Trefoil factor-2 reverses airway remodeling changes in allergic airways disease.

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Royce, Simon G; Lim, Clarice; Muljadi, Ruth C; Samuel, Chrishan S; Ververis, Katherine; Karagiannis, Tom C; Giraud, Andrew S; Tang, Mimi L K

2013-01-01

Trefoil factor 2 (TFF2) is a small peptide with an important role in mucosal repair. TFF2 is up-regulated in asthma, suggesting a role in asthma pathogenesis. Given its known biological role in promoting epithelial repair, TFF2 might be expected to exert a protective function in limiting the progression of airway remodeling in asthma. The contribution of TFF2 to airway remodeling in asthma was investigated by examining the expression of TFF2 in the airway and lung, and evaluating the effects of recombinant TFF2 treatment on established airway remodeling in a murine model of chronic allergic airways disease (AAD). BALB/c mice were sensitized and challenged with ovalbumin (OVA) or saline for 9 weeks, whereas mice with established OVA-induced AAD were treated with TFF2 or vehicle control (intranasally for 14 d). Effects on airway remodeling, airway inflammation, and airway hyperresponsiveness were then assessed, whereas TFF2 expression was determined by immunohistochemistry. TFF2 expression was significantly increased in the airways of mice with AAD, compared with expression levels in control mice. TFF2 treatment resulted in reduced epithelial thickening, subepithelial collagen deposition, goblet-cell metaplasia, bronchial epithelium apoptosis, and airway hyperresponsiveness (all P < 0.05, versus vehicle control), but TFF2 treatment did not influence airway inflammation. The increased expression of endogenous TFF2 in response to chronic allergic inflammation is insufficient to prevent the progression of airway inflammation and remodeling in a murine model of chronic AAD. However, exogenous TFF2 treatment is effective in reversing aspects of established airway remodeling. TFF2 has potential as a novel treatment for airway remodeling in asthma.

Radioaerosol lung imaging in small airways disease

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Weiss, T; Dorow, P; Felix, R

1981-06-01

Aerosol inhalation lung imaging was performed in 35 asymptomatic smokers who have been selected on the basis of abnormal findings in small airways pulmonary function tests. Qualitative (image inspection) and quantitative (aerosol distribution index = ADI) analysis of the radioaerosol lung patterns was accomplished. Compared to healthy subjects as well as to patients with chronic obstructive lung disease significant differences of mean aerosol distribution homogeneity were observed. A characteristic type of abnormal aerosol pattern, indicating peripheral airways obstruction, was found in 71% of the patients with small airways disease.

Assessment of airway lesion in obstructive lung diseases by CT

International Nuclear Information System (INIS)

Niimi, Akio; Matsumoto, Hisako; Ueda, Tetsuya; Mishima, Michiaki

2002-01-01

Airway lesion in obstructive pulmonary diseases, such as asthma or chronic obstructive pulmonary disease (COPD), has recently been assessed quantitatively. Especially in asthma, wall thickening of central airways, and its relation to the severity of disease or airflow obstruction has been clarified. Pathophysiologic importance of peripheral airway lesion has also been highlighted by pathologic or physiologic studies. However, direct evaluation of peripheral airway lesion is beyond resolutional limitation of CT. To assess airway trapping, an indirect CT finding of peripheral airway disease, by quantitative and semiquantitative measures and compare them with clinical indices such as pulmonary function, airway responsiveness, or airway inflammation. Patients with stable asthma (n=20) were studied. HRCT at 3 levels of both lungs were scanned. Low attenuation area (LAA)% and mean lung density were quantitatively assessed by an automatic method. Distribution of mosaic pattern was visually scored semiquantitatively. LAA% and mean lung density at full expiratory phase correlated with the degree of airflow obstruction. Mosaic score at full inspiratory phase correlated with the severity of disease and airflow obstruction. Expiratory/inspiratory ratio of mean lung density was also associated with airway responsiveness or residual volume/total lung capacity (RV/TLC). These CT findings may be useful as markers of asthma pathophysiology. (author)

Protective effects of valproic acid against airway hyperresponsiveness and airway remodeling in a mouse model of allergic airways disease.

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Royce, Simon G; Dang, William; Ververis, Katherine; De Sampayo, Nishika; El-Osta, Assam; Tang, Mimi L K; Karagiannis, Tom C

2011-12-01

Airway remodeling and airway hyperresponsiveness are major aspects of asthma pathology that are not targeted optimally by existing anti-inflammatory drugs. Histone deacetylase inhibitors have a wide range of effects that may potentially abrogate aspects of remodeling. One such histone deacetylase inhibitor is valproic acid (2-propylvaleric acid). Valproic acid is used clinically as an anti-epileptic drug and is a potent inhibitor of class I histone deacetylases but also inhibits class II histone deacetylases. We used valproic acid as a molecular model of histone deacetylase inhibition in vivo in chronic allergic airways disease mice with airway remodeling and airway hyperresponsiveness. Wild-type Balb/c mice with allergic airways disease were treated with valproic acid or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and examination of lung tissue sections. Remodeling was assessed by morphometric analysis of histochemically stained slides and lung function was assessed by invasive plethysmography measurement of airway resistance. Valproic acid treatment did not affect inflammation parameters; however, valproic acid treatment resulted in reduced epithelial thickness as compared to vehicle treated mice (p < 0.01), reduced subepithelial collagen deposition (p < 0.05) and attenuated airway hyperresponsiveness (p < 0.05 and p < 0.01 for the two highest doses of methacholine, respectively). These findings show that treatment with valproic acid can reduce structural airway remodeling changes and hyperresponsiveness, providing further evidence for the potential use of histone deacetylase inhibitors for the treatment of asthma.

Alcohol and airways function in health and disease.

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Sisson, Joseph H

2007-08-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol- and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Aspergillus in chronic lung disease: Modeling what goes on in the airways.

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Takazono, Takahiro; Sheppard, Donald C

2017-01-01

Aspergillus species cause a range of respiratory diseases in humans. While immunocompromised patients are at risk for the development of invasive infection with these opportunistic molds, patients with underlying pulmonary disease can develop chronic airway infection with Aspergillus species. These conditions span a range of inflammatory and allergic diseases including Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, and severe asthma with fungal sensitization. Animal models are invaluable tools for the study of the molecular mechanism underlying the colonization of airways by Aspergillus and the host response to these non-invasive infections. In this review we summarize the state-of-the-art with respect to the available animal models of noninvasive and allergic Aspergillus airway disease; the key findings of host-pathogen interaction studies using these models; and the limitations and future directions that should guide the development and use of models for the study of these important pulmonary conditions. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Airway stents

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Keyes, Colleen

2018-01-01

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

Small airways disease: time for a revisit?

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Stockley JA

2017-08-01

Full Text Available James A Stockley,1 Brendan G Cooper,1 Robert A Stockley,2 Elizabeth Sapey3 1Department of Lung Function and Sleep, 2Department of Respiratory Medicine, University Hospital Birmingham, 3Institute of Inflammation and Ageing, Centre for Translational Inflammation Research, University of Birmingham, Edgbaston, Birmingham, UK Abstract: It is increasingly acknowledged that delays in the diagnosis of chronic inflammatory lung conditions have hampered our understanding of pathogenesis and thus our ability to design efficacious therapies. This is particularly true for COPD, where most patients are diagnosed with moderate-to-severe airflow obstruction and little is known about the inflammatory processes present in early disease. There is great interest in developing screening tests that can identify those most at risk of developing COPD before airflow obstruction has developed for the purpose of research and clinical care. Landmark pathology studies have suggested that damage to the small airways precedes the development of airflow obstruction and emphysema and, thus, presents an opportunity to identify those at risk of COPD. However, despite a number of physiological tests being available to assess small airways function, none have been adopted into routine care in COPD. The reasons that tests of small airways have not been utilized widely include variability in test results and a lack of validated reference ranges from which to compare results for some methodologies. Furthermore, population studies have not consistently demonstrated their ability to diagnose disease. However, the landscape may be changing. As the equipment that delivers tests of small airways become more widely available, reference ranges are emerging and newer methodologies specifically seek to address variability and difficulty in test performance. Moreover, there is evidence that while tests of small airways may not be helpful across the full range of established disease severity

Occupational upper airway disease: how work affects the nose

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Hox, V.; Steelant, B.; Fokkens, W.; Nemery, B.; Hellings, P. W.

2014-01-01

Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two well-characterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents

Critical Role of Airway Macrophages in Modulating Disease Severity during Influenza Virus Infection of Mice ▿

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Tate, Michelle D.; Pickett, Danielle L.; van Rooijen, Nico; Brooks, Andrew G.; Reading, Patrick C.

2010-01-01

Airway macrophages provide a first line of host defense against a range of airborne pathogens, including influenza virus. In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. Virus strain BJx109 (H3N2) infected macrophages with high efficiency and was associated with mild disease following intranasal infection of mice. In contrast, virus strain PR8 (H1N1) was poor in its ability to infect macrophages and highly virulent for mice. Depletion of airway macrophages by clodronate-loaded liposomes led to the development of severe viral pneumonia in BJx109-infected mice but did not modulate disease severity in PR8-infected mice. The severe disease observed in macrophage-depleted mice infected with BJx109 was associated with exacerbated virus replication in the airways, leading to severe airway inflammation, pulmonary edema, and vascular leakage, indicative of lung injury. Thymic atrophy, lymphopenia, and dysregulated cytokine and chemokine production were additional systemic manifestations associated with severe disease. Thus, airway macrophages play a critical role in limiting lung injury and associated disease caused by BJx109. Furthermore, the inability of PR8 to infect airway macrophages may be a critical factor contributing to its virulence for mice. PMID:20504924

Early cystic fibrosis lung disease: Role of airway surface dehydration and lessons from preventive rehydration therapies in mice.

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Mall, Marcus A; Graeber, Simon Y; Stahl, Mirjam; Zhou-Suckow, Zhe

2014-07-01

Cystic fibrosis (CF) lung disease starts in the first months of life and remains one of the most common fatal hereditary diseases. Early therapeutic interventions may provide an opportunity to prevent irreversible lung damage and improve outcome. Airway surface dehydration is a key disease mechanism in CF, however, its role in the in vivo pathogenesis and as therapeutic target in early lung disease remains poorly understood. Mice with airway-specific overexpression of the epithelial Na(+) channel (βENaC-Tg) recapitulate airway surface dehydration and phenocopy CF lung disease. Recent studies in neonatal βENaC-Tg mice demonstrated that airway surface dehydration produces early mucus plugging in the absence of mucus hypersecretion, which triggers airway inflammation, promotes bacterial infection and causes early mortality. Preventive rehydration therapy with hypertonic saline or amiloride effectively reduced mucus plugging and mortality in neonatal βENaC-Tg mice. These results support clinical testing of preventive/early rehydration strategies in infants and young children with CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of airways in computed tomography

DEFF Research Database (Denmark)

Petersen, Jens

Chronic Obstructive Pulmonary Disease (COPD) is major cause of death and disability world-wide. It affects lung function through destruction of lung tissue known as emphysema and inflammation of airways, leading to thickened airway walls and narrowed airway lumen. Computed Tomography (CT) imaging...

Neutralisation of interleukin-13 in mice prevents airway pathology caused by chronic exposure to house dust mite.

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Kate L Tomlinson

Full Text Available BACKGROUND: Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13 in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM. METHODOLOGY/PRINCIPAL FINDINGS: Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb administered subcutaneously (s.c.. Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR by invasive measurement of lung resistance (R(L and dynamic compliance (C(dyn. Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05 the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05 the increase in baseline R(L and the decrease in baseline C(dyn caused by chronic exposure to inhaled HDM. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.

Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

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Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

2016-11-01

Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Covered Bronchial Stent Insertion to Manage Airway Obstruction with Hemoptysis Caused by Lung Cancer

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Lee, Sae Ah; Kim, Do Hyeong [Dankook University College of Medicine, Dankook University Hospital, Cheonan (Korea, Republic of); Jen, Gyeong Sik [Bundang CHA General Hospital, CHA University, Seongnam (Korea, Republic of)

2012-07-15

Malignant airway obstruction and hemoptysis are common in lung cancer patients. Recently, airway stent is commonly used to preserve airway in malignant airway obstruction. Hemoptysis can be managed through various methods including conservative treatment, endobronchial tamponade, bronchoscopic intervention, embolization and surgery. In our case studies, we sought to investigate the effectiveness of airway stents for re-opening the airway as well as tamponade effects in four patients with malignant airway obstruction and bleeding caused by tumors or lymph node invasions.

Markers of Airway Remodeling in Bronchopulmonary Diseases

Directory of Open Access Journals (Sweden)

O.Ye. Chernyshova

2014-10-01

Full Text Available The article presents information about markers of airway remodeling in bronchopulmonary diseases. There is described the influence of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, collagen autoantibodies III type, endothelin-1 on the processes of morphological airway reconstruction as smooth muscle hypertrophy, enhanced neovascularization, epithelial cell hyperplasia, collagen deposition, compaction of the basal membrane, observed in bronchial asthma.

The airway microbiota in early cystic fibrosis lung disease.

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Frayman, Katherine B; Armstrong, David S; Grimwood, Keith; Ranganathan, Sarath C

2017-11-01

Infection plays a critical role in the pathogenesis of cystic fibrosis (CF) lung disease. Over the past two decades, the application of molecular and extended culture-based techniques to microbial analysis has changed our understanding of the lungs in both health and disease. CF lung disease is a polymicrobial disorder, with obligate and facultative anaerobes recovered alongside traditional pathogens in varying proportions, with some differences observed to correlate with disease stage. While healthy lungs are not sterile, differences between the lower airway microbiota of individuals with CF and disease-controls are already apparent in childhood. Understanding the evolution of the CF airway microbiota, and its relationship with clinical treatments and outcome at each disease stage, will improve our understanding of the pathogenesis of CF lung disease and potentially inform clinical management. This review summarizes current knowledge of the early development of the respiratory microbiota in healthy children and then discusses what is known about the airway microbiota in individuals with CF, including how it evolves over time and where future research priorities lie. © 2017 Wiley Periodicals, Inc.

Hypertrophic anterior cervical osteophytes causing dysphagia and airway obstruction.

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Lin, Harrison W; Quesnel, Alicia M; Holman, Allison S; Curry, William T; Rho, Michael B

2009-10-01

Hyperostosis of anterior cervical vertebral osteophytes can produce otolaryngological symptoms ranging from mild dysphagia, dysphonia, and foreign body sensation to severe food impaction and stridulous dyspnea. Airway compromise necessitating a tracheostomy is very rare. We discuss the case of an elderly man who presented with progressive dysphagia and a large hypopharyngeal mass as his initial manifestations of hypertrophic anterior cervical osteophytes. After a biopsy of the mass, the patient went into airway distress due to bilateral vocal fold fixation by the enlarging mass and consequently required a surgical airway. A combined team approach to the removal of the osteophytes successfully resolved his symptoms. The clinical, diagnostic, radiologic, and therapeutic principles involved in this case are presented and discussed. The recognition of hypertrophic osteophytes as a potential cause of common otolaryngological symptoms in the elderly population is paramount, as these symptoms can rapidly progress and lead to life-threatening airway obstruction. Medical and surgical interventions can be employed for the treatment of hypertrophic anterior cervical osteophytes, and they often result in favorable outcomes.

Prolonged ozone exposure in an allergic airway disease model: Adaptation of airway responsiveness and airway remodeling

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Park Chang-Soo

2006-02-01

Full Text Available Abstract Background Short-term exposure to high concentrations of ozone has been shown to increase airway hyper-responsiveness (AHR. Because the changes in AHR and airway inflammation and structure after chronic ozone exposure need to be determined, the goal of this study was to investigate these effects in a murine model of allergic airway disease. Methods We exposed BALB/c mice to 2 ppm ozone for 4, 8, and 12 weeks. We measured the enhanced pause (Penh to methacholine and performed cell differentials in bronchoalveolar lavage fluid. We quantified the levels of IL-4 and IFN-γ in the supernatants of the bronchoalveolar lavage fluids using enzyme immunoassays, and examined the airway architecture under light and electron microscopy. Results The groups exposed to ozone for 4, 8, and 12 weeks demonstrated decreased Penh at methacholine concentrations of 12.5, 25, and 50 mg/ml, with a dose-response curve to the right of that for the filtered-air group. Neutrophils and eosinophils increased in the group exposed to ozone for 4 weeks compared to those in the filtered-air group. The ratio of IL-4 to INF-γ increased significantly after exposure to ozone for 8 and 12 weeks compared to the ratio for the filtered-air group. The numbers of goblet cells, myofibroblasts, and smooth muscle cells showed time-dependent increases in lung tissue sections from the groups exposed to ozone for 4, 8, and 12 weeks. Conclusion These findings demonstrate that the increase in AHR associated with the allergic airway does not persist during chronic ozone exposure, indicating that airway remodeling and adaptation following repeated exposure to air pollutants can provide protection against AHR.

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

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Van de Moortele, Tristan

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

The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

International Nuclear Information System (INIS)

Yahaba, Misuzu; Kawata, Naoko; Iesato, Ken; Matsuura, Yukiko; Sugiura, Toshihiko; Kasai, Hajime; Sakurai, Yoriko; Terada, Jiro; Sakao, Seiichiro; Tada, Yuji; Tanabe, Nobuhiro; Tatsumi, Koichiro

2014-01-01

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. Objective: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Methods: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. Results: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV 1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. Conclusions: A significant correlation exists between airway parameters and FEV 1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD

The effects of emphysema on airway disease: Correlations between multi-detector CT and pulmonary function tests in smokers

Energy Technology Data Exchange (ETDEWEB)

Yahaba, Misuzu, E-mail: mis_misuzu@yahoo.co.jp; Kawata, Naoko, E-mail: chumito_03@yahoo.co.jp; Iesato, Ken, E-mail: iesato_k@yahoo.co.jp; Matsuura, Yukiko, E-mail: matsuyuki_future@yahoo.co.jp; Sugiura, Toshihiko, E-mail: sugiura@js3.so-net.ne.jp; Kasai, Hajime, E-mail: daikasai6075@yahoo.co.jp; Sakurai, Yoriko, E-mail: yoliri@nifty.com; Terada, Jiro, E-mail: jirotera@chiba-u.jp; Sakao, Seiichiro, E-mail: sakao@faculty.chiba-u.jp; Tada, Yuji, E-mail: ytada@faculty.chiba-u.jp; Tanabe, Nobuhiro, E-mail: ntanabe@faculty.chiba-u.jp; Tatsumi, Koichiro, E-mail: tatsumi@faculty.chiba-u.jp

2014-06-15

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. Objective: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. Methods: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. Results: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV{sub 1.} No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. Conclusions: A significant correlation exists between airway parameters and FEV{sub 1} in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

Specific immune responses against airway epithelial cells in a transgenic mouse-trachea transplantation model for obliterative airway disease

NARCIS (Netherlands)

Qu, N; de Haan, A; Harmsen, MC; Kroese, FGM; de Leij, LFMH; Prop, J

2003-01-01

Background. Immune injury to airway epithelium is suggested to play a central role in the pathogenesis of obliterative bronchiolitis (OB) after clinical lung transplantation. In several studies, a rejection model of murine trachea transplants is used, resulting in obliterative airway disease (OAD)

Quantitative computed tomography measurements to evaluate airway disease in chronic obstructive pulmonary disease: Relationship to physiological measurements, clinical index and visual assessment of airway disease

International Nuclear Information System (INIS)

Nambu, Atsushi; Zach, Jordan; Schroeder, Joyce; Jin, Gongyoung; Kim, Song Soo; Kim, Yu-IL; Schnell, Christina; Bowler, Russell; Lynch, David A.

2016-01-01

Purpose: To correlate currently available quantitative CT measurements for airway disease with physiological indices and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in patients with chronic obstructive pulmonary disease (COPD). Materials and methods: This study was approved by our institutional review board (IRB number 2778). Written informed consent was obtained from all subjects. The subjects included 188 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had physiological measurements for the evaluation of airflow limitation, including FEF25-75%, airway resistance (Raw), and specific airway conductance (sGaw). The BODE index was used as the index of clinical symptoms. Quantitative CT measures included % low attenuation areas [% voxels ≤ 950 Hounsfield unit (HU) on inspiratory CT, %LAA −950ins ], percent gas trapping (% voxels ≤ −856 HU on expiratory CT, %LAA −856exp ), relative inspiratory to expiratory volume change of voxels with attenuation values from −856 to −950 HU [Relative Volume Change (RVC) −856 to −950 ], expiratory to inspiratory ratio of mean lung density (E/I-ratio MLD ), Pi10, and airway wall thickness (WT), luminal diameter (LD) and airway wall area percent (WA%) in the segmental, subsegmental and subsubsegmental bronchi on inspiratory CT. Correlation coefficients were calculated between the QCT measurements and physiological measurements in all subjects and in the subjects with mild emphysema (%LAA −950ins <10%). Univariate and multiple variable analysis for the BODE index were also performed. Adjustments were made for age, gender, smoking pack years, FEF25-75%, Raw, and sGaw. Results: Quantitative CT measurements had significant correlations with physiological indices. Among them, E/I-ratio MLD had the strongest correlations with FEF25-75% (r = −0.648, <0.001) and sGaw (r = −0.624, <0.001) while in the subjects with

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Directory of Open Access Journals (Sweden)

Deepak A. Deshpande

2018-01-01

Full Text Available Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+ signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3 and CD38-cyclic ADP-ribose (CD38/cADPR are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

Science.gov (United States)

Deshpande, Deepak A.; Guedes, Alonso G. P.; Graeff, Richard; Dogan, Soner; Subramanian, Subbaya; Walseth, Timothy F.

2018-01-01

Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed. PMID:29576747

Carbon Particles in Airway Macrophage as a Surrogate Marker in the Early Detection of Lung Diseases

Directory of Open Access Journals (Sweden)

NK Kalappanavar

2012-03-01

Full Text Available Background: It has been shown that inhalation of carbonaceous particulate matter may impair lung function in children. Objective: Using the carbon content of airway macrophages as a marker of individual exposure to particulate matter derived from fossil fuel, we sought direct evidence for this association. Methods: 300 children from puffed rice industrial areas and 300 children from population living in green zone were selected randomly. Airway macrophages were obtained from healthy children through sputum induction, and the grading of ultrafine carbon particles in airway macrophages was measured. Pulmonary function was also measured by spirometry. Results: Pulmonary function tests showed that in industrial area 42.6% and 20.3% of children had moderate obstructive airway disease and restrictive airway disease, respectively. In the green zone area, 7% of children had obstructive airway disease and 6% had restrictive airway disease. Evaluation of airway macrophages for ultrafine carbon particles revealed that in industrial area there were ultrafine carbon particles of grade 2 in 23% of subjects and grade 3 in 8.33% of individuals with obstructive airway disease. In the green zone area, the rates were 1.67% and 0.7%, respectively. Conclusion: The study provides a first evidence of the strong association between air pollution and development of airway diseases. Carbon particles in the sputum can be used as a marker for air pollution.

Airway inflammation in chronic obstructive pulmonary disease (COPD): a true paradox.

Science.gov (United States)

Eapen, Mathew Suji; Myers, Stephen; Walters, Eugene Haydn; Sohal, Sukhwinder Singh

2017-10-01

Chronic obstructive pulmonary disease (COPD) is primarily an airway condition, which mainly affects cigarette smokers and presents with shortness of breath that is progressive and poorly reversible. In COPD research, there has been a long held belief that airway disease progression is due to inflammation. Although this may be true in the airway lumen with innate immunity activated by the effect of smoke or secondary to infection, the accurate picture of inflammatory cells in the airway wall, where the pathophysiological COPD remodeling occurs, is uncertain and debatable. Areas covered: The current review provides a comprehensive literature survey of the changes in the main inflammatory cells in human COPD patients and focuses on contrarian views that affect the prevailing dogma on inflammation. The review also delves into the role of oxidative stress and inflammasomes in modulating the immune response in COPD. Further, the effects of inflammation in affecting the epithelium, fibroblasts, and airway remodeling are discussed. Expert commentary: Inflammation as a driving force for airway wall damage and remodelling in early COPD is at the very least 'oversimplified' and is likely to be misleading. This has serious implications for rational thinking about the illness, including pathogenesis and designing therapy.

Treatable traits: toward precision medicine of chronic airway diseases

NARCIS (Netherlands)

Agusti, Alvar; Bel, Elisabeth; Thomas, Mike; Vogelmeier, Claus; Brusselle, Guy; Holgate, Stephen; Humbert, Marc; Jones, Paul; Gibson, Peter G.; Vestbo, Jørgen; Beasley, Richard; Pavord, Ian D.

2016-01-01

Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms (i.e. endotypes), and present similar clinical, functional,

Precision medicine in airway diseases: moving to clinical practice

NARCIS (Netherlands)

Agustí, Alvar; Bafadhel, Mona; Beasley, Richard; Bel, Elisabeth H.; Faner, Rosa; Gibson, Peter G.; Louis, Renaud; McDonald, Vanessa M.; Sterk, Peter J.; Thomas, Mike; Vogelmeier, Claus; Pavord, Ian D.

2017-01-01

On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often

Quantitative computed tomography measurements to evaluate airway disease in chronic obstructive pulmonary disease: Relationship to physiological measurements, clinical index and visual assessment of airway disease

Energy Technology Data Exchange (ETDEWEB)

Nambu, Atsushi, E-mail: nambu-a@gray.plala.or.jp [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States); Zach, Jordan, E-mail: ZachJ@NJHealth.org [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States); Schroeder, Joyce, E-mail: Joyce.schroeder@stanfordalumni.org [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States); Jin, Gongyoung, E-mail: gyjin@chonbuk.ac.kr [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States); Kim, Song Soo, E-mail: haneul88@hanmail.net [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States); Kim, Yu-IL, E-mail: kyionly@chonnam.ac.kr [Department of Medicine, National Jewish Health, Denver, CO (United States); Schnell, Christina, E-mail: SchnellC@NJHealth.org [Department of Medicine, National Jewish Health, Denver, CO (United States); Bowler, Russell, E-mail: BowlerR@NJHealth.org [Division of Pulmonary Medicine, Department of Medicine, National Jewish Health (United States); Lynch, David A., E-mail: LynchD@NJHealth.org [Department of Radiology, National Jewish Health, 1400 Jackson Street, Denver, CO, 80206 (United States)

2016-11-15

Purpose: To correlate currently available quantitative CT measurements for airway disease with physiological indices and the body-mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index in patients with chronic obstructive pulmonary disease (COPD). Materials and methods: This study was approved by our institutional review board (IRB number 2778). Written informed consent was obtained from all subjects. The subjects included 188 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had physiological measurements for the evaluation of airflow limitation, including FEF25-75%, airway resistance (Raw), and specific airway conductance (sGaw). The BODE index was used as the index of clinical symptoms. Quantitative CT measures included % low attenuation areas [% voxels ≤ 950 Hounsfield unit (HU) on inspiratory CT, %LAA{sub −950ins}], percent gas trapping (% voxels ≤ −856 HU on expiratory CT, %LAA {sub −856exp}), relative inspiratory to expiratory volume change of voxels with attenuation values from −856 to −950 HU [Relative Volume Change (RVC){sub −856} {sub to} {sub −950}], expiratory to inspiratory ratio of mean lung density (E/I-ratio {sub MLD}), Pi10, and airway wall thickness (WT), luminal diameter (LD) and airway wall area percent (WA%) in the segmental, subsegmental and subsubsegmental bronchi on inspiratory CT. Correlation coefficients were calculated between the QCT measurements and physiological measurements in all subjects and in the subjects with mild emphysema (%LAA{sub −950ins} <10%). Univariate and multiple variable analysis for the BODE index were also performed. Adjustments were made for age, gender, smoking pack years, FEF25-75%, Raw, and sGaw. Results: Quantitative CT measurements had significant correlations with physiological indices. Among them, E/I-ratio {sub MLD} had the strongest correlations with FEF25-75% (r = −0.648, <0.001) and sGaw (r = −0

Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease.

Science.gov (United States)

Cruz, E A; Reuter, S; Martin, H; Dehzad, N; Muzitano, M F; Costa, S S; Rossi-Bergmann, B; Buhl, R; Stassen, M; Taube, C

2012-01-15

Aqueous extract of Kalanchoe pinnata (Kp) have been found effective in models to reduce acute anaphylactic reactions. In the present study, we investigate the effect of Kp and the flavonoid quercetin (QE) and quercitrin (QI) on mast cell activation in vitro and in a model of allergic airway disease in vivo. Treatment with Kp and QE in vitro inhibited degranulation and cytokine production of bone marrow-derived mast cells following IgE/FcɛRI crosslinking, whereas treatment with QI had no effect. Similarly, in vivo treatment with Kp and QE decreased development of airway hyperresponsiveness, airway inflammation, goblet cell metaplasia and production of IL-5, IL-13 and TNF. In contrast, treatment with QI had no effect on these parameters. These findings demonstrate that treatment with Kp or QE is effective in treatment of allergic airway disease, providing new insights to the immunomodulatory functions of this plant. Copyright © 2011 Elsevier GmbH. All rights reserved.

The treatment of complex airway diseases with inverted Y-shaped self-expandable metal stent

International Nuclear Information System (INIS)

Li Jianming; Jia Guangzhi

2011-01-01

Objective: To investigate the application and therapeutic effects of inverted Y-shaped self-expandable metal airway stent in treating complex airway diseases (stenosis or fistula). Methods: According to the distinctive anatomic structure and the pathological changes of complex airway stenosis or fistula, the inverted y-shaped self-expandable metal airway stent was designed. Under fluoroscopic monitoring, a total of 12 inverted Y-shaped self-expandable metal stents were implanted in 12 patients with complex airway diseases. Results: Stent placement in the trachea-bronchial tree was technically successful in all patients. After the operation, the symptom of dyspnea was immediately relieved and the bucking following food intake disappeared. The general physical condition and living quality were much improved in all patients. Conclusion: The use of inverted Y-shaped self-expandable metal airway stent for the management of complex airway stenosis involving the tracheal carina was a simple and safe procedure and it has satisfactory short-term clinical results. (authors)

Gender disparity of changes in heart rate during the six-minute walk test among patients with chronic obstructive airway disease

OpenAIRE

Esmaeil Alibakhshi; Luis Lores Obradors; Raffaele Fiorillo; Mostafa Ghaneii; Ali Qazvini

2017-01-01

Background Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide. Clarify; COPD is the fifth leading cause of death and disease burden globally. Aims The purpose of this study is to compare the gender disparity of changes in heart rate during 6-minute walk test (6MWT) among patients with chronic obstructive airway disease (COPD). We also aimed to assess the relationship between change in heart rate and body mas...

Relation between small airways disease and parenchymal destruction in surgical lung specimens.

Science.gov (United States)

Willems, L N; Kramps, J A; Stijnen, T; Sterk, P J; Weening, J J; Dijkman, J H

1990-01-01

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema. PMID:2315880

European symposium on precision medicine in allergy and airways diseases

DEFF Research Database (Denmark)

Muraro, A; Fokkens, W J; Pietikainen, S

2015-01-01

David Borrelli and with active participation of the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA) and the Respiratory....... This report summarizes the key messages delivered during the symposium by the speakers, including the EU Commissioner for Health and Food Safety Vitenys Andriukaitis. The Commissioner underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient...... the epidemic of Allergy and Asthma in Europe. The socio-economic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic non-communicable diseases in the EU. Despite the fact that 30% of the total European population is nowadays...

Do expandable metallic airway stents have a role in the management of patients with benign tracheobronchial disease?

Science.gov (United States)

Madden, Brendan P; Loke, Tuck-Kay; Sheth, Abhijat C

2006-07-01

With increasing availability many centers are deploying expandable metallic stents to manage patients with diverse endobronchial disorders. Although these devices have an important role in malignant disease their usefulness in benign large airway disorders is less defined. Between 1997 and 2005, 31 patients aged 34 to 83 years with benign large airway compromise secondary to tracheomalacia (n = 7), posttracheostomy stricture (n = 8), posttracheostomy rupture (n = 2), postpneumonectomy bronchopleural fistula (n = 2), stricture after lung transplantation (n = 3), lobectomy, tuberculosis, traumatic injury to right main bronchus (n = 1 patient each), and external compression of the airway secondary to achalasia, multinodular goiter, aortic aneurysm, right brachiocephalic artery aneurysm, right interrupted aortic arch, and dissecting aneurysm (n = 1 patient each) who were medically unfit for formal surgical intervention were treated by Ultraflex stent deployment. The range of follow-up was 1 week to 96 months. Stents were deployed under anesthesia using rigid bronchoscopy. Complications included granulation tissue formation (n = 11) treated with Nd: YAG laser ablation, stent migration (n = 1; stent removed, another deployed), metal fatigue (n = 1), stent removal (n = 1), mucus plugging (n = 2), and halitosis (n = 6) difficult to treat despite antibiotics. Thirteen patients died of unrelated causes between 1 week and 15 months after stent deployment. Endobronchial metallic stents should be considered only for selected patients with large airway compromise secondary to benign airway diseases for whom other medical comorbidities contraindicate formal airway surgery. Once deployed, they are difficult to remove, are associated with significant complications, and require prospective bronchoscopic surveillance and often further therapeutic intervention.

Early sensitisation and development of allergic airway disease - risk factors and predictors

DEFF Research Database (Denmark)

Halken, Susanne

2003-01-01

The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first...... development of allergic disease at birth. Early sensitisation, cow's milk allergy and atopic eczema are predictors for later development of allergic airway disease. Exposure to indoor allergens, especially house dust mite allergens, is a risk factor for sensitisation and development of asthma later...

Chronic Lymphocytic Leukemia as an Unusual Cause of Rapid Airway Compromise

Directory of Open Access Journals (Sweden)

Adrian R. Bersabe

2017-01-01

Full Text Available Chronic Lymphocytic Leukemia (CLL is the most prevalent form of non-Hodgkin’s lymphoma (NHL in Western countries predominantly affecting adults over the age of 65. CLL is commonly indolent in nature but can present locally and aggressively at extranodal sites. Although CLL may commonly present with cervical lymphadenopathy, manifestation in nonlymphoid regions of the head and neck is not well described. CLL causing upper airway obstruction is even more uncommon. We describe a case of a patient with known history of CLL and stable lymphocytosis that developed an enlarging lymphoid base of tongue (BOT mass resulting in rapid airway compromise.

Hereditary and microbiological factors influencing the airway immunological profile of neonates

DEFF Research Database (Denmark)

Følsgaard, Nilofar

2012-01-01

is well-recognized, with estimated heritability as high as 60% in asthma. Atopic hereditary disease linkage in the offspring seems stronger for maternal than paternal atopic disease. But it is not known how parental atopic disease may affect early immunity in the target organ, the airways. COPSAC has...... mucosa. There was no paternal linkage to the mucosal immune response pattern, suggesting maternal programming of the fetus or neonate is causing an aberrant local airway immune profile in the newborn child. Furthermore our results suggest an association between maternal atopic disease and the expression...... recently reported an association between abnormal bacterial colonization with M. catarrhalis, S. pneumoniae, H. influenzae of the upper airways of neonates and later development of asthma. This led to the hypothesis that the interaction between genetics and this microbiome in very early life may cause...

Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Patel, Bipen D; Coxson, Harvey O; Pillai, Sreekumar G

2008-01-01

RATIONALE: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. OBJECTIVES: To determine whether airway wall thickening and emphysema (1...... to airflow obstruction in COPD. These phenotypes show independent aggregation within families of individuals with COPD, suggesting that different genetic factors influence these disease processes....... the severity of airway wall thickening and emphysema. MEASUREMENTS AND MAIN RESULTS: A total of 3,096 individuals were recruited to the study, of whom 1,159 (519 probands and 640 siblings) had technically adequate high-resolution computed tomography scans without significant non-COPD-related thoracic disease...

European symposium on precision medicine in allergy and airways diseases

DEFF Research Database (Denmark)

Muraro, A; Fokkens, W J; Pietikainen, S

2015-01-01

suffering from allergies and asthma, more than half of these patients are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach in medicine, embracing 4 key features: personalized care based on molecular, immunologic and functional endotyping of the disease......On 14 October 2015, the European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP......, with participation of the patient in the decision making process of therapeutic actions, and taking into account predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice may help to achieve the arrest of the Epidemic of Allergies and Chronic Airways Diseases...

The role of anaerobic bacteria in the cystic fibrosis airway.

