility in women was associated with an approximately twofold increase in peak inspiratory airflow (P = 0.003) and inspiratory duty cycle (P = 0.017) in response to prolonged periods of UAO and an ∼20% lower minute ventilation during baseline unobstructed breathing (ventilatory demand) (P = 0.027). Thus, during UAO, women compared with men had greater upper airway and respiratory timing responses and a lower ventilatory demand that may account for sex differences in sleep-disordered breathing severity during NREM sleep, independent of upper airway structural properties and sleep apnea severity during REM sleep.

  3. Tongue and lateral upper airway movement with mandibular advancement.

    Science.gov (United States)

    Brown, Elizabeth C; Cheng, Shaokoon; McKenzie, David K; Butler, Jane E; Gandevia, Simon C; Bilston, Lynne E

    2013-03-01

    To characterize tongue and lateral upper airway movement and to image tongue deformation during mandibular advancement. Dynamic imaging study of a wide range of apnea hypopnea index (AHI), body mass index (BMI) subjects. Not-for-profit research institute. 30 subjects (aged 31-69 y, AHI 0-75 events/h, BMI 17-39 kg/m(2)). Subjects were imaged using dynamic tagged magnetic resonance imaging during mandibular advancement. Tissue displacements were quantified with the harmonic phase technique. Mean mandibular advancement was 5.6 ± 1.8 mm (mean ± standard deviation). This produced movement through a connection from the ramus of the mandible to the pharyngeal lateral walls in all subjects. In the sagittal plane, 3 patterns of posterior tongue deformation were seen with mandibular advancement-(A) en bloc anterior movement, (B) anterior movement of the oropharyngeal region, and (C) minimal anterior movement. Subjects with lower AHI were more likely to have en bloc movement (P = 0.04) than minimal movement. Antero-posterior elongation of the tongue increased with AHI (R = 0.461, P = 0.01). Mean anterior displacements of the posterior nasopharyngeal and oropharyngeal regions of the tongue were 20% ± 13% and 31% ± 17% of mandibular advancement. The posterior tongue compressed 1.1 ± 2.2 mm supero-inferiorly. Mandibular advancement has two mechanisms of action which increase airway size. In subjects with low AHI, the entire tongue moves forward. Mandibular advancement also produces lateral airway expansion via a direct connection between the lateral walls and the ramus of the mandible. Brown EC; Cheng S; McKenzie DK; Butler JE; Gandevia SC; Bilston LE. Tongue and lateral upper airway movement with mandibular advancement. SLEEP 2013;36(3):397-404.

  4. TWEAK/Fn14 interaction induces proliferation and migration in human airway smooth muscle cells via activating the NF-κB pathway.

    Science.gov (United States)

    Zhu, Cuimin; Zhang, Leguo; Liu, Zhiming; Li, Chen; Bai, Yajie

    2017-11-16

    Asthma, an increasingly common chronic disease among children, are characterized by airway remodeling, which is partly attributed to the proliferation and migration of airway smooth muscle cell (ASMC). The purpose of the present study was to investigate potential roles and mechanisms of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis on cell proliferation and migration in HASMCs. Compared to HASMCs from non-asthmatic patients, those from asthmatic patients showed elevated expression levels of both Fn14 and TWEAK. Additionally, similar to the response triggered by platelet-derived growth factor-BB, stimulation with recombinant TWEAK strongly induced cell proliferation and migration in HASMCs. However, depletion of Fn14 remarkably abrogated the enhancement of TWEAK on the cell proliferation and migration of HASMCs. Furthermore, treatment with TWEAK led to the activation of NF-κB. This effect was eliminated by silencing Fn14, indicating that TWEAK-induced NF-κB signaling was mediated via Fn14. Moreover, the TWEAK/Fn14 interaction promoted cell proliferation and migration. These effects were blocked by NF-κB inhibitor SN50, which suggest that the TWEAK/Fn14 signaling system partially depends on NF-κB activity. Collectively, we demonstrated that the TWEAK/Fn14 axis accelerated HASMC cell proliferation and migration by activating the NF-κB pathway, thereby exacerbating airway remodeling in asthma. Altogether, these findings indicate a novel role for the TWEAK/Fn14/NF- B pathway as a potent option for limiting airway remodeling in asthma. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis. Members of the Ceftibuten Pharyngitis International Study Group.