Science.gov (United States)

Sherrard, Laura J; Bell, Scott C; Tunney, Michael M

2016-11-01

Anaerobic bacteria are not only normal commensals, but are also considered opportunistic pathogens and have been identified as persistent members of the lower airway community in people with cystic fibrosis of all ages and stages of disease. Currently, the role of anaerobic bacteria in cystic fibrosis lower airway disease is not well understood. Therefore, this review describes the recent studies relating to the potential pathophysiological role(s) of anaerobes within the cystic fibrosis lungs. The most frequently identified anaerobic bacteria in the lower airways are common to both cystic fibrosis and healthy lungs. Studies have shown that in cystic fibrosis, the relative abundance of anaerobes fluctuates in the lower airways with reduced lung function and increased inflammation associated with a decreased anaerobic load. However, anaerobes found within the lower airways also produce virulence factors, may cause a host inflammatory response and interact synergistically with recognized pathogens. Anaerobic bacteria are potentially members of the airway microbiota in health but could also contribute to the pathogenesis of lower airway disease in cystic fibrosis via both direct and indirect mechanisms. A personalized treatment strategy that maintains a normal microbial community may be possible in the future.

High resolution CT in obstructive and air-ways lung disease

Energy Technology Data Exchange (ETDEWEB)

Webb, W R [California Univ., San Francisco, CA (United States). Dept. of Radiology

1996-12-31

The topics briefly discussed i.e. emphysema, its diagnosis, bronchiectasis etc. HRTC (high resolution computerized tomography) in diagnosing both disease and small airways abnormalities also discussed. (33 refs.).

High resolution CT in obstructive and air-ways lung disease

International Nuclear Information System (INIS)

Webb, W.R.

1995-01-01

The topics briefly discussed i.e. emphysema, its diagnosis, bronchiectasis etc. HRTC (high resolution computerized tomography) in diagnosing both disease and small airways abnormalities also discussed. (33 refs.)

Occupational rhinitis and occupational asthma; one airway two diseases?

International Nuclear Information System (INIS)

Seed, M J; Gittins, M; De Vocht, F; Agius, R M.

2009-01-01

The concept of 'one airway, one disease' refers to the frequent comorbidity of asthma and rhinitis. However, only limited research has been done on this association for the diverse range of occupational respiratory sensitisers. The relative frequency of rhinitis was determined for the 15 respiratory sensitisers reported to cause at least 10 cases of rhinitis or asthma to The Health and Occupation Reporting (THOR) network between 1997 and 2006. Of 1408 cases, 1190 were sole diagnoses of asthma, 138 sole diagnoses of rhinitis and in 80 cases asthma coexisted with rhinitis. The six sensitisers for which rhinitis featured in over 15% of cases were all particulates and known to cause release of mast cell mediators, either directly or through IgE antibodies. Four of the other nine sensitisers often exist as vapours and only two have been consistently associated with IgE-mediated disease mechanisms. Particle size did not appear to correlate with the relative frequency of rhinitis. Despite its limitations this study would support the hypothesis that there are at least two mechanistic categories of respiratory sensitisation with rhinitis being relatively more common where the mechanism is IgE-mediated. Particulate nature may be another important factor to consider in future studies.

Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

DEFF Research Database (Denmark)

Barfod, Kenneth Klingenberg; Roggenbuck, Michael; Al-Shuweli, Suzan

2017-01-01

Background SP-D is an important host defense lectin in innate immunity and SP-D deficient mice show several abnormal immune effects and are susceptible to allergen-induced airway disease. At the same time, host microbiome interactions play an important role in the development of allergic airway...... disease, and alterations to gut microbiota have been linked to airway disease through the gut-lung axis. Currently, it is unknown if the genotype (Sftpd-/- or Sftpd+/+) of the standard SP-D mouse model can affect the host microbiota to such an degree that it would overcome the cohousing effect...... on microbiota and interfere with the interpretation of immunological data from the model. Generally, little is known about the effect of the SP-D protein in itself and in combination with airway disease on the microbiota. In this study, we tested the hypothesis that microbiome composition would change...

The involvement of glycosaminoglycans in airway disease associated with cystic fibrosis.

LENUS (Irish Health Repository)

Reeves, Emer P

2012-02-01

Individuals with cystic fibrosis (CF) present with severe airway destruction and extensive bronchiectasis. It has been assumed that these structural airway changes have occurred secondary to infection and inflammation, but recent studies suggest that glycosaminoglycan (GAG) remodelling may be an important independent parallel process. Evidence is accumulating that not only the concentration, but also sulphation of GAGs is markedly increased in CF bronchial cells and tissues. Increased expression of GAGs and, in particular, heparan sulphate, has been linked to a sustained inflammatory response and neutrophil recruitment to the CF airways. This present review discusses the biological role of GAGs in the lung, as well as their involvement in CF respiratory disease, and their potential as therapeutic targets.

Air Pollution and Allergic Airway Diseases: Social Determinantsand Sustainability in the Control and Prevention.

Science.gov (United States)

Paramesh, H

2018-04-01

Air pollution, global warming and climate change are the major contributing factors in causing the increase prevalence of allergic airway diseases like asthma and allergic rhinitis and they will be the defining issues for health system in the twenty-first century. Asthma is an early onset non-communicable environmental disease with global epidemic and contributes a greatest psycho socio economic burden. Nearly 8 million global deaths are from air pollution. Over one billion population are the sufferers during 2015 and will increase to 4 billion by 2050. Air pollution not only triggers the asthma episodes but also changes the genetic pattern in initiating the disease process. Over the years our concept of management of allergic airway disease has changed from control of symptoms to prevention of the disease. To achieve this we need positive development on clean air policies with standard norms, tracking progress, monitoring and evaluation, partnership and conventions with local and global authorities. We do have challenges to overcome like rapid urbanization, lack of multisectorial policy making, lack of finance for research and development and lack of monitoring exposure to health burden from air pollution. We need to prioritize our strategy by sustainable, safe, human settlement, cities, sustainable energy, industrialization, and research. The measures to be adopted are highlighted in this review article. With effective measures by all stake holders we can reduce air pollution and prevent the global warming by 2030, along with 194 countries as adopted by WHO in May 2015.

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

Energy Technology Data Exchange (ETDEWEB)

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

1998-07-01

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

A passive quantitative measurement of airway resistance using depth data.

Science.gov (United States)

Ostadabbas, Sarah; Bulach, Christoph; Ku, David N; Anderson, Larry J; Ghovanloo, Maysam

2014-01-01

The Respiratory Syncytial Virus (RSV) is the most common cause of serious lower respiratory tract infections in infants and young children. RSV often causes increased airway resistance, clinically detected as wheezing by chest auscultation. In this disease, expiratory flows are significantly reduced due to the high resistance in patient's airway passages. A quantitative method for measuring resistance can have a great benefit to diagnosis and management of children with RSV infections as well as with other lung diseases. Airway resistance is defined as the lung pressure divided by the airflow. In this paper, we propose a method to quantify resistance through a simple, non-contact measurement of chest volume that can act as a surrogate measure of the lung pressure and volumetric airflow. We used depth data collected by a Microsoft Kinect camera for the measurement of the lung volume over time. In our experimentation, breathing through a number of plastic straws induced different airway resistances. For a standard spirometry test, our volume/flow estimation using Kinect showed strong correlation with the flow data collected by a commercially-available spirometer (five subjects, each performing 20 breathing trials, correlation coefficient = 0.88, with 95% confidence interval). As the number of straws decreased, emulating a higher airway obstruction, our algorithm was sufficient to distinguish between several levels of airway resistance.

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease : Role of Cigarette Smoke Exposure

NARCIS (Netherlands)

Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S.; Heijink, Irene H.

The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are

Epiglottic abscess causing acute airway obstruction in an adult

International Nuclear Information System (INIS)

Vasileiadis, I.; Kapetanakis, S.; Vasileiadis, D.; Petousis, A.

2013-01-01

Acute epiglottitis is an acute inflammation in the supraglottic region of the oropharynx which is a potentially life-threatening condition leading to rapid upper airway obstruction. An infrequent sequel of acute epiglottitis is the epiglottic abscess. Less than 50 cases have been reported in the international literature and even less are the cases that acute surgical intervention was necessary to secure the airway. We report a young man with sudden onset of odynophagia, dysphonia and dyspnea and rapidly progression of upper airway obstruction. Clinical examination with fiberoptic nasopharyngolaryngoscope in emergency department demonstrated an epiglottic abscess. An urgent tracheostomy was performed in order to secure patient's airway and afterward, the patient underwent direct laryngoscopy and drainage of abscess and intravenous antibiotics were administrated. The diagnosis of epiglottic abscess should be considered in adult patients with odynophagia and dysphonia. Principles of treatment include aggressive airway management, surgical drainage of abscess and intravenous antibiotics. (author)

Chronic airway obstruction in children. Most common causes, diagnosis and Surgical and Endoscopic Treatment

Directory of Open Access Journals (Sweden)

Ana Isabel NAVAZO-EGUÍA

2018-03-01

Full Text Available Introduction: Obstructive airway pathology in children may be congenital or acquired. Fortunately, it is a rare condition, but in most cases, it implies a diagnostic and therapeutic challenge. Endoscopic techniques have experienced in the last years a breakthrough in the treatment of these lesions, but open surgery still plays an important role. Objective: Our objective was to review the most frequent causes of obstruction of the central airway in the child, their diagnostic and current treatment status. Conclusions: Obstructive airway pathology in children requires immediate stabilization, detailed assessment, meticulous planning and individualized treatment. Management of patients with airway obstruction requires a close cooperation between specialists organized in multidisciplinary teams, whose main objective is the diagnosis and timely resolution of the various congenital malformations and acquired lesions that affect the larynx, trachea and bronchi. In many cases the decision of the treatment of choice is not easy. Selection of the most suitable treatment depends on the patient’s clinical situation and the anatomic type of stenosis. The surgeon must master all available techniques, to solve each specific situation.

Acute effects of short term use of e-cigarettes on airways physiology and respiratory symptoms in smokers with and without airways obstructive diseases and in healthy non smokers

OpenAIRE

Anastasios Palamidas; Stamatoula Tsikrika; Paraskevi A. Katsaounou; Sofia Vakali; Sofia-Antiopi Gennimata; George kaltsakas; Christina Gratziou; Nikolaos Koulouris

2017-01-01

Introduction Although the use of e-cigarettes is increasing worldwide, their short and long-term effects remain undefined. We aimed to study the acute effect of short-term use of e-cigarettes containing nicotine on lung function and respiratory symptoms in smokers with airways obstructive disease (COPD, asthma), “healthy” smokers, and healthy never smokers. Methods Respiratory symptoms, vital signs, exhaled NO, airways temperature, and airways resistance (Raw), specific airway condu...

Cordyceps sinensis inhibits airway remodeling in rats with chronic obstructive pulmonary disease.

Science.gov (United States)

Yang, Lei; Jiao, Xingai; Wu, Jinxiang; Zhao, Jiping; Liu, Tian; Xu, Jianfeng; Ma, Xiaohui; Cao, Liuzao; Liu, Lin; Liu, Yahui; Chi, Jingyu; Zou, Minfang; Li, Shuo; Xu, Jiawei; Dong, Liang

2018-03-01

Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor-α, interleukin-8 and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α-smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)-Smad2, p-Smad3, TGF-β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.

Raising awareness of upper airway diseases: Overview of management and prevention strategies

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De-yun WANG

2017-11-01

Full Text Available The nose together with the paranasal sinuses is the main part of the upper airway, which is lined with pseudostratified columnar ciliated epithelium. There are several important physiological functions such as conditioning and filtration of the inspired air and the provision of end organ for the sense of smell. Besides the nose also fulfills a physical and immunological barrier as the nasal epithelium is the first site of interaction between the host tissue and foreign invaders, such as viruses, bacteria, fungi, allergens, and harmful particulates. Hence, nasal diseases such as rhinitis (allergic and infectious and rhinosinusitis are the most common health problems worldwide, affecting millions of people of all ages. In the past 10 to 20 years, our understanding of the immuno-pathophysiological mechanisms underlying the common nasal diseases has been significantly enhanced by in vivo and in vitro studies. This allows the development of novel therapeutic strategies designed to improve the physiological and immune defense functions of the nose, as well as for other common airway diseases. Since the dynamically external changes of atmosphere, environment (pollution and susceptible population, we are now facing some of new features on epidemiology and the types of upper airway diseases that require us to in-deep study the diseases through basic and clinical researches, so as to further understand the prevention, diagnosis and treatment of the diseases. DOI: 10.118555/j.issn.0577-7402.2017.10.01

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 ...

Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease.

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Silva, Karla Kristine Dames da; Faria, Alvaro Camilo Dias; Lopes, Agnaldo José; Melo, Pedro Lopes de

2015-07-01

Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm) as well as values for the inspiration (Zi) and expiration cycles (Ze) at the beginning of inspiration (Zbi) and expiration (Zbe), respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi) and the respiratory cycle dependence (ΔZrs=Ze-Zi) were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01888705. Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=-0.65, pdisease patients presented significant expiratory-inspiratory differences (p90%). We conclude the following: (1) chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2) this increase is proportional to airway obstruction, and (3) the within-breath forced oscillation technique may provide novel parameters that facilitate the diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.

Within-breath respiratory impedance and airway obstruction in patients with chronic obstructive pulmonary disease

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Karla Kristine Dames da Silva

2015-07-01

Full Text Available OBJECTIVE: Recent work has suggested that within-breath respiratory impedance measurements performed using the forced oscillation technique may help to noninvasively evaluate respiratory mechanics. We investigated the influence of airway obstruction on the within-breath forced oscillation technique in smokers and chronic obstructive pulmonary disease patients and evaluated the contribution of this analysis to the diagnosis of chronic obstructive pulmonary disease. METHODS: Twenty healthy individuals and 20 smokers were assessed. The study also included 74 patients with stable chronic obstructive pulmonary disease. We evaluated the mean respiratory impedance (Zm as well as values for the inspiration (Zi and expiration cycles (Ze at the beginning of inspiration (Zbi and expiration (Zbe, respectively. The peak-to-peak impedance (Zpp=Zbe-Zbi and the respiratory cycle dependence (ΔZrs=Ze-Zi were also analyzed. The diagnostic utility was evaluated by investigating the sensitivity, the specificity and the area under the receiver operating characteristic curve. ClinicalTrials.gov: NCT01888705. RESULTS: Airway obstruction increased the within-breath respiratory impedance parameters that were significantly correlated with the spirometric indices of airway obstruction (R=−0.65, p90%. CONCLUSIONS: We conclude the following: (1 chronic obstructive pulmonary disease introduces higher respiratory cycle dependence, (2 this increase is proportional to airway obstruction, and (3 the within-breath forced oscillation technique may provide novel parameters that facilitate the diagnosis of respiratory abnormalities in chronic obstructive pulmonary disease.

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

Science.gov (United States)

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

2017-01-01

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

Spi2 gene polymorphism is not associated with recurrent airway obstruction and inflammatory airway disease in thoroughbred horses

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Aline Correa da Silva

2011-01-01

Full Text Available The aim was to detect the presence of polymorphisms at exons 1, 2, 3 and 4 of the Spi2 gene, and evaluate a possible association between them and recurrent airway obstruction (RAO or inflammatory airway disease (IAD in thoroughbred horses, through single-strand conformational-polymorphism (SSCP screening. Although polymorphism was not detected in exons 1, 2 and 3, three alleles and six genotypes were identified in exon 4. The frequencies of allele A (0.6388 and genotype AA (0.3888 were higher in horses affected by RAO, although no association was found between polymorphism and horses with either RAO or IAD.

Lung Metastases from Bile Duct Adenocarcinoma Mimicking Chronic Airway Infection and Causing Diagnostic Difficulty.

Science.gov (United States)

Sato, Mitsuo; Okachi, Shotaro; Fukihara, Jun; Shimoyama, Yoshie; Wakahara, Keiko; Sakakibara, Toshihiro; Hase, Tetsunari; Onishi, Yasuharu; Ogura, Yasuhiro; Maeda, Osamu; Hasegawa, Yoshinori

2018-05-15

We herein report a case of lung metastases with unusual radiological appearances that mimicked those of chronic airway infection, causing diagnostic difficulty. A 60-year-old woman who underwent liver transplantation from a living donor was incidentally diagnosed with bile duct adenocarcinoma after a histopathological analysis of her explanted liver. Six months later, chest computed tomography (CT) revealed bilateral bronchogenic dissemination that had gradually worsened, suggesting chronic airway infection. A biopsy with bronchoscopy from a mass lesion beyond a segmental bronchus revealed adenocarcinoma identical to that of her bile duct adenocarcinoma, leading to the diagnosis of multiple lung metastases from bile duct adenocarcinoma.

Airway disease: similarities and differences between asthma, COPD and bronchiectasis

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Rodrigo Athanazio

2012-11-01

Full Text Available Airway diseases are highly prevalent worldwide; however, the prevalence of these diseases is underestimated. Although these diseases present several common characteristics, they have different clinical outcomes. The differentiation between asthma, chronic obstructive pulmonary disease and bronchiectasis in the early stage of disease is extremely important for the adoption of appropriate therapeutic measures. However, because of the high prevalence of these diseases and the common pathophysiological pathways, some patients with different diseases may present with similar symptoms. The objective of this review is to highlight the similarities and differences between these diseases in terms of the risk factors, pathophysiology, symptoms, diagnosis and treatment.

Composition of nasal airway surface liquid in cystic fibrosis and other airway diseases determined by X-ray microanalysis.

Science.gov (United States)

Vanthanouvong, V; Kozlova, I; Johannesson, M; Nääs, E; Nordvall, S L; Dragomir, A; Roomans, G M

2006-04-01

The ionic composition of the airway surface liquid (ASL) in healthy individuals and in patients with cystic fibrosis (CF) has been debated. Ion transport properties of the upper airway epithelium are similar to those of the lower airways and it is easier to collect nasal ASL from the nose. ASL was collected with ion exchange beads, and the elemental composition of nasal fluid was determined by X-ray microanalysis in healthy subjects, CF patients, CF heterozygotes, patients with rhinitis, and with primary ciliary dyskinesia (PCD). In healthy subjects, the ionic concentrations were approximately isotonic. In CF patients, CF heterozygotes, rhinitis, and PCD patients, [Na] and [Cl] were significantly higher compared when compared with those in controls. [K] was significantly higher in CF and PCD patients compared with that in controls. Severely affected CF patients had higher ionic concentrations in their nasal ASL than in patients with mild or moderate symptoms. Female CF patients had higher levels of Na, Cl, and K than male patients. As higher salt concentrations in the ASL are also found in other patients with airway diseases involving chronic inflammation, it appears likely that inflammation-induced epithelial damage is important in determining the ionic composition of the ASL. Copyright (c) 2006 Wiley-Liss, Inc.

Non-invasive assessment of right ventricular function at rest and on exercise in obstructive airways disease

International Nuclear Information System (INIS)

Tweddel, A.; Martin, W.; McGhie, I.; Neilly, B.; Stevenson, R.; Hutton, I.

1985-01-01

Non-invasive assessment of right ventricular function is of clinical interest in the patient with obstructive airways disease. Gated Xenon 133 scanning allows right ventricular function to be evaluated in isolation from the left ventricle, and with rapid clearance from the lungs, scans may be repeated within 5 minutes. 400mBq of Xenon 133 were injected intravenously over 20 seconds and images were obtained using a mobile gamma camera. Maximal symptom limited exercise was performed on a supine bicycle ergometer. The normal range for right ventricular ejection fraction (RVEF) was obtained from 10 volunteers - 40-55% at rest rising by 5-15% during exercise. In 10 patients with acute obstructive airways disease, all had reduced RVEF 21 +- 3%. In chronic obstructive airways disease, if resting RVEF was greater than 30%, ejection fraction increased on exercise. If resting ejection fraction was abnormal than RVEF was reduced or unchanged on exercise (mean 15 +- 9%), and this was associated with dilatation of both the right ventricle and atrium. In conclusion, gated Xenon 133 offers a simple method of assessing right ventricular function at rest and on exercise in the patient with obstructive airways disease

Epidemiology of pollution-induced airway disease in Japan

International Nuclear Information System (INIS)

Miyamoto, T.

1997-01-01

Air pollution has been implicated as one of the factors responsible for the increased incidence of allergic diseases seen over recent years. Epidemiological studies in Japan demonstrate that atopic subjects living in urban areas are more likely to suffer from the effects of air pollution, with increased coughing, sputum production, wheezing and throat irritation. Furthermore, animal studies show that high concentrations of pollutant gases can promote airway sensitization. The incidence of allergic Rhinitis and asthma have been shown to be greater in areas where there is heavy traffic and hence high levels of automobile exhaust emissions. Intranasal administration of diesel exhaust particles in mice produces a stimulatory effect on immunoglobulin E production, and a similar finding has also been shown with suspended particulate matter in air. Air pollutants, such as ozone and nitrogen dioxide (NO 2 ), have been shown to stimulate the production of granulocyte-macrophage colony stimulating factor, which may play a vital role in airway hyperreactivity and asthma. In comparative studies of asthma in urban and rural areas, history of airway infection and a younger age of onset were found to be significantly greater in urban areas. When the asthmatic patients were divided into two groups according to environmental NO 2 levels (group I: NO 2 >30 ppb, group II: NO 2 <30 ppb), no significant difference regarding the various parameters was noted between the two groups, except for a greater severity of asthma in adults in group I, and a greater severity in chrildren in group II. These studies imply that air pollution may be one reason for the increase in allergic diseases in Japan, but a definitive conclusion cannot be drawn, and further, investigation is warranted. (au)

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

Science.gov (United States)

Pickles, Raymond J

2013-01-01

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

A single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice

Science.gov (United States)

The data presented here shows that a single exposure to photochemical smog causes airway irritation and cardiac dysrhythmia in mice. Smog, which is a complex mixture of particulate matter and gaseous irritants (ozone, sulfur dioxide, reactive aldehydes), as well as components whi...

Management of upper airway edema caused by hereditary angioedema

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Farkas Henriette

2010-07-01

Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

The protective effect of a beta 2 agonist against excessive airway narrowing in response to bronchoconstrictor stimuli in asthma and chronic obstructive lung disease.

Science.gov (United States)

Bel, E. H.; Zwinderman, A. H.; Timmers, M. C.; Dijkman, J. H.; Sterk, P. J.

1991-01-01

Beta 2 agonists reduce airway hypersensitivity to bronchoconstrictor stimuli acutely in patients with asthma and chronic obstructive lung disease. To determine whether these drugs also protect against excessive airway narrowing, the effect of inhaled salbutamol on the position and shape of the dose-response curves for histamine or methacholine was investigated in 12 patients with asthma and 11 with chronic obstructive lung disease. After pretreatment with salbutamol (200 or 400 micrograms) or placebo in a double blind manner dose-response curves for inhaled histamine and methacholine were obtained by a standard method on six days in random order. Airway sensitivity was defined as the concentration of histamine or methacholine causing a 20% fall in FEV1 (PC20). A maximal response plateau on the log dose-response curve was considered to be present if two or more data points for FEV1 fell within a 5% response range. In the absence of a plateau, the test was continued until a predetermined level of severe bronchoconstriction was reached. Salbutamol caused an acute increase in FEV1 (mean increase 11.5% predicted in asthma, 7.2% in chronic obstructive lung disease), and increase in PC20 (mean 15 fold in asthma, fivefold in chronic obstructive lung disease), and an increase in the slope of the dose-response curves in both groups. In subjects in whom a plateau of FEV1 response could be measured salbutamol did not change the level of the plateau. In subjects without a plateau salbutamol did not lead to the development of a plateau, despite achieving a median FEV1 of 44% predicted in asthma and 39% in chronic obstructive lung disease. These results show that, although beta 2 agonists acutely reduce the airway response to a given strength of bronchoconstrictor stimulus, they do not protect against excessive airflow obstruction if there is exposure to relatively strong stimuli. This, together with the steepening of the dose-response curve, could be a disadvantage of beta 2

Correlations of sleep disorders with severity of obstructive airway disease in mustard gas-injured patients.

Science.gov (United States)

Vahedi, Ensieh; Taheri, Saeed; Alaedini, Farshid; Poursaleh, Zohreh; Ameli, Javad; Ghanei, Mostafa

2012-06-01

Mustard gas has serious adverse effects on several organs and functions in humans. In this study, we analyzed potential correlations between obstructive airway disease and sleep disorders in Iranian mustard gas-injured patients. We enrolled 30 male mustard gas-injured veterans and civilians from the Chemical Warfare Exposure Clinic at Baqiyatallah Hospital, Tehran. All the subjects underwent comprehensive polysomnographic and spirometric evaluations for diagnosis of sleep disorders. Patients were categorized into three groups according to the severity of their obstructive airway disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: group 1 (GOLD I and II), group 2 (GOLD III), and group 3 (GOLD IV). Patients with less severe obstructive airway disease had significantly higher rate of hypopnea (p = 0.05) and AHI (p = 0.05). The number of REM events was significantly higher in patients with less severe airway disease (p = 0.028). Stage 1 sleep among patients with higher FEV1 significantly constituted a higher proportion of sleep, and stage 4 sleep was significantly longer in patients with higher DLCO (p = 0.043, both). We found that sleep parameters in SM-exposed patients have some relations with spirometric parameters. Future studies with large patient populations are needed for confirmation of our results, and therapeutic interventions are needed to evaluate endeavors we can do to enhance health and quality of life in our mustard gas-injured population.

The saw-tooth sign as a clinical clue for intrathoracic central airway obstruction

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Nakajima Akira

2012-07-01

Full Text Available Abstract Background The saw-tooth sign was first described by Sanders et al in patients with obstructive sleep apnea syndrome as one cause of extrathoracic central airway obstruction. The mechanism of the saw-tooth sign has not been conclusively clarified. The sign has also been described in various extrathoracic central airway diseases, such as in burn victims with thermal injury to the upper airways, Parkinson’s disease, tracheobronchomalacia, laryngeal dyskinesia, and pedunculated tumors of the upper airway. Case presentation A 61-year-old man was referred to our hospital with a two-month history of persistent dry cough and dyspnea. He was diagnosed with lung cancer located in an intrathoracic central airway, which was accompanied by the saw-tooth sign on flow-volume loops. This peculiar sign repeatedly improved and deteriorated, in accordance with the waxing and waning of central airway stenosis by anti-cancer treatments. Conclusion This report suggests that the so-called saw-tooth sign may be found even in intrathoracic central airway obstruction due to lung cancer.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Energy Technology Data Exchange (ETDEWEB)

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

Endotracheal tube connector defect causing airway obstruction in an ...

African Journals Online (AJOL)

detected during routine visual inspection before their use, while some go unnoticed during such inspection and can lead to partial or complete airway obstruction in intubated patients. We report one case of partial airway obstruction resulting from manufacturing defect in the ET connector. A 3-month-old infant girl weighing 5 ...

The Laryngeal Mask Airway (LMA) as an alternative to airway ...

African Journals Online (AJOL)

Background: To evaluate the possibility of airway management using a laryngeal mask airway (LMA) during dental procedures on mentally retarded (MR) patients and patients with genetic diseases. Design: A prospective pilot study. Setting: University Hospital. Methods: A pilot study was designed to induce general ...

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Directory of Open Access Journals (Sweden)

Lewindon PJ

2005-07-01

Full Text Available Abstract Background Gastroesophageal reflux disease (GORD can cause respiratory disease in children from recurrent aspiration of gastric contents. GORD can be defined in several ways and one of the most common method is presence of reflux oesophagitis. In children with GORD and respiratory disease, airway neutrophilia has been described. However, there are no prospective studies that have examined airway cellularity in children with GORD but without respiratory disease. The aims of the study were to compare (1 BAL cellularity and lipid laden macrophage index (LLMI and, (2 microbiology of BAL and gastric juices of children with GORD (G+ to those without (G-. Methods In 150 children aged Results BAL neutrophil% in G- group (n = 63 was marginally but significantly higher than that in the G+ group (n = 77, (median of 7.5 and 5 respectively, p = 0.002. Lipid laden macrophage index (LLMI, BAL percentages of lymphocyte, eosinophil and macrophage were similar between groups. Viral studies were negative in all, bacterial cultures positive in 20.7% of BALs and in 5.3% of gastric aspirates. BAL cultures did not reflect gastric aspirate cultures in all but one child. Conclusion In children without respiratory disease, GORD defined by presence of reflux oesophagitis, is not associated with BAL cellular profile or LLMI abnormality. Abnormal microbiology of the airways, when present, is not related to reflux oesophagitis and does not reflect that of gastric juices.

Severe Chronic Upper Airway Disease (SCUAD) in children. Definition issues and requirements.

Science.gov (United States)

Karatzanis, A; Kalogjera, L; Scadding, G; Velegrakis, S; Kawauchi, H; Cingi, C; Prokopakis, E

2015-07-01

Upper airway diseases are extremely common, and a significant proportion of patients are not adequately controlled by contemporary treatment algorithms. The term SCUAD (Severe Chronic Upper Airway Disease) has been previously introduced to describe such cases. However, this term has not been adequately focused on children. This study aims to address the necessity of the term, as well as further details specifically for children. For this purpose, a review was performed of the current literature, with specific focus on issues regarding SCUAD in children. Paediatric SCUAD represents a heterogeneous group of patients and has significant clinical and socioeconomic implications. Relevant literature is generally lacking and questions regarding definition and pathogenesis remain unanswered. Accurate definition and acknowledgement of paediatric SCUAD cases may lead to better design of future clinical and molecular research protocols. This may provide improved understanding of the underlying disease processes, more accurate data regarding socioeconomic burden, and, above all, more successful treatment and prevention strategies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis.

Science.gov (United States)

Frayman, Katherine B; Armstrong, David S; Carzino, Rosemary; Ferkol, Thomas W; Grimwood, Keith; Storch, Gregory A; Teo, Shu Mei; Wylie, Kristine M; Ranganathan, Sarath C

2017-12-01

In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain. To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years. Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records. Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2-78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years. In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age. 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/.

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

Science.gov (United States)

Kanwar, R K; Macgibbon, A K; Black, P N; Kanwar, J R; Rowan, A; Vale, M; Krissansen, G W

2008-01-01

It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

Airway inflammation in severe chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

Turato, Graziella; Zuin, Renzo; Miniati, Massimo

2002-01-01

Very few studies have been made in-patient with severe chronic obstructive pulmonary disease and some of them carried out, have demonstrated an increment in the intensity of the inflammatory answer in the space and these patients' alveolar walls. However, there are not enough studies on the inflammatory answer in the small airway and in the lung glasses, object of the present study, comparing it with patient with light (COPD) or without COPD, in spite of similar history of smoker

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.

[Acute pulmonary edema in adult caused by tonsillar hypertrophy following removal of laryngeal mask airway].

Science.gov (United States)

Iizuka, Toru; Shimoyama, Naohito; Notoya, Atsuko

2010-12-01

Negative pressure pulmonary edema (NPPE) has been described after acute airway obstruction. In the following case, we observed a rare occurrence of pulmonary edema caused by chronic tonsillar hypertrophy in a woman following removal of laryngeal mask airway (LMA). A 38-year-old woman with breast cancer underwent mastectomy under general anesthesia using the LMA. With the patient fully awake, the LMA was removed. Abruptly 7 minutes afterward, she showed signs of intense dyspnea, generalized rhonchus and progressive desaturation, and obstructive tonsillar hypertrophy was noticed. Acute lung edema was suspected and treatment started with oxygen therapy, bronchodilators, intravenous corticoids and loop diuretics. She was then intubated to secure airway and provide adequate ventilation with PEEP. Fortunately, the symptoms progressively remitted satisfactorily, and she was subsequently extubated 18 hours later with no complications. NPPE is an infrequent medical emergency and its early diagnosis and recognition are likely to lead to successful management of this potentially serious complication.

Exploring Airway Diseases by NMR-Based Metabonomics: A Review of Application to Exhaled Breath Condensate

Directory of Open Access Journals (Sweden)

Matteo Sofia

2011-01-01

Full Text Available There is increasing evidence that biomarkers of exhaled gases or exhaled breath condensate (EBC may help in detecting abnormalities in respiratory diseases mirroring increased, oxidative stress, airways inflammation and endothelial dysfunction. Beside the traditional techniques to investigate biomarker profiles, “omics” sciences have raised interest in the clinical field as potentially improving disease phenotyping. In particular, metabonomics appears to be an important tool to gain qualitative and quantitative information on low-molecular weight metabolites present in cells, tissues, and fluids. Here, we review the potential use of EBC as a suitable matrix for metabonomic studies using nuclear magnetic resonance (NMR spectroscopy. By using this approach in airway diseases, it is now possible to separate specific EBC profiles, with implication in disease phenotyping and personalized therapy.

Role of eosinophils in airway inflammation of chronic obstructive pulmonary disease

Directory of Open Access Journals (Sweden)

Tashkin DP

2018-01-01

Full Text Available Donald P Tashkin,1 Michael E Wechsler2 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, National Jewish Health, Denver, CO, USA Abstract: COPD is a significant cause of morbidity and mortality. In some patients with COPD, eosinophils contribute to inflammation that promotes airway obstruction; approximately a third of stable COPD patients have evidence of eosinophilic inflammation. Although the eosinophil threshold associated with clinical relevance in patients with COPD is currently subject to debate, eosinophil counts hold potential as biomarkers to guide therapy. In particular, eosinophil counts may be useful in assessing which patients may benefit from inhaled corticosteroid therapy, particularly regarding exacerbation prevention. In addition, several therapies targeting eosinophilic inflammation are available or in development, including monoclonal antibodies targeting the IL5 ligand, the IL5 receptor, IL4, and IL13. The goal of this review was to describe the biologic characteristics of eosinophils, their role in COPD during exacerbations and stable disease, and their use as biomarkers to aid treatment decisions. We also propose an algorithm for inhaled corticosteroid use, taking into consideration eosinophil counts and pneumonia history, and emerging eosinophil-targeted therapies in COPD. Keywords: lung disease, pulmonary diseases, corticosteroids, asthma, pneumonia

Airway Clearance Techniques (ACTs)

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

Airway hyperresponsiveness in chronic obstructive pulmonary disease : A marker of asthma-chronic obstructive pulmonary disease overlap syndrome?

NARCIS (Netherlands)

Tkacova, Ruzena; Dai, Darlene L. Y.; Vonk, Judith M.; Leung, Janice M.; Hiemstra, Pieter S.; van den Berge, Maarten; Kunz, Lisette; Hollander, Zsuzsanna; Tashkin, Donald; Wise, Robert; Connett, John; Ng, Raymond; McManus, Bruce; Man, S. F. Paul; Postma, Dirkje S.; Sin, Don D.

2016-01-01

Background: The impact of airway hyperreactivity (AHR) on respiratory mortality and systemic inflammation among patients with chronic obstructive pulmonary disease (COPD) is largely unknown. We used data from 2 large studies to determine the relationship between AHR and FEV1 decline, respiratory

Nasopharyngeal encephalocele: a rare cause of upper airway obstruction.

Science.gov (United States)

Kalkan, Gokhan; Paksu, Sukru; Asilioglu, Nazik; Kiliç, Mehmet

2013-04-01

Nasopharyngeal encephalocele is a rare, benign congenital anomaly. It has the potential to be fatal due to airway obstruction. Here, we report on a 34-day-old infant with pneumonia who underwent mechanical ventilation. An upper airway evaluation was performed due to prolonged intubation, and revealed the presence of a nasopharyngeal encephalocele. The patient tolerated extubation and oral feeding after surgical resection of the lesion. Awareness of the condition can help clinicians arrive at an earlier diagnosis and enhance management.

RELATIONSHIP OF AIRWAY HYPERRESPONSIVENESS TO RESPIRATORY SYMPTOMS AND DIURNAL PEAK FLOW VARIATION IN PATIENTS WITH OBSTRUCTIVE LUNG-DISEASE

NARCIS (Netherlands)

BRAND, PLP; POSTMA, DS; KERSTJENS, HAM; KOETER, GH

This study reports on the relationship of airway hyperresponsiveness (AH) with respiratory symptoms and diurnal peak flow expiratory (PEF) variation in 221 hyperresponsive patients with moderately severe airways obstruction. The disease was in a stable phase in all patients. Closely adhering to the

Automatic airway-artery analysis on lung CT to quantify airway wall thickening and bronchiectasis

DEFF Research Database (Denmark)

Perez-Rovira, Adria; Kuo, Wieying; Petersen, Jens

2016-01-01

Purpose: Bronchiectasis and airway wall thickening are commonly assessed in computed tomography (CT) by comparing the airway size with the size of the accompanying artery. Thus, in order to automate the quantification of bronchiectasis and wall thickening following a similar principle......, and pairs airway branches with the accompanying artery, then quantifies airway wall thickening and bronchiectasis by measuring the wall-artery ratio (WAR) and lumen and outer wall airway-artery ratio (AAR). Measurements that do not use the artery size for normalization are also extracted, including wall...... area percentage (WAP), wall thickness ratio (WTR), and airway diameters. Results: The method was thoroughly evaluated using 8000 manual annotations of airway-artery pairs from 24 full-inspiration pediatric CT scans (12 diseased and 12 controls). Limits of agreement between the automatically...

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

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Adil Aldhahrani

2017-03-01

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

Relapsing polychondritis and airway involvement.

Science.gov (United States)

Ernst, Armin; Rafeq, Samaan; Boiselle, Phillip; Sung, Arthur; Reddy, Chakravarthy; Michaud, Gaetane; Majid, Adnan; Herth, Felix J F; Trentham, David

2009-04-01

To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

Airway inflammation in nonobstructive and obstructive chronic bronchitis with chronic haemophilus influenzae airway infection. Comparison with noninfected patients with chronic obstructive pulmonary disease

NARCIS (Netherlands)

Bresser, P.; Out, T. A.; van Alphen, L.; Jansen, H. M.; Lutter, R.

2000-01-01

Nonencapsulated Haemophilus influenzae often causes chronic infections of the lower respiratory tract in both nonobstructive and obstructive chronic bronchitis. We assessed airway inflammation in clinically stable, chronically H. influenzae-infected patients with nonobstructive (CB-HI, n = 10) and

Endotracheal tube defects: Hidden causes of airway obstruction

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Sofi Khalid

2010-01-01

Full Text Available Manufacturing defects of endotracheal tube (ETT are still encountered in anesthesia practice. Many such defects go unnoticed during routine inspection prior to their use. Such defects in ETT may lead to partial or complete airway obstruction in an intubated patient. We report a case of partial airway obstruction with a prepacked, single use, uncuffed ETT due to a manufacturing defect in the form of a plastic meniscus at the distal end of the tube. This case report highlights the significance of standard monitoring of ventilation and the role of a vigilant clinician in detecting such defects in avoiding critical events as can arise from the use of such defective ETTs. It also emphasizes the need for double checking ETTs prior to their use.

Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease

Science.gov (United States)

Flynn, Jeffrey M.; Niccum, David; Dunitz, Jordan M.

2016-01-01

Chronic lung infections in cystic fibrosis (CF) patients are composed of complex microbial communities that incite persistent inflammation and airway damage. Despite the high density of bacteria that colonize the lower airways, nutrient sources that sustain bacterial growth in vivo, and how those nutrients are derived, are not well characterized. In this study, we examined the possibility that mucins serve as an important carbon reservoir for the CF lung microbiota. While Pseudomonas aeruginosa was unable to efficiently utilize mucins in isolation, we found that anaerobic, mucin-fermenting bacteria could stimulate the robust growth of CF pathogens when provided intact mucins as a sole carbon source. 16S rRNA sequencing and enrichment culturing of sputum also identified that mucin-degrading anaerobes are ubiquitous in the airways of CF patients. The collective fermentative metabolism of these mucin-degrading communities in vitro generated amino acids and short chain fatty acids (propionate and acetate) during growth on mucin, and the same metabolites were also found in abundance within expectorated sputum. The significance of these findings was supported by in vivo P. aeruginosa gene expression, which revealed a heightened expression of genes required for the catabolism of propionate. Given that propionate is exclusively derived from bacterial fermentation, these data provide evidence for an important role of mucin fermenting bacteria in the carbon flux of the lower airways. More specifically, microorganisms typically defined as commensals may contribute to airway disease by degrading mucins, in turn providing nutrients for pathogens otherwise unable to efficiently obtain carbon in the lung. PMID:27548479

Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy.

Science.gov (United States)

Davis, Benjamin B; Zeki, Amir A; Bratt, Jennifer M; Wang, Lei; Filosto, Simone; Walby, William F; Kenyon, Nicholas J; Goldkorn, Tzipora; Schelegle, Edward S; Pinkerton, Kent E

2013-08-01

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. The statin drugs may have therapeutic potential in respiratory diseases such as COPD, but whether they prevent bronchial epithelial injury is unknown. We hypothesised that simvastatin attenuates acute tobacco smoke-induced neutrophilic lung inflammation and airway epithelial injury. Spontaneously hypertensive rats were given simvastatin (20 mg·kg(-1) i.p.) daily for either 7 days prior to tobacco smoke exposure and during 3 days of smoke exposure, or only during tobacco smoke exposure. Pretreatment with simvastatin prior to and continued throughout smoke exposure reduced the total influx of leukocytes, neutrophils and macrophages into the lung and airways. Simvastatin attenuated tobacco smoke-induced cellular infiltration into lung parenchymal and airway subepithelial and interstitial spaces. 1 week of simvastatin pretreatment almost completely prevented smoke-induced denudation of the airway epithelial layer, while simvastatin given only concurrently with the smoke exposure had no effect. Simvastatin may be a novel adjunctive therapy for smoke-induced lung diseases, such as COPD. Given the need for statin pretreatment there may be a critical process of conditioning that is necessary for statins' anti-inflammatory effects. Future work is needed to elucidate the mechanisms of this statin protective effect.

Contributions of COPD, asthma, and ten comorbid conditions to health care utilization and patient-centered outcomes among US adults with obstructive airway disease.

Science.gov (United States)

Murphy, Terrence E; McAvay, Gail J; Allore, Heather G; Stamm, Jason A; Simonelli, Paul F

2017-01-01

Among persons with obstructive airway disease, the relative contributions of chronic obstructive pulmonary disease (COPD), asthma, and common comorbid conditions to health care utilization and patient-centered outcomes (PCOs) have not been previously reported. We followed a total of 3,486 persons aged ≥40 years with COPD, asthma, or both at baseline, from the Medical Expenditure Panel Survey (MEPS) cohorts enrolled annually from 2008 through 2012 for 1 year. MEPS is a prospective observational study of US households recording self-reported COPD, asthma, and ten medical conditions: angina, arthritis, cancer, coronary heart disease, cognitive impairment, diabetes, hypertension, lung cancer, myocardial infarction, and stroke/transient ischemic attack. We studied the separate contributions of these conditions to health care utilization (all-cause and respiratory disease hospitalization, any emergency department [ED] visit, and six or more outpatient visits) and PCOs (seven or more days spent in bed due to illness, incident loss of mobility, and incident decline in self-perceived health). COPD made the largest contributions to all-cause and respiratory disease hospitalization and ED visits, while arthritis made the largest contribution to outpatient health care. Arthritis and COPD, respectively, made the greatest contributions to the PCOs. COPD made the largest and second largest contributions to health care utilization and PCOs among US adults with obstructive airway disease. The twelve medical conditions collectively accounted for between 52% and 61% of the health care utilization outcomes and between 53% and 68% of the PCOs. Cognitive impairment, diabetes, hypertension, and stroke also made significant contributions.

Quantitative evaluation of inhaled radioactive aerosol deposition patterns in the lungs in obstructive airways disease

Energy Technology Data Exchange (ETDEWEB)

Teshima, Takeo; Isawa, Toyoharu; Hirano, Tomio; Ebina, Akio; Shiraishi, Koichiro; Konno, Kiyoshi

1985-12-01

Uneven distribution of inhaled aerosol in the lungs is the characteristics of obstructive airways disease such as chronic bronchitis and pulmonary emphysema, and has been classified typically into peripheral and central deposition patterns, respectively by visual inspection, whereas in the normal the distribution is homogeneous throughout the lungs. The purpose of the present study was to analyse the distribution of inhaled radioactivity in the lungs by way of matrixes by a computer. The seemingly homogeneous distribution pattern in normal subjects has been found to indicate a gradual change in count profile between the neighboring matrixes. The peripheral pattern indicates the patchy presence of small number of matrixes with excessive radioactivity throughout the lungs, and the central pattern, the presence of matrixes of excessive radioactivity along the major central airways forming a comma-like configuration superimposed on the peripheral pattern. Our computer analysis has a potentiality to characterize obstructive airways disease for a better understanding of their pathophysiology, which is not feasible by a simple visual inspection of images on a polaroid picture.

The effect of disease and respiration on airway shape in patients with moderate persistent asthma.

Directory of Open Access Journals (Sweden)

Spyridon Montesantos

Full Text Available Computational models of gas transport and aerosol deposition frequently utilize idealized models of bronchial tree structure, where airways are considered a network of bifurcating cylinders. However, changes in the shape of the lung during respiration affect the geometry of the airways, especially in disease conditions. In this study, the internal airway geometry was examined, concentrating on comparisons between mean lung volume (MLV and total lung capacity (TLC. A set of High Resolution CT images were acquired during breath hold on a group of moderate persistent asthmatics at MLV and TLC after challenge with a broncho-constrictor (methacholine and the airway trees were segmented and measured. The airway hydraulic diameter (Dh was calculated through the use of average lumen area (Ai and average internal perimeter (Pi at both lung volumes and was found to be systematically higher at TLC by 13.5±9% on average, with the lower lobes displaying higher percent change in comparison to the lower lobes. The average internal diameter (Din was evaluated to be 12.4±6.8% (MLV and 10.8±6.3% (TLC lower than the Dh, for all the examined bronchi, a result displaying statistical significance. Finally, the airway distensibility per bronchial segment and per generation was calculated to have an average value of 0.45±0.28, exhibiting high variability both between and within lung regions and generations. Mixed constriction/dilation patterns were recorded between the lung volumes, where a number of airways either failed to dilate or even constricted when observed at TLC. We conclude that the Dh is higher than Din, a fact that may have considerable effects on bronchial resistance or airway loss at proximal regions. Differences in caliber changes between lung regions are indicative of asthma-expression variability in the lung. However, airway distensibility at generation 3 seems to predict distensibility more distally.

Rhinovirus inhalation causes long-lasting excessive airway narrowing in response to methacholine in asthmatic subjects in vivo

NARCIS (Netherlands)

Cheung, D.; Dick, E. C.; Timmers, M. C.; de Klerk, E. P.; Spaan, W. J.; Sterk, P. J.

1995-01-01

Exacerbations of asthma are often associated with respiratory infections, and particularly those caused by rhinovirus. The causative role of rhinovirus in these acute episodes is still unclear, since it has not been determined whether or not infection with the virus promotes excessive airway

Rhinosinusitis and the lower airways

NARCIS (Netherlands)

Hellings, Peter W.; Hens, Greet

2009-01-01

The interaction between upper and lower airway disease has been recognized for centuries, with recent studies showing a direct link between upper and airway inflammation in allergic patients. The mechanisms underlying the interaction between nasal and bronchial inflammation have primarily been

Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol.

Science.gov (United States)

Cancado, Jose E; Mendes, Eliana S; Arana, Johana; Horvath, Gabor; Monzon, Maria E; Salathe, Matthias; Wanner, Adam

2015-04-02

In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (ΔQ̇aw) were assessed. Mean ± SE EBC pH (units) and ΔQ̇aw (μl.min(-1).mL(-1)) were 6.4 ± 0.1 and 16.8 ± 1.9 during quiet breathing, 6.3 ± 0.1 and 14.5 ± 2.4 during eucapnic hyperventilation, 6.6 ± 0.2 and -0.2 ± 1.8 during hypocapnic hyperventilation (p = 0.02 and <0.01 vs. quiet breathing), and 5.9 ± 0.1 and 2.0 ± 1.5 during hypercapnic hyperventilation (p = 0.02 and <0.02 vs quiet breathing). Albuterol responsiveness in the airway as assessed by ΔQ̇aw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH. Registered at clinicaltrials.gov: NCT01216748 .

The Nature and Causes of Chronic Obstructive Pulmonary Disease: A Historical Perspective

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C Peter W Warren

2009-01-01

Full Text Available Chronic obstructive pulmonary disease (COPD is the currently favoured name for the diseases formerly known as emphysema and bronchitis. COPD has been recognized for more than 200 years. Its cardinal symptoms are cough, phlegm and dyspnea, and its pathology is characterized by enlarged airspaces and obstructed airways. In the 19th century, the diagnosis of COPD depended on its symptoms and signs of a hyperinflated chest, and reduced expiratory breath sounds. The airflow obstruction evident on spirometry was identified in that century, but did not enter into clinical practice. Bronchitis, and the mechanical forces required to overcome its obstruction, was believed to be responsible for emphysema, although the inflammation present was recognized. The causes of bronchitis, and hence emphysema, included atmospheric and domestic air pollution, as well as dusty occupations. Cigarette smoking only became recognized as the dominant cause in the 20th century. The lessons learned of the risks for COPD in 19th-century Britain are very pertinent to the world today.

The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD.

Science.gov (United States)

Liu, Xianyan; Hao, Binwei; Ma, Ailing; He, Jinxi; Liu, Xiaoming; Chen, Juan

Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF- β ) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF- β , along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α -SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF- β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF- β signaling in the pathogenesis of COPD, which warrants further investigation.

Contribution of SRF, Elk-1, and myocardin to airway smooth muscle remodeling in heaves, an asthma-like disease of horses.

Science.gov (United States)

Chevigny, Mylène; Guérin-Montpetit, Karine; Vargas, Amandine; Lefebvre-Lavoie, Josiane; Lavoie, Jean-Pierre

2015-07-01

Myocyte hyperplasia and hypertrophy contribute to the increased mass of airway smooth muscle (ASM) in asthma. Serum-response factor (SRF) is a transcription factor that regulates myocyte differentiation in vitro in vascular and intestinal smooth muscles. When SRF is associated with phosphorylated (p)Elk-1, it promotes ASM proliferation while binding to myocardin (MYOCD) leading to the expression of contractile elements in these tissues. The objective of this study was therefore to characterize the expression of SRF, pElk-1, and MYOCD in ASM cells from central and peripheral airways in heaves, a spontaneously occurring asthma-like disease of horses, and in controls. Six horses with heaves and five aged-matched controls kept in the same environment were studied. Nuclear protein expression of SRF, pElk-1, and MYOCD was evaluated in peripheral airways and endobronchial biopsies obtained during disease remission and after 1 and 30 days of naturally occurring antigenic exposure using immunohistochemistry and immunofluorescence techniques. Nuclear expression of SRF (P = 0.03, remission vs. 30 days) and MYOCD (P = 0.05, controls vs. heaves at 30 days) increased in the peripheral airways of horses with heaves during disease exacerbation, while MYOCD (P = 0.04, remission vs. 30 days) decreased in the central airways of control horses. No changes were observed in the expression of pElk-1 protein in either tissue. In conclusion, SRF and its cofactor MYOCD likely contribute to the hypertrophy of peripheral ASM observed in equine asthmatic airways, while the remodeling of the central airways is more static or involves different transcription factors. Copyright © 2015 the American Physiological Society.

Atopic asthmatic immune phenotypes associated with airway microbiota and airway obstruction.

Directory of Open Access Journals (Sweden)

Benjamin A Turturice

Full Text Available Differences in asthma severity may be related to inflammation in the airways. The lower airway microbiota has been associated with clinical features such as airway obstruction, symptom control, and response to corticosteroids.To assess the relationship between local airway inflammation, severity of disease, and the lower airway microbiota in atopic asthmatics.A cohort of young adult, atopic asthmatics with intermittent or mild/moderate persistent symptoms (n = 13 were assessed via bronchoscopy, lavage, and spirometry. These individuals were compared to age matched non-asthmatic controls (n = 6 and to themselves after six weeks of treatment with fluticasone propionate (FP. Inflammation of the airways was assessed via a cytokine and chemokine panel. Lower airway microbiota composition was determined by metagenomic shotgun sequencing.Unsupervised clustering of cytokines and chemokines prior to treatment with FP identified two asthmatic phenotypes (AP, termed AP1 and AP2, with distinct bronchoalveolar lavage inflammatory profiles. AP2 was associated with more obstruction, compared to AP1. After treatment with FP reduced MIP-1β and TNF-α and increased IL-2 was observed. A module of highly correlated cytokines that include MIP-1β and TNF-α was identified that negatively correlated with pulmonary function. Independently, IL-2 was positively correlated with pulmonary function. The airway microbiome composition correlated with asthmatic phenotypes. AP2, prior to FP treatment, was enriched with Streptococcus pneumoniae. Unique associations between IL-2 or the cytokine module and the microbiota composition of the airways were observed in asthmatics subjects prior to treatment but not after or in controls.The underlying inflammation in atopic asthma is related to the composition of microbiota and is associated with severity of airway obstruction. Treatment with inhaled corticosteroids was associated with changes in the airway inflammatory response to

Laryngeal debridement: an alternative treatment for a laryngopyocele presenting with severe airway obstruction.

Science.gov (United States)

Fraser, L; Pittore, B; Frampton, S; Brennan, P; Puxeddu, R

2011-04-01

The laryngocele is an abnormal saccular dilatation of the ventricle of Morgagni, which maintains its communication with the laryngeal vestibule. Three types of laryngoceles have been described: internal, external, and combined or mixed in relation to the position of the sac with respect to the thyrohyoid membrane. If the laryngocele becomes obstructed and infected it leads to the so-called laryngopyocele which, although a rare disease (8% of laryngoceles), can become an emergency causing severe airway obstruction needing urgent management, even tracheostomy. An alternative method is presented of emergency management of an internal laryngopyocele causing severe airway obstruction using a laryngeal microdebrider and avoiding tracheostomy.

Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening

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Sverzellati, Nicola; Rastelli, Andrea; Schembri, Valentina; Filippo, Massimo de [University of Parma, Department of Clinical Sciences, Section of Radiology, Parma (Italy); Chetta, Alfredo [University of Parma, Department of Clinical Sciences, Section of Respiratory Diseases, Parma (Italy); Fasano, Luca; Pacilli, Angela Maria [Policlinico Sant' Orsola-Malpighi, Unita Operativa di Fisiopatologia Respiratoria, Bologna (Italy); Di Scioscio, Valerio; Bartalena, Tommaso; Zompatori, Maurizio [University of Bologna, Department of Radiology, Cardiothoracic Institute, Policlinico S.Orsola-Malpighi, Bologna (Italy)

2009-07-15

The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as {>=}50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening. (orig.)

Airway malacia in chronic obstructive pulmonary disease: prevalence, morphology and relationship with emphysema, bronchiectasis and bronchial wall thickening

International Nuclear Information System (INIS)

Sverzellati, Nicola; Rastelli, Andrea; Schembri, Valentina; Filippo, Massimo de; Chetta, Alfredo; Fasano, Luca; Pacilli, Angela Maria; Di Scioscio, Valerio; Bartalena, Tommaso; Zompatori, Maurizio

2009-01-01

The aim of this study was to determine the prevalence of airway malacia and its relationship with ancillary morphologic features in patients with chronic obstructive pulmonary disease (COPD). A retrospective review was performed of a consecutive series of patients with COPD who were imaged with inspiratory and dynamic expiratory multidetector computed tomography (MDCT). Airway malacia was defined as ≥50% expiratory reduction of the airway lumen. Both distribution and morphology of airway malacia were assessed. The extent of emphysema, extent of bronchiectasis and severity of bronchial wall thickness were quantified. The final study cohort was comprised of 71 patients. Airway malacia was seen in 38 of 71 patients (53%), and such proportion was roughly maintained in each stage of COPD severity. Almost all tracheomalacia cases (23/25, 92%) were characterised by an expiratory anterior bowing of the posterior membranous wall. Both emphysema and bronchiectasis extent did not differ between patients with and without airway malacia (p > 0.05). Bronchial wall thickness severity was significantly higher in patients with airway malacia and correlated with the degree of maximal bronchial collapse (p < 0.05). In conclusion, we demonstrated a strong association between airway malacia and COPD, disclosing a significant relationship with bronchial wall thickening. (orig.)

Advancing the management of Obstructive Airways Diseases through Translational Research

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Porsbjerg, Celeste; Sverrild, Asger; Baines, Katherine J

2018-01-01

Obstructive airways diseases (OAD) represent a huge burden of illness worldwide, and in spite of the development of effective therapies, significant morbidity and mortality related to asthma and COPD still remains. Over the past decade, our understanding of OAD has improved vastly, and novel...... treatments have evolved. This evolution is the result of successful translational research, which has connected clinical presentations of OAD and underlying disease mechanisms, thereby enabling the development of targeted treatments. The next challenge of translational research will be to position...... these novel treatments for OAD for optimal clinical use. At the same time, there is great potential in these treatments providing even better insights into disease mechanisms in OAD, by studying the effects of blocking individual immunological pathways. To optimise this potential, there is a need to ensure...

European Symposium on Precision Medicine in Allergy and Airways Diseases

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Muraro, A; Fokkens, W J; Pietikainen, S

2016-01-01

: personalized care based on molecular, immunologic and functional endotyping of the disease, with participation of the patient in the decision making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of Precision Medicine into clinical practice......The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS) and the European Medical Association (EMA) organized, on 14 October 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP...... the most frequently diagnosed chronic non-communicable diseases in the EU. 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision Medicine represents a novel approach, embracing 4 key features...

Continuous positive airway pressure for the treatment of obstructive sleep apnea.

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Nurwidya, Fariz; Susanto, Agus Dwi; Juzar, Dafsah A; Kobayashi, Isao; Yunus, Faisal

2016-01-01

Obstructive sleep apnea (OSA) is a recurrent episode of partial or complete upper airway obstruction during sleep despite ongoing respiratory efforts and is implicated as the risk factor of cardiovascular disease. The OSA syndrome is typified by recurring partial or total occlusion of the pharynx, sleep fragmentation, episodes of gasping, and, eventually, daytime sleepiness. If it is left untreated, OSA syndrome can cause hypertension, coronary artery disease congestive heart disease, insulin resistance and death. In this review, we describe the pathogenesis and diagnosis of OSA. We also focused on the continuous positive airway pressure (CPAP) as the main therapy for OSA. CPAP has been shown to provide benefit for not only respiratory system, but also for cardiovascular system and metabolic system. Finally, we discussed briefly about the issue of adherence of using CPAP that could contribute to lower compliant in patient with OSA.

Effects of concentrated ambient particles on normal and hypersecretory airways in rats.

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Harkema, Jack R; Keeler, Gerald; Wagner, James; Morishita, Masako; Timm, Edward; Hotchkiss, Jon; Marsik, Frank; Dvonch, Timothy; Kaminski, Norbert; Barr, Edward

2004-08-01

.5 from this local urban atmosphere. Rats in the inhalation studies were exposed for 1 day or for 4 or 5 consecutive days (10 hours/day) to either filtered air (controls) or concentrated ambient particles (CAPs) delivered by a Harvard ambient fine particle concentrator. Rats were killed 24 hours after the end of the exposure. Biochemical, morphometric, and molecular techniques were used to identify airway epithelial and inflammatory responses to CAPs. Lung lobes were also either intratracheally lavaged with saline to determine cellular composition and protein in bronchoalveolar lavage fluid (BALF) or removed for analysis by inductively coupled plasma-mass spectrometry (ICPMS) to detect retention of ambient PM2.5--derived trace elements. The Harvard concentrator effectively concentrated the fine ambient particles from this urban atmosphere (10-30 times) without significantly changing the major physicochemical features of the atmospheric particles. Daily CAPs mass concentrations during the 10-hour exposure period (0800-1800) in July ranged from 16 to 895 microg/m3 and in September ranged from 81 to 755 microg/m3. In general, chemical characteristics of ambient particles were conserved through the concentrator into the exposure chamber. Single or repeated exposures to CAPs did not cause adverse effects in the nasal or pulmonary airways of healthy F344 or BN rats. In addition, CAPs-related toxicity was not observed in F344 rats pretreated with bacterial endotoxin. Variable airway responses to CAPs exposure were observed in BN rats with preexisting allergic airway disease induced by OVA sensitization and challenge. Only OVA-challenged BN rats exposed to CAPs for 5 consecutive days in September 2000 had significant increases in airway mucosubstances and pulmonary inflammation compared to saline-challenged/air-exposed control rats. OVA-challenged BN rats that were repeatedly exposed to CAPs in July 2000 had only minor CAPs-related effects. In only the September 5-day exposure

Airway necrosis after salvage esophagectomy

International Nuclear Information System (INIS)

Tanaka, Norimitsu; Hokamura, Nobukazu; Tachimori, Yuji

2010-01-01

Salvage esophagectomy is the sole curative intent treatment for patients with persistent or recurrent locoregional disease after definitive chemoradiotherapy (CRT) for esophageal carcinoma. However, salvage esophagectomy is a very high-risk operation, and airway necrosis is a fatal complication. Between 1997 and 2007, 49 patients with thoracic esophageal cancer underwent salvage esophagectomy after definitive CRT. We retrospectively compared patients with and without airway necrosis, and investigated operative procedures related to airway necrosis. Airway necrosis occurred in five patients (10.2%), of four patients (80%) died during their hospitalization. Airway necrosis seemed to be closely related to operative procedures, such as resection of bronchial artery and cervical and subcarinal lymph node dissection. Bronchogastric fistula following necrosis of gastric conduit occured in 2 patients reconstructed through posterior mediastinal route. Airway necrosis is a highly lethal complication after salvage esophagectomy. It is important in salvage esophagectomy to take airway blood supply into consideration sufficiently and to reconstruct through retrosternal route to prevent bronchogastric fistula. (author)

Efficacy of Surgical Airway Plasty for Benign Airway Stenosis.

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Tsukioka, Takuma; Takahama, Makoto; Nakajima, Ryu; Kimura, Michitaka; Inoue, Hidetoshi; Yamamoto, Ryoji

2016-01-01

Long-term patency is required during treatment for benign airway stenosis. This study investigated the effectiveness of surgical airway plasty for benign airway stenosis. Clinical courses of 20 patients, who were treated with surgical plasty for their benign airway stenosis, were retrospectively investigated. Causes of stenosis were tracheobronchial tuberculosis in 12 patients, post-intubation stenosis in five patients, malacia in two patients, and others in one patient. 28 interventional pulmonology procedures and 20 surgical plasty were performed. Five patients with post-intubation stenosis and four patients with tuberculous stenosis were treated with tracheoplasty. Eight patients with tuberculous stenosis were treated with bronchoplasty, and two patients with malacia were treated with stabilization of the membranous portion. Anastomotic stenosis was observed in four patients, and one to four additional treatments were required. Performance status, Hugh-Jones classification, and ventilatory functions were improved after surgical plasty. Outcomes were fair in patients with tuberculous stenosis and malacia. However, efficacy of surgical plasty for post-intubation stenosis was not observed. Surgical airway plasty may be an acceptable treatment for tuberculous stenosis. Patients with malacia recover well after surgical plasty. There may be untreated patients with malacia who have the potential to benefit from surgical plasty.

Airway contractility and remodeling : Links to asthma symptoms

NARCIS (Netherlands)

West, Adrian R.; Syyong, Harley T.; Siddiqui, Sana; Pascoe, Chris D.; Murphy, Thomas M.; Maarsingh, Harm; Deng, Linhong; Maksym, Geoffrey N.; Bosse, Ynuk

Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental triggers, such as viruses or allergens, are

Airway obstruction due to tracheomalacia caused by innominate artery compression and a kyphotic cervical spine.

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Liu, Chia-Hsin; Huang, Wen-Sheng; Wang, Hong-Hau; Wu, Chin-Pyng; Chian, Chih-Feng; Perng, Wann-Cherng; Tsai, Chen-Liang

2015-02-01

Tracheomalacia can cause variable degrees of intrathoracic airway obstruction and is an easily overlooked cause of respiratory distress in adults. Here, we report a case of acute respiratory failure in which subglottic stenosis was accidentally identified during endotracheal intubation. Subsequent bronchoscopy and computed tomography of the thorax and neck revealed tracheal compression with tracheomalacia caused by a tortuous innominate artery and a kyphotic cervical spine. The patient underwent rigid bronchoscopy with metal stent implantation, and her symptoms were alleviated. These findings outline the importance of precise diagnosis and interventions for preventing recurrent life-threatening respiratory failure in such cases. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In Vitro Microfluidic Models of Mucus-Like Obstructions in Small Airways

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Mulligan, Molly K.; Grotberg, James B.; Sznitman, Josué

2012-11-01

Liquid plugs can form in the lungs as a result of a host of different diseases, including cystic fibrosis and chronic obstructive pulmonary disease. The existence of such fluid obstructions have been found as far down in the bronchiole tree as the sixteenth generation, where bronchiole openings have diameters on the order of a hundred to a few hundred microns. Understanding the propagation of liquid plugs within the bifurcating branches of bronchiole airways is important because their presence in the lungs, and their rupture and break-up, can cause injury to the epithelial cells lining the airway walls as a result of high wall shear stresses. In particular, liquid plug rupture and break-up frequently occurs at airway bifurcations. Until present, however, experimental studies of liquid plugs have generally been restricted to Newtonian fluids that do not reflect the actual pseudoplastic properties of lung mucus. The present work attempts to uncover the propagation, rupture and break-up of mucus-like liquid plugs in the lower generations of the airway tree using microfluidic models. Our approach allows the dynamics of mucus-like plug break-up to be studied in real-time, in a one-to-one in vitro model, as a function of mucus rheology and bronchial tree geometry.

Research highlights from the 2017 ERS International Congress: airway diseases in focus

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Cecilia Andersson

2018-03-01

Full Text Available For another year, high-quality research studies from around the world transformed the annual ERS International Congress into a vivid platform to discuss trending research topics, to produce new research questions and to further push the boundaries of respiratory medicine and science. This article reviews only some of the high-quality research studies on asthma, chronic obstructive pulmonary disease (COPD, bronchiectasis and chronic cough that were presented during the congress through the Airway Diseases Assembly (ERS Assembly 5 and places them into the context of current knowledge and research challenges.

Incense smoke: clinical, structural and molecular effects on airway disease

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Krishnaswamy Guha

2008-04-01

Full Text Available Abstract In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes contains particulate matter (PM, gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs. The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.

Bacteriology and treatment of infections in the upper and lower airways in patients with primary ciliary dyskinesia

DEFF Research Database (Denmark)

Alanin, Mikkel Christian

2017-01-01

The respiratory tract is lined with motile cilia that transport respiratory mucus. Primary ciliary dyskinesia (PCD) is a chronic genetic disease caused by mutations in genes responsible for ciliary structure and function. Non-functional airway cilia impair the mucociliary clearance (MCC), causing...

A hybrid method for airway segmentation and automated measurement of bronchial wall thickness on CT.

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Xu, Ziyue; Bagci, Ulas; Foster, Brent; Mansoor, Awais; Udupa, Jayaram K; Mollura, Daniel J

2015-08-01

Inflammatory and infectious lung diseases commonly involve bronchial airway structures and morphology, and these abnormalities are often analyzed non-invasively through high resolution computed tomography (CT) scans. Assessing airway wall surfaces and the lumen are of great importance for diagnosing pulmonary diseases. However, obtaining high accuracy from a complete 3-D airway tree structure can be quite challenging. The airway tree structure has spiculated shapes with multiple branches and bifurcation points as opposed to solid single organ or tumor segmentation tasks in other applications, hence, it is complex for manual segmentation as compared with other tasks. For computerized methods, a fundamental challenge in airway tree segmentation is the highly variable intensity levels in the lumen area, which often causes a segmentation method to leak into adjacent lung parenchyma through blurred airway walls or soft boundaries. Moreover, outer wall definition can be difficult due to similar intensities of the airway walls and nearby structures such as vessels. In this paper, we propose a computational framework to accurately quantify airways through (i) a novel hybrid approach for precise segmentation of the lumen, and (ii) two novel methods (a spatially constrained Markov random walk method (pseudo 3-D) and a relative fuzzy connectedness method (3-D)) to estimate the airway wall thickness. We evaluate the performance of our proposed methods in comparison with mostly used algorithms using human chest CT images. Our results demonstrate that, on publicly available data sets and using standard evaluation criteria, the proposed airway segmentation method is accurate and efficient as compared with the state-of-the-art methods, and the airway wall estimation algorithms identified the inner and outer airway surfaces more accurately than the most widely applied methods, namely full width at half maximum and phase congruency. Copyright © 2015. Published by Elsevier B.V.

Equine recurrent airway obstruction

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Artur Niedźwiedź

2014-10-01

Full Text Available Equine Recurrent Airway Obstruction (RAO, also known as heaves or broken wind, is one of the most common disease in middle-aged horses. Inflammation of the airway is inducted by organic dust exposure. This disease is characterized by neutrophilic inflammation, bronchospasm, excessive mucus production and pathologic changes in the bronchiolar walls. Clinical signs are resolved in 3-4 weeks after environmental changes. Horses suffering from RAO are susceptible to allergens throughout their lives, therefore they should be properly managed. In therapy the most importanthing is to eliminate dustexposure, administration of corticosteroids and use bronchodilators to improve pulmonary function.

Oral fungal immunomodulatory protein-Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: A mouse model

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Po-Yu Chu

2017-06-01

Conclusion: Oral FIP-fve had an anti-inflammatory effect on the acute phase of the airway inflammatory process induced by HDM in the mouse model and might have a potentially therapeutic role for allergic airway diseases.

Muc5b is required for airway defence

Science.gov (United States)

Roy, Michelle G.; Livraghi-Butrico, Alessandra; Fletcher, Ashley A.; McElwee, Melissa M.; Evans, Scott E.; Boerner, Ryan M.; Alexander, Samantha N.; Bellinghausen, Lindsey K.; Song, Alfred S.; Petrova, Youlia M.; Tuvim, Michael J.; Adachi, Roberto; Romo, Irlanda; Bordt, Andrea S.; Bowden, M. Gabriela; Sisson, Joseph H.; Woodruff, Prescott G.; Thornton, David J.; Rousseau, Karine; de La Garza, Maria M.; Moghaddam, Seyed J.; Karmouty-Quintana, Harry; Blackburn, Michael R.; Drouin, Scott M.; Davis, C. William; Terrell, Kristy A.; Grubb, Barbara R.; O'Neal, Wanda K.; Flores, Sonia C.; Cota-Gomez, Adela; Lozupone, Catherine A.; Donnelly, Jody M.; Watson, Alan M.; Hennessy, Corinne E.; Keith, Rebecca C.; Yang, Ivana V.; Barthel, Lea; Henson, Peter M.; Janssen, William J.; Schwartz, David A.; Boucher, Richard C.; Dickey, Burton F.; Evans, Christopher M.

2014-01-01

Respiratory surfaces are exposed to billions of particulates and pathogens daily. A protective mucus barrier traps and eliminates them through mucociliary clearance (MCC). However, excessive mucus contributes to transient respiratory infections and to the pathogenesis of numerous respiratory diseases. MUC5AC and MUC5B are evolutionarily conserved genes that encode structurally related mucin glycoproteins, the principal macromolecules in airway mucus. Genetic variants are linked to diverse lung diseases, but specific roles for MUC5AC and MUC5B in MCC, and the lasting effects of their inhibition, are unknown. Here we show that mouse Muc5b (but not Muc5ac) is required for MCC, for controlling infections in the airways and middle ear, and for maintaining immune homeostasis in mouse lungs, whereas Muc5ac is dispensable. Muc5b deficiency caused materials to accumulate in upper and lower airways. This defect led to chronic infection by multiple bacterial species, including Staphylococcus aureus, and to inflammation that failed to resolve normally. Apoptotic macrophages accumulated, phagocytosis was impaired, and interleukin-23 (IL-23) production was reduced in Muc5b-/- mice. By contrast, in mice that transgenically overexpress Muc5b, macrophage functions improved. Existing dogma defines mucous phenotypes in asthma and chronic obstructive pulmonary disease (COPD) as driven by increased MUC5AC, with MUC5B levels either unaffected or increased in expectorated sputum. However, in many patients, MUC5B production at airway surfaces decreases by as much as 90%. By distinguishing a specific role for Muc5b in MCC, and by determining its impact on bacterial infections and inflammation in mice, our results provide a refined framework for designing targeted therapies to control mucin secretion and restore MCC.

The Influence of Asian Dust, Haze, Mist, and Fog on Hospital Visits for Airway Diseases.