    Science.gov (United States)

    Pichichero, M E; Mclinn, S E; Gooch, W M; Rodriguez, W; Goldfarb, J; Reidenberg, B E

    1995-07-01

    The efficacy and safety of a 10-day course of ceftibuten oral suspension (9 mg/kg once daily) were compared with those of penicillin V (25 mg/kg/day in 3 divided doses) in children 3 to 18 years old treated for symptomatic pharyngitis and scarlet fever caused by group A beta-hemolytic streptococci (Streptococcus pyogenes). The study was prospective, randomized, multicenter and investigator-blinded; patients were randomized in a 2:1 ratio (ceftibuten:penicillin V). Overall clinical success (cure/improvement) at the primary end point of treatment (5 to 7 days posttherapy) was achieved in 97% (285 of 294) of ceftibuten-treated patients vs. 89% (117 of 132) of penicillin V-treated patients (P ceftibuten-treated patients vs 80% (105 of 132) of penicillin V-treated patients (P ceftibuten is as safe as and more effective than three times daily penicillin V for the treatment of group A beta-hemolytic streptococcal pharyngitis.

  6. 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

    Pre-operative airway assessment in Denmark is based on a non-specific clinical assessment. Systematic, evidence-based and consistent airway assessment may reduce the incidence of unanticipated difficult airway management. By assessing multiple predictors for difficult airway management......, the predictive value of the assessment increases. The Simplified Airway Risk Index (SARI) is a multivariate risk score for predicting difficult intubation.This study aims to compare the use of the SARI with a non-specified clinical airway assessment on predicting difficult intubation. Further, to compare......-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...

  7. Distinct PKA and Epac compartmentalization in airway function and plasticity

    NARCIS (Netherlands)

    Dekkers, Bart G. J.; Racke, Kurt; Schmidt, Martina

    Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases characterized by airway obstruction, airway inflammation and airway remodelling. Next to inflammatory cells and airway epithelial cells, airway mesenchymal cells, including airway smooth muscle cells and

  8. Smoking is associated with shortened airway cilia.

    Directory of Open Access Journals (Sweden)

    Philip L Leopold

    2009-12-01

    Full Text Available Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers.Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples were brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced by 15% compared to nonsmokers (p<0.05. In 39 air-dried samples of airway epithelial cells, smoker cilia length was reduced by 13% compared to nonsmokers (p<0.0001. Analysis of the length of individual, detached cilia in 27 samples showed that smoker cilia length was reduced by 9% compared to nonsmokers (p<0.05. Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05. Using genome-wide analysis of airway epithelial gene expression we identified 6 cilia-related genes whose expression levels were significantly reduced in healthy smokers compared to healthy nonsmokers.Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia play a significant role in the pathogenesis of smoking-induced lung disease.