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Park, Jinkyeong; Lim, Myoung Nam; Hong, Yoonki; Kim, Woo Jin

2015-10-01

Asian dust is known to have harmful effects on the respiratory system. Respiratory conditions are also influenced by environmental conditions regardless of the presence of pollutants. The same pollutant can have different effects on the airway when the air is dry compared with when it is humid. We investigated hospital visits for chronic obstructive pulmonary disease (COPD) and asthma in relation to the environmental conditions. We conducted a retrospective study using the Korean National Health Insurance Service claims database of patients who visited hospitals in Chuncheon between January 2006 and April 2012. Asian dust, haze, mist, and fog days were determined using reports from the Korea Meteorological Administration. Hospital visits for asthma or COPD on the index days were compared with the comparison days. We used two-way case-crossover techniques with one to two matching. The mean hospital visits for asthma and COPD were 59.37 ± 34.01 and 10.04 ± 6.18 per day, respectively. Hospital visits for asthma significantly increased at lag0 and lag1 for Asian dust (relative risk [RR], 1.10; 95% confidence interval [CI], 1.01-1.19; pfog (RR, 0.85; 95% CI, 0.75-0.97; pfog, which occur in humid air conditions, showed the opposite effects on airway diseases, after adjusting to the pollutants. It would require more research to investigate the effects of various air conditions on airway diseases.

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015).

Science.gov (United States)

Muraro, A; Fokkens, W J; Pietikainen, S; Borrelli, D; Agache, I; Bousquet, J; Costigliola, V; Joos, G; Lund, V J; Poulsen, L K; Price, D; Rolland, C; Zuberbier, T; Hellings, P W

2016-05-01

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP David Borrelli, and with active participation of the EU Commissioner for Health and Food Safety Vytenis Andriukaitis, MEP Sirpa Pietikainen, Chair of the European Parliament Interest Group on Allergy and Asthma, the European Respiratory Society (ERS), the European Federations of Allergy and Airways Diseases Patients Associations (EFA), the Global Allergy and Asthma European Network (Ga2len), Allergic Rhinitis and Its Impact on Asthma (ARIA), and the Respiratory Effectiveness Group (REG). The socioeconomic impact of allergies and chronic airways diseases cannot be underestimated, as they represent the most frequently diagnosed chronic noncommunicable diseases in the EU; 30% of the total European population is suffering from allergies and asthma, and more than half are deprived from adequate diagnosis and treatment. Precision medicine represents a novel approach, embracing four key features: personalized care based on molecular, immunologic, and functional endotyping of the disease, with participation of the patient in the decision-making process of therapeutic actions, and considering predictive and preventive aspects of the treatment. Implementation of precision medicine into clinical practice may help to achieve the arrest of the epidemic of allergies and chronic airways diseases. Participants underscored the need for optimal patient care in Europe, supporting joint action plans for disease prevention, patient empowerment, and cost-effective treatment strategies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice.

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Seys, Leen J M; Verhamme, Fien M; Dupont, Lisa L; Desauter, Elke; Duerr, Julia; Seyhan Agircan, Ayca; Conickx, Griet; Joos, Guy F; Brusselle, Guy G; Mall, Marcus A; Bracke, Ken R

2015-01-01

Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown. We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na⁺ channel (βENaC). βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured. Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements. We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

Surfactant protein D attenuates sub-epithelial fibrosis in allergic airways disease through TGF-β.

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Ogawa, Hirohisa; Ledford, Julie G; Mukherjee, Sambuddho; Aono, Yoshinori; Nishioka, Yasuhiko; Lee, James J; Izumi, Keisuke; Hollingsworth, John W

2014-11-29

Surfactant protein D (SP-D) can regulate both innate and adaptive immunity. Recently, SP-D has been shown to contribute to the pathogenesis of airway allergic inflammation and bleomycin-induced pulmonary fibrosis. However, in allergic airways disease, the role of SP-D in airway remodeling remains unknown. The objective of this study was to determine the contribution of functional SP-D in regulating sub-epithelial fibrosis in a mouse chronic house dust mite model of allergic airways disease. C57BL/6 wild-type (WT) and SP-D-/- mice (C57BL/6 background) were chronically challenged with house dust mite antigen (Dermatophagoides pteronyssinus, Dp). Studies with SP-D rescue and neutralization of TGF-β were conducted. Lung histopathology and the concentrations of collagen, growth factors, and cytokines present in the airspace and lung tissue were determined. Cultured eosinophils were stimulated by Dp in presence or absence of SP-D. Dp-challenged SP-D-/- mice demonstrate increased sub-epithelial fibrosis, collagen production, eosinophil infiltration, TGF-β1, and IL-13 production, when compared to Dp-challenged WT mice. By immunohistology, we detected an increase in TGF-β1 and IL-13 positive eosinophils in SP-D-/- mice. Purified eosinophils stimulated with Dp produced TGF-β1 and IL-13, which was prevented by co-incubation with SP-D. Additionally, treatment of Dp challenged SP-D-/- mice with exogenous SP-D was able to rescue the phenotypes observed in SP-D-/- mice and neutralization of TGF-β1 reduced sub-epithelial fibrosis in Dp-challenged SP-D-/- mice. These data support a protective role for SP-D in the pathogenesis of sub-epithelial fibrosis in a mouse model of allergic inflammation through regulation of eosinophil-derived TGF-β.

A pediatric case of life-threatening airway obstruction caused by a cervicomediastinal thymic cyst

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Komura, Makoto; Kanamori, Yutaka; Sugiyama, Masahiko; Iwanaka, Tadashi [University of Tokyo Hospital, Department of Pediatric Surgery, Tokyo (Japan); Fukushima, Noriyoshi [University of Tokyo Hospital, Department of Pathology, Tokyo (Japan)

2010-09-15

Most patients with thymic cysts complain of a slowly enlarging, asymptomatic cervical mass. Only 6-10% suffer dysphagia, dyspnoea, stridor, cervical pain or vocal paralysis. In some rare cases sudden onset of severe dyspnoea or asphyxia is the first symptom, especially in neonates and small infants. We report a unique case of a 20-month-old child, who required emergency tracheal intubation due to asphyxia. Cervicomediastinal thymic cyst might need to be included in causes of life-threatening airway obstruction in young children. (orig.)

Functional phenotype of airway myocytes from asthmatic airways

NARCIS (Netherlands)

Wright, David B.; Trian, Thomas; Siddiqui, Sana; Pascoe, Chris D.; Ojo, Oluwaseun O.; Johnson, Jill R.; Dekkers, Bart G. J.; Dakshinamurti, Shyamala; Bagchi, Rushita; Burgess, Janette K.; Kanabar, Varsha

In asthma, the airway smooth muscle (ASM) cell plays a central role in disease pathogenesis through cellular changes which may impact on its microenvironment and alter ASM response and function. The answer to the long debated question of what makes a 'healthy' ASM cell become 'asthmatic' still

Bactericidal/Permeability-increasing protein fold-containing family member A1 in airway host protection and respiratory disease.

Science.gov (United States)

Britto, Clemente J; Cohn, Lauren

2015-05-01

Bactericidal/permeability-increasing protein fold-containing family member A1 (BPIFA1), formerly known as SPLUNC1, is one of the most abundant proteins in respiratory secretions and has been identified with increasing frequency in studies of pulmonary disease. Its expression is largely restricted to the respiratory tract, being highly concentrated in the upper airways and proximal trachea. BPIFA1 is highly responsive to airborne pathogens, allergens, and irritants. BPIFA1 actively participates in host protection through antimicrobial, surfactant, airway surface liquid regulation, and immunomodulatory properties. Its expression is modulated in multiple lung diseases, including cystic fibrosis, chronic obstructive pulmonary disease, respiratory malignancies, and idiopathic pulmonary fibrosis. However, the role of BPIFA1 in pulmonary pathogenesis remains to be elucidated. This review highlights the versatile properties of BPIFA1 in antimicrobial protection and its roles as a sensor of environmental exposure and regulator of immune cell function. A greater understanding of the contribution of BPIFA1 to disease pathogenesis and activity may clarify if BPIFA1 is a biomarker and potential drug target in pulmonary disease.

Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

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Yunye Ning

Full Text Available BACKGROUND: Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD and asthma. Cigarette smoking (CS is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. METHODS: Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. RESULTS: Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. CONCLUSION: Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.

Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

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Carla M. P. Ribeiro

2017-01-01

Full Text Available Cystic fibrosis (CF pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR. This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease.

Identification of common allergens for united airway disease by skin prick test

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Vikas Deep Mishra

2016-01-01

Full Text Available Objective: Identification of common allergens by skin prick test in patients of united airway disease. Materials and Methods: Skin prick test was performed in 60 patients of United Airway Disease to identify the common allergens. A total of 62 allergens consisting of 36 types of pollen, 5 fungi, 4 insects, 8 type of dusts, 4 dander, 3 fabrics, Dust mite and Parthenium leaves were tested. Result: Most common allergens were Dust mite (60% followed by Parthenium leaves (45%, insects (18.75%, pollen (14.81%, dust allergens (8.51%, fabrics (8.33%, fungi (5.66%, dander (5%. Most common insect allergens were cockroach (female (30%, cockroach (male (23.33%. Common pollens were Ricinus communis (28.33%, Amaranthus spinosus (28.33%, Parthenium hysterophorus (26.66%, Eucalyptus tereticornis (26.66% and Cynodon dactylon (25%. Common dust allergens were house dust (21.66%, paper dust (11.66% and cotton mill dust (10%. Among fabrics kapok cotton (13.33% showed maximum positivity. Among fungi Aspergillus fumigatus (10% followed by A. niger (6.66% were most common. In animal dander group common ones were cat dander followed by dog dander. Conclusion: In conclusion it can be said that the knowledge drawn by above study will help to treat patients by immunotherapy or avoidance strategy.

Detecting airway remodeling in COPD and emphysema using low-dose CT imaging

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Rudyanto, R.; Ceresa, M.; Muñoz-Barrutia, A.; Ortiz-de-Solorzano, C.

2012-03-01

In this study, we quantitatively characterize lung airway remodeling caused by smoking-related emphysema and Chronic Obstructive Pulmonary Disease (COPD), in low-dose CT scans. To that end, we established three groups of individuals: subjects with COPD (n=35), subjects with emphysema (n=38) and healthy smokers (n=28). All individuals underwent a low-dose CT scan, and the images were analyzed as described next. First the lung airways were segmented using a fast marching method and labeled according to its generation. Along each airway segment, cross-section images were resampled orthogonal to the airway axis. Next 128 rays were cast from the center of the airway lumen in each crosssection slice. Finally, we used an integral-based method, to measure lumen radius, wall thickness, mean wall percentage and mean peak wall attenuation on every cast ray. Our analysis shows that both the mean global wall thickness and the lumen radius of the airways of both COPD and emphysema groups were significantly different from those of the healthy group. In addition, the wall thickness change starts at the 3rd airway generation in the COPD patients compared with emphysema patients, who display the first significant changes starting in the 2nd generation. In conclusion, it is shown that airway remodeling happens in individuals suffering from either COPD or emphysema, with some local difference between both groups, and that we are able to detect and accurately quantify this process using images of low-dose CT scans.

IgE sensitization to inhalant allergens and the risk of airway infection and disease

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Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Thuesen, Betina Heinsbæk

2017-01-01

.26, 95% CI: 1.79, 2.86), and other chronic lower airway disease (HR = 1.31, 95% CI: 1.08, 1.58). In never smokers, the higher risk of pneumonia (HR = 1.73, 95% CI: 1.23, 2.44) and asthma (HR = 3.17, 95% CI: 2.10, 4.76) among IgE sensitized was more pronounced. CONCLUSIONS: IgE sensitization......-analysed, and expressed as hazard ratios, HRs (95% confidence intervals, CIs). RESULTS: The relative risks for IgE sensitized vs. non-sensitized were: for pneumonia (HR = 1.20, 95% CI: 1.01, 1.41), other acute airway infection (HR = 0.86, 95% CI: 0.60, 1.22), infection (HR = 1.06, 95% CI: 0.90, 1.24), asthma (HR = 2...

Stenting of major airway constriction

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Wu Xiaomei

2002-01-01

Objective: To investigate the correlated issues in the stenting treatment of major airway constriction. Methods: Nineteen cases of major airway stenting procedure were studied retrospectively. The clinical choice of stents of different advantages or deficiencies were discussed. The importance of intravenous anesthesia supporting, life-parameters monitoring during the procedures and the prevention of complications were analysed. Results: Under intravenous and local anesthesia, 19 Wallstents had been successively placed and relieved 19 cases of major airway constrictions due to malignant or benign diseases (15 of tumors, 3 of tuberculosis, 1 of tracheomalacia). Intravenous anesthesia and life-parameters monitoring had made the procedures more safe and precise. Conclusions: Major airway stenting is an reliable method for relieving tracheobronchial stenosis; and intravenous anesthesia supporting and life-parameters monitoring guarantee the satisfactions of procedures

Contributions of COPD, asthma, and ten comorbid conditions to health care utilization and patient-centered outcomes among US adults with obstructive airway disease

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Murphy TE

2017-08-01

Full Text Available Terrence E Murphy,1 Gail J McAvay,1 Heather G Allore,1 Jason A Stamm,2 Paul F Simonelli2 1Department of Internal Medicine, Section of Geriatrics, Yale University School of Medicine, New Haven, CT, USA; 2Department of Internal Medicine, Section of Thoracic Medicine, Geisinger Medical Center, Danville, PA, USA Background: Among persons with obstructive airway disease, the relative contributions of chronic obstructive pulmonary disease (COPD, asthma, and common comorbid conditions to health care utilization and patient-centered outcomes (PCOs have not been previously reported.Methods: We followed a total of 3,486 persons aged ≥40 years with COPD, asthma, or both at baseline, from the Medical Expenditure Panel Survey (MEPS cohorts enrolled annually from 2008 through 2012 for 1 year. MEPS is a prospective observational study of US households recording self-reported COPD, asthma, and ten medical conditions: angina, arthritis, cancer, coronary heart disease, cognitive impairment, diabetes, hypertension, lung cancer, myocardial infarction, and stroke/transient ischemic attack. We studied the separate contributions of these conditions to health care utilization (all-cause and respiratory disease hospitalization, any emergency department [ED] visit, and six or more outpatient visits and PCOs (seven or more days spent in bed due to illness, incident loss of mobility, and incident decline in self-perceived health.Results: COPD made the largest contributions to all-cause and respiratory disease hospitalization and ED visits, while arthritis made the largest contribution to outpatient health care. Arthritis and COPD, respectively, made the greatest contributions to the PCOs.Conclusion: COPD made the largest and second largest contributions to health care utilization and PCOs among US adults with obstructive airway disease. The twelve medical conditions collectively accounted for between 52% and 61% of the health care utilization outcomes and between 53

Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.

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Thorburn, Alison N; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

2012-05-01

Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.

Analysis of the Airway Microbiota of Healthy Individuals and Patients with Chronic Obstructive Pulmonary Disease by T-RFLP and Clone Sequencing

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Zakharkina, Tetyana; Heinzel, Elke; Koczulla, Rembert A

2013-01-01

Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease that affects a large number of patients and has significant impact. One hallmark of the disease is the presence of bacteria in the lower airways....

Recurrent airway obstructions in a patient with benign tracheal stenosis and a silicone airway stent: a case report

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Sriram, KB; Robinson, PC

2008-01-01

Airway stents (silicone and metal stents) are used to treat patients with benign tracheal stenosis, who are symptomatic and in whom tracheal surgical reconstruction has failed or is not appropriate. However airway stents are often associated with complications such as migration, granuloma formation and mucous hypersecretion, which cause significant morbidity, especially in patients with benign tracheal stenosis and relatively normal life expectancy. We report a patient who had frequent critical airway obstructions over 8 years due to granuloma and mucus hypersecretion in a silicone airway stent. The problem was resolved when the silicone stent was removed and replaced with a covered self expanding metal stent. PMID:18840299

Management of the Upper Airway in Cystic Fibrosis

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Illing, Elisa A.; Woodworth, Bradford A.

2015-01-01

Purpose of Review Upper airway disease engenders significant morbidity for patients with cystic fibrosis and is increasingly recognized as having a much greater role in pulmonary outcomes and quality of life than originally believed. Widespread disparate therapeutic strategies for cystic fibrosis chronic rhinosinusitis underscore the absence of a standardized treatment paradigm. This review outlines the most recent evidence-based trends in the management of upper airway disease in cystic fibrosis. Recent Findings The unified airway theory proposes that the sinuses are a focus of initial bacterial colonization which seeds the lower airway and may play a large role in maintaining lung infections. Mounting evidence suggests more aggressive treatment of the sinuses may confer significant improvement in pulmonary disease and quality of life outcomes in cystic fibrosis patients. However, there is a lack of high-level evidence regarding medical and surgical management of cystic fibrosis chronic rhinosinusitis that makes generalizations difficult. Summary Well designed clinical trials with long-term follow-up concerning medical and surgical interventions for cystic fibrosis sinus disease are required to establish standardized treatment protocols, but increased interest in the sinuses as a bacterial reservoir for pulmonary infections has generated considerable attention. PMID:25250804

Epithelial and endothelial cell plasticity in chronic obstructive pulmonary disease (COPD).

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Sohal, Sukhwinder Singh

2017-03-01

Chronic Obstructive Pulmonary Disease (COPD) is mainly caused by smoking and presents with shortness of breath that is progressive and irreversible. It is a worldwide health problem and the fourth most common cause of chronic disability and mortality (even in developed countries). It is a complex disease involving both the airway and lung parenchyma. Small-airway fibrosis is the main contributor to physiological airway dysfunction in COPD. One potential mechanism contributing to small-airway fibrosis is epithelial mesenchymal transition (EMT). When associated with angiogenesis (EMT-type-3), EMT may well also be linked to the development of airway epithelial cancer, which is closely associated with COPD and predominantly observed in large airways. Vascular remodeling has also been widely reported in smokers and patients with COPD but the mechanisms behind it are poorly understood. It is quite possible that the process of endothelial to mesenchymal transition (EndMT) is also active in COPD lungs, in addition to EMT. Understanding these pathological mechanisms will greatly enhance our knowledge of the immunopathology of smoking-related lung disease. Only by understanding these processes can new therapies be developed. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Cystic fibrosis lung disease: genetic influences, microbial interactions, and radiological assessment

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Moskowitz, Samuel M.; Gibson, Ronald L.; Effmann, Eric L.

2005-01-01

Cystic fibrosis (CF) is a multiorgan disease caused by mutation of the CF transmembrane conductance regulator (CFTR) gene. Obstructive lung disease is the predominant cause of morbidity and mortality; thus, most efforts to improve outcomes are directed toward slowing or halting lung-disease progression. Current therapies, such as mucolytics, airway clearance techniques, bronchodilators, and antibiotics, aim to suppress airway inflammation and the processes that stimulate it, namely, retention and infection of mucus plaques at the airway surface. New approaches to therapy that aim to ameliorate specific CFTR mutations or mutational classes by restoring normal expression or function are being investigated. Because of its sensitivity in detecting changes associated with early airway obstruction and regional lung disease, high-resolution CT (HRCT) complements pulmonary function testing in defining disease natural history and measuring response to both conventional and experimental therapies. In this review, perspectives on the genetics and microbiology of CF provide a context for understanding the increasing importance of HRCT and other imaging techniques in assessing CF therapies. (orig.)

Can a giant cervical osteophyte cause dysphagia and airway obstruction? A case report.

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Kapetanakis, Stylianos; Vasileiadis, Ioannis; Papanas, Nikolaos; Goulimari, Reggina; Maltezos, Eustratios

2011-05-01

Cervical spondylosis is a common disorder mainly affecting elderly people. It frequently presents with excessive bone formation (osteophytes). These may lead to pain and neurological deficits due to root compression. Dysphagia and airway obstruction due to a giant anterior osteophyte of the cervical spine are extremely rare. We present the case of an 81-year-old patient suffering from dysphagia and slight dyspnoea due to a giant cervical osteophyte. Osteophyte resection was performed and the patient was relieved from symptoms. This case highlights that a large cervical osteophyte may, albeit rarely, be the cause of simultaneously presenting dysphagia and dyspnoea, and should, therefore, be included in the diagnostic workup in such cases.

Effect of lung volume on airway luminal area assessed by computed tomography in chronic obstructive pulmonary disease.

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Kenta Kambara

Full Text Available BACKGROUND: Although airway luminal area (Ai is affected by lung volume (LV, how is not precisely understood. We hypothesized that the effect of LV on Ai would differ by airway generation, lung lobe, and chronic obstructive pulmonary disease (COPD severity. METHODS: Sixty-seven subjects (15 at risk, 18, 20, and 14 for COPD stages 1, 2, and 3 underwent pulmonary function tests and computed tomography scans at full inspiration and expiration (at functional residual capacity. LV and eight selected identical airways were measured in the right lung. Ai was measured at the mid-portion of the 3(rd, the segmental bronchus, to 6(th generation of the airways, leading to 32 measurements per subject. RESULTS: The ratio of expiratory to inspiratory LV (LV E/I ratio and Ai (Ai E/I ratio was defined for evaluation of changes. The LV E/I ratio increased as COPD severity progressed. As the LV E/I ratio was smaller, the Ai E/I ratio was smaller at any generation among the subjects. Overall, the Ai E/I ratios were significantly smaller at the 5(th (61.5% and 6(th generations (63.4% and than at the 3(rd generation (73.6%, p<0.001 for each, and also significantly lower in the lower lobe than in the upper or middle lobe (p<0.001 for each. And, the Ai E/I ratio decreased as COPD severity progressed only when the ratio was corrected by the LV E/I ratio (at risk v.s. stage 3 p<0.001, stage 1 v.s. stage 3 p<0.05. CONCLUSIONS: From full inspiration to expiration, the airway luminal area shrinks more at the distal airways compared with the proximal airways and in the lower lobe compared with the other lobes. Generally, the airways shrink more as COPD severity progresses, but this phenomenon becomes apparent only when lung volume change from inspiration to expiration is taken into account.

Alteration of Airway Reactivity and Reduction of Ryanodine Receptor Expression by Cigarette Smoke in Mice.

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Donovan, Chantal; Seow, Huei Jiunn; Royce, Simon G; Bourke, Jane E; Vlahos, Ross

2015-10-01

Small airways are a major site of airflow limitation in chronic obstructive pulmonary disease (COPD). Despite the detrimental effects of long-term smoking in COPD, the effects of acute cigarette smoke (CS) exposure on small airway reactivity have not been fully elucidated. Balb/C mice were exposed to room air (sham) or CS for 4 days to cause airway inflammation. Changes in small airway lumen area in response to contractile agents were measured in lung slices in situ using phase-contrast microscopy. Separate slices were pharmacologically maintained at constant intracellular Ca(2+) using caffeine/ryanodine before contractile measurements. Gene and protein analysis of contractile signaling pathways were performed on separate lungs. Monophasic contraction to serotonin became biphasic after CS exposure, whereas contraction to methacholine was unaltered. This altered pattern of contraction was normalized by caffeine/ryanodine. Expression of contractile agonist-specific receptors was unaltered; however, all isoforms of the ryanodine receptor were down-regulated. This is the first study to show that acute CS exposure selectively alters small airway contraction to serotonin and down-regulates ryanodine receptors involved in maintaining Ca(2+) oscillations in airway smooth muscle. Understanding the contribution of ryanodine receptors to altered airway reactivity may inform the development of novel treatment strategies for COPD.

THE ROLE OF MICROBIAL COMMUNITIES OF AIRWAYS IN PATHOGENESIS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

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S. V. Fedosenko

2014-01-01

Full Text Available This review summarizes the results of studies on the composition of microbial communities in the airways of healthy subjects and in patients with chronic obstructive pulmonary disease. Modern technologies of molecular-genetic identification methods of microorganisms allow to perform a deep analysis  of  the  respiratory  microbiom.  It  is  of  considerable  interest  to  determine  the  role  of  the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the efficacy of current therapy.

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

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Bernard, Alfred, E-mail: Alfred.bernard@uclouvain.be; Nickmilder, Marc; Dumont, Xavier

2015-07-15

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers

International Nuclear Information System (INIS)

Bernard, Alfred; Nickmilder, Marc; Dumont, Xavier

2015-01-01

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19–8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28–14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11–3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22–11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17–11.0), HDM (OR 5.20, 95% CI 1.40–24.2) or pollen (OR 5.82, 95% CI 1.51–27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools. - Highlights: • We conducted a cross-sectional study of 835 school adolescents. • The airway epithelium integrity was evaluated by measuring serum pneumoproteins. • The risk of allergic diseases was associated with a defective airway epithelium. • Childhood swimming in chlorinated pools can cause persistent epithelial

Pulmonary haemodynamics in coal workers pneumoconiosis and non-plneumoconiotic patients with chronic obstructive airways disease

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Bugalho de Almeida, A A; Schott, D; Zimmermann, I; Ulmer, W T

1980-01-01

The pulmonary haemodynamics of 22 patients with advanced forms of coal workers pneumoconiosis and chronic obstructive airways disease, and 24 patients with advanced forms of COAD without pneumoconiosis were studied. The results obtained permitted a haemodynamic distinction between these two groups of patients. The differences, at rest and during 25 W exercise, are discussed.

Thin-section CT imaging that correlates with pulmonary function tests in obstructive airway disease

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Arakawa, Hiroaki, E-mail: arakawa@dokkyomed.ac.jp [Department of Radiology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293 (Japan); Fujimoto, Kiminori [Department of Radiology, Kurume University School of Medicine (Japan); Fukushima, Yasutugu [Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University (Japan); Kaji, Yasushi [Department of Radiology, Dokkyo Medical University, 880 Kita-Kobayashi, Mibu, Tochigi 321-0293 (Japan)

2011-11-15

Purpose: The purpose of this study was to identify independent CT findings that correlated with pulmonary function tests (PFTs) in patients with obstructive airway diseases. Materials and methods: Sixty-eight patients with obstructive airway disease and 29 normal subjects (mean age, 52 years; 36 men and 61 women) underwent inspiratory and expiratory thin-section CT and PFTs. Patient with obvious emphysema was excluded. Two radiologists independently reviewed the images and semi-quantitatively evaluated lung attenuation (mosaic perfusion, air trapping) and airway abnormalities (extent and severity of bronchial wall thickening and bronchiectasis, bronchiolectasis or centrilobular nodules, mucous plugging). Univariate, multivariate and receiver operating characteristic (ROC) analyses were performed with CT findings and PFTs. Results: Forty-two patients showed obstructive PFTs, 26 symptomatic patients showed near-normal PFTs. On univariate analysis, air trapping and bronchial wall thickening showed highest correlation with obstructive PFTs such as FEV1.0/FVC, MMEF and FEF75 (r ranged from -0.712 to -0.782; p < 0.001), while mosaic perfusion and mucous plugging showed moderate correlation, and bronchiectasis, bronchiolectasis and nodules showed the least, but significant, correlation. Multiple logistic analyses revealed air trapping and bronchial wall thickening as the only significant independent determinants of obstructive PFTs. ROC analysis revealed the cut-off value of air trapping for obstructive PFTs to be one-third of whole lung (area under curve, 0.847). Conclusions: Our study confirmed air trapping and bronchial wall thickening are the most important observations when imaging obstructive PFTs. The cut-off value of air trapping for identifying obstructive PFTs was one-third of lung irrespective of inspiratory CT findings.

Spray cryotherapy (SCT): institutional evolution of techniques and clinical practice from early experience in the treatment of malignant airway disease.

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Browning, Robert; Turner, J Francis; Parrish, Scott

2015-12-01

Spray cryotherapy (SCT) was initially developed for gastroenterology (GI) endoscopic use in the esophagus. In some institutions where a device has been utilized by GI, transition to use in the airways by pulmonologists and thoracic surgeons occurred. Significant differences exist, however, in the techniques for safely using SCT in the airways. We describe the early experience at Walter Reed National Military Medical Center from 2011 to 2013 using SCT in patients with malignant airway disease and the evolution of our current techniques and clinical practice patterns for SCT use in patients. In November 2013 enrollment began in a multi-institutional prospective SCT registry in which we are still enrolling and will be reported on separately. Twenty-seven patients that underwent 80 procedures (2.96 procedures/patient). The average age was 63 years with a range of 20 to 87 years old. The average Eastern Cooperative Oncology Group (ECOG) status was 1.26. All malignancies were advanced stage disease. All procedures were performed in the central airways. Other modalities were used in combination with SCT in 31 (39%) of procedures. Additionally 45 of the 80 (56%) procedures were performed in proximity to a silicone, hybrid, or metal stent. Three complications occurred out of the 80 procedures. All three were transient hypoxia that limited continued SCT treatments. These patients were all discharged from the bronchoscopy recovery room to their pre-surgical state. SCT can be safely used for treatment of malignant airway tumor (MAT) in the airways. Understanding passive venting of the nitrogen gas produced as the liquid nitrogen changes to gas is important for safe use of the device. Complications can be minimized by adopting strict protocols to maximize passive venting and to allow for adequate oxygenation in between sprays.

Obstructive sleep apnea syndrome as a novel cause for Ménière's disease.

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Nakayama, Meiho; Kabaya, Kayoko

2013-10-01

Several recent reports have described the relation between sleep disorders and inner ear function. There are also many reports that insomnia is observed in Ménière's patients. However, the possibility that obstructive sleep apnea syndrome (OSAS) might affect Ménière's disease or other neurotological consequences was not noticed, until studies using polysomnography for these patients. OSAS may cause not only vestibular but also auditory dysfunction. Several reports suggest that insufficient supply of blood via the vertebral basilar artery, which supplies the inner ear, may cause hydropic distension of the endolymphatic system and lead to Ménière's disease. However, few people noticed that in OSAS this insufficient supply might be exacerbated in the night while patients are sleeping. Even more, we should note that Ménière's patients may not only suffer from insomnia, but also that the impaired sleep might be caused by OSAS. Physicians routinely prescribe benzodiazepines or other drugs that have hypnotic, muscle relaxing, antianxiety, and anticonvulsant properties for insomnia, but these properties may have the effect of aggravating OSAS symptoms. Continuous positive airway pressure (CPAP) is an effective therapy used worldwide for the treatment of OSAS. CPAP or surgeries for OSAS may also be useful as one aspect of treatment for Ménière's disease patients with OSAS.

Disruption of the Hepcidin/Ferroportin Regulatory System Causes Pulmonary Iron Overload and Restrictive Lung Disease

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Joana Neves

2017-06-01

Full Text Available Emerging evidence suggests that pulmonary iron accumulation is implicated in a spectrum of chronic lung diseases. However, the mechanism(s involved in pulmonary iron deposition and its role in the in vivo pathogenesis of lung diseases remains unknown. Here we show that a point mutation in the murine ferroportin gene, which causes hereditary hemochromatosis type 4 (Slc40a1C326S, increases iron levels in alveolar macrophages, epithelial cells lining the conducting airways and lung parenchyma, and in vascular smooth muscle cells. Pulmonary iron overload is associated with oxidative stress, restrictive lung disease with decreased total lung capacity and reduced blood oxygen saturation in homozygous Slc40a1C326S/C326S mice compared to wild-type controls. These findings implicate iron in lung pathology, which is so far not considered a classical iron-related disorder.

[Diseases to differentiate from COPD, with emphasis on bronchial asthma].

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Kanazawa, Minoru

2007-04-01

Differential diagnosis of chronic obstructive pulmonary disease (COPD) from asthma is not a difficult task for many clinicians. Patients with COPD have a history of heavy smoking and show a slowly progressive dyspnea on exertion and there is little variability in symptoms, and they show a poor response to bronchodilators and corticosteroids. Asthma usually begins in early childhood with atopy, shows episodic dyspnea with wheezing, especially during night and early morning. Some patients, however, show adult onset, irreversible airflow limitation, and neutrophilic airway inflammation. The airway remodeling in asthma may be the cause of confusing pathophysiology. Other diseases showing airway hyperresponsiveness, such as allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, and left heart failure presenting cardiac asthma, may sometimes show similar clinical pictures to COPD. Chronic airway diseases are also possible candidates for differential diagnosis of COPD. Bronchiectasis, sinobronchial syndrome, diffuse panbronchiolitis, obliterative bronchiolitis, and other chronic airway diseases should be considered. Some interstitial lung diseases, such as smoking-related interstitial lung diseases and lymphangioleiomyomatosis, often show obstructive ventilatory impairment, and therefore should be considered in differential diagnosis of COPD.

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 ...

Tracheostomy and radiotherapy in the management of laryngeal carcinoma causing airway obstruction

Energy Technology Data Exchange (ETDEWEB)

Dawes, P.J.D. [Sunderland District General Hospital (United Kingdom); Agrawal, R.K.; Dawes, P.J.D.K. [Newcastle General Hospital (United Kingdom); Williams, S. [Otago Univ., Dunedin (New Zealand)

1997-09-01

Between 1977 and 1985, 66 patients presenting with airway obstruction due to laryngeal squamous cell carcinoma were treated by tracheostomy and subsequent radiotherapy. Female survival (64% at 2 years and 35% at 5 years) was significantly better than male survival (19% at 2 years and 10% at 5 years). When four forms of management were compared, it appeared that 40 Gy in ten fractions over 21 days was associated with better survival. Because two of the treatment groups contained few patients, these were excluded from further analysis. When adjustments were made for sex, delay between tracheostomy and treatment, and residual disease, the difference in treatment response between those receiving 60+ Gy in 28-30 fractions over 42 days and those receiving 40 Gy in ten fractions over 21 days was not significant (hazard ratio 1.37; 95% CI 0.64-3.91). (author).

Tracheostomy and radiotherapy in the management of laryngeal carcinoma causing airway obstruction

International Nuclear Information System (INIS)

Dawes, P.J.D.; Agrawal, R.K.; Dawes, P.J.D.K.; Williams, S.

1997-01-01

Between 1977 and 1985, 66 patients presenting with airway obstruction due to laryngeal squamous cell carcinoma were treated by tracheostomy and subsequent radiotherapy. Female survival (64% at 2 years and 35% at 5 years) was significantly better than male survival (19% at 2 years and 10% at 5 years). When four forms of management were compared, it appeared that 40 Gy in ten fractions over 21 days was associated with better survival. Because two of the treatment groups contained few patients, these were excluded from further analysis. When adjustments were made for sex, delay between tracheostomy and treatment, and residual disease, the difference in treatment response between those receiving 60+ Gy in 28-30 fractions over 42 days and those receiving 40 Gy in ten fractions over 21 days was not significant (hazard ratio 1.37; 95% CI 0.64-3.91). (author)

Airway Secretory microRNAome Changes during Rhinovirus Infection in Early Childhood.

Directory of Open Access Journals (Sweden)

Maria J Gutierrez

Full Text Available Innate immune responses are fine-tuned by small noncoding RNA molecules termed microRNAs (miRs that modify gene expression in response to the environment. During acute infections, miRs can be secreted in extracellular vesicles (EV to facilitate cell-to-cell genetic communication. The purpose of this study was to characterize the baseline population of miRs secreted in EVs in the airways of young children (airway secretory microRNAome and examine the changes during rhinovirus (RV infection, the most common cause of asthma exacerbations and the most important early risk factor for the development of asthma beyond childhood.Nasal airway secretions were obtained from children (≤3 yrs. old during PCR-confirmed RV infections (n = 10 and age-matched controls (n = 10. Nasal EVs were isolated with polymer-based precipitation and global miR profiles generated using NanoString microarrays. We validated our in vivo airway secretory miR data in an in vitro airway epithelium model using apical secretions from primary human bronchial epithelial cells (HBEC differentiated at air-liquid interface (ALI. Bioinformatics tools were used to determine the unified (nasal and bronchial signature airway secretory miRNAome and changes during RV infection in children.Multiscale analysis identified four signature miRs comprising the baseline airway secretory miRNAome: hsa-miR-630, hsa-miR-302d-3p, hsa- miR-320e, hsa-miR-612. We identified hsa-miR-155 as the main change in the baseline miRNAome during RV infection in young children. We investigated the potential biological relevance of the airway secretion of hsa-mir-155 using in silico models derived from gene datasets of experimental in vivo human RV infection. These analyses confirmed that hsa-miR-155 targetome is an overrepresented pathway in the upper airways of individuals infected with RV.Comparative analysis of the airway secretory microRNAome in children indicates that RV infection is associated with airway

Scaled experiments for improving diagnosis of pathological lower-airway obstruction

Science.gov (United States)

Liu, Chang; Kiger, Ken; Hariprasad, Daniel; Sul, Bora; Wallqvist, Anders; Reifman, Jaques

2017-11-01

Many lung diseases, such as asthma and chronic obstructive pulmonary disease, are characterized by obstructed airflow, particularly, in the lower airway branches in the lung. Existing diagnostic tools cannot detect some diseases due to a lack of instrumentation capable of resolving the flow in the lower airways. Recent developments in MRI techniques using hyperpolarized 3He now permit measurement of velocity profiles within the trachea. Motivated by these advances, we aim to provide a better understanding of the connection between lower-airway obstruction and velocity profiles within the trachea. Specifically, we asked whether the flow deficits created by lower-airway obstructions could be detected in the trachea to permit diagnosis of the pathology. To test this idea, we used refractive index-matched materials to construct a scaled, patient-specific, transparent lung model, and coupled it to 5 independently controlled piston pumps that could generate arbitrary flow histories (healthy or diseased) for the 5 different lung lobes. Results obtained by stereo PIV within various regions of the airway network will be presented documenting the system performance and examining the detectability of under-performing lobes within the tracheal flow profile. This work supported by the Henry M. Jackson Foundation under award #3270.

Nonstent Combination Interventional Therapy for Treatment of Benign Cicatricial Airway Stenosis

OpenAIRE

Xiao-Jian Qiu; Jie Zhang; Ting Wang; Ying-Hua Pei; Min Xu

2015-01-01

Background: Benign cicatricial airway stenosis (BCAS) is a life-threatening disease. While there are numerous therapies, all have their defects, and stenosis can easily become recurrent. This study aimed to investigate the efficacy and complications of nonstent combination interventional therapy (NSCIT) when used for the treatment of BCAS of different causes and types. Methods: This study enrolled a cohort of patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and othe...

Airway Clearance Techniques (ACTs)

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Full Text Available ... many challenges, including medical, social, and financial. By learning more about how you can manage your disease every day, you can ultimately help find a ... Cycle of Breathing Technique Airway Clearance Techniques Autogenic ...

Immunomodulation of afferent neurons in guinea-pig isolated airway.

Science.gov (United States)

Riccio, M M; Myers, A C; Undem, B J

1996-03-01

1. The trachea, larynx and main bronchi with the right vagus nerve and nodose ganglion were isolated from guinea-pigs passively immunized 24 h previously with serum containing anti-ovalbumin antibody. 2. The airways were placed in one compartment of a Perspex chamber for recording of isometric tension while the nodose ganglion and attached vagus nerve were pulled into another compartment. Action potentials arriving from single airway afferent nerve endings were monitored extracellularly using a glass microelectrode positioned near neuronal cell bodies in the ganglion. Mechanosensitivity of the nerve endings was quantified using calibrated von Frey filaments immediately before and after exposure to antigen (10 micrograms ml-1 ovalbumin). 3. Ten endings responded to the force exerted by the lowest filament (0.078 mN) and were not further investigated. In airways from thirteen immunized guinea-pigs, the mechanical sensitivity of A delta afferent fibres (conduction velocity = 4.3 +/- 0.6 m s-1) was enhanced 4.1 +/- 0.9-fold following airway exposure to antigen (P action potential generation except in one instance when the receptive field was located over the smooth muscle. This ending also responded to methacholine suggesting that spatial changes in the receptive field, induced by muscle contraction, were responsible for the activation. 5. The mediators responsible for these effects are unknown, although histamine, prostaglandins, leukotrienes and tachykinins do not appear to be essential. The increase in mechanical responsiveness was not associated with the smooth muscle contraction since leukotriene C4, histamine and tachykinins, which all caused a similar contraction to antigen, did not affect mechanical thresholds. Moreover, the antigen-induced increases in excitability persisted beyond the duration of the smooth muscle contraction. 6. These results demonstrate that antigen-antibody-mediated inflammatory processes may enhance the excitability of vagal afferent

Inhaled antibiotics for lower airway infections.

Science.gov (United States)

Quon, Bradley S; Goss, Christopher H; Ramsey, Bonnie W

2014-03-01

Inhaled antibiotics have been used to treat chronic airway infections since the 1940s. The earliest experience with inhaled antibiotics involved aerosolizing antibiotics designed for parenteral administration. These formulations caused significant bronchial irritation due to added preservatives and nonphysiologic chemical composition. A major therapeutic advance took place in 1997, when tobramycin designed for inhalation was approved by the U.S. Food and Drug Administration (FDA) for use in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa infection. Attracted by the clinical benefits observed in CF and the availability of dry powder antibiotic formulations, there has been a growing interest in the use of inhaled antibiotics in other lower respiratory tract infections, such as non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and in the post-lung transplant setting over the past decade. Antibiotics currently marketed for inhalation include nebulized and dry powder forms of tobramycin and colistin and nebulized aztreonam. Although both the U.S. Food and Drug Administration and European Medicines Agency have approved their use in CF, they have not been approved in other disease areas due to lack of supportive clinical trial evidence. Injectable formulations of gentamicin, tobramycin, amikacin, ceftazidime, and amphotericin are currently nebulized "off-label" to manage non-CF bronchiectasis, drug-resistant nontuberculous mycobacterial infections, ventilator-associated pneumonia, and post-transplant airway infections. Future inhaled antibiotic trials must focus on disease areas outside of CF with sample sizes large enough to evaluate clinically important endpoints such as exacerbations. Extrapolating from CF, the impact of eradicating organisms such as P. aeruginosa in non-CF bronchiectasis should also be evaluated.

NEUROTROPHIN MEDIATION OF ALLERGIC AIRWAYS RESPONSES TO INHALED DIESEL PARTICLES IN MICE

Science.gov (United States)

Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway hyper-responsiveness. Diesel exhaust particulates (DEP) associated with the combustion of diesel fuel exacerbate many of these allergic airways respons...

Diagnosis of bronchiectasis and airway wall thickening in children with cystic fibrosis. Objective airway-artery quantification

International Nuclear Information System (INIS)

Kuo, Wieying; Tiddens, Harm A.W.M.; Bruijne, Marleen de; Petersen, Jens; Nasserinejad, Kazem; Ozturk, Hadiye; Chen, Yong; Perez-Rovira, Adria

2017-01-01

To quantify airway and artery (AA)-dimensions in cystic fibrosis (CF) and control patients for objective CT diagnosis of bronchiectasis and airway wall thickness (AWT). Spirometer-guided inspiratory and expiratory CTs of 11 CF and 12 control patients were collected retrospectively. Airway pathways were annotated semi-automatically to reconstruct three-dimensional bronchial trees. All visible AA-pairs were measured perpendicular to the airway axis. Inner, outer and AWT (outer-inner) diameter were divided by the adjacent artery diameter to compute A in A-, A out A- and A WT A-ratios. AA-ratios were predicted using mixed-effects models including disease status, lung volume, gender, height and age as covariates. Demographics did not differ significantly between cohorts. Mean AA-pairs CF: 299 inspiratory; 82 expiratory. Controls: 131 inspiratory; 58 expiratory. All ratios were significantly larger in inspiratory compared to expiratory CTs for both groups (p<0.001). A out A- and A WT A-ratios were larger in CF than in controls, independent of lung volume (p<0.01). Difference of A out A- and A WT A-ratios between patients with CF and controls increased significantly for every following airway generation (p<0.001). Diagnosis of bronchiectasis is highly dependent on lung volume and more reliably diagnosed using outer airway diameter. Difference in bronchiectasis and AWT severity between the two cohorts increased with each airway generation. (orig.)

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.

Airway Clearance Techniques (ACTs)

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

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 ...

Airway Clearance Techniques (ACTs)

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

Rule-based detection of intrathoracic airway trees

International Nuclear Information System (INIS)

Sonka, M.; Park, W.; Hoffman, E.A.

1996-01-01

New sensitive and reliable methods for assessing alterations in regional lung structure and function are critically important for the investigation and treatment of pulmonary diseases. Accurate identification of the airway tree will provide an assessment of airway structure and will provide a means by which multiple volumetric images of the lung at the same lung volume over time can be used to assess regional parenchymal changes. The authors describe a novel rule-based method for the segmentation of airway trees from three-dimensional (3-D) sets of computed tomography (CT) images, and its validation. The presented method takes advantage of a priori anatomical knowledge about pulmonary airway and vascular trees and their interrelationships. The method is based on a combination of 3-D seeded region growing that is used to identify large airways, rule-based two-dimensional (2-D) segmentation of individual CT slices to identify probable locations of smaller diameter airways, and merging of airway regions across the 3-D set of slices resulting in a tree-like airway structure. The method was validated in 40 3-mm-thick CT sections from five data sets of canine lungs scanned via electron beam CT in vivo with lung volume held at a constant pressure. The method's performance was compared with that of the conventional 3-D region growing method. The method substantially outperformed an existing conventional approach to airway tree detection

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

Evaluation of obstructive airway lesions in complex congenital heart disease using composite volume-rendered images from multislice CT

International Nuclear Information System (INIS)

Choo, Ki Seok; Kim, Chang Won; Lee, Tae Hong; Kim, Suk; Kim, Kun Il; Lee, Hyoung Doo; Ban, Ji Eun; Sung, Si Chan; Chang, Yun Hee

2006-01-01

Multislice CT (MSCT) allows high-quality volume-rendered (VR) and composite volume-rendered images. To investigate the clinical usefulness of composite VR images in the evaluation of the relationship between cardiovascular structures and the airway in children with complex congenital heart disease (CHD). Four- or 16-slice MSCT scanning was performed consecutively in 77 children (mean age 6.4 months) with CHD and respiratory symptoms, a chest radiographic abnormality, or abnormal course of the pulmonary artery on ECHO. MSCT scanning was performed during breathing or after sedation. Contrast medium (2 ml/kg) was administered through a pedal venous route or arm vein in all patients. The VR technique was used to reconstruct the cardiovascular structures and airway, and then both VR images were composed using the commercial software (VoxelPlus 2 ; Daejeon, Korea). Stenoses were seen in the trachea in 1 patient and in the bronchi in 14 patients (19%). Other patients with complex CHD did not have significant airway stenoses. Composite VR images with MSCT can provide more exact airway images in relationship to the surrounding cardiovascular structures and thus help in optimizing management strategies in treating CHD. (orig.)

Airway ciliary dysfunction and respiratory symptoms in patients with transposition of the great arteries.

Science.gov (United States)

Zahid, Maliha; Bais, Abha; Tian, Xin; Devine, William; Lee, Dong Ming; Yau, Cyrus; Sonnenberg, Daniel; Beerman, Lee; Khalifa, Omar; Lo, Cecilia W

2018-01-01

Our prior work on congenital heart disease (CHD) with heterotaxy, a birth defect involving randomized left-right patterning, has shown an association of a high prevalence of airway ciliary dysfunction (CD; 18/43 or 42%) with increased respiratory symptoms. Furthermore, heterotaxy patients with ciliary dysfunction were shown to have more postsurgical pulmonary morbidities. These findings are likely a reflection of the common role of motile cilia in both airway clearance and left-right patterning. As CHD comprising transposition of the great arteries (TGA) is commonly thought to involve disturbance of left-right patterning, especially L-TGA with left-right ventricular inversion, we hypothesize CHD patients with transposition of great arteries (TGA) may have high prevalence of airway CD with increased respiratory symptoms. We recruited 75 CHD patients with isolated TGA, 28% L and 72% D-TGA. Patients were assessed using two tests typically used for evaluating airway ciliary dysfunction in patients with primary ciliary dyskinesia (PCD), a recessive sinopulmonary disease caused by respiratory ciliary dysfunction. This entailed the measurement of nasal nitric oxide (nNO), which is typically low with PCD. We also obtained nasal scrapes and conducted videomicroscopy to assess respiratory ciliary motion (CM). We observed low nNO in 29% of the patients, and abnormal CM in 57%, with 22% showing both low nNO and abnormal CM. No difference was observed for the prevalence of either low nNO or abnormal ciliary motion between patients with D vs. L-TGA. Respiratory symptoms were increased with abnormal CM, but not low nNO. Sequencing analysis showed no compound heterozygous or homozygous mutations in 39 genes known to cause PCD, nor in CFTR, gene causing cystic fibrosis. As both are recessive disorders, these results indicate TGA patients with ciliary dysfunction do not have PCD or cystic fibrosis (which can cause low nNO or abnormal ciliary motion). TGA patients have high

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

Science.gov (United States)

Chotirmall, Sanjay H.; Al-Alawi, Mazen; Logan, P. Mark; Greene, Catherine M.; McElvaney, Noel G.

2013-01-01

Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit. PMID:23971044

Motorcycle exhaust particles induce airway inflammation and airway hyperresponsiveness in BALB/C mice.

Science.gov (United States)

Lee, Chen-Chen; Liao, Jiunn-Wang; Kang, Jaw-Jou

2004-06-01

A number of large studies have reported that environmental pollutants from fossil fuel combustion can cause deleterious effects to the immune system, resulting in an allergic reaction leading to respiratory tract damage. In this study, we investigated the effect of motorcycle exhaust particles (MEP), a major pollutant in the Taiwan urban area, on airway inflammation and airway hyperresponsiveness in laboratory animals. BALB/c mice were instilled intratracheally (i.t.) with 1.2 mg/kg and 12 mg/kg of MEP, which was collected from two-stroke motorcycle engines. The mice were exposed 3 times i.t. with MEP, and various parameters for airway inflammation and hyperresponsiveness were sequentially analyzed. We found that MEP would induce airway and pulmonary inflammation characterized by infiltration of eosinophils, neutrophils, lymphocytes, and macrophages in bronchoalveolar lavage fluid (BALF) and inflammatory cell infiltration in lung. In addition, MEP treatment enhanced BALF interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) cytokine levels and serum IgE production. Bronchial response measured by unrestrained plethysmography with methacholine challenge showed that MEP treatment induced airway hyperresponsiveness (AHR) in BALB/c mice. The chemical components in MEP were further fractionated with organic solvents, and we found that the benzene-extracted fraction exerts a similar biological effect as seen with MEP, including airway inflammation, increased BALF IL-4, serum IgE production, and induction of AHR. In conclusion, we present evidence showing that the filter-trapped particles emitted from the unleaded-gasoline-fueled two-stroke motorcycle engine may induce proinflammatory and proallergic response profiles in the absence of exposure to allergen.

25-Hydroxyvitamin D, IL-31, and IL-33 in Children with Allergic Disease of the Airways

Directory of Open Access Journals (Sweden)

Anna Bonanno

2014-01-01

Full Text Available Low vitamin D is involved in allergic asthma and rhinitis. IL-31 and IL-33 correlate with Th2-associated cytokines in allergic disease. We investigated whether low vitamin D is linked with circulating IL-31 and IL-33 in children with allergic disease of the airways. 25-Hydroxyvitamin D [25(OH Vit D], IL-31, and IL-33 plasma levels were measured in 28 controls (HC, 11 allergic rhinitis (AR patients, and 35 allergic asthma with rhinitis (AAR patients. We found significant lower levels of 25(OH Vit D in AR and in AAR than in HC. IL-31 and IL-33 plasma levels significantly increased in AAR than HC. IL-31 and IL-33 positively correlated in AR and AAR. 25(OH Vit D deficient AAR had higher levels of blood eosinophils, exacerbations, disease duration, and total IgE than patients with insufficient or sufficient 25(OH Vit D. In AAR 25(OH Vit D levels inversely correlated with total allergen sIgE score and total atopy index. IL-31 and IL-33 did not correlate with 25(OH Vit D in AR and AAR. In conclusion, low levels of 25(OH Vit D might represent a risk factor for the development of concomitant asthma and rhinitis in children with allergic disease of the airways independently of IL-31/IL-33 Th2 activity.

Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases.

Science.gov (United States)

Hodge, Sandra; Tran, Hai B; Hamon, Rhys; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Ween, Miranda; Reynolds, Paul N; Yeung, Arthur; Treiberg, Jennifer; Wilbert, Sibylle

2017-05-01

We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides-2'-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2'-desoxy molecule (GS-560660)-with significantly diminished antibiotic activity against Staphylococcus aureus , Streptococcus pneumonia , Moraxella catarrhalis , and H. influenzae We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5-1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll

Differential distribution of inflammatory cells in large and small airways in smokers

NARCIS (Netherlands)

Battaglia, Salvatore; Mauad, Thais; van Schadewijk, Annemarie M.; Vignola, Antonia M.; Rabe, Klaus F.; Bellia, Vincenzo; Sterk, Peter J.; Hiemstra, Pieter S.

2007-01-01

BACKGROUND: Smoking induces structural changes in the airways, and is considered a major factor in the development of airflow obstruction in chronic obstructive pulmonary disease. However, differences in inflammatory cell distribution between large airways (LA) and small airways (SA) have not been

The potassium channel KCa3.1 as new therapeutic target for the prevention of obliterative airway disease

DEFF Research Database (Denmark)

Hua, Xiaoqin; Deuse, Tobias; Chen, Yi-Je

2013-01-01

The calcium-activated potassium channel KCa3.1 is critically involved in T-cell activation as well as in the proliferation of smooth muscle cells and fibroblasts. We sought to investigate whether KCa3.1 contributes to the pathogenesis of obliterative airway disease (OAD) and whether knockout or p...

Small airway disease after mycoplasma pneumonia in children: HRCT findings and correlation with radiographic findings

Energy Technology Data Exchange (ETDEWEB)

Cheon, Jung Eun; Kim, Woo Sun; Kim, In One; Koh, Young Yull; Lee, Hoan Jong; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2003-04-01

To assess the high-resolution CT (HRCT) findings of small airway abnormalities after mycoplasma pneumonia and correlate them with the findings of chest radiography performed during the acute and follow-up phases of the condition. We retrospectively evaluated HRCT and chest radiographic findings of 18 patients with clinical diagnosis of small airway disease after mycoplasma pneumonia (M:F=8:10, mean age: 8.3 years, mean time interval after the initial infection; 26 menths). We evaluated the lung parenchymal and bronchial abnormalities on HRCT (n=18). In addition, presence of air-trapping was assessed on expiratory scans (n=13). The findings of HRCT were correlated with those of chest radiography performed during the acute phase of initial infection (n=15) and at the time of CT examination (n=18), respectively. HRCT revealed lung parenchymal abnormalities in 13 patients (72%). A mosaic pattern of lung attenuation was noted in ten patients (10/18, 56%) and air-trapping on expiratory scans was observed in nine (9/13), 69%). In nine of 14 (64%) with negative findings at follow-up chest radiography, one or both of the above parenchymal abnormalities was observed at HRCT. In four patients (27%), parenchymal abnormalities were seen at HRCT in areas considered normal at acute-phase chest radiography. Bronchiectasis or ateclectasis was observed in eight (44%) and four (22%) patients, respectively, at HRCT. The CT features of Swyer-James syndrome such as a unilateral hyperlucent lung with reduced lung volume and attenuated vessels were noted in two patients(11%). HRCT can clearly demonstrate lung parenchymal and bronchial abnormalities of small airway disease after mycoplasma pneumonia in children.

Small airway disease after mycoplasma pneumonia in children: HRCT findings and correlation with radiographic findings

International Nuclear Information System (INIS)

Cheon, Jung Eun; Kim, Woo Sun; Kim, In One; Koh, Young Yull; Lee, Hoan Jong; Yeon, Kyung Mo

2003-01-01

To assess the high-resolution CT (HRCT) findings of small airway abnormalities after mycoplasma pneumonia and correlate them with the findings of chest radiography performed during the acute and follow-up phases of the condition. We retrospectively evaluated HRCT and chest radiographic findings of 18 patients with clinical diagnosis of small airway disease after mycoplasma pneumonia (M:F=8:10, mean age: 8.3 years, mean time interval after the initial infection; 26 menths). We evaluated the lung parenchymal and bronchial abnormalities on HRCT (n=18). In addition, presence of air-trapping was assessed on expiratory scans (n=13). The findings of HRCT were correlated with those of chest radiography performed during the acute phase of initial infection (n=15) and at the time of CT examination (n=18), respectively. HRCT revealed lung parenchymal abnormalities in 13 patients (72%). A mosaic pattern of lung attenuation was noted in ten patients (10/18, 56%) and air-trapping on expiratory scans was observed in nine (9/13), 69%). In nine of 14 (64%) with negative findings at follow-up chest radiography, one or both of the above parenchymal abnormalities was observed at HRCT. In four patients (27%), parenchymal abnormalities were seen at HRCT in areas considered normal at acute-phase chest radiography. Bronchiectasis or ateclectasis was observed in eight (44%) and four (22%) patients, respectively, at HRCT. The CT features of Swyer-James syndrome such as a unilateral hyperlucent lung with reduced lung volume and attenuated vessels were noted in two patients(11%). HRCT can clearly demonstrate lung parenchymal and bronchial abnormalities of small airway disease after mycoplasma pneumonia in children

Dilemmas, Confusion, and Misconceptions Related to Small Airways Directed Therapy

DEFF Research Database (Denmark)

Lavorini, Federico; Pedersen, Søren; Usmani, Omar S.

2017-01-01

During the past decade, there has been increasing evidence that the small airways (ie, airways < 2 mm in internal diameter) contribute substantially to the pathophysiologic and clinical expression of asthma and COPD. The increased interest in small airways is, at least in part, a result of innova......During the past decade, there has been increasing evidence that the small airways (ie, airways COPD. The increased interest in small airways is, at least in part, a result...... of innovation in small-particle aerosol formulations that better target the distal lung and also advanced physiologic methods of assessing small airway responses. Increasing the precision of drug deposition may improve targeting of specific diseases or receptor locations, decrease airway drug exposure...... benefit, compared with large-particle aerosol treatment. However, a number of questions remain unanswered about the pragmatic approach relevant for clinicians to consider the role of small airways directed therapy in the day-to-day management of asthma and COPD. We thus have tried to clarify the dilemmas...

Diagnosis of bronchiectasis and airway wall thickening in children with cystic fibrosis. Objective airway-artery quantification

Energy Technology Data Exchange (ETDEWEB)

Kuo, Wieying; Tiddens, Harm A.W.M. [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Erasmus MC, Department of Radiology, Rotterdam (Netherlands); Bruijne, Marleen de [Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Rotterdam (Netherlands); University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Petersen, Jens [University of Copenhagen, Department of Computer Science, Copenhagen (Denmark); Nasserinejad, Kazem [Erasmus MC Cancer Institute, HOVON Data Center, Clinical Trial Center, Rotterdam (Netherlands); Erasmus MC, Department of Biostatistics, Rotterdam (Netherlands); Ozturk, Hadiye [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Chen, Yong [General Hospital of Ningxia Medical University, Department of Radiology, Yinchuan (China); Perez-Rovira, Adria [Erasmus MC - Sophia Children' s Hospital, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); Erasmus MC, Biomedical Imaging Group Rotterdam, Departments of Medical Informatics and Radiology, Rotterdam (Netherlands)

2017-11-15

To quantify airway and artery (AA)-dimensions in cystic fibrosis (CF) and control patients for objective CT diagnosis of bronchiectasis and airway wall thickness (AWT). Spirometer-guided inspiratory and expiratory CTs of 11 CF and 12 control patients were collected retrospectively. Airway pathways were annotated semi-automatically to reconstruct three-dimensional bronchial trees. All visible AA-pairs were measured perpendicular to the airway axis. Inner, outer and AWT (outer-inner) diameter were divided by the adjacent artery diameter to compute A{sub in}A-, A{sub out}A- and A{sub WT}A-ratios. AA-ratios were predicted using mixed-effects models including disease status, lung volume, gender, height and age as covariates. Demographics did not differ significantly between cohorts. Mean AA-pairs CF: 299 inspiratory; 82 expiratory. Controls: 131 inspiratory; 58 expiratory. All ratios were significantly larger in inspiratory compared to expiratory CTs for both groups (p<0.001). A{sub out}A- and A{sub WT}A-ratios were larger in CF than in controls, independent of lung volume (p<0.01). Difference of A{sub out}A- and A{sub WT}A-ratios between patients with CF and controls increased significantly for every following airway generation (p<0.001). Diagnosis of bronchiectasis is highly dependent on lung volume and more reliably diagnosed using outer airway diameter. Difference in bronchiectasis and AWT severity between the two cohorts increased with each airway generation. (orig.)

Airways obstruction, coal mining, and disability.

OpenAIRE

Lapp, N L; Morgan, W K; Zaldivar, G

1994-01-01

It has recently been suggested that the inhalation of coal in the absence of complicated coal workers' pneumoconiosis (CWP) or smoking can lead to disabling airways obstruction. The cause of such obstruction has been variously attributed to emphysema or bronchitis. The frequency of significant airways obstruction in a group of United States coal miners seeking compensation for occupationally induced pulmonary impairment was therefore determined. In a sample of 611 "Black Lung" claimants there...

Management of benign stenoses of the large airways in the university hospital in Prague, Czech Republic, in 1998-2003.

Science.gov (United States)

Marel, Miloslav; Pekarek, Zdenek; Spasova, Irena; Pafko, Pavel; Schutzner, Jan; Betka, Jan; Pospisil, Ronald

2005-01-01

Clinically significant benign stenoses of the large airways develop in about 1% of patients after intubation. The management of benign stenoses is not unified around the world, nor are there any accepted methods for their screening. The purpose of this study is to describe and compare results of interventional bronchoscopy and surgical therapy of benign stenoses as well as to propose an algorithm for the management of this airways disorder. Prospective study on 80 consecutive patients with benign stenoses of the large airways admitted to the Pulmonary Department of the University Hospital of Prague-Motol. Sixty-two patients developed stenoses after endotracheal intubation or tracheostomy, in 18 patients the stenosis was caused by other diseases or pathological situations. Thirty-eight patients were sent for surgical resection of the stenotic part of the airways. 2 surgically treated patients developed recurrence of the stenosis and had to be reoperated on. Narrowing of the trachea at the site of end-to-end anastomosis developed in 6 other patients and was cured by interventional bronchoscopy. The remaining 42 patients were treated by interventional bronchoscopy (Nd-YAG laser, electrocautery, stent) which was curative in 35 patients. Sixty-five patients were alive at the time of evaluation, 15 patients died. Five of them died between 3 and 14 (median 4) months after surgery from a disease other than airway stenosis. Ten nonresected patients also died, with 1 exception, due to a disease other than airway stenosis; the median survival was 9 months. We recommend to assess the patient for surgery after the initial diagnosis and therapeutic bronchoscopy with dilatation of the stenosis. If the patient is not a suitable candidate for resection, interventional bronchoscopy is an appropriate alternative for the management of benign stenoses of the large airways. Copyright (c) 2005 S. Karger AG, Basel.

Recurrent airway obstructions in a patient with benign tracheal stenosis and a silicone airway stent: a case report

OpenAIRE

Sriram, KB; Robinson, PC

2008-01-01

Airway stents (silicone and metal stents) are used to treat patients with benign tracheal stenosis, who are symptomatic and in whom tracheal surgical reconstruction has failed or is not appropriate. However airway stents are often associated with complications such as migration, granuloma formation and mucous hypersecretion, which cause significant morbidity, especially in patients with benign tracheal stenosis and relatively normal life expectancy. We report a patient who had frequent critic...

The asthma–COPD overlap syndrome: do we really need another syndrome in the already complex matrix of airway disease?

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Kostikas K

2016-06-01

Full Text Available Konstantinos Kostikas, Andreas Clemens, Francesco Patalano Novartis Pharma AG, Basel, Switzerland Abstract: The term asthma–COPD overlap syndrome (ACOS is one of multiple terms used to describe patients with characteristics of both COPD and asthma, representing ~20% of patients with obstructive airway diseases. The recognition of both sets of morbidities in patients is important to guide practical treatment decisions. It is widely recognized that patients with COPD and coexisting asthma present with a higher disease burden, despite the conceptual expectation that the “reversible” or “treatable” component of asthma would allow for more effective management and better outcomes. However, subcategorization into terms such as ACOS is complicated by the vast spectrum of heterogeneity that is encapsulated by asthma and COPD, resulting in different clinical clusters. In this review, we discuss the possibility that these different clusters are suboptimally described by the umbrella term “ACOS”, as this additional categorization may lead to clinical confusion and potential inappropriate use of resources. We suggest that a more clinically relevant approach would be to recognize the extreme variability and the numerous phenotypes encompassed within obstructive airway diseases, with various degrees of overlapping in individual patients. In addition, we discuss some of the evidence to be considered when making practical decisions on the treatment of patients with overlapping characteristics between COPD and asthma, as well as the potential options for phenotype and biomarker-driven management of airway disease with the aim of providing more personalized treatment for patients. Finally, we highlight the need for more evidence in patients with overlapping disease characteristics and to facilitate better characterization of potential treatment responders. Keywords: emphysema, chronic bronchitis, COPD, asthma, ACOS, overlap syndrome

Airway remodeling and its reversibility in equine asthma

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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

The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics.

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Sonia R Rosner

Full Text Available Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM cells to stretch, but underlying molecular mechanisms-and their failure in asthma-remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma.

Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis.

Science.gov (United States)

Kuranishi, Lilian Tiemi; Leslie, Kevin O; Ferreira, Rimarcs Gomes; Coletta, Ester Aparecida Ney; Storrer, Karin Mueller; Soares, Maria Raquel; de Castro Pereira, Carlos Alberto

2015-05-09

Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic pattern observed in our practice. The objectives of this study are to describe the causes associated with ACIF in a large sample of patients and its effect on survival. A retrospective study in three centers of interstitial lung disease in São Paulo, between January of 1995 and December of 2012. The surgical lung biopsy specimens were reviewed by three pathologists. The clinical, functional and tomographic findings were analyzed by a standardized protocol. There were 68 cases of ACIF, most of them women. The mean age was 57 ± 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen desaturation at exercise were common. A reticular pattern with peribronchovascular infiltrates was found in 79% of the cases. The etiologies of ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of them in 15 cases and idiopathic in 3 (4.4%). The median survival was 116 months (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of cough and some histological findings--organizing tissue in the airways, fibroblastic foci and microscopic honeycombing--were predictors of worse survival. ACIF is an interstitial lung disease with a better survival when compared with IPF. The main etiologies are HP and GERD. The oxygen saturation at rest, the presence of cough and some histological findings are predictors of survival.

Use of radioisotope techniques for the diagnosis of obstructive airway disease

Energy Technology Data Exchange (ETDEWEB)

Furudate, M; Itoh, K; Shida, A; Minami, Y [Hokkaido Univ., Sapporo (Japan). School of Medicine

1981-07-01

Perfusion scintigraphy, radioaerosol inhalation scintigraphy, /sup 133/Xe studies and sup(81m)Kr studies are useful radioisotope techniques for the detection of regional pulmonary abnormalities in obstructive airway disease. The patient during asthmatic attack shows the perfusion defects with indefinite boundary, which may change during the following several days. Decreased ventilation are seen on the regions with perfusion defects, and ventilatory defects are more marked than those of perfusion. On the other hand, these abnomal findings are reversible. In chronic emphysema or chronic bronchitis, the regions with decreased perfusion usually cannot be correlated with any specific segments, and scintigraphys done repeatedly fail to show re-vascularization on the regions. In the radioaerosol inhalation scintigraphy, deposition pattern reveal the severity of COPD. In addition, xenon studies in the diseases show marked or moderate prolongation of wash-out from the abnormal region, and the abnormalities of ventilation are equal to or exceed the abnormalities of perfusion.

Minimum concentrations of NO/sub 2/ causing acute effects on the respiratory gas exchange and airway-resistance in patients with chronic bronchitis

Energy Technology Data Exchange (ETDEWEB)

von Nieding, G; Wagner, M; Krekeler, H; Smidt, U; Muysers, K

1971-01-01

Nitrogen dioxide-air mixtures containing 0.5 to 5.0 ppM NO/sub 2/ were inhaled by 88 patients with chronic bronchitis over a 15-minute period for a total of 30 breaths during studies investigating the effects of the gas on airway resistance and respiratory gas exchange. End-expiratory oxygen pressures remained nearly constant during inhalation of 4 or 5 ppM NO/sub 2/, though significant decreases in arterial oxygen pressure accompanied by increases in end-expiratory-arterial oxygen pressure difference occurred. Inhalation of 2 ppM NO/sub 2/ did not decrease arterial oxygen pressure. Airway resistances increased significantly down to 1.5 ppM NO/sub 2/ concentrations. Lower concentrations caused no significant effects.

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

Science.gov (United States)

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

2001-12-01

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

L-Arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction

NARCIS (Netherlands)

Maarsingh, H.; Bossenga, B. E.; Bos, I. S. T.; Volders, H. H.; Zaagsma, J.; Meurs, H.

Peroxynitrite has been shown to be crucially involved in airway hyperresponsiveness (AHR) after the late asthmatic reaction (LAR). Peroxynitrite production may result from simultaneous synthesis of nitric oxide (NO) and superoxide by inducible NO-synthase (iNOS) at low L-arginine concentrations.

Aspergillus-Associated Airway Disease, Inflammation, and the Innate Immune Response

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Sanjay H. Chotirmall

2013-01-01

Full Text Available Aspergillus moulds exist ubiquitously as spores that are inhaled in large numbers daily. Whilst most are removed by anatomical barriers, disease may occur in certain circumstances. Depending on the underlying state of the human immune system, clinical consequences can ensue ranging from an excessive immune response during allergic bronchopulmonary aspergillosis to the formation of an aspergilloma in the immunocompetent state. The severest infections occur in those who are immunocompromised where invasive pulmonary aspergillosis results in high mortality rates. The diagnosis of Aspergillus-associated pulmonary disease is based on clinical, radiological, and immunological testing. An understanding of the innate and inflammatory consequences of exposure to Aspergillus species is critical in accounting for disease manifestations and preventing sequelae. The major components of the innate immune system involved in recognition and removal of the fungus include phagocytosis, antimicrobial peptide production, and recognition by pattern recognition receptors. The cytokine response is also critical facilitating cell-to-cell communication and promoting the initiation, maintenance, and resolution of the host response. In the following review, we discuss the above areas with a focus on the innate and inflammatory response to airway Aspergillus exposure and how these responses may be modulated for therapeutic benefit.

The multifunctional host defense peptide SPLUNC1 is critical for homeostasis of the mammalian upper airway.

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Glen McGillivary

2010-10-01

Full Text Available Otitis media (OM is a highly prevalent pediatric disease caused by normal flora of the nasopharynx that ascend the Eustachian tube and enter the middle ear. As OM is a disease of opportunity, it is critical to gain an increased understanding of immune system components that are operational in the upper airway and aid in prevention of this disease. SPLUNC1 is an antimicrobial host defense peptide that is hypothesized to contribute to the health of the airway both through bactericidal and non-bactericidal mechanisms. We used small interfering RNA (siRNA technology to knock down expression of the chinchilla ortholog of human SPLUNC1 (cSPLUNC1 to begin to determine the role that this protein played in prevention of OM. We showed that knock down of cSPLUNC1 expression did not impact survival of nontypeable Haemophilus influenzae, a predominant causative agent of OM, in the chinchilla middle ear under the conditions tested. In contrast, expression of cSPLUNC1 was essential for maintenance of middle ear pressure and efficient mucociliary clearance, key defense mechanisms of the tubotympanum. Collectively, our data have provided the first in vivo evidence that cSPLUNC1 functions to maintain homeostasis of the upper airway and, thereby, is critical for protection of the middle ear.

The Groningen Laryngomalacia Classification System-Based on Systematic Review and Dynamic Airway Changes

NARCIS (Netherlands)

van der Heijden, Martijn; Dikkers, Frederik G.; Halmos, Gyorgy B.

2015-01-01

Objective: Laryngomalacia is the most common cause of dyspnea and stridor in newborn infants. Laryngomalacia is a dynamic change of the upper airway based on abnormally pliable supraglottic structures, which causes upper airway obstruction. In the past, different classification systems have been

Impending Airway Compromise due to Cystic Hygroma

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Itai Shavit

2011-05-01

Full Text Available We report on a 3-month-old infant, who arrived in the pediatric emergency department (ED with a cervical cystic hygroma causing an impending compromise of the airway. We recognize that such a lesion can rapidly progress, and the judicious use of imaging in the ED may help to avoid airway compromise and possibly fatal complications. [West J Emerg Med. 2011;12(4:368–369.

In vivo models of human airway epithelium repair and regeneration

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C. Coraux

2005-12-01

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

The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease

International Nuclear Information System (INIS)

Diaz-Sanchez, D.