  9. Airway epithelial cell tolerance to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Verghese Margrith W

    2005-04-01

    Full Text Available Abstract Background The respiratory tract epithelium is a critical environmental interface that regulates inflammation. In chronic infectious airway diseases, pathogens may permanently colonize normally sterile luminal environments. Host-pathogen interactions determine the intensity of inflammation and thus, rates of tissue injury. Although many cells become refractory to stimulation by pathogen products, it is unknown whether the airway epithelium becomes either tolerant or hypersensitive in the setting of chronic infection. Our goals were to characterize the response of well-differentiated primary human tracheobronchial epithelial cells to Pseudomonas aeruginosa, to understand whether repeated exposure induced tolerance and, if so, to explore the mechanism(s. Methods The apical surface of well-differentiated primary human tracheobronchial epithelial cell cultures was repetitively challenged with Pseudomonas aeruginosa culture filtrates or the bacterial media control. Toxicity, cytokine production, signal transduction events and specific effects of dominant negative forms of signaling molecules were examined. Additional experiments included using IL-1β and TNFα as challenge agents, and performing comparative studies with a novel airway epithelial cell line. Results An initial challenge of the apical surface of polarized human airway epithelial cells with Pseudomonas aeruginosa culture filtrates induced phosphorylation of IRAK1, JNK, p38, and ERK, caused degradation of IκBα, generation of NF-κB and AP-1 transcription factor activity, and resulted in IL-8 secretion, consistent with activation of the Toll-like receptor signal transduction pathway. These responses were strongly attenuated following a second Pseudomonas aeruginosa, or IL-1β, but not TNFα, challenge. Tolerance was associated with decreased IRAK1 protein content and kinase activity and dominant negative IRAK1 inhibited Pseudomonas aeruginosa -stimulated NF-κB transcriptional

  10. Obstetric airway management

    African Journals Online (AJOL)

    The use of video laryngoscopy in obstetric theatres must be explored and consideration given to it being placed permanently in high-volume theatres. References. 1. Preston R, Jee R. Obstetric airway management. Int Anesthesiol Clin. 2014;52(2):1-28. 2. Boutonnet M, Faitot V, Katz A, et al. Mallampati class changes during.

  11. The HIV Airway

    African Journals Online (AJOL)

    Adele

    been reported to result in airway obstruction. Conditions not limited to immunocomromised states such as epiglottitis, retropharyngeal abcesses, mediastinal masses and. Ludwig's angina are seen, with increased severity, in HIV in- fected individuals. Knowledge of a patients' HIV status may alert one to potential.

  12. Total airway reconstruction.

    Science.gov (United States)

    Connor, Matthew P; Barrera, Jose E; Eller, Robert; McCusker, Scott; O'Connor, Peter

    2013-02-01

    We present a case of obstructive sleep apnea (OSA) that required multilevel surgical correction of the airway and literature review and discuss the role supraglottic laryngeal collapse can have in OSA. A 34-year-old man presented to a tertiary otolaryngology clinic for treatment of OSA. He previously had nasal and palate surgeries and a Repose tongue suspension. His residual apnea hypopnea index (AHI) was 67. He had a dysphonia associated with a true vocal cord paralysis following resection of a benign neck mass in childhood. He also complained of inspiratory stridor with exercise and intolerance to continuous positive airway pressure. Physical examination revealed craniofacial hypoplasia, full base of tongue, and residual nasal airway obstruction. On laryngoscopy, the paretic aryepiglottic fold arytenoid complex prolapsed into the laryngeal inlet with each breath. This was more pronounced with greater respiratory effort. Surgical correction required a series of operations including awake tracheostomy, supraglottoplasty, midline glossectomy, genial tubercle advancement, maxillomandibular advancement, and reconstructive rhinoplasty. His final AHI was 1.9. Our patient's supraglottic laryngeal collapse constituted an area of obstruction not typically evaluated in OSA surgery. In conjunction with treating nasal, palatal, and hypopharyngeal subsites, our patient's supraglottoplasty represented a key component of his success. This case illustrates the need to evaluate the entire upper airway in a complicated case of OSA. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  13. 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 ... Autogenic Drainage Positive Expiratory Pressure High-Frequency Chest ...

  14. Airway management and morbid obesity

    DEFF Research Database (Denmark)

    Kristensen, Michael S

    2010-01-01

    airway and the function of the lungs (decreased residual capacity and aggravated ventilation perfusion mismatch) worse than in lean patients. Proper planning and preparation of airway management is essential, including elevation of the patient's upper body, head and neck. Preoxygenation is mandatory...... 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...

  15. 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......: 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...

  16. 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.

  17. Ageing and muscular dystrophy differentially affect murine pharyngeal muscles in a region-dependent manner

    Science.gov (United States)

    Randolph, Matthew E; Luo, Qingwei; Ho, Justin; Vest, Katherine E; Sokoloff, Alan J; Pavlath, Grace K

    2014-01-01

    The inability to swallow, or dysphagia, is a debilitating and life-threatening condition that arises with ageing or disease. Dysphagia results from neurological or muscular impairment of one or more pharyngeal muscles, which function together to ensure proper swallowing and prevent the aspiration of food or liquid into the lungs. Little is known about the effects of age or disease on pharyngeal muscles as a group. Here we show ageing affected pharyngeal muscle growth and atrophy in wild-type mice depending on the particular muscle analysed. Furthermore, wild-type mice also developed dysphagia with ageing. Additionally, we studied pharyngeal muscles in a mouse model for oculopharyngeal muscular dystrophy, a dysphagic disease caused by a polyalanine expansion in the RNA binding protein, PABPN1. We examined pharyngeal muscles of mice overexpressing either wild-type A10 or mutant A17 PABPN1. Overexpression of mutant A17 PABPN1 differentially affected growth of the palatopharyngeus muscle dependent on its location within the pharynx. Interestingly, overexpression of wild-type A10 PABPN1 was protective against age-related muscle atrophy in the laryngopharynx and prevented the development of age-related dysphagia. These results demonstrate that pharyngeal muscles are differentially affected by both ageing and muscular dystrophy in a region-dependent manner. These studies lay important groundwork for understanding the molecular and cellular mechanisms that regulate pharyngeal muscle growth and atrophy, which may lead to novel therapies for individuals with dysphagia. PMID:25326455

  18. Cervical osteomyelitis after carbon dioxide laser excision of recurrent carcinoma of the posterior pharyngeal wall.

    Science.gov (United States)

    Timmermans, A Jacqueline; Brandsma, Dieta; Smeele, Ludi E; Rosingh, Andert W; van den Brekel, Michiel W M; Lohuis, Peter J F M

    2013-04-01

    Two patients with recurrent carcinoma of the posterior pharyngeal wall, previously treated with carbon dioxide (CO2) laser excision and (chemo)radiotherapy, presented with neck pain due to cervical osteomyelitis. In one patient this led to cervical spine instability, for which a haloframe was applied. Our working hypothesis was that cervical osteomyelitis was caused by an infected wound bed induced by CO2 laser excision of the tumor in the already vascular-compromised area of the irradiated posterior pharyngeal wall. We discuss the risks of leaving a wound for secondary granulation after CO2 laser excision of the posterior pharyngeal wall and prophylactic antibiotic treatment.

  19. Amplicon mapping and expression profiling identify the fas-associated death domain gene as a new driver in the 11q13.3 amplicon in Laryngeal/Pharyngeal cancer

    NARCIS (Netherlands)

    Gibcus, J.H.; Menkema, L.; Mastik, M.F.; Hermsen, M.A.; de Bock, G.H.; van Velthuysen, M.L.; Takes, R.P.; Kok, K.; Alvarez Marcos, C.A.; van der Laan, B.F.; van den Brekel, M.W.; Langendijk, J.A.; Kluin, P.M.; van der Wal, J.E.; Schuuring, E.

    2007-01-01

    Purpose: Amplification of the 11q13 region is a frequent event in human cancer, The highest incidence (36%) is found in head and neck squamous cell carcinomas. Recently, we reported that the amplicon size in 30 laryngeal and pharyngeal carcinomas with 11q13 amplification is determined by unique

  20. The Role of IgE-Receptors in IgE-Dependent Airway Smooth Muscle Cell Remodelling

    OpenAIRE

    Michael Roth; Jun Zhong; Celine Zumkeller; Chong Teck S'ng; Stephanie Goulet; Michael Tamm

    2013-01-01

    BACKGROUND: In allergic asthma, IgE increases airway remodelling but the mechanism is incompletely understood. Airway remodelling consists of two independent events increased cell numbers and enhanced extracellular matrix deposition, and the mechanism by which IgE up-regulates cell proliferation and extracellular matrix deposition by human airway smooth muscle cells in asthma is unclear. OBJECTIVE: Characterise the role of the two IgE receptors and associated signalling cascades in airway smo...