1997-01-01

The increase in allergic airway disease has paralleled the increase in the use of fossil fuels. Studies were undertaken to examine whether extracts of polyaromatic hydrocarbons (PAH) from diesel exhaust particles (DEP) (PAH-DEP) acted as mucosal adjuvants to help initiate or enhance immunoglobulin E (IgE) production in response to common inhaled allergens. In vitro studies demonstrated that PAH-DEP enhanced IgE production by tonsilar B-cells in the presence of interleukin-4 (IL-4) and CD40 monoclonal antibody, and altered the nature of the IgE produced, i.e. a decrease in the CH4'-CHe5 variant, a marker for differentiation of IgE-producing B-cells, and an increase in the M2' variant. In vivo nasal provocation studies using 0.30 mg DEP in saline also showed enhanced IgE production in the human upper respiratory mucosa, accompanied by a reduced CH4'-CHe5 mRNA splice variant. The effect of DEP were also isotype-specific, with no effect on IgG, IgA, IgM, or albumin, but it produced a small increase in the IgG 4 subclass. The ability of DEP to act as an adjuvant to the ragweed allergen Amb a I was examined by nasal provocation in ragweed allergic subjects using 0.3 mg DEP, Amb a I, or both. Although allergen and DEP each enhanced ragweed-specific IgE, DEP plus allergen promoted a 16-times greater antigen-specific IgE production. Nasal challenge with DEP also influenced cytokine production. Ragweed challenge resulted in a weak response, DEP challenge caused a strong but non-specific response, while allergen plus DEP caused a significant increase in the expression of mRNA for TH 0 and TH 2 -type cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) with a pronounced inhibitory effect on IFN-γ gene expression. These studies suggest that DEP can enhance B-cell differentiation, and by initiating and elevating IgE production, may play an important role in the increased incidence of allergic airway disease. (au)

SPDEF regulates goblet cell hyperplasia in the airway epithelium

Science.gov (United States)

Park, Kwon-Sik; Korfhagen, Thomas R.; Bruno, Michael D.; Kitzmiller, Joseph A.; Wan, Huajing; Wert, Susan E.; Khurana Hershey, Gurjit K.; Chen, Gang; Whitsett, Jeffrey A.

2007-01-01

Goblet cell hyperplasia and mucous hypersecretion contribute to the pathogenesis of chronic pulmonary diseases including cystic fibrosis, asthma, and chronic obstructive pulmonary disease. In the present work, mouse SAM pointed domain-containing ETS transcription factor (SPDEF) mRNA and protein were detected in subsets of epithelial cells lining the trachea, bronchi, and tracheal glands. SPDEF interacted with the C-terminal domain of thyroid transcription factor 1, activating transcription of genes expressed selectively in airway epithelial cells, including Sftpa, Scgb1a1, Foxj1, and Sox17. Expression of Spdef in the respiratory epithelium of adult transgenic mice caused goblet cell hyperplasia, inducing both acidic and neutral mucins in vivo, and stainined for both acidic and neutral mucins in vivo. SPDEF expression was increased at sites of goblet cell hyperplasia caused by IL-13 and dust mite allergen in a process that was dependent upon STAT-6. SPDEF was induced following intratracheal allergen exposure and after Th2 cytokine stimulation and was sufficient to cause goblet cell differentiation of Clara cells in vivo. PMID:17347682

Peripherally Generated Foxp3+ Regulatory T Cells Mediate the Immunomodulatory Effects of IVIg in Allergic Airways Disease.

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Massoud, Amir H; Kaufman, Gabriel N; Xue, Di; Béland, Marianne; Dembele, Marieme; Piccirillo, Ciriaco A; Mourad, Walid; Mazer, Bruce D

2017-04-01

IVIg is widely used as an immunomodulatory therapy. We have recently demonstrated that IVIg protects against airway hyperresponsiveness (AHR) and inflammation in mouse models of allergic airways disease (AAD), associated with induction of Foxp3 + regulatory T cells (Treg). Using mice carrying a DTR/EGFP transgene under the control of the Foxp3 promoter (DEREG mice), we demonstrate in this study that IVIg generates a de novo population of peripheral Treg (pTreg) in the absence of endogenous Treg. IVIg-generated pTreg were sufficient for inhibition of OVA-induced AHR in an Ag-driven murine model of AAD. In the absence of endogenous Treg, IVIg failed to confer protection against AHR and airway inflammation. Adoptive transfer of purified IVIg-generated pTreg prior to Ag challenge effectively prevented airway inflammation and AHR in an Ag-specific manner. Microarray gene expression profiling of IVIg-generated pTreg revealed upregulation of genes associated with cell cycle, chromatin, cytoskeleton/motility, immunity, and apoptosis. These data demonstrate the importance of Treg in regulating AAD and show that IVIg-generated pTreg are necessary and sufficient for inhibition of allergen-induced AAD. The ability of IVIg to generate pure populations of highly Ag-specific pTreg represents a new avenue to study pTreg, the cross-talk between humoral and cellular immunity, and regulation of the inflammatory response to Ags. Copyright © 2017 by The American Association of Immunologists, Inc.

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure.

Science.gov (United States)

Aghapour, Mahyar; Raee, Pourya; Moghaddam, Seyed Javad; Hiemstra, Pieter S; Heijink, Irene H

2018-02-01

The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.

The pharmacological rationale for combining muscarinic receptor antagonists and beta-adrenoceptor agonists in the treatment of airway and bladder disease

NARCIS (Netherlands)

Dale, Philippa R.; Cernecka, Hana; Schmidt, Martina; Dowling, Mark R.; Charlton, Steven J.; Pieper, Michael P.; Michel, Martin C.

Muscarinic receptor antagonists and beta-adrenoceptor agonists are used in the treatment of obstructive airway disease and overactive bladder syndrome. Here we review the pharmacological rationale for their combination. Muscarinic receptors and beta-adrenoceptors are physiological antagonists for

Short-term effects of positive expiratory airway pressure in patients being weaned from mechanical ventilation

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Marcelo de Mello Rieder

2009-05-01

Full Text Available OBJECTIVE: To investigate the feasibility and the cardiorespiratory effects of using positive expiratory airway pressure, a physiotherapeutic tool, in comparison with a T-tube, to wean patients from mechanical ventilation. METHODS/DESIGN: A prospective, randomized, cross-over study. SETTING: Two intensive care units. PATIENTS AND INTERVENTIONS: We evaluated forty patients who met weaning criteria and had been mechanically-ventilated for more than 48 hours, mean age 59 years, including 23 males. All patients were submitted to the T-tube and Expiratory Positive Airway Pressure devices, at 7 cm H2O, during a 30-minute period. Cardiorespiratory variables including work of breathing, respiratory rate (rr, peripheral oxygen saturation (SpO2, heart rate (hr, systolic, diastolic and mean arterial pressures (SAP, DAP, MAP were measured in the first and thirtieth minutes. The condition was analyzed as an entire sample set (n=40 and was also divided into subconditions: chronic obstructive pulmonary disease (n=14 and non-chronic obstructive pulmonary disease (non- chronic obstructive pulmonary disease (n=26 categories. Comparisons were made using a t-test and Analysis of Variance. The level of significance was p < 0.05. RESULTS: Our data showed an increase in work of breathing in the first and thirtieth minutes in the EPAP condition (0.86+ 0.43 and 1.02+1.3 as compared with the T-tube condition (0.25+0.26 and 0.26+0.35 (p<0.05, verified by the flow-sensor monitor (values in J/L. No statistical differences were observed when comparing the Expiratory Positive Airway Pressure and T-tube conditions with regard to cardiorespiratory measurements. The same result was observed for both chronic obstructive pulmonary disease and non- chronic obstructive pulmonary disease subconditions. CONCLUSIONS: Our study demonstrated that, in weaning patients from mechanical ventilation, the use of a fixed level of Expiratory Positive Airway Pressure caused an increase in work of

Effects of Ex Vivo y-Tocopherol on Airway Macrophage ...

Science.gov (United States)

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate y-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6)and mild house dust mite-sensitive allergic asthmatics (n =6) were treated ex vivo with GT (300 uM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206,CD36 and CD86 in allergic asthmatics but not in corntrols. Overall, GT caused down regulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor. Recent studies on the effects of the fat-soluble steriod hormone vitamins D and E suggest that dietary suplementation with these vitamins may be helpful for the prevention or in the treatment of inflammatory and immune-mediated diseases, including atopic asthma.

Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

International Nuclear Information System (INIS)

Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham; Boyaka, Prosper N.; Cormet-Boyaka, Estelle

2012-01-01

Highlights: ► Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. ► Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. ► Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. ► Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-κB dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium

Directory of Open Access Journals (Sweden)

Zhang Xiaohui

2008-05-01

Full Text Available Abstract Background Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal and intrathoracic (bronchial epithelium in healthy current and never smokers. Results Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome", we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure. Conclusion Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for

Effects of inhaled high-molecular weight hyaluronan in inflammatory airway disease.

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Lamas, Adelaida; Marshburn, Jamie; Stober, Vandy P; Donaldson, Scott H; Garantziotis, Stavros

2016-10-03

Cystic fibrosis (CF) is a chronic inflammatory disease that is affecting thousands of patients worldwide. Adjuvant anti-inflammatory treatment is an important component of cystic fibrosis treatment, and has shown promise in preserving lung function and prolonging life expectancy. Inhaled high molecular weight hyaluronan (HMW-HA) is reported to improve tolerability of hypertonic saline and thus increase compliance, and has been approved in some European countries for use as an adjunct to hypertonic saline treatment in cystic fibrosis. However, there are theoretical concerns that HMW-HA breakdown products may be pro-inflammatory. In this clinical pilot study we show that sputum cytokines in CF patients receiving HMW-HA are not increased, and therefore HMW-HA does not appear to adversely affect inflammatory status in CF airways.

Human airway xenograft models of epithelial cell regeneration

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Puchelle Edith

2000-10-01

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

Immunoregulation by airway epithelial cells (AECs against respiratory virus infection

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Yan YAN

2017-11-01

Full Text Available The respiratory tract is primary contact site of the body and environment, and it is ventilated by 10-20 thousand liters of air per day. Inevitably, the respiratory system comes into contact with airborne microbes, which contain the disease-causing pathogens. Airway epithelial cells (AECs are known to have innate sensor functions, which are similar to the "professional" immune cells, such as alveolar macrophage and sub- or intra-epithelial dendritic cells (DCs. Thus AECs are able to detect invading microbial danger including different types of respiratory viruses, and mount a potent host response, for example, activating type Ⅰ interferon signaling pathway genes. To avoid chronic inflammation and maintain the immunological homeostasis, the pulmonary system has developed intrinsic mechanisms to control local immune responses. Most recently, the role of AECs in control of local immunity has gained much attention, as 1 AECs express the pattern recognition receptors (PRRs, such as Toll-like receptors, retinoic acid inducible gene Ⅰ (RIG-I-like receptor, and so on, thus AECs are equipped to participate in innate detection of microbial encounter; 2 To keep immunological homeostasis in the respiratory tract, AECs behave not only as innate immune sensors but also as immune modulators in parallel, through modulating the sensitivity of innate immune sensing of both AECs per se and sub- or intra-epithelial immune cells; 3 Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases. In present review, how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis- and trans-factors (direct and indirect factors, as well as the consequence of impairment of this control of local immunity, in the development and exacerbation of airway diseases, such as acute and chronic rhinosinusitis. DOI: 10.11855/j.issn.0577-7402.2017.10.02

Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS.

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Verena A Lambermont

Full Text Available Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages.Lambs were delivered spontaneously at term (147d and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM and mast cells staining were evaluated.PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages.PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.

Intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells

International Nuclear Information System (INIS)

Verhaeghe, Catherine; Tabruyn, Sebastien P.; Oury, Cecile; Bours, Vincent; Griffioen, Arjan W.

2007-01-01

Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditioned media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications

L-ornithine derived polyamines in cystic fibrosis airways.

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Hartmut Grasemann

Full Text Available Increased arginase activity contributes to airway nitric oxide (NO deficiency in cystic fibrosis (CF. Whether down-stream products of arginase activity contribute to CF lung disease is currently unknown. The objective of this study was to test whether L-ornithine derived polyamines are present in CF airways and contribute to airway pathophysiology. Polyamine concentrations were measured in sputum of patients with CF and in healthy controls, using liquid chromatography-tandem mass spectrometry. The effect of spermine on airway smooth muscle mechanical properties was assessed in bronchial segments of murine airways, using a wire myograph. Sputum polyamine concentrations in stable CF patients were similar to healthy controls for putrescine and spermidine but significantly higher for spermine. Pulmonary exacerbations were associated with an increase in sputum and spermine levels. Treatment for pulmonary exacerbations resulted in decreases in arginase activity, L-ornithine and spermine concentrations in sputum. The changes in sputum spermine with treatment correlated significantly with changes in L-ornithine but not with sputum inflammatory markers. Incubation of mouse bronchi with spermine resulted in an increase in acetylcholine-induced force and significantly reduced nitric oxide-induced bronchial relaxation. The polyamine spermine is increased in CF airways. Spermine contributes to airways obstruction by reducing the NO-mediated smooth muscle relaxation.

Reflex Cough and Disease Duration as Predictors of Swallowing Dysfunction in Parkinson's Disease.

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Troche, Michelle S; Schumann, Beate; Brandimore, Alexandra E; Okun, Michael S; Hegland, Karen W

2016-12-01

Patients with Parkinson's disease (PD) have progressive and pervasive disorders of airway protection. Recent work has highlighted the relationship between reflex and voluntary cough and swallowing safety. The goal of this study was to test the sensitivity and specificity of several airway protective and disease-specific factors for predicting swallowing safety outcomes in PD. Sixty-four participants (44 males) completed measures of voluntary and reflex cough, and swallowing safety. Clinical predictors included disease severity and duration, and cough airflow and sensitivity measures. ROC and Chi-square analyses identified predictors of swallowing safety (penetration-aspiration score) in PD. Disease duration significantly discriminated between patients with normal and abnormal swallowing safety (p = 0.027, sensitivity: 71 %, specificity: 55.4 %). Cough reflex sensitivity significantly discriminated between patients who penetrated above the level of the vocal folds and those with more severe penetration/aspiration (p = 0.021, sensitivity: 71.0 %, specificity 57.6 %). Urge-to-cough sensitivity (log-log linear slope) was the only variable which significantly discriminated between patients with penetration versus aspiration (p = 0.017, sensitivity: 85.7 %, specificity 73.2 %). It is important to identify the factors which influence airway protective outcomes in PD especially given that aspiration pneumonia is a leading cause of death. Results from this study highlight the ecological validity of reflex cough in the study of airway protection and this study further identifies important factors to consider in the screening of airway protective deficits in PD.

Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections.

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Hisert, Katherine B; Heltshe, Sonya L; Pope, Christopher; Jorth, Peter; Wu, Xia; Edwards, Rachael M; Radey, Matthew; Accurso, Frank J; Wolter, Daniel J; Cooke, Gordon; Adam, Ryan J; Carter, Suzanne; Grogan, Brenda; Launspach, Janice L; Donnelly, Seamas C; Gallagher, Charles G; Bruce, James E; Stoltz, David A; Welsh, Michael J; Hoffman, Lucas R; McKone, Edward F; Singh, Pradeep K

2017-06-15

Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established. To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections. We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans. Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging. Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.

Role of airway epithelial barrier dysfunction in pathogenesis of asthma.

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Gon, Yasuhiro; Hashimoto, Shu

2018-01-01

Bronchial asthma is characterized by persistent cough, increased sputum, and repeated wheezing. The pathophysiology underlying these symptoms is the hyper-responsiveness of the airway along with chronic airway inflammation. Repeated injury, repair, and regeneration of the airway epithelium following exposure to environmental factors and inflammation results in histological changes and functional abnormalities in the airway mucosal epithelium; such changes are believed to have a significant association with the pathophysiology of asthma. Damage to the barrier functions of the airway epithelium enhances mucosal permeability of foreign substances in the airway epithelium of patients with asthma. Thus, epithelial barrier fragility is closely involved in releasing epithelial cytokines (e.g., TSLP, IL-25, and IL-33) because of the activation of airway epithelial cells, dendritic cells, and innate group 2 innate lymphoid cells (ILC2). Functional abnormalities of the airway epithelial cells along with the activation of dendritic cells, Th2 cells, and ILC2 form a single immunopathological unit that is considered to cause allergic airway inflammation. Here we use the latest published literature to discuss the potential pathological mechanisms regarding the onset and progressive severity of asthma with regard to the disruption of the airway epithelial function. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

acquisition of antigens by airway dendritic cells. do we know enough?

African Journals Online (AJOL)

kiama

These responses are thought to be mediated via dendritic cells, which are located in the basal ... delivery to the DC in the airways. Are the ... feature of inflammatory airway disease, like asthma .... drug delivery and as vectors in delivery of.

Development and Analysis of Patient-Based Complete Conducting Airways Models.

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Rafel Bordas

Full Text Available The analysis of high-resolution computed tomography (CT images of the lung is dependent on inter-subject differences in airway geometry. The application of computational models in understanding the significance of these differences has previously been shown to be a useful tool in biomedical research. Studies using image-based geometries alone are limited to the analysis of the central airways, down to generation 6-10, as other airways are not visible on high-resolution CT. However, airways distal to this, often termed the small airways, are known to play a crucial role in common airway diseases such as asthma and chronic obstructive pulmonary disease (COPD. Other studies have incorporated an algorithmic approach to extrapolate CT segmented airways in order to obtain a complete conducting airway tree down to the level of the acinus. These models have typically been used for mechanistic studies, but also have the potential to be used in a patient-specific setting. In the current study, an image analysis and modelling pipeline was developed and applied to a number of healthy (n = 11 and asthmatic (n = 24 CT patient scans to produce complete patient-based airway models to the acinar level (mean terminal generation 15.8 ± 0.47. The resulting models are analysed in terms of morphometric properties and seen to be consistent with previous work. A number of global clinical lung function measures are compared to resistance predictions in the models to assess their suitability for use in a patient-specific setting. We show a significant difference (p < 0.01 in airways resistance at all tested flow rates in complete airway trees built using CT data from severe asthmatics (GINA 3-5 versus healthy subjects. Further, model predictions of airways resistance at all flow rates are shown to correlate with patient forced expiratory volume in one second (FEV1 (Spearman ρ = -0.65, p < 0.001 and, at low flow rates (0.00017 L/s, FEV1 over forced vital capacity (FEV1

Suppression of Th17-polarized airway inflammation by rapamycin.

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Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

2017-11-10

Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

Mast cell mediators in citric acid-induced airway constriction of guinea pigs

International Nuclear Information System (INIS)

Lin, C.-H.; Lai, Y.-L.

2005-01-01

We demonstrated previously that mast cells play an important role in citric acid (CA)-induced airway constriction. In this study, we further investigated the underlying mediator(s) for this type of airway constriction. At first, to examine effects caused by blocking agents, 67 young Hartley guinea pigs were divided into 7 groups: saline + CA; methysergide (serotonin receptor antagonist) + CA; MK-886 (leukotriene synthesis inhibitor) + CA; mepyramine (histamine H 1 receptor antagonist) + CA; indomethacin (cyclooxygenase inhibitor) + CA; cromolyn sodium (mast cell stabilizer) + CA; and compound 48/80 (mast cell degranulating agent) + CA. Then, we tested whether leukotriene C 4 (LTC 4 ) or histamine enhances CA-induced airway constriction in compound 48/80-pretreated guinea pigs. We measured dynamic respiratory compliance (Crs) and forced expiratory volume in 0.1 s (FEV 0.1 ) during either baseline or recovery period. In addition, we detected histamine level, an index of pulmonary mast cell degranulation, in bronchoalveolar lavage (BAL) samples. Citric acid aerosol inhalation caused decreases in Crs and FEV 0.1 , indicating airway constriction in the control group. This airway constriction was significantly attenuated by MK-886, mepyramine, cromolyn sodium, and compound 48/80, but not by either methysergide or indomethacin. Both LTC 4 and histamine infusion significantly increased the magnitude of CA-induced airway constriction in compound 48/80-pretreated guinea pigs. Citric acid inhalation caused significant increase in histamine level in the BAL sample, which was significantly suppressed by compound 48/80. These results suggest that leukotrienes and histamine originating from mast cells play an important role in CA inhalation-induced noncholinergic airway constriction

Airway remodeling and long-term decline in lung function in asthma

NARCIS (Netherlands)

Ten Hacken, NHT; Postma, DS; Timens, W

Asthma is a heterogeneous disease that frequently shows progression of airway obstruction. There are indications that ongoing airway inflammation is responsible for the more severe hyperresponsiveness, lower lung function, and accelerated loss of forced expiratory volume in 1 second. At this moment,

Airway disease in highway and tunnel construction workers exposed to silica.

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Oliver, L Christine; Miracle-McMahill, Heidi

2006-12-01

Construction workers employed in a unique type of tunnel construction known as tunnel jacking were exposed over an 18-month period to respirable crystalline silica at concentrations that exceeded the OSHA permissible exposure limit. The present study examines workplace exposures and occurrence of airway disease in these workers. Medical and occupational histories and chest radiographs were obtained on 343 active construction workers who had worked on the site during the period in question. Chest radiographs were interpreted according to the ILO-1980 system of classification. Standardized questions were used to develop an algorithm to define symptoms consistent with asthma (SCA) and to determine these respiratory outcomes: chronic bronchitis, shortness of breath (SOB), and physician-diagnosed asthma (current vs. not current). Relationships with each of three work activities were examined: slurry wall breakthrough (SWB), chipping caisson overpour, and tunneling/mining. Participants included laborers, carpenters, tunnel workers, ironworkers, operating engineers, and electricians. No cases of silicosis were found on chest X-ray. Overall prevalence of chronic bronchitis, SCA, SOB, and physician-diagnosed asthma was 10.7%, 25%, 29%, and 6.6%, respectively. Odds ratios (OR) for carpenters compared to laborers were significantly elevated for chronic bronchitis, SCA, and SOB. SWB was associated with chronic bronchitis and SCA (OR 4.93, 95% CI = 1.01, 24.17; OR 3.32, 95% CI = 1.25, 8.84, respectively). The interaction between SWB, SCA, and trade was significant for carpenters (OR 6.87, 95% CI = 1.66, 28.39). Inverse trends were observed for months on the site and chronic bronchitis, SCA, and SOB (P = 0.0374, 0.0006, and 0.0307, respectively). Tunnel construction workers exposed to respirable crystalline silica and cement dust are at increased risk for airway disease. Extent of risk varies by trade and work activity. Our data indicate the importance of bystander exposures and

Airway management of a rare huge-size supraglottic mass

International Nuclear Information System (INIS)

Abou-Zeid, Haitham A.; Al-Ghamdi, Abdel Mohsin A.; Al-Qurain, Abdel-Aziz A.; Mokhazy, Khalid M.

2006-01-01

Laser excision of a huge-sized supraglottic mass nearly obstructing the airway passage is a real challenge to anesthesiologists. Upper airway obstruction due to neoplasm in supraglottic region, is traditionally managed by preoperative tracheostomy, however, such a common procedure can potentially have an impact on long-term outcome. A 26-year-old patient presented with dysphagia caused by left cystic vallecular synovial sarcoma. The airway was successfully secured via fiberoptic bronchoscopy, followed by excision of the supraglottic tumor with CO2 laser surgery. Tracheostomy was not required. The patient was discharged from the hospital on the 4th day of surgery. This case, highlights the possibility to secure the airway passage without performing preoperative tracheostomy resulting in good outcome and short hospital stay. (author)

The use of radioisotope techniques for the diagnosis of obstructive airway disease

International Nuclear Information System (INIS)

Furudate, Masatsugu; Itoh, Kazuo; Shida, Akira; Minami, Yukisato

1981-01-01

Perfusion scintigraphy, radioaerosol inhalation scintigraphy, 133 Xe studies and sup(81m)Kr studies are useful radioisotope techniques for the detection of regional pulmonary abnormalities in obstructive airway disease. The patient during asthmatic attack shows the perfusion defects with indefinite boundary, which may change during the following several days. Decreased ventilation are seen on the regions with perfusion defects, and ventilatory defects are more marked than those of perfusion. On the other hand, these abnomal findings is reversible. In chronic emphysema or chronic bronchitis, the regions with decreased perfusion usually cannot be correlated with any specific segments, and scintigraphys done repeatedly fail to show re-vascularization on the regions. In the radioaerosol inhalation scintigraphy, deposition pattern reveal the severity of COPD. In addition, xenon studies in the diseases show marked or moderate prolongation of wash-out from the abnormal region, and the abnormalities of ventilation are equal to or exceed the abnormalities of perfusion. (author)

Probiotics as Additives on Therapy in Allergic Airway Diseases: A Systematic Review of Benefits and Risks

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Rashmi Ranjan Das

2013-01-01

Full Text Available Background. We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases.  Methods. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. Results. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD −1.9 (95% CI −3.62, −0.19; P = 0.03, though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. Conclusion. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended.

allergy, asthma airway and anaphylaxis

African Journals Online (AJOL)

The perioperative preparation of children presenting for surgery aims to identify medical problems that might influence the outcome and to institute management strategies to reduce those risks. Respiratory and airway complications remain the most significant cause of morbidity and mortality in modern paediatric ...

Measurement of lung airways in three dimensions using hyperpolarized helium-3 MRI

International Nuclear Information System (INIS)

Peterson, Eric T; Fain, Sean B; Dai Jionghan; Holmes, James H

2011-01-01

Large airway measurement is clinically important in cases of airway disease and trauma. The gold standard is computed tomography (CT), which allows for airway measurement. However, the ionizing radiation dose associated with CT is a major limitation in longitudinal studies and trauma. To avoid ionizing radiation from CT, we present a method for measuring the large airway diameter in humans using hyperpolarized helium-3 (HPHe) MRI in conjunction with a dynamic 3D radial acquisition. An algorithm is introduced which utilizes the significant airway contrast for semi-automated segmentation and skeletonization which is used to derive the airway lumen diameter. The HPHe MRI method was validated with quantitative CT in an excised and desiccated porcine lung (linear regression R 2 = 0.974 and slope = 0.966 over 32 airway segments). The airway lumen diameters were then compared in 24 human subjects (22 asthmatics and 2 normals; linear regression R 2 value of 0.799 and slope = 0.768 over 309 airway segments). The feasibility for airway path analysis to areas of ventilation defect is also demonstrated.

Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium

Energy Technology Data Exchange (ETDEWEB)

Rennolds, Jessica; Malireddy, Smitha; Hassan, Fatemat; Tridandapani, Susheela; Parinandi, Narasimham [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States); Boyaka, Prosper N. [Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210 (United States); Cormet-Boyaka, Estelle, E-mail: Estelle.boyaka@osumc.edu [Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH 43210 (United States)

2012-01-06

Highlights: Black-Right-Pointing-Pointer Cadmium induces secretion of IL-6 and IL-8 by two distinct pathways. Black-Right-Pointing-Pointer Cadmium increases NAPDH oxidase activity leading to Erk activation and IL-8 secretion. Black-Right-Pointing-Pointer Curcumin prevents cadmium-induced secretion of both IL-6 and IL-8 by airway cells. Black-Right-Pointing-Pointer Curcumin could be use to suppress lung inflammation due to cadmium inhalation. -- Abstract: Cadmium is a toxic metal present in the environment and its inhalation can lead to pulmonary disease such as lung cancer and chronic obstructive pulmonary disease. These lung diseases are characterized by chronic inflammation. Here we show that exposure of human airway epithelial cells to cadmium promotes a polarized apical secretion of IL-6 and IL-8, two pivotal pro-inflammatory cytokines known to play an important role in pulmonary inflammation. We also determined that two distinct pathways controlled secretion of these proinflammatory cytokines by human airway epithelial cells as cadmium-induced IL-6 secretion occurs via an NF-{kappa}B dependent pathway, whereas IL-8 secretion involves the Erk1/2 signaling pathway. Interestingly, the natural antioxidant curcumin could prevent both cadmium-induced IL-6 and IL-8 secretion by human airway epithelial cells. In conclusion, curcumin could be used to prevent airway inflammation due to cadmium inhalation.

Ectopic Intratracheal Thyroid: A Rare Cause of Airway Obstruction

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Waheed Rahman

2018-01-01

Full Text Available Ectopic intratracheal thyroid tissue (EITT is a rare abnormality with only limited cases reported so far. The presenting symptoms can be very similar to those of bronchial asthma. We discuss the case of a 29-year-old man with subglottic ectopic thyroid, with a history of thyroid surgery for goiter, which has been managed with laser-assisted endoscopic approach. We have also included presenting symptoms, pathophysiology, diagnosis, and management of EITT. We aim to include EITT in the differentials of airway obstruction, particularly in those patients who have goiter or previous thyroid surgeries.

Airborne chemicals cause respiratory symptoms in individuals with contact allergy

DEFF Research Database (Denmark)

Elberling, J; Linneberg, A; Mosbech, H

2005-01-01

Exposure to fragrance chemicals causes various eye and airway symptoms. Individuals with perfume contact allergy report these symptoms more frequently than individuals with nickel allergy or no contact allergies. However, the associations between contact allergy and respiratory symptoms elicited...... by airborne chemicals other than perfumes are unclear. The study aimed to investigate the association between eye and airway symptoms elicited by airborne chemicals (other than perfumes) and contact allergy in a population-based sample. A questionnaire on respiratory symptoms was posted, in 2002, to 1189...... individuals who participated in 1997/1998 in a Danish population-based study of allergic diseases. Questions about eye and airway symptoms elicited by different airborne chemicals and airborne proteins were included in the questionnaire. Data from the questionnaire were compared with data on patch testing...

Link between vitamin D and airway remodeling

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Berraies A

2014-04-01

Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

HemoHIM, a herbal preparation, alleviates airway inflammation caused by cigarette smoke and lipopolysaccharide.

Science.gov (United States)

Shin, Na-Rae; Kim, Sung-Ho; Ko, Je-Won; Park, Sung-Hyeuk; Lee, In-Chul; Ryu, Jung-Min; Kim, Jong-Choon; Shin, In-Sik

2017-03-01

HemoHIM, herbal preparation has designed for immune system recovery. We investigated the anti-inflammatory effect of HemoHIM on cigarette smoke (CS) and lipopolysaccharide (LPS) induced chronic obstructive pulmonary disease (COPD) mouse model. To induce COPD, C57BL/6 mice were exposed to CS for 1 h per day (eight cigarettes per day) for 4 weeks and intranasally received LPS on day 26. HemoHIM was administrated to mice at a dose of 50 or 100 mg/kg 1h before CS exposure. HemoHIM reduced the inflammatory cell count and levels of tumor necrosis factor receptor (TNF)-α, interleukin (IL)-6 and IL-1β in the broncho-alveolar lavage fluid (BALF) induced by CS+LPS exposure. HemoHIM decreased the inflammatory cell infiltration in the airway and inhibited the expression of iNOS and MMP-9 and phosphorylation of Erk in lung tissue exposed to CS+LPS. In summary, our results indicate that HemoHIM inhibited a reduction in the lung inflammatory response on CS and LPS induced lung inflammation via the Erk pathway. Therefore, we suggest that HemoHIM has the potential to treat pulmonary inflammatory disease such as COPD.

European Symposium on Precision Medicine in Allergy and Airways Diseases: Report of the European Union Parliament Symposium (October 14, 2015)

NARCIS (Netherlands)

Muraro, A.; Fokkens, W. J.; Pietikainen, S.; Borrelli, D.; Agache, I.; Bousquet, J.; Costigliola, V.; Joos, G.; Lund, V. J.; Poulsen, L. K.; Price, D.; Rolland, C.; Zuberbier, T.; Hellings, P. W.

2016-01-01

The European Academy of Allergy and Clinical Immunology (EAACI), the European Rhinologic Society (ERS), and the European Medical Association (EMA) organized, on October 14, 2015, a symposium in the European Parliament in Brussels on Precision Medicine in Allergy and Airways Diseases, hosted by MEP

Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads

Energy Technology Data Exchange (ETDEWEB)

Donnelley, Martin, E-mail: martin.donnelley@adelaide.edu.au; Farrow, Nigel; Parsons, David [Respiratory & Sleep Medicine, Women’s and Children’s Hospital, North Adelaide, South Australia (Australia); Robinson Research Institute, University of Adelaide, South Australia (Australia); School of Paediatrics and Reproductive Health, University of Adelaide, South Australia (Australia); Morgan, Kaye; Siu, Karen [School of Physics, Monash University, Victoria (Australia)

2016-01-28

Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.

Non-invasive airway health measurement using synchrotron x-ray microscopy of high refractive index glass microbeads

Science.gov (United States)

Donnelley, Martin; Morgan, Kaye; Farrow, Nigel; Siu, Karen; Parsons, David

2016-01-01

Cystic fibrosis (CF) is caused by a gene defect that compromises the ability of the mucociliary transit (MCT) system to clear the airways of debris and pathogens. To directly characterise airway health and the effects of treatments we have developed a synchrotron X-ray microscopy method that non-invasively measures the local rate and patterns of MCT behaviour. Although the nasal airways of CF mice exhibit the CF pathophysiology, there is evidence that nasal MCT is not altered in CF mice1. The aim of this experiment was to determine if our non-invasive local airway health assessment method could identify differences in nasal MCT rate between normal and CF mice, information that is potentially lost in bulk MCT measurements. Experiments were performed on the BL20XU beamline at the SPring-8 Synchrotron in Japan. Mice were anaesthetized, a small quantity of micron-sized marker particles were delivered to the nose, and images of the nasal airways were acquired for 15 minutes. The nasal airways were treated with hypertonic saline or mannitol to increase surface hydration and MCT. Custom software was used to locate and track particles and calculate individual and bulk MCT rates. No statistically significant differences in MCT rate were found between normal and CF mouse nasal airways or between treatments. However, we hope that the improved sensitivity provided by this technique will accelerate the ability to identify useful CF lung disease-modifying interventions in small animal models, and enhance the development and efficacy of proposed new therapies.

Relationship of airway dimensions with airflow limitation or lung volumes in chronic obstructive pulmonary disease (COPD

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Masaru Hasegawa

2006-12-01

Full Text Available We have recently developed new software to obtain longitudinal images and accurate short axis images of airways with an inner diameter > 2 mm located anywhere in the lung, using curved multiplanar reconstruction. Using this software, we demonstrated in patients with COPD that FEV1 (%predicted was highly correlated with airway dimensions and the correlation coefficients improved as the airway became smaller in size (3. In this study, our aims are to further confirm the significant relationship between airway dimensions and airflow limitation in larger number of subjects, and to examine the relationship of airway dimensions with lung volumes in 95 patients with COPD (stage 0, 10; stage I, 23; stage II, 35; stage III, 24; stage IV, 3. We analyzed the airway dimensions from the 3rd to the 6th generations of the apical bronchus (B1 of the right upper lobe and the anterior basal bronchus (B8 of the right lower lobe. Lung volumes were measured by the helium closed circuit method. Both airway luminal area (Ai and wall area percent (WA% of all the generations, except a few, from the two bronchi were significantly correlated with RV and RV/TLC, but not with TLC or FRC. More importantly, the correlation coefficients (r between airway dimensions and RV/TLC improved as the airways became smaller in size from the 3rd to 6th generations in both bronchi (r = –0.483, –0482, –0.553, –0.624 for Ai of B8; r = 0.316, 0.380, 0.499, 0.551 for WA% of B8. These findings provide further evidence that distal (small airways rather than proximal (large airways are the determinants for airflow limitation in COPD.