  1. Microbial ecology and adaptation in cystic fibrosis airways

    DEFF Research Database (Denmark)

    Yang, Lei; Jelsbak, Lars; Molin, Søren

    2011-01-01

    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......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...

  2. Modulation of Airway Epithelial Antiviral Immunity by Fungal Exposure

    OpenAIRE

    Zhu, Lingxiang; Lee, Boram; Zhao, Fangkun; Zhou, Xu; Chin, Vanessa; Ling, Serena C.; Chen, Yin

    2014-01-01

    Multiple pathogens, such as bacteria, fungi, and viruses, have been frequently found in asthmatic airways and are associated with the pathogenesis and exacerbation of asthma. Among these pathogens, Alternaria alternata (Alt), a universally present fungus, and human rhinovirus have been extensively studied. However, their interactions have not been investigated. In the present study, we tested the effect of Alt exposure on virus-induced airway epithelial immunity using live virus and a synthet...

  3. Virtual 3-D {sup 18}F-FDG PET/CT panendoscopy for assessment of the upper airways of head and neck cancer patients: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Buchbender, Christian; Heusner, Till A. [University Duesseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany); University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Treffert, Jon [Siemens Health Care, Molecular Imaging, Knoxville, TN (United States); Lehnerdt, Goetz; Mattheis, Stefan [University Duisburg-Essen, Medical Faculty, Department of Otorhinolaryngology, Essen (Germany); Geiger, Bernhard [Siemens Corporate Research Inc., Princeton, NJ (United States); Bockisch, Andreas [University Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Forsting, Michael [University Duisburg-Essen, Medical Faculty, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Antoch, Gerald [University Duesseldorf, Medical Faculty, Department of Diagnostic and Interventional Radiology, Duesseldorf (Germany)

    2012-09-15

    The aim of this study was to evaluate whether a virtual 3-D {sup 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 {sup 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 {sup 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 {sup 18}F-FDG PET/CT panendoscopies was 145 {+-} 98 s. Virtual {sup 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.)

  4. 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.

  5. Optimizing education in difficult airway management: meeting the challenge.

    Science.gov (United States)

    Myatra, Sheila N; Kalkundre, Rupali S; Divatia, Jigeeshu V

    2017-09-21

    The last 2 decades have seen a vast change in the science and technology of airway management. As a result, there is an increasing need to equip anesthesiologists with the new knowledge and skills for the safe management of a difficult airway. In addition to knowledge and expertise, human factors and nontechnical skills (NTS), including situational awareness, communication and team work, play an important role during difficult airway management and contribute to the outcome. Didactic sessions are useful to impart knowledge. Self-learning, interactive discussions, simulation and debriefing are important tools for teaching and training in difficult airway management. Manikin training and simulation enable development of technical as well as NTS without subjecting patients to risk and allow multiple training sessions of relatively uncommon scenarios. Guidelines are useful teaching tools, whereas cognitive tools such as the Vortex approach may be useful during a difficult airway. There is need for research on difficult airway management and optimized training methods. Research is also required to determine the barriers to adoption of guidelines and strategies to ensure widespread dissemination and implementation of guidelines and best practices for difficult airway management.

  6. Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

    Science.gov (United States)

    Dorward, David A.; Sharma, Sidharth; Rennie, Jillian; Felton, Jennifer M.; Alessandri, Ana L.; Duffin, Rodger; Schwarze, Jurgen; Haslett, Christopher; Rossi, Adriano G.

    2015-01-01

    Rationale: Eosinophils are key effector cells in allergic diseases, including allergic rhinitis, eczema, and asthma. Their tissue presence is regulated by both recruitment and increased longevity at inflamed sites. Objectives: To investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate eosinophil-dominant allergic inflammation in vivo in mice. Methods: Human and mouse eosinophil apoptosis in response to wogonin was investigated by cellular morphology, flow cytometry, mitochondrial membrane permeability, and pharmacological caspase inhibition. Allergic lung inflammation was modeled in mice sensitized and challenged with ovalbumin. Bronchoalveolar lavage (BAL) and lung tissue were examined for inflammation, mucus production, and inflammatory mediator production. Airway hyperresponsiveness to aerosolized methacholine was measured. Measurements and Main Results: Wogonin induced time- and concentration-dependent human and mouse eosinophil apoptosis in vitro. Wogonin-induced eosinophil apoptosis occurred with activation of caspase-3 and was inhibited by pharmacological caspase inhibition. Wogonin administration attenuated allergic airway inflammation in vivo with reductions in BAL and interstitial eosinophil numbers, increased eosinophil apoptosis, reduced airway mucus production, and attenuated airway hyperresponsiveness. This wogonin-induced reduction in allergic airway inflammation was prevented by concurrent caspase inhibition in vivo. Conclusions: Wogonin induces eosinophil apoptosis and attenuates allergic airway inflammation, suggesting that it has therapeutic potential for the treatment of allergic inflammation in humans. PMID:25629436

  7. Periodic fever accompanied by aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA syndrome) in adults

    National Research Council Canada - National Science Library

    Padeh, Shai; Stoffman, Nava; Berkun, Yackov

    2008-01-01

    The new syndrome, known as PFAPA, of periodic fever characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy has been described only in pediatric patients...

  8. Evaluation of penicillins, cephalosporins, and macrolides for therapy of streptococcal pharyngitis.

    Science.gov (United States)

    Shulman, S T

    1996-06-01

    To review recent clinical experience with treatment of acute streptococcal pharyngitis with penicillins, cephalosporins, and macrolide antibiotics. Literature review and analysis. Oral penicillin V administered two to three times daily for 10 days is the treatment of choice for acute streptococcal pharyngitis and is the oral standard against which other treatments should be measured. A single intramuscular dose of benzathine penicillin also remains highly effective. Recent studies evaluating alternative oral agents given for less than 10 days or in once-daily regimens have yielded promising results. Studies should make efforts to exclude chronic streptococcal carriers with intercurrent viral pharyngitis because their inclusion in treatment trials substantially confounds the data. As issues of health care costs assume increasing importance, the cost of newer antimicrobial agents will deter their usage for acute streptococcal pharyngitis.

  9. 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.

  10. Perturbed airway closure

    Science.gov (United States)

    Grotberg, James B.; Halpern, David

    1998-11-01

    The small airways of the lungs are lined with a thin viscous film. A surface-tension driven instability at the air-liquid interface may induce the formation of a liquid bridge blocking airflow if there is sufficient fluid within the film. As a result of the pressures generated within the non-uniform film, the airway wall may also collapse. These instabilities often occur in premature neonates who do not produce sufficient quantities of surfactant. Often, they are placed in ventilators to diminish the risk of airway closure. Two fundamental parameters are the frequency of the ventilation and the tidal volume of the delivered gas. In the current study, we consider the effect of an oscillatory shear stress impinged by the air on a thin film coating a single compliant tube. Nonlinear evolution equations are derived for the film thickness and the wall position. Numerical solutions show that the oscillatory shear stress can saturate the growth of a disturbance at the air-liquid interface. For a given film thickness, there is a critical frequency, dependent on wall parameters, above which closure does not occur when forced by oscillatory shear but will close when unforced.