Perinatal paracetamol exposure in mice does not affect the development of allergic airways disease in early life

Science.gov (United States)

Lee, Debbie C P; Walker, Simone A; Byrne, Adam J; Gregory, Lisa G; Buckley, James; Bush, Andrew; Shaheen, Seif O; Saglani, Sejal; Lloyd, Clare M

2015-01-01

Background Current data concerning maternal paracetamol intake during pregnancy, or intake during infancy and risk of wheezing or asthma in childhood is inconclusive based on epidemiological studies. We have investigated whether there is a causal link between maternal paracetamol intake during pregnancy and lactation and the development of house dust mite (HDM) induced allergic airways disease (AAD) in offspring using a neonatal mouse model. Methods Pregnant mice were administered paracetamol or saline by oral gavage from the day of mating throughout pregnancy and/or lactation. Subsequently, their pups were exposed to intranasal HDM or saline from day 3 of life for up to 6 weeks. Assessments of airway hyper-responsiveness, inflammation and remodelling were made at weaning (3 weeks) and 6 weeks of age. Results Maternal paracetamol exposure either during pregnancy and/or lactation did not affect development of AAD in offspring at weaning or at 6 weeks. There were no effects of maternal paracetamol at any time point on airway remodelling or IgE levels. Conclusions Maternal paracetamol did not enhance HDM induced AAD in offspring. Our mechanistic data do not support the hypothesis that prenatal paracetamol exposure increases the risk of childhood asthma. PMID:25841236

Fiberoptic intubation through laryngeal mask airway for management of difficult airway in a child with Klippel-Feil syndrome

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Ravi Bhat

2014-01-01

Full Text Available The ideal airway management modality in pediatric patients with syndromes like Klippel-Feil syndrome is a great challenge and is technically difficult for an anesthesiologist. Half of the patients present with the classic triad of short neck, low hairline, and fusion of cervical vertebra. Numerous associated anomalies like scoliosis or kyphosis, cleft palate, respiratory problems, deafness, genitourinary abnormalities, Sprengel′s deformity (wherein the scapulae ride high on the back, synkinesia, cervical ribs, and congenital heart diseases may further add to the difficulty. Fiberoptic bronchoscopy alone can be technically difficult and patient cooperation also becomes very important, which is difficult in pediatric patients. Fiberoptic bronchoscopy with the aid of supraglottic airway devices is a viable alternative in the management of difficult airway in children. We report a case of Klippel-Feil syndrome in an 18-month-old girl posted for cleft palate surgery. Imaging of spine revealed complete fusion of the cervical vertebrae with hypoplastic C3 and C6 vertebrae and thoracic kyphosis. We successfully managed airway in this patient by fiberoptic intubation through classic laryngeal mask airway (LMA. After intubation, we used second smaller endotracheal tube (ETT to stabilize and elongate the first ETT while removing the LMA.

Lipids in airway secretions

International Nuclear Information System (INIS)

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

1987-01-01

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

A link between skin and airways regarding sensitivity to fragrance products?

DEFF Research Database (Denmark)

Elberling, J; Linneberg, A; Mosbech, Holger Fausbøll

2004-01-01

Exposure to volatile fragrances is commonplace and may be related to various eye and airway symptoms. Skin exposure to fragrances is known to cause perfume contact allergy and eczema, but it is unknown whether eye or airway symptoms elicited by fragrance products are associated with contact allergy...

Automatic 2D segmentation of airways in thorax computed tomography images

International Nuclear Information System (INIS)

Cavalcante, Tarique da Silveira; Cortez, Paulo Cesar; Almeida, Thomaz Maia de; Felix, John Hebert da Silva; Holanda, Marcelo Alcantara

2013-01-01

Introduction: much of the world population is affected by pulmonary diseases, such as the bronchial asthma, bronchitis and bronchiectasis. The bronchial diagnosis is based on the airways state. In this sense, the automatic segmentation of the airways in Computed Tomography (CT) scans is a critical step in the aid to diagnosis of these diseases. Methods: this paper evaluates algorithms for airway automatic segmentation, using Neural Network Multilayer Perceptron (MLP) and Lung Densities Analysis (LDA) for detecting airways, along with Region Growing (RG), Active Contour Method (ACM) Balloon and Topology Adaptive to segment them. Results: we obtained results in three stages: comparative analysis of the detection algorithms MLP and LDA, with a gold standard acquired by three physicians with expertise in CT imaging of the chest; comparative analysis of segmentation algorithms ACM Balloon, ACM Topology Adaptive, MLP and RG; and evaluation of possible combinations between segmentation and detection algorithms, resulting in the complete method for automatic segmentation of the airways in 2D. Conclusion: the low incidence of false negative and the significant reduction of false positive, results in similarity coefficient and sensitivity exceeding 91% and 87% respectively, for a combination of algorithms with satisfactory segmentation quality. (author)

Predominant constitutive CFTR conductance in small airways

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Lytle Christian

2005-01-01

Full Text Available Abstract Background The pathological hallmarks of chronic obstructive pulmonary disease (COPD are inflammation of the small airways (bronchiolitis and destruction of lung parenchyma (emphysema. These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter. Methods We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole. Results In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25, but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25 were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM+IBMX (100 μM, ATP (100 μM, or adenosine (100 μM, but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM, GlyH-101* (5–50 μM, and CFTRInh-172* (5 μM. RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways. Conclusion These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR.

Bronchoconstriction Induces TGF-β Release and Airway Remodelling in Guinea Pig Lung Slices.

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Tjitske A Oenema

Full Text Available Airway remodelling, including smooth muscle remodelling, is a primary cause of airflow limitation in asthma. Recent evidence links bronchoconstriction to airway remodelling in asthma. The mechanisms involved are poorly understood. A possible player is the multifunctional cytokine TGF-β, which plays an important role in airway remodelling. Guinea pig lung slices were used as an in vitro model to investigate mechanisms involved in bronchoconstriction-induced airway remodelling. To address this aim, mechanical effects of bronchoconstricting stimuli on contractile protein expression and TGF-β release were investigated. Lung slices were viable for at least 48 h. Both methacholine and TGF-β1 augmented the expression of contractile proteins (sm-α-actin, sm-myosin, calponin after 48 h. Confocal fluorescence microscopy showed that increased sm-myosin expression was enhanced in the peripheral airways and the central airways. Mechanistic studies demonstrated that methacholine-induced bronchoconstriction mediated the release of biologically active TGF-β, which caused the increased contractile protein expression, as inhibition of actin polymerization (latrunculin A or TGF-β receptor kinase (SB431542 prevented the methacholine effects, whereas other bronchoconstricting agents (histamine and KCl mimicked the effects of methacholine. Collectively, bronchoconstriction promotes the release of TGF-β, which induces airway smooth muscle remodelling. This study shows that lung slices are a useful in vitro model to study mechanisms involved in airway remodelling.

A Rare Cause of Upper Airway Obstruction in a Child

OpenAIRE

Ahmed, H.; Ndiaye, C.; Barry, M. W.; Thiongane, Aliou; Mbaye, A.; Zemene, Y.; Ndiaye, I. C.

2017-01-01

Ventricular band cyst is a rare condition in children but can result in severe upper airway obstruction with laryngeal dyspnea or death. The diagnosis should be considered in any stridor in children with previous history of intubation or respiratory infections. We report a case of a 4-year-old girl, received in an array of severe respiratory distress, emergency endoscopy was done, and a large ventricular tape band cyst obstructing the air way was found. Complete excision was made, and postope...

Nrf2 protects against airway disorders

International Nuclear Information System (INIS)

Cho, Hye-Youn; Kleeberger, Steven R.

2010-01-01

Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2-directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies.

The who, where, and when of IgE in allergic airway disease.

Science.gov (United States)

Dullaers, Melissa; De Bruyne, Ruth; Ramadani, Faruk; Gould, Hannah J; Gevaert, Philippe; Lambrecht, Bart N

2012-03-01

Allergic asthma and allergic rhinitis/conjunctivitis are characterized by a T(H)2-dominated immune response associated with increased serum IgE levels in response to inhaled allergens. Because IgE is a key player in the induction and maintenance of allergic inflammation, it represents a prime target for therapeutic intervention. However, our understanding of IgE biology remains fragmentary. This article puts together our current knowledge on IgE in allergic airway diseases with a special focus on the identity of IgE-secreting cells ("who"), their location ("where"), and the circumstances in which they are induced ("when"). We further consider the therapeutic implications of the insights gained. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

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Daly Melissa

2006-08-01

Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

New approaches to the modulation of inflammatory processes in airway disease models: ATS 2001, May 18-23, San Francisco

Directory of Open Access Journals (Sweden)

Hele David J

2001-07-01

Full Text Available Abstract The 97th American Thoracic Society meeting proved to be an excellent meeting, providing a wealth of new information on inflammatory diseases of the airways. Once again there appeared to be an increased emphasis on chronic obstructive pulmonary disease (COPD with most of the major drug companies concentrating a large part of their efforts in this field. An assessment of the new British Thoracic Society guidelines, which are designed to promote better management of COPD, was also presented at the meeting. Potential new treatments for inflammatory diseases of the airways including COPD were described, ranging from phase III trial data with GlaxoSmithKline's PDE4 inhibitor, Cilomilast (Ariflo® to the development of AstraZeneca's novel dual dopamine D2-receptor/β2-adrenoreceptor agonist, Viozan™. Of particular interest was Byk Gulden's Ciclesonide, a new corticosteroid with equivalent efficacy to the market leaders but with an improved safety profile. The same company also presented data on their PDE4 inhibitor, Roflumilast, which is now in phase II/III. Bayer presented data on their PDE4 inhibitor, BAY 19-8004, in a smoking animal model and claimed greater anti-inflammatory efficacy than with a steroid. Asta Medica (now known as Elbion also described a new potent PDE4 inhibitor, AWD 12-281, with anti-inflammatory activity. In the bronchodilator field, an analysis of data from a one-year trial with Boehringer Ingelheim's Tiotropium revealed a possible improvement in lung function in COPD patients; this needs to be confirmed in a specifically designed study. Inhibitors of p38 (c-Jun NH2-terminal kinase and syk kinase were also discussed as anti-inflammatory agents with potential in the treatment of COPD and asthma. GlaxoSmithKline's p38 kinase inhibitor, SB 239063, appeared to be the most advanced of these with clinical data expected in two to three years. Lyn kinase was also discussed as a novel target for inflammatory airway diseases.

Covered Balloon-Expanding Stents in Airway Stenosis.

Science.gov (United States)

Majid, Adnan; Kheir, Fayez; Chung, Jey; Alape, Daniel; Husta, Bryan; Oh, Scott; Folch, Erik

2017-04-01

The balloon-expanding stents are widely available but rarely described for use within the tracheobronchial tree. This report describes our experience with these stents in airway stenosis particularly as a lobar salvage therapy. This was a retrospective review of all records in which the balloon-expanding stents were used at a tertiary medical center. Ages, sex, location of stenosis, etiology of stenosis, stent size, duration of stent placement and associated interventions for airway stenosis were recorded. Patient's self-reported respiratory symptoms, dyspnea scale, and radiographic imaging at baseline and after stent placement were also reported. Twenty-one Atrium iCAST stents were inserted in 18 patients with malignant and benign airway disease. The median age was 69.5 years (interquartile range, 53.5 to 74). Most stents (n=20, 95%) were deployed in the lobar airways. There was a significant improvement in the modified Medical Research Council dyspnea scale from median of 3 to 2 (Pstent placement was achieved in 15 patients (83%). No deaths were related to airway stenting complications. Adverse events related to stents included migration (n=2, 9.5%), granulation tissue formation (n=2, 9.5%) and mucus plugging (n=1, 4.8%). Lobar stenting with balloon-expanding metallic stents appears feasible, safe and improves symptoms as well as radiographic atelectasis in patients with lobar airway stenosis in this small case series. Larger studies are needed to confirm this observation and to address long-term safety.

Ionotropic and Metabotropic Proton-Sensing Receptors Involved in Airway Inflammation in Allergic Asthma

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Haruka Aoki

2014-01-01

Full Text Available An acidic microenvironment has been shown to evoke a variety of airway responses, including cough, bronchoconstriction, airway hyperresponsiveness (AHR, infiltration of inflammatory cells in the lung, and stimulation of mucus hyperproduction. Except for the participation of transient receptor potential vanilloid-1 (TRPV1 and acid-sensing ion channels (ASICs in severe acidic pH (of less than 6.0-induced cough and bronchoconstriction through sensory neurons, the molecular mechanisms underlying extracellular acidic pH-induced actions in the airways have not been fully understood. Recent studies have revealed that ovarian cancer G protein-coupled receptor 1 (OGR1-family G protein-coupled receptors, which sense pH of more than 6.0, are expressed in structural cells, such as airway smooth muscle cells and epithelial cells, and in inflammatory and immune cells, such as eosinophils and dendritic cells. They function in a variety of airway responses related to the pathophysiology of inflammatory diseases, including allergic asthma. In the present review, we discuss the roles of ionotropic TRPV1 and ASICs and metabotropic OGR1-family G protein-coupled receptors in the airway inflammation and AHR in asthma and respiratory diseases.

An Integrative Systems Biology Approach to Understanding Pulmonary Diseases

NARCIS (Netherlands)

Auffray, Charles; Adcock, Ian M.; Chung, Kian Fan; Djukanovic, Ratko; Pison, Christophe; Sterk, Peter J.

2010-01-01

Chronic inflammatory pulmonary diseases such as COPD and asthma are highly prevalent and associated with a major health burden worldwide. Despite a wealth of biologic and clinical information on normal and pathologic airway structure and function, the primary causes and mechanisms of disease remain

Training induces cognitive bias: the case of a simulation-based emergency airway curriculum.

Science.gov (United States)

Park, Christine S; Stojiljkovic, Ljuba; Milicic, Biljana; Lin, Brian F; Dror, Itiel E

2014-04-01

Training-induced cognitive bias may affect performance. Using a simulation-based emergency airway curriculum, we tested the hypothesis that curriculum design would induce bias and affect decision making. Twenty-three novice anesthesiology residents were randomized into 2 groups. The primary outcome measure was the initiation of supraglottic airway and cricothyroidotomy techniques in a simulated cannot-ventilate, cannot-intubate scenario during 3 evaluation sessions. Secondary outcomes were response times for device initiation. After a baseline evaluation and didactic lecture, residents received an initial practical training in either surgical cricothyroidotomy (CRIC group) or supraglottic airway (SGA group). After the midtest, the groups switched to receive the alternate training. From baseline to midtest, the SGA group increased initiation of supraglottic airway but not cricothyroidotomy. The CRIC group increased initiation of cricothyroidotomy but not supraglottic airway. After completion of training in both techniques, the SGA group increased initiation of both supraglottic airway and cricothyroidotomy. In contrast, the CRIC group increased initiation of cricothyroidotomy but failed to change practice in supraglottic airway. Final test response times showed that the CRIC group was slower to initiate supraglottic airway and faster to initiate cricothyroidotomy. Practical training in only 1 technique caused bias in both groups despite a preceding didactic lecture. The chief finding was an asymmetrical effect of training sequence even after training in both techniques. Initial training in cricothyroidotomy caused bias that did not correct despite subsequent supraglottic airway training. Educators must be alert to the risk of inducing cognitive bias when designing curricula.

On-site customization of silicone stents: towards optimal palliation of complex airway conditions.

Science.gov (United States)

Breen, David P; Dutau, Hervé

2009-01-01

Stents may be indicated as treatment of benign and malignant conditions of the central airways. Occasionally, aberrant and/or distorted airways secondary to therapy or surgery may preclude the use of commercially manufactured stents. The customization of stents is well described for nonpulmonary diseases, but to date there are only limited data in the literature on prosthesis customization for airway disease. To review all the different techniques and indications of on-site silicone stent customizations and their related complications. A retrospective study was undertaken to identify all patients who underwent treatment with a silicone stent which was customized on site by the physician. The study included subjects treated during an 8-year period. Forty-nine on-site customizations were performed in 43 patients (34 males, mean age 63 +/- 5.2 years). Stent customization was performed in 5.4% of the cases. Stent customization was performed for malignant and benign disease in 35 (81.3%) and 8 (18.7%) cases, respectively. In all cases, the stent deployed successfully and performed well while in situ. Stent manipulation did not increase complications. Customization of airway stents by the physician can lead to successful stenting of difficult airway lesions with a good short-term safety profile. Standard commercially available stents may have resulted in suboptimal management of complex airway pathologies. A prospective study is warranted to further investigate the safety profile and complications associated with stent customization. Copyright 2009 S. Karger AG, Basel.

Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

International Nuclear Information System (INIS)

Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J.

2016-01-01

Ozone (O 3 )-related cardiorespiratory effects are a growing public health concern. Ground level O 3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O 3 -induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O 3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O 3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O 2 ) or hypoxia (10.0% O 2 ), followed by a 4-h exposure to either 1 ppm O 3 or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O 3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O 3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O 3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O 3 -induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive pulmonary disease (COPD). • It is unknown if comorbid

Lipopolysaccharide does not alter small airway reactivity in mouse lung slices.

Science.gov (United States)

Donovan, Chantal; Royce, Simon G; Vlahos, Ross; Bourke, Jane E

2015-01-01

The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 μg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases.

Lipopolysaccharide does not alter small airway reactivity in mouse lung slices.

Directory of Open Access Journals (Sweden)

Chantal Donovan

Full Text Available The bacterial endotoxin, lipopolysaccharide (LPS has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 μg/ml for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases.

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.

Incidence of unanticipated difficult airway using an objective airway score versus a standard clinical airway assessment

DEFF Research Database (Denmark)

Nørskov, Anders Kehlet; Rosenstock, Charlotte Valentin; Wetterslev, Jørn

2013-01-01

-specific assessment. Data from patients' pre-operative airway assessment are registered in the Danish Anaesthesia Database. Objective scores for intubation and mask ventilation grade the severity of airway managements. The accuracy of predicting difficult intubation and mask ventilation is measured for each group...... the examination and registration of predictors for difficult mask ventilation with a non-specified clinical airway assessment on prediction of difficult mask ventilation.Method/Design: We cluster-randomized 28 Danish departments of anaesthesia to airway assessment either by the SARI or by usual non...... that registration of the SARI and predictors for difficult mask ventilation are mandatory for the intervention group but invisible to controls....

Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

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Vij, Neeraj

2011-09-01

The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

Understanding the use of continuous oscillating positive airway pressure (bubble CPAP) to treat neonatal respiratory disease: an engineering approach.

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Manilal-Reddy, P I; Al-Jumaily, A M

2009-01-01

A continuous oscillatory positive airway pressure with pressure oscillations incidental to the mean airway pressure (bubble CPAP) is defined as a modified form of traditional continuous positive airway pressure (CPAP) delivery where pressure oscillations in addition to CPAP are administered to neonates with lung diseases. The mechanical effect of the pressure oscillations on lung performance is investigated by formulating mathematical models of a typical bubble CPAP device and a simple representation of a neonatal respiratory system. Preliminary results of the respiratory system's mechanical response suggest that bubble CPAP may improve lung performance by minimizing the respiratory system impedance and that the resonant frequency of the respiratory system may be a controlling factor. Additional steps in terms of clinical trials and a more complex respiratory system model are required to gain a deeper insight into the mechanical receptiveness of the respiratory system to pressure oscillations. However, the current results are promising in that they offer a deeper insight into the trends of variations that can be expected in future extended models as well as the model philosophies that need to be adopted to produce results that are compatible with experimental verification.

Bronchoscopic guidance of endovascular stenting limits airway compression.

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Ebrahim, Mohammad; Hagood, James; Moore, John; El-Said, Howaida

2015-04-01

Bronchial compression as a result of pulmonary artery and aortic arch stenting may cause significant respiratory distress. We set out to limit airway narrowing by endovascular stenting, by using simultaneous flexible bronchoscopy and graduated balloon stent dilatation, or balloon angioplasty to determine maximum safe stent diameter. Between August 2010 and August 2013, patients with suspected airway compression by adjacent vascular structures, underwent CT or a 3D rotational angiogram to evaluate the relationship between the airway and the blood vessels. If these studies showed close proximity of the stenosed vessel and the airway, simultaneous bronchoscopy and graduated stent re-dilation or graduated balloon angioplasty were performed. Five simultaneous bronchoscopy and interventional catheterization procedures were performed in four patients. Median age/weight was 33 (range 9-49) months and 14 (range 7.6-24) kg, respectively. Three had hypoplastic left heart syndrome, and one had coarctation of the aorta (CoA). All had confirmed or suspected left main stem bronchial compression. In three procedures, serial balloon dilatation of a previously placed stent in the CoA was performed and bronchoscopy was used to determine the safest largest diameter. In the other two procedures, balloon testing with simultaneous bronchoscopy was performed to determine the stent size that would limit compression of the adjacent airway. In all cases, simultaneous bronchoscopy allowed selection of an ideal caliber of the stent that optimized vessel diameter while minimizing compression of the adjacent airway. In cases at risk for airway compromise, flexible bronchoscopy is a useful tool to guide endovascular stenting. Maximum safe stent diameter can be determined without risking catastrophic airway compression. © 2014 Wiley Periodicals, Inc.

Chronic obstructive pulmonary disease : a proteomics approach

OpenAIRE

Alexandre, Bruno Miguel Coelho, 1980-

2011-01-01

Tese de doutoramento, Biologia (Biologia Molecular), Universidade de Lisboa, Faculdade de Ciências, 2012 Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation that is not fully reversible even under bronchodilators effect, caused by a mixture of small airway disease – obstructive bronchiolitis – and parenchymal destruction – emphysema. At the present time, COPD is the fourth leading cause of death and its prevalence and mortality are expected to contin...

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

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

2018-02-01

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

Microfibrillar-associated protein 4 modulates airway smooth muscle cell phenotype in experimental asthma

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Pilecki, Bartosz; Schlosser, Anders; Wulf-Johansson, Helle

2015-01-01

to evaluate MFAP4-dependent airway smooth muscle responses. RESULTS: MFAP4 deficiency attenuated classical hallmarks of asthma, such as eosinophilic inflammation, eotaxin production, airway remodelling and hyperresponsiveness. In wild-type mice, serum MFAP4 was increased after disease development...

Electronic nose breathprints are independent of acute changes in airway caliber in asthma

NARCIS (Netherlands)

Lazar, Zsofia; Fens, Niki; Van der Maten, Jan; van der Schee, Marc P.; Wagener, Ariane H.; de Nijs, Selma B.; Dijkers, Erica; Sterk, Peter J.

2010-01-01

Molecular profiling of exhaled volatile organic compounds (VOC) by electronic nose technology provides breathprints that discriminate between patients with different inflammatory airway diseases, such as asthma and COPD. However, it is unknown whether this is determined by differences in airway

Electronic Nose Breathprints Are Independent of Acute Changes in Airway Caliber in Asthma

NARCIS (Netherlands)

Lazar, Z.; Fens, N.; Van der Maten, J.; van der Schee, M.P.; Wagener, A.H.; de Nijs, S.B.; Dijkers, E.; Sterk, P.J.

2010-01-01

Molecular profiling of exhaled volatile organic compounds (VOC) by electronic nose technology provides breathprints that discriminate between patients with different inflammatory airway diseases, such as asthma and COPD. However, it is unknown whether this is determined by differences in airway

Reproducibility of airway luminal size in asthma measured by HRCT.

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Brown, Robert H; Henderson, Robert J; Sugar, Elizabeth A; Holbrook, Janet T; Wise, Robert A

2017-10-01

Brown RH, Henderson RJ, Sugar EA, Holbrook JT, Wise RA, on behalf of the American Lung Association Airways Clinical Research Centers. Reproducibility of airway luminal size in asthma measured by HRCT. J Appl Physiol 123: 876-883, 2017. First published July 13, 2017; doi:10.1152/japplphysiol.00307.2017.-High-resolution CT (HRCT) is a well-established imaging technology used to measure lung and airway morphology in vivo. However, there is a surprising lack of studies examining HRCT reproducibility. The CPAP Trial was a multicenter, randomized, three-parallel-arm, sham-controlled 12-wk clinical trial to assess the use of a nocturnal continuous positive airway pressure (CPAP) device on airway reactivity to methacholine. The lack of a treatment effect of CPAP on clinical or HRCT measures provided an opportunity for the current analysis. We assessed the reproducibility of HRCT imaging over 12 wk. Intraclass correlation coefficients (ICCs) were calculated for individual airway segments, individual lung lobes, both lungs, and air trapping. The ICC [95% confidence interval (CI)] for airway luminal size at total lung capacity ranged from 0.95 (0.91, 0.97) to 0.47 (0.27, 0.69). The ICC (95% CI) for airway luminal size at functional residual capacity ranged from 0.91 (0.85, 0.95) to 0.32 (0.11, 0.65). The ICC measurements for airway distensibility index and wall thickness were lower, ranging from poor (0.08) to moderate (0.63) agreement. The ICC for air trapping at functional residual capacity was 0.89 (0.81, 0.94) and varied only modestly by lobe from 0.76 (0.61, 0.87) to 0.95 (0.92, 0.97). In stable well-controlled asthmatic subjects, it is possible to reproducibly image unstimulated airway luminal areas over time, by region, and by size at total lung capacity throughout the lungs. Therefore, any changes in luminal size on repeat CT imaging are more likely due to changes in disease state and less likely due to normal variability. NEW & NOTEWORTHY There is a surprising lack

Impulse Oscillometry and Spirometry Small-Airway Parameters in Mild to Moderate Bronchiectasis.

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Guan, Wei-Jie; Yuan, Jing-Jing; Gao, Yong-Hua; Li, Hui-Min; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

2016-11-01

Both impulse oscillometry and spirometry can reflect small-airway disorders. The objective of this work was to investigate the diagnostic value of impulse oscillometry and spirometry small-airway parameters and their correlation with radiology, disease severity, and sputum bacteriology in mild to moderate bronchiectasis (bronchiectasis severity index spirometry, and sputum culture were performed. Correlation between small-airway parameters and clinical indices was determined, adjusting for age, sex, body mass index, and smoking history. Sensitivity analyses were repeated when excluding subjects with bronchiectasis severity index ≥9 or HRCT score ≥13. Impulse oscillometry and spirometry small-airway parameters could discriminate mild to moderate bronchiectasis from healthy subjects and correlated significantly with HRCT score and the number of bronchiectatic lobes and the bronchiectasis severity index (all P Spirometry, but not impulse oscillometry, small-airway parameters differed statistically between subjects with isolated peripheral-airway bronchiectasis and those with peripheral plus central-airway bronchiectasis (all P spirometry small-airway parameters have similar diagnostic value in reflecting peripheral-airway disorders and correlate with the HRCT scores, the bronchiectasis severity index, and the number of bronchiectatic lobes in mild to moderate bronchiectasis. Assessment of small-airway parameters should be incorporated in future lung function investigations in bronchiectasis. Copyright © 2016 by Daedalus Enterprises.

Epidemiology of pollution-induced airway disease: urban/rural differences in East and West Germany

International Nuclear Information System (INIS)

Nicolai, T.

1997-01-01

The prevalence of asthma and allergic disorders was assessed in 9-11 year-old children in Leipzig and Halle in East Germany, as well as in Munich, West Germany. Both East German cities are heavily polluted due to private burning of coal and industrial emissions, while Munich has low smoke emissions but heavy road traffic. All fourth grade pupils in Munich were compared with those in Leipzig and Halle. Non-specific airway disease (bronchitis), cough, and autumn/winter nasal symptoms were most prevalent in Leipzig and Halle. Hay fever and skin test reacitivity to aeroallergens were higher in West Germany compared with east Germany. Furthermore, the prevalence of asthma was also higher in the West German study area. Increased skin prick test reactivity in the West explained the increased prevalence of asthma. Longitudinal analysis showed increased respiratory symptoms on days with high mean levels of sulphur dioxide and oxides of nitrogen, as well as on days with a high peak level of 10 μ respirable particles (PM10) in East Germany. The effects of these pollutants were additive. Exposure to heavy road traffic in Munich was related to decreased pulmonary function and non-specific airway symptoms, but not to allergic sensitization and asthma. (au)

Th-2 signature in chronic airway diseases: towards the extinction of asthma-COPD overlap syndrome?

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Cosío, Borja G; Pérez de Llano, Luis; Lopez Viña, Antolin; Torrego, Alfons; Lopez-Campos, Jose Luis; Soriano, Joan B; Martinez Moragon, Eva; Izquierdo, Jose Luis; Bobolea, Irina; Callejas, Javier; Plaza, Vicente; Miravitlles, Marc; Soler-Catalunya, Juan Jose

2017-05-01

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction ( F eNO )) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·μL -1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease. Copyright ©ERS 2017.

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

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Hotzel Helmut

2008-01-01

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

Haemophilus influenzae from Patients with Chronic Obstructive Pulmonary Disease Exacerbation Induce More Inflammation than Colonizers

Science.gov (United States)

Chin, Cecilia L.; Manzel, Lori J.; Lehman, Erin E.; Humlicek, Alicia L.; Shi, Lei; Starner, Timothy D.; Denning, Gerene M.; Murphy, Timothy F.; Sethi, Sanjay; Look, Dwight C.

2005-01-01

Rationale: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Objective: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. Methods: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. Results: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-κB and p38 mitogen-activated protein kinase signaling pathways. Conclusions: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function. PMID:15805181

Airway Reflux, Cough and Respiratory Disease

Science.gov (United States)

Molyneux, Ian D.; Morice, Alyn H.

2011-01-01

It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752

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

Science.gov (United States)

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

2013-10-01

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

Bronchoscopic management of patients with symptomatic airway stenosis and prognostic factors for survival.

Science.gov (United States)

Okiror, Lawrence; Jiang, Li; Oswald, Nicola; Bille, Andrea; Rajesh, Pala; Bishay, Ehab; Steyn, Richard; Naidu, Babu; Kalkat, Maninder

2015-05-01

Interventional bronchoscopy is effective in the management of patients with symptomatic airway obstruction for both malignant and benign conditions. The main aim of this study is to report our experience with emergency interventional bronchoscopy in patients with symptomatic airway obstruction and identify prognostic factors for survival. This is a retrospective observational study of patients undergoing emergency interventional bronchoscopy over a 4-year period. Survival times were analyzed separately for patients with benign and malignant airway obstruction by the Kaplan-Meier method. Between June 2009 and July 2013, 168 emergency interventional bronchoscopies were performed in 112 patients for airway obstruction. The median age was 63 years (range, 20 to 86), and 91 patients (54%) patients were female. Seventy-two cases (43%) had airway obstruction due to malignant disease. There were 3 in-hospital deaths (2.7%). Median survival of the study population was 5.6 months (range, 0 to 51) with a median follow-up of 7.3 months (range, 0 to 51). Median survival for patients with malignant airway obstruction was 3.5 months (range, 0 to 21), and 9.8 months (range, 0.1 to 51) for those with benign disease. Airway intervention facilitated palliative chemotherapy in 32 patients (44%) of those with malignant airway obstruction. At multivariate analysis in patients with malignant airway obstruction, presence of stridor (hazard ratio 1.919, 95% confidence interval: 1.082 to 3.404, p = 0.026) and not receiving postprocedure chemotherapy (hazard ratio 2.05, 95% confidence interval: 1.156 to 3.636, p = 0.014) were independent prognostic factors for death. Emergency interventional bronchoscopy for airway obstruction is safe, relieved symptoms, and facilitated palliative chemotherapy, which improved survival. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Laringocele: uma causa de obstrução de vias aéreas superiores Laryngocele: a cause of upper airway obstruction

Directory of Open Access Journals (Sweden)

Jose Antonio de Paula Felix

2008-02-01

Full Text Available Laringoceles são dilatações anormais do sáculo do ventrículo de Morgani da laringe, localizando-se entre a falsa prega vocal e a face interna da cartilagem tireóide. Relevância clínica é rara, sendo o achado de laringoceles assintomáticas em necropsia muito alto. Algumas vezes, pode se apresentar já como uma grande massa cervical, levando à obstrução de vias aéreas e necessitando de intervenção de urgência. Neste trabalho, os autores relatam um caso de laringocele levando à obstrução de vias aéreas superiores, necessitando de traqueostomia de urgência e fazem uma revisão da literatura sobre o tema. Complicações de laringocele incluem infecção (formação de piocele, aspiração de patógenos e subseqüente bronquite e pneumonia, infecção do espaço lateral da faringe (depois de ruptura e obstrução de vias aéreas superiores, como no caso apresentado. A laringocele, apesar de ser uma doença benigna, é uma causa potencial de obstrução respiratória que pode ameaçar a vida do paciente. O correto diagnóstico e manejo adequado precoce podem evitar que situações de emergência, como a do paciente do caso relatado, levem à morte.Laryngoceles are abnormal dilatations of the laryngeal saccule, which rises between the ventricular folds, the base of the epiglottis and the inner surface of the thyroid cartilage. Clinical symptoms are rare, and the find of asymptomatic laryngoceles in pathology studies are frequent. Sometimes it is presented as cervical swelling causing airway obstruction in need of emergency intervention. In this study, we report a case of upper airway obstruction due to laryngocele treated by emergency tracheotomy and we review of the literature. Laryngocele complications include infection (pyocele formation, pathogens aspirations with subsequent bronchitis and pneumonia and upper airway obstruction, as in the case reported. Despite being benign tumors, laryngoceles cause relevant airway obstruction

Individual canine Airway Response Variability to a Deep Inspiration

Directory of Open Access Journals (Sweden)

Robert H. Brown

2011-01-01

Full Text Available In healthy individuals, a DI can reverse (bronchodilation or prevent (bronchoprotection induced airway constriction. For individuals with asthma or COPD, these effects may be attenuated or absent. Previous work showed that the size and duration of a DI affected the subsequent response of the airways. Also, increased airway tone lead to increased airway size variability. The present study examined how a DI affected the temporal variability in individual airway baseline size and after methacholine challenge in dogs using High-Resolution Computed Tomography. Dogs were anesthetized and ventilated, and on 4 separate days, HRCT scans were acquired before and after a DI at baseline and during a continuous intravenous infusion of methacholine (Mch at 3 dose rates (17, 67, and 200 μg/mm. The Coefficient of Variation was used as an index of temporal variability in airway size. We found that at baseline and the lowest dose of Mch, variability decreased immediately and 5 minutes after the DI ( P < 0.0001. In contrast, with higher doses of Mch, the DI caused a variable response. At a rate of 67 μg/min of Mch, the temporal variability increased after 5 minutes, while at a rate of 200 μg/min of Mch, the temporal variability increased immediately after the DI. Increased airway temporal variability has been shown to be associated with asthma. Although the mechanisms underlying this temporal variability are poorly understood, the beneficial effects of a DI to decrease airway temporal variability was eliminated when airway tone was increased. If this effect is absent in asthmatics, this may suggest a possible mechanism for the loss of bronchoprotective and bronchodilatory effects after a DI in asthma.

Silibinin attenuates allergic airway inflammation in mice

International Nuclear Information System (INIS)

Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

2012-01-01

Highlights: ► Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. ► Silibinin reduces the levels of various cytokines into the lung of allergic mice. ► Silibinin prevents the development of airway hyperresponsiveness in allergic mice. ► Silibinin suppresses NF-κB transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-κB) pathway. Because NF-κB activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-κB activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-κB activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

Airway dysfunction in elite swimmers: prevalence, impact, and challenges

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Lomax M

2016-05-01

Full Text Available Mitch Lomax Department of Sport and Exercise Science, University of Portsmouth, Portsmouth, UK Abstract: The prevalence of airway dysfunction in elite swimmers is among the highest in elite athletes. The traditional view that swimmers naturally gravitate toward swimming because of preexisting respiratory disorders has been challenged. There is now sufficient evidence that the higher prevalence of bronchial tone disorders in elite swimmers is not the result of a natural selection bias. Rather, the combined effects of repeated chlorine by-product exposure and chronic endurance training can lead to airway dysfunction and atopy. This review will detail the underpinning causes of airway dysfunction observed in elite swimmers. It will also show that airway dysfunction does not prevent success in elite level swimming. Neither does it inhibit lung growth and might be partially reversible when elite swimmers retire from competition. Keywords: exercise, aquatic athletes, bronchoconstriction

Reduced immune responses in chimeric mice engrafted with bone marrow cells from mice with airways inflammation.

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Scott, Naomi M; Ng, Royce L X; McGonigle, Terence A; Gorman, Shelley; Hart, Prue H

2015-11-01

During respiratory inflammation, it is generally assumed that dendritic cells differentiating from the bone marrow are immunogenic rather than immunoregulatory. Using chimeric mice, the outcomes of airways inflammation on bone marrow progenitor cells were studied. Immune responses were analyzed in chimeric mice engrafted for >16 weeks with bone marrow cells from mice with experimental allergic airways disease (EAAD). Responses to sensitization and challenge with the allergen causing inflammation in the bone marrow-donor mice were significantly reduced in the chimeric mice engrafted with bone marrow cells from mice with EAAD (EAAD-chimeric). Responses to intranasal LPS and topical fluorescein isothiocyanate (non-specific challenges) were significantly attenuated. Fewer activated dendritic cells from the airways and skin of the EAAD-chimeric mice could be tracked to the draining lymph nodes, and may contribute to the significantly reduced antigen/chemical-induced hypertrophy in the draining nodes, and the reduced immune responses to sensitizing allergens. Dendritic cells differentiating in vitro from the bone marrow of >16 weeks reconstituted EAAD-chimeric mice retained an ability to poorly prime immune responses when transferred into naïve mice. Dendritic cells developing from bone marrow progenitors during airways inflammation are altered such that daughter cells have reduced antigen priming capabilities.

Crisis management during anaesthesia: obstruction of the natural airway.

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Visvanathan, T; Kluger, M T; Webb, R K; Westhorpe, R N

2005-06-01

Obstruction of the natural airway, while usually easily recognised and managed, may present simply as desaturation, have an unexpected cause, be very difficult to manage, and have serious consequences for the patient. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for obstruction of the natural airway, in the management of acute airway obstruction occurring in association with anaesthesia. The potential performance for this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. There were 62 relevant incidents among the first 4000 reports to the AIMS. It was considered that the correct use of the structured approach would have led to earlier recognition of the problem and/or better management in 11% of cases. Airway management is a fundamental anaesthetic responsibility and skill. Airway obstruction demands a rapid and organised approach to its diagnosis and management and undue delay usually results in desaturation and a potential threat to life. An uncomplicated pre-learned sequence of airway rescue instructions is an essential part of every anaesthetist's clinical practice requirements.

Relationship between airway responsiveness to mannitol and to methacholine and markers of airway inflammation, peak flow variability and quality of life in asthma patients

DEFF Research Database (Denmark)

Porsbjerg, C.; Brannan, J.D.; Anderson, S.D.

2008-01-01

Background Airway hyperresponsiveness (AHR) to stimuli that cause bronchial smooth muscle (BSM) contraction indirectly through the release of endogenous mediators is thought to reflect air-way inflammation more closely compared with AHR measured by stimuli that act directly on BSM. Methods Fifty......, there was a stronger correlation between AHR to mannitol and the level of eNO [PD15 to mannitol vs. eNO (p.p.b.): r: -0.63, P

Anatomic and physiopathologic changes affecting the airway of the elderly patient: implications for geriatric-focused airway management

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Johnson KN

2015-12-01

Full Text Available Kathleen N Johnson,1 Daniel B Botros,1 Leanne Groban,1–4 Yvon F Bryan11Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Hypertension and Vascular Research Center, Wake Forest School of Medicine, Winston-Salem, NC, USAAbstract: There are many anatomical, physiopathological, and cognitive changes that occur in the elderly that affect different components of airway management: intubation, ventilation, oxygenation, and risk of aspiration. Anatomical changes occur in different areas of the airway from the oral cavity to the larynx. Common changes to the airway include tooth decay, oropharyngeal tumors, and significant decreases in neck range of motion. These changes may make intubation challenging by making it difficult to visualize the vocal cords and/or place the endotracheal tube. Also, some of these changes, including but not limited to, atrophy of the muscles around the lips and an edentulous mouth, affect bag mask ventilation due to a difficult face-mask seal. Physiopathologic changes may impact airway management as well. Common pulmonary issues in the elderly (eg, obstructive sleep apnea and COPD increase the risk of an oxygen desaturation event, while gastrointestinal issues (eg, achalasia and gastroesophageal reflux disease increase the risk of aspiration. Finally, cognitive changes (eg, dementia not often seen as related to airway management may affect patient cooperation, especially if an awake intubation is required. Overall, degradation of the airway along with other physiopathologic and cognitive changes makes the elderly population more prone to complications related to airway management. When deciding which airway devices and techniques to use for intubation, the clinician should also consider the

An official American Thoracic Society proceedings: work-related asthma and airway diseases. Presentations and discussion from the Fourth Jack Pepys Workshop on Asthma in the Workplace.

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Tarlo, Susan M; Malo, Jean-Luc

2013-08-01

Work-related asthma is a common occupational lung disease. The scope of the Fourth Jack Pepys Workshop that was held in May 2010 went beyond asthma to include discussion of other occupational airway diseases, in particular occupationally related chronic obstructive pulmonary disease (COPD) and bronchiolitis. Aspects explored included public health considerations, environmental aspects, outcome after diagnosis, prevention and surveillance, and other work-related obstructive airway diseases. Consistent methods are needed to accurately estimate the comparative burden of occupation-related airway diseases among different countries. Challenges to accomplishing this include variability in health care delivery, compensation systems, cultural contexts, and social structures. These factors can affect disease estimates, while heterogeneity in occupations and workplace exposures can affect the underlying true prevalence of morbidity. Consideration of the working environment included discussion of practical methods of limiting exposure to respiratory sensitizers, methods to predict new sensitizers before introduction into workplaces, the role of legislated exposure limits, and models to estimate relative validity of various ameliorative measures when complete avoidance of the sensitizer is not feasible. Other strategies discussed included medical surveillance measures and education, especially for young individuals with asthma and new workers about to enter the workforce. Medical outcomes after development of sensitizer-induced occupational asthma are best following earlier diagnosis and removal from further exposure, but a subset may be able to continue working safely provided that exposure is reduced under close follow-up monitoring. It was recognized that occupationally related COPD is common but underappreciated, deserving further study and prevention efforts.

Effects of Ginger and Its Constituents on Airway Smooth Muscle Relaxation and Calcium Regulation

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Siviski, Matthew E.; Zhang, Yi; Xu, Carrie; Hoonjan, Bhupinder; Emala, Charles W.

2013-01-01

The prevalence of asthma has increased in recent years, and is characterized by airway hyperresponsiveness and inflammation. Many patients report using alternative therapies to self-treat asthma symptoms as adjuncts to short-acting and long-acting β-agonists and inhaled corticosteroids (ICS). As many as 40% of patients with asthma use herbal therapies to manage asthma symptoms, often without proven efficacy or known mechanisms of action. Therefore, investigations of both the therapeutic and possible detrimental effects of isolated components of herbal treatments on the airway are important. We hypothesized that ginger and its active components induce bronchodilation by modulating intracellular calcium ([Ca2+]i) in airway smooth muscle (ASM). In isolated human ASM, ginger caused significant and rapid relaxation. Four purified constituents of ginger were subsequently tested for ASM relaxant properties in both guinea pig and human tracheas: [6]-gingerol, [8]-gingerol, and [6]-shogaol induced rapid relaxation of precontracted ASM (100–300 μM), whereas [10]-gingerol failed to induce relaxation. In human ASM cells, exposure to [6]-gingerol, [8]-gingerol, and [6]-shogaol, but not [10]-gingerol (100 μM), blunted subsequent Ca2+ responses to bradykinin (10 μM) and S-(−)-Bay K 8644 (10 μM). In A/J mice, the nebulization of [8]-gingerol (100 μM), 15 minutes before methacholine challenge, significantly attenuated airway resistance, compared with vehicle. Taken together, these novel data show that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, relax ASM, and [8]-gingerol attenuates airway hyperresponsiveness, in part by altering [Ca2+]i regulation. These purified compounds may provide a therapeutic option alone or in combination with accepted therapeutics, including β2-agonists, in airway diseases such as asthma. PMID:23065130

IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

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L. Amniai

2007-01-01

These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.

A Rare Cause of Upper Airway Obstruction in a Child

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H. Ahmed

2017-01-01

Full Text Available Ventricular band cyst is a rare condition in children but can result in severe upper airway obstruction with laryngeal dyspnea or death. The diagnosis should be considered in any stridor in children with previous history of intubation or respiratory infections. We report a case of a 4-year-old girl, received in an array of severe respiratory distress, emergency endoscopy was done, and a large ventricular tape band cyst obstructing the air way was found. Complete excision was made, and postoperative prophylaxis tracheotomy was done. The postoperative course was uneventful with improvement of clinical and endoscopic signs.

Airway resistance at maximum inhalation as a marker of asthma and airway hyperresponsiveness

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O'Connor George T

2011-07-01

Full Text Available Abstract Background Asthmatics exhibit reduced airway dilation at maximal inspiration, likely due to structural differences in airway walls and/or functional differences in airway smooth muscle, factors that may also increase airway responsiveness to bronchoconstricting stimuli. The goal of this study was to test the hypothesis that the minimal airway resistance achievable during a maximal inspiration (Rmin is abnormally elevated in subjects with airway hyperresponsiveness. Methods The Rmin was measured in 34 nonasthmatic and 35 asthmatic subjects using forced oscillations at 8 Hz. Rmin and spirometric indices were measured before and after bronchodilation (albuterol and bronchoconstriction (methacholine. A preliminary study of 84 healthy subjects first established height dependence of baseline Rmin values. Results Asthmatics had a higher baseline Rmin % predicted than nonasthmatic subjects (134 ± 33 vs. 109 ± 19 % predicted, p = 0.0004. Sensitivity-specificity analysis using receiver operating characteristic curves indicated that baseline Rmin was able to identify subjects with airway hyperresponsiveness (PC20 min % predicted, FEV1 % predicted, and FEF25-75 % predicted, respectively. Also, 80% of the subjects with baseline Rmin min > 145% predicted had hyperresponsive airways, regardless of clinical classification as asthmatic or nonasthmatic. Conclusions These findings suggest that baseline Rmin, a measurement that is easier to perform than spirometry, performs as well as or better than standard spirometric indices in distinguishing subjects with airway hyperresponsiveness from those without hyperresponsive airways. The relationship of baseline Rmin to asthma and airway hyperresponsiveness likely reflects a causal relation between conditions that stiffen airway walls and hyperresponsiveness. In conjunction with symptom history, Rmin could provide a clinically useful tool for assessing asthma and monitoring response to treatment.

Management of airway obstruction and stridor in pediatric patients [digest].

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Marchese, Ashley; Langhan, Melissa L; Pade, Kathryn H

2017-11-22

Stridor is a result of turbulent air-flow through the trachea from upper airway obstruction, and although in children it is often due to croup, it can also be caused by noninfectious and/or congenital conditions as well as life-threatening etiologies. The history and physical examination guide initial management, which includes reduction of airway inflammation, treatment of bacterial infection, and, less often, imaging, emergent airway stabilization, or surgical management. This issue discusses the most common as well as the life-threatening etiologies of acute and chronic stridor and its management in the emergency department. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

Symptoms and Causes of Celiac Disease

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... Symptoms & Causes of Celiac Disease What are the symptoms of celiac disease? Most people with celiac disease have one or ... the rash and no other symptoms. Why are celiac disease symptoms so varied? Symptoms of celiac disease vary from ...

Inhibition of aldose reductase prevents experimental allergic airway inflammation in mice.

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Umesh C S Yadav

2009-08-01

Full Text Available The bronchial asthma, a clinical complication of persistent inflammation of the airway and subsequent airway hyper-responsiveness, is a leading cause of morbidity and mortality in critically ill patients. Several studies have shown that oxidative stress plays a key role in initiation as well as amplification of inflammation in airways. However, still there are no good anti-oxidant strategies available for therapeutic intervention in asthma pathogenesis. Most recent studies suggest that polyol pathway enzyme, aldose reductase (AR, contributes to the pathogenesis of oxidative stress-induced inflammation by affecting the NF-kappaB-dependent expression of cytokines and chemokines and therefore inhibitors of AR could be anti-inflammatory. Since inhibitors of AR have already gone through phase-III clinical studies for diabetic complications and found to be safe, our hypothesis is that AR inhibitors could be novel therapeutic drugs for the prevention and treatment of asthma. Hence, we investigated the efficacy of AR inhibition in the prevention of allergic responses to a common natural airborne allergen, ragweed pollen that leads to airway inflammation and hyper-responsiveness in a murine model of asthma.Primary Human Small Airway Epithelial Cells (SAEC were used to investigate the in vitro effects of AR inhibition on ragweed pollen extract (RWE-induced cytotoxic and inflammatory signals. Our results indicate that inhibition of AR prevents RWE -induced apoptotic cell death as measured by annexin-v staining, increase in the activation of NF-kappaB and expression of inflammatory markers such as inducible nitric oxide synthase (iNOS, cycloxygenase (COX-2, Prostaglandin (PG E(2, IL-6 and IL-8. Further, BALB/c mice were sensitized with endotoxin-free RWE in the absence and presence of AR inhibitor and followed by evaluation of perivascular and peribronchial inflammation, mucin production, eosinophils infiltration and airway hyperresponsiveness. Our results

High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

International Nuclear Information System (INIS)

Tendulkar, Rahul D.; Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

2008-01-01

Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV 1 ), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV 1 improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively

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

Science.gov (United States)

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

2006-01-01

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

Differential effects of allergen challenge on large and small airway reactivity in mice.

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Chantal Donovan

Full Text Available The relative contributions of large and small airways to hyperresponsiveness in asthma have yet to be fully assessed. This study used a mouse model of chronic allergic airways disease to induce inflammation and remodelling and determine whether in vivo hyperresponsiveness to methacholine is consistent with in vitro reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14 and challenged (3 times/week, 6 weeks with ovalbumin. Airway reactivity was compared with saline-challenged controls in vivo assessing whole lung resistance, and in vitro measuring the force of tracheal contraction and the magnitude/rate of small airway narrowing within lung slices. Increased airway inflammation, epithelial remodelling and fibrosis were evident following allergen challenge. In vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In contrast, methacholine induced slower narrowing, with reduced potency in small airways compared to controls. In vitro incubation with IL-1/TNFα did not alter reactivity. The hyporesponsiveness to methacholine in small airways within lung slices following chronic ovalbumin challenge was unexpected, given hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal preparations. This finding may reflect the altered interactions of small airways with surrounding parenchymal tissue after allergen challenge to oppose airway narrowing and closure.

Use of Respiratory Support in the Biphase Ventilation Airway Mode in the Newborn

OpenAIRE

S. N. Koval; A. Ye. Kulagin

2006-01-01

Biphasic positive airway pressure (BIPAP) (also known as DuoPAP, BiLevel, BiVent, PCV+, SPAP) is a mode of ventilation with cycling variations between two continuous positive airway pressure levels. It is a mixture of pressure controlled ventilation and spontaneous breathing, which is unrestricted in each phase of the respiratory cycle. The volume displacement caused by the difference between Phigh and Plow airway pressure level. The phase time ratio (PTR — the BIPAP frequency) is calculated ...

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease: an Interasma (Global Asthma Association - GAA and World Allergy Organization (WAO document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA and Global Allergy and Asthma European Network (GA2LEN

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F. Braido

2016-10-01

Full Text Available Abstract Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD has led INTERASMA (Global Asthma Association and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled

Fisetin-treatment alleviates airway inflammation through inhbition of MyD88/NF-κB signaling pathway.

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Huang, Wei; Li, Ming-Li; Xia, Ming-Yue; Shao, Jian-Ying

2018-07-01

Asthma is a common chronic airway inflammation disease and is considered as a major public health problem. Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid abundantly found in different vegetables and fruits. Fisetin has been reported to exhibit various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. We evaluated the effects of fisetin on allergic asthma regulation in mice. Mice were first sensitized, then airway-challenged with ovalbumin (OVA). Whether fisetin treatment attenuated OVA-induced airway inflammation was examined via inflammation inhibition through MyD88-related NF-κB (p65) signaling pathway. Mice were divided into the control (Con), OVA-induced asthma (Mod), 40 (FL) and 50 (FH) mg/kg fisetin-treated OVA-induced asthma groups. Our results found that OVA-induced airway inflammation in mice caused a significant inflammatory response via the activation of MyD88 and NF-κB signaling pathways, leading to release of pro-inflammatory cytokines. In contrast, fisetin-treated mice after OVA induction inhibited activation of MyD88 and NF-κB signaling pathways, resulting in downregulation of pro-inflammatory cytokine secretion. Further, fisetin significantly ameliorated the airway hyperresponsiveness (AHR) towards methacholine (Mch). In addition, fisetin reduced the number of eosinophil, monocyte, neutrophil and total white blood cell in the bronchoalveolar lavage fluid (BALF) of OVA-induced mice. The serum and BALF samples obtained from the OVA-induced mice with fisetin showed lower levels of pro-inflammatory cytokines. The results of our study illustrated that fisetin may be a new promising candidate to inhibit airway inflammation response induced by OVA.

Airway hyperresponsiveness induced by repeated esophageal infusion of HCl in guinea pigs.

Science.gov (United States)

Cheng, Yan-Mei; Cao, Ai-Li; Zheng, Jian-Pu; Wang, Hong-Wei; Sun, Yong-Shun; Liu, Chun-Fang; Zhang, Bei-Bei; Wang, Yi; Zhu, Sheng-Liang; Wu, Da-Zheng

2014-11-01

Gastroesophageal reflux is a common disorder closely related to chronic airway diseases, such as chronic cough, asthma, chronic bronchitis, and chronic obstructive disease. Indeed, gastroesophageal acid reflux into the respiratory tract causes bronchoconstriction, but the underlying mechanisms have still not been clarified. This study aimed to elucidate functional changes of bronchial smooth muscles (BSMs) isolated from guinea pigs in an animal model of gastroesophageal reflux. The marked airway inflammation, hyperresponsiveness and remodeling were observed after guinea pigs were exposed to intraesophageal HCl infusion for 14 days. In addition, contractile responses to acetylcholine (ACh), KCl, electrical field stimulation, and extracellular Ca(2+) were greater in guinea pigs infused with HCl compared with control groups. The L-type voltage-dependent Ca(2+) channels (L-VDCC) blocker, nicardipine, significantly inhibited ACh- and Ca(2+)-enhanced BSM contractions in guinea pigs infused with HCl. The Rho-kinase inhibitor, Y27632, attenuated ACh-enhanced BSM contractions in guinea pigs infused with HCl. Moreover, mRNA and protein expressions for muscarinic M2 and M3 receptors, RhoA, and L-VDCC in BSM were detected by real-time PCR and Western blot. Expressions of mRNA and protein for muscarinic M3 receptors, RhoA, and L-VDCC were greater than in BSM of HCl-infused guinea pigs, whereas levels of muscarinic M2 receptors were unchanged. We demonstrate that acid infusion to the lower esophagus and, subsequently, microaspiration into the respiratory tract in guinea pigs leads to airway hyperresponsiveness and overactive BSM. Functional and molecular results indicate that overactive BSM is the reason for enhancement of extracellular Ca(2+) influx via L-VDCC and Ca(2+) sensitization through Rho-kinase signaling.

Silibinin attenuates allergic airway inflammation in mice

Energy Technology Data Exchange (ETDEWEB)

Choi, Yun Ho [Department of Anatomy, Medical School, Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Jin, Guang Yu [Department of Radiology, Yanbian University Hospital, YanJi 133002 (China); Guo, Hui Shu [Centralab, The First Affiliated Hospital of Dalian Medical University, Dalian 116011 (China); Piao, Hong Mei [Department of Respiratory Medicine, Yanbian University Hospital, YanJi 133000 (China); Li, Liang chang; Li, Guang Zhao [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China); Lin, Zhen Hua [Department of Pathology, Yanbian University School of Basic Medical Sciences, YanJi 133000 (China); Yan, Guang Hai, E-mail: ghyan@ybu.edu.cn [Department of Anatomy and Histology and Embryology, Yanbian University School of Basic Medical Sciences, 977 Gongyuan Road, YanJi 133002, Jilin (China)

2012-10-26

Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

Airway inflammatory and atopy-related responses in athletes

African Journals Online (AJOL)

O3), sulphur dioxide (SO2), nitrogen dioxide (NO2), .... training may also cause positive adaptations at the airway ... Patients with mild asthma also had significantly ..... mones with immunosuppressive but neutrophil-priming potentials rise after.

Respiratory health of elite athletes - preventing airway injury: a critical review.

Science.gov (United States)

Kippelen, Pascale; Fitch, Kenneth D; Anderson, Sandra Doreen; Bougault, Valerie; Boulet, Louis-Philippe; Rundell, Kenneth William; Sue-Chu, Malcolm; McKenzie, Donald C

2012-06-01

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established.

CT analysis of peripheral airway and lung lesions of patients with asthma and COPD

International Nuclear Information System (INIS)

Itoh, Takayuki; Tanaka, Hiroshi; Sahara, Shin; Ohnishi, Tetsuro; Abe, Shosaku; Ueno, Kan

2002-01-01

We compared peripheral airway and lung parenchyma images among patients with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls using high-resolution CT images taken by a multidetector-row CT scanner (Aquillion, Toshiba, Japan). CT images were saved as digital image and communication (DICOM) files and %low attenuation area (LAA) (<-960 Hounsfield Unit) was calculated with the imaging software. %LAA was significantly increased in patients with COPD (p<0.0001) and smokers with stable asthma (p<0.01) as compared with healthy controls. In stable asthma, mucous plugging in the airway sometime appeared, while during asthma exacerbation small nodules and mosaic pattern of peripheral lung field appeared. Since smoker's patients with asthma have hyper-secretion of sputum due to smoking, mucous plugging and airway inflammation may easily occur and consequently air trapping may increase. In the future, image diagnosis of peripheral airway should develop for early detection of airway diseases as a non-invasive examination. On the other hand, micro focus X-ray computed tomography system (Hitachi Medico Technology Co., Japan) can display CT images closely similar to the pictures of microscopic findings and it will be a useful tool to analyze radiologic-pathologic correlations of peripheral airways and lung parenchyma. (author)

Airway hyperresponsiveness and development of lung function in adolescence and adulthood

DEFF Research Database (Denmark)

Harmsen, Lotte; Ulrik, Charlotte S; Porsbjerg, Celeste

2014-01-01

with and without airway hyperresponsiveness. In a repeated measures regression model with adjustment for asthma and smoking, airway hyperresponsiveness was independently associated with reduced rates of growth in lung function in both sexes of 23 ml/year. Reduced growth rates resulted in deficits in maximal......BACKGROUND: Long-term longitudinal studies of lung function from childhood to adulthood are important in linking our understanding of childhood risk factors to adult disease. Airway hyperresponsiveness has been shown to independently affect lung function growth in studies of adolescence....... The objective of the study was to test the hypothesis that airway hyperresponsiveness has an independent deleterious effect on lung function in adolescence that extends into adulthood. METHODS: A random population sample (n = 983) aged 7-17 from Copenhagen was followed longitudinally for 20 years with four...

Eosinophilic airway inflammation in asthmatic patients is associated with an altered airway microbiome

DEFF Research Database (Denmark)

Sverrild, Asger; Kiilerich, Pia; Brejnrod, Asker Daniel

2017-01-01

BACKGROUND: Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti......-inflammatory treatment. OBJECTIVE: We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects. METHODS: Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10...... and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients...

High rhinovirus burden in lower airways of children with cystic fibrosis.

Science.gov (United States)

Kieninger, Elisabeth; Singer, Florian; Tapparel, Caroline; Alves, Marco P; Latzin, Philipp; Tan, Hui-Leng; Bossley, Cara; Casaulta, Carmen; Bush, Andrew; Davies, Jane C; Kaiser, Laurent; Regamey, Nicolas

2013-03-01

Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children with CF compared with a control group and children with other chronic respiratory diseases. RV presence and load were measured by real-time reverse transcription-polymerase chain reaction in BAL samples and were related to antiviral and inflammatory mediators measured in BAL and to clinical parameters. BAL samples were obtained from children with CF (n = 195), non-CF bronchiectasis (n = 40), or asthma (n = 29) and from a control group (n = 35) at a median (interquartile range [IQR]) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar among groups. RV load (median [IQR] x 10(3) copies/mL) was higher in children with CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared with children with asthma (3.0 [1.3-25.8], P = .006) and the control group (0.5 [0.3-0.5], P < .001), but similar to patients with non-CF bronchiectasis (122.1 [2.7-4423.5], P = not significant). In children with CF, RV load was negatively associated with interferon (IFN)- b and IFN- l , IL-1ra levels, and FEV 1 , and positively with levels of the cytokines CXCL8 and CXCL10. RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of antiviral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.

Comparison of the effects of esomeprazole and fundoplication on airway responsiveness in patients with gastro-oesophageal reflux disease.

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Kiljander, Toni; Rantanen, Tuomo; Kellokumpu, Ilmo; Kööbi, Tiit; Lammi, Lauri; Nieminen, Markku; Poussa, Tuija; Ranta, Arto; Saarelainen, Seppo; Salminen, Paulina

2013-07-01

Gastro-oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non-acidic reflux. To compare the effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness, forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory symptoms in patients with moderate-to-severe GORD. Sixty-nine GORD patients had methacholine inhalation challenge performed on them, and FEV1, exhaled NO and respiratory symptoms were measured at baseline, after a 3-month treatment with esomeprazole and 3 months after fundoplication. Primary outcome variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine challenge divided with the amount of methacholine administered (%/μmol). Pre-defined subgroup analysis was performed among those with concomitant asthma (n = 12). There was no improvement in DRS, FEV1 or exhaled NO after esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual analog scale improved with esomeprazole treatment (P < 0.001), and further after fundoplication (P < 0.001). Among those with concomitant asthma, significant improvements in St George Respiratory Questionnaire (SGRQ) scores could be seen after fundoplication. Neither esomeprazole treatment nor fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1 in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after GORD treatments could be detected. However, as this was not a placebo-controlled study, the findings in these secondary endpoints should not be emphasised. ClinicalTrials.cov: NCT00994708. © 2012 John Wiley & Sons Ltd.

The role of endotoxin in grain dust exposure and airway obstruction.

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Von Essen, S

1997-05-01

Grain dust exposure is a common cause of respiratory symptoms in grain workers, feed mill employees, and farmers. Many of these workers develop wheezing and acute and chronic bronchitis symptoms, which can be associated with obstructive changes on pulmonary function testing. It has recently been demonstrated that grain dust exposure causes neutrophilic airways inflammation and systemic symptoms related to release of interleukin-1, tumor necrosis factor, interleukin-6, and other mediators of inflammation. Although grain dust is a heterogenous substance, endotoxin has received the greatest amount of attention as a possible cause of the airway inflammation that occurs after grain dust exposure. Although endotoxin undoubtedly causes a portion of the changes seen after grain dust exposure, it is becoming clear that other substances play a role as well.

Difficult Airway Response Team: A Novel Quality Improvement Program for Managing Hospital-Wide Airway Emergencies

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Mark, Lynette J.; Herzer, Kurt R.; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I.; Berkow, Lauren C.; Haut, Elliott R.; Hillel, Alexander T.; Miller, Christina R.; Feller-Kopman, David J.; Schiavi, Adam J.; Xie, Yanjun J.; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W.; Mirski, Marek A.

2015-01-01

Background Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. Methods We developed a quality improvement program—the Difficult Airway Response Team (DART)—to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had three core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Results Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index > 40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous

Difficult airway response team: a novel quality improvement program for managing hospital-wide airway emergencies.

Science.gov (United States)

Mark, Lynette J; Herzer, Kurt R; Cover, Renee; Pandian, Vinciya; Bhatti, Nasir I; Berkow, Lauren C; Haut, Elliott R; Hillel, Alexander T; Miller, Christina R; Feller-Kopman, David J; Schiavi, Adam J; Xie, Yanjun J; Lim, Christine; Holzmueller, Christine; Ahmad, Mueen; Thomas, Pradeep; Flint, Paul W; Mirski, Marek A

2015-07-01

Difficult airway cases can quickly become emergencies, increasing the risk of life-threatening complications or death. Emergency airway management outside the operating room is particularly challenging. We developed a quality improvement program-the Difficult Airway Response Team (DART)-to improve emergency airway management outside the operating room. DART was implemented by a team of anesthesiologists, otolaryngologists, trauma surgeons, emergency medicine physicians, and risk managers in 2005 at The Johns Hopkins Hospital in Baltimore, Maryland. The DART program had 3 core components: operations, safety, and education. The operations component focused on developing a multidisciplinary difficult airway response team, standardizing the emergency response process, and deploying difficult airway equipment carts throughout the hospital. The safety component focused on real-time monitoring of DART activations and learning from past DART events to continuously improve system-level performance. This objective entailed monitoring the paging system, reporting difficult airway events and DART activations to a Web-based registry, and using in situ simulations to identify and mitigate defects in the emergency airway management process. The educational component included development of a multispecialty difficult airway curriculum encompassing case-based lectures, simulation, and team building/communication to ensure consistency of care. Educational materials were also developed for non-DART staff and patients to inform them about the needs of patients with difficult airways and ensure continuity of care with other providers after discharge. Between July 2008 and June 2013, DART managed 360 adult difficult airway events comprising 8% of all code activations. Predisposing patient factors included body mass index >40, history of head and neck tumor, prior difficult intubation, cervical spine injury, airway edema, airway bleeding, and previous or current tracheostomy. Twenty

Electronic Nose Breathprints Are Independent of Acute Changes in Airway Caliber in Asthma

Directory of Open Access Journals (Sweden)

Jan van der Maten

2010-10-01

Full Text Available Molecular profiling of exhaled volatile organic compounds (VOC by electronic nose technology provides breathprints that discriminate between patients with different inflammatory airway diseases, such as asthma and COPD. However, it is unknown whether this is determined by differences in airway caliber. We hypothesized that breathprints obtained by electronic nose are independent of acute changes in airway caliber in asthma. Ten patients with stable asthma underwent methacholine provocation (Visit 1 and sham challenge with isotonic saline (Visit 2. At Visit 1, exhaled air was repetitively collected pre-challenge, after reaching the provocative concentration (PC20 causing 20% fall in forced expiratory volume in 1 second (FEV1 and after subsequent salbutamol inhalation. At Visit 2, breath was collected pre-challenge, post-saline and post-salbutamol. At each occasion, an expiratory vital capacity was collected after 5 min of tidal breathing through an inspiratory VOC-filter in a Tedlar bag and sampled by electronic nose (Cyranose 320. Breathprints were analyzed with principal component analysis and individual factors were compared with mixed model analysis followed by pairwise comparisons. Inhalation of methacholine led to a 30.8 ± 3.3% fall in FEV1 and was followed by a significant change in breathprint (p = 0.04. Saline inhalation did not induce a significant change in FEV1, but altered the breathprint (p = 0.01. However, the breathprint obtained after the methacholine provocation was not significantly different from that after saline challenge (p = 0.27. The molecular profile of exhaled air in patients with asthma is altered by nebulized aerosols, but is not affected by acute changes in airway caliber. Our data demonstrate that breathprints by electronic nose are not confounded by the level of airway obstruction.

Intrathoracic manifestations of collagen vascular diseases on high-resolution chest computed tomography

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Silva, C. Isabela S. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital]. E-mail: isabela.silva@vch.ca; Mueller, Nestor L. [University of British Columbia, Vancouver (Canada). Vancouver General Hospital. Dept. of Radiology

2008-05-15

Intrathoracic manifestations of collagen vascular diseases are very common. The frequency of intrathoracic manifestations and the patterns of abnormality are variable depending on the type of collagen vascular disease and may simultaneously involve one or more of the following: lung parenchyma, airways, pulmonary vessels, pericardium, and pleura. The most common pulmonary manifestations are diffuse interstitial pneumonia and pulmonary hypertension which together represent the main causes of morbidity and mortality of these patients. Pulmonary, airway and pleural involvement may also be secondary to the disease therapy, or result from bacterial pneumonia or opportunistic infection. In the present review, the authors summarize the main intrathoracic manifestations of collagen vascular diseases and the differential diagnosis on high-resolution chest computed tomography. (author)

What Causes COPD?

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... please turn JavaScript on. Feature: The Challenge of COPD What Causes COPD? Past Issues / Fall 2014 Table of Contents Long- ... and the airways usually is the cause of COPD. In the United States, the most common irritant ...

Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition in the large airways.

Directory of Open Access Journals (Sweden)

Jill R Johnson

Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.

Transient receptor potential ankyrin 1 channel localized to non-neuronal airway cells promotes non-neurogenic inflammation

DEFF Research Database (Denmark)

Nassini, Romina; Pedretti, Pamela; Moretto, Nadia

2012-01-01

The transient receptor potential ankyrin 1 (TRPA1) channel, localized to airway sensory nerves, has been proposed to mediate airway inflammation evoked by allergen and cigarette smoke (CS) in rodents, via a neurogenic mechanism. However the limited clinical evidence for the role of neurogenic...... inflammation in asthma or chronic obstructive pulmonary disease raises an alternative possibility that airway inflammation is promoted by non-neuronal TRPA1.By using Real-Time PCR and calcium imaging, we found that cultured human airway cells, including fibroblasts, epithelial and smooth muscle cells express...... functional TRPA1 channels. By using immunohistochemistry, TRPA1 staining was observed in airway epithelial and smooth muscle cells in sections taken from human airways and lung, and from airways and lung of wild-type, but not TRPA1-deficient mice. In cultured human airway epithelial and smooth muscle cells...

Airway Clearance Techniques (ACTs)

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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 ...

Optimal surface segmentation using flow lines to quantify airway abnormalities in chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Petersen, Jens; Nielsen, Mads; Lo, Pechin Chien Pau

2014-01-01

are not well suited for surfaces with high curvature, we therefore propose to derive columns from properly generated, non-intersecting flow lines. This guarantees solutions that do not self-intersect. The method is applied to segment human airway walls in computed tomography images in three-dimensions. Phantom.......5%, the alternative approach in 11.2%, and in 20.3% no method was favoured. Airway abnormality measurements obtained with the method on 490 scan pairs from a lung cancer screening trial correlate significantly with lung function and are reproducible; repeat scan R(2) of measures of the airway lumen diameter and wall...

Kaempferol Inhibits Endoplasmic Reticulum Stress-Associated Mucus Hypersecretion in Airway Epithelial Cells And Ovalbumin-Sensitized Mice.

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Park, Sin-Hye; Gong, Ju-Hyun; Choi, Yean-Jung; Kang, Min-Kyung; Kim, Yun-Ho; Kang, Young-Hee

2015-01-01

Mucus hypersecretion is an important pathological feature of chronic airway diseases, such as asthma and pulmonary diseases. MUC5AC is a major component of the mucus matrix forming family of mucins in the airways. The initiation of endoplasmic reticulum (ER)-mediated stress responses contributes to the pathogenesis of airway diseases. The present study investigated that ER stress was responsible for airway mucus production and this effect was blocked by the flavonoid kaempferol. Oral administration of ≥10 mg/kg kaempferol suppressed mucus secretion and goblet cell hyperplasia observed in the bronchial airway and lung of BALB/c mice sensitized with ovalbumin (OVA). TGF-β and tunicamycin promoted MUC5AC induction after 72 h in human bronchial airway epithelial BEAS-2B cells, which was dampened by 20 μM kaempferol. Kaempferol inhibited tunicamycin-induced ER stress of airway epithelial cells through disturbing the activation of the ER transmembrane sensor ATF6 and IRE1α. Additionally, this compound demoted the induction of ER chaperones such as GRP78 and HSP70 and the splicing of XBP-1 mRNA by tunicamycin. The in vivo study further revealed that kaempferol attenuated the induction of XBP-1 and IRE1α in epithelial tissues of OVA-challenged mice. TGF-β and tunicamycin induced TRAF2 with JNK activation and such induction was deterred by kaempferol. The inhibition of JNK activation encumbered the XBP-1 mRNA splicing and MUC5AC induction by tunicamycin and TGF-β. These results demonstrate that kaempferol alleviated asthmatic mucus hypersecretion through blocking bronchial epithelial ER stress via the inhibition of IRE1α-TRAF2-JNK activation. Therefore, kaempferol may be a potential therapeutic agent targeting mucus hypersecretion-associated pulmonary diseases.

Imaging of Occupational Lung Disease.

Science.gov (United States)

Champlin, Jay; Edwards, Rachael; Pipavath, Sudhakar

2016-11-01

Occupational lung diseases span a variety of pulmonary disorders caused by inhalation of dusts or chemical antigens in a vocational setting. Included in these are the classic mineral pneumoconioses of silicosis, coal worker's pneumoconiosis, and asbestos-related diseases as well as many immune-mediated and airway-centric diseases, and new and emerging disorders. Although some of these have characteristic imaging appearances, a multidisciplinary approach with focus on occupational exposure history is essential to proper diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Sealing of Airway Fistulas for Metallic Covered Z-type Stents

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Hongwu WANG

2011-08-01

Full Text Available Background and objective Treating airway fistulas, including esophagorespiratory fistulas (ERFs, bronchopleural fistulas (BPFs, and tracheomediastinal fistulas (TMFs, is difficult. The aim of this study is to evaluate the safety and clinical efficacy of metallic covered Z-type stents (CZTS for the treatment of airway fistulas through bronchoscopy or fluroscopy. Methods Thirty-eight patients with fistulas between the esophagus, mediastina, and airways (32 ERFs, 5 BPFs, and 1 TMF were retrospectively reviewed after treatment with covered metallic esophageal and airway stents. The fistulas were caused by esophageal (n=26, bronchogenic (n=11, and thyroid (n=1 carcinomas. Results Forty-six fistulas were found in 38 patients. The fistula size ranged from 0.5 cm to 7.0 cm. Forty airway covered metal stents (24 Y-type, 8 L-type, and 8 I-type and 24 esophageal metal stents were placed. Complete responses to the sealing effects of fistulas were noted in 4.3% of all the fistulas, 60.9% showed complete