  11. Appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria.

    Science.gov (United States)

    Saengcharoen, Woranuch; Jaisawang, Pornchanok; Udomcharoensab, Palita; Buathong, Kittika; Lerkiatbundit, Sanguan

    2016-10-01

    Background Inappropriate use of antibiotic treatment for pharyngitis by community pharmacists is prevalent in developing countries. Little is known about how the pharmacists identify patients with bacterial pharyngitis. Objective To ascertain the appropriateness of diagnosis of streptococcal pharyngitis among Thai community pharmacists according to the Centor criteria and to identify factors related to antibiotic dispensing. Setting 1040 Thai community pharmacists. Method A cross-sectional survey of community pharmacists was conducted in November 2012 to March 2013. The self-administered questionnaires were mailed to 57 % of community pharmacists in the south of Thailand (n = 1040). The survey included questions on diagnosis of streptococcal pharyngitis, knowledge on pharyngitis, and attitudes and control beliefs regarding antibiotic dispensing. Main outcome measure The appropriateness of diagnosis of streptococcal pharyngitis according to the original and modified Centor criteria and determinants of antibiotic dispensing including demographic characteristics of pharmacists, knowledge on pharyngitis, and attitudes and control beliefs on antibiotic dispensing. Results Approximately 68 % completed the questionnaires (n = 703). Compared to the pharmacists who reported not dispensing antibiotics in the hypothetical case with common cold, those reported dispensing antibiotics were more likely to consider the following conditions-presence of cough, mild sore throat and patients with age >60 years as cues for diagnosis of streptococcal pharyngitis (p 5 years) [odds ratio (OR) 1.52; 95 % confidence interval (CI) 1.03-2.23], belief that antibiotics could shorten duration of pharyngitis (OR 1.48; 95 % CI 1.11-1.99), belief that antibiotics could prevent the complications (OR 1.44; 95 % CI 1.09-1.91) and belief that dispensing antibiotics could satisfy the patients (OR 1.31; 95 % CI 1.01-1.71). Nonetheless, antibiotic dispensing was negatively associated with

  12. 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.

  13. 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.

  14. Effects of meteorologic factors and schooling on the seasonality of group A streptococcal pharyngitis

    Science.gov (United States)

    Hervás, Daniel; Hervás-Masip, Juan; Ferrés, Laia; Ramírez, Antonio; Pérez, José L.; Hervás, Juan A.

    2016-05-01

    The objective of this study was to determine the seasonal pattern of group A streptococcal pharyngitis in children attended at a hospital emergency department in the Mediterranean island of Mallorca (Spain), and its association with meteorologic factors and schooling. We conducted a retrospective review of the medical records of children aged 1-15 years with a diagnosis of Streptococcus pyogenes pharyngitis between January 2006 and December 2011. The number of S. pyogenes pharyngitis was correlated to temperature, humidity, rainfall, atmospheric pressure, wind speed, solar radiation, and schooling, using regression and time series techniques. A total of 906 patients (median, 4 years old) with S. pyogenes pharyngitis, confirmed by throat culture, were attended during the study period. A seasonal pattern was observed with a peak activity in June and a minimum in September. Mean temperature, solar radiation, and school holidays were the best predicting variables ( R 2 = 0.68; p pyogenes activity increased with the decrease of mean temperature ( z = -2.4; p pyogenes pharyngitis had a clear seasonality predominating in springtime, and an association with mean temperature, solar radiation, and schooling was observed. The resulting model predicted 68 % of S. pyogenes pharyngitis.

  15. Measurement of lung airways in three dimensions using hyperpolarized helium-3 MRI

    Science.gov (United States)

    Peterson, Eric T; Dai, Jionghan; Holmes, James H; Fain, Sean B

    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 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 airway lumen diameter. The HPHe MRI method was validated with quantitative CT in an excised and desiccated porcine lung (linear regression R2 = 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 R2 value of 0.799 and slope = 0.768 over 309 airway segments). Feasibility for airway path analysis to areas of ventilation defect is also demonstrated. PMID:21521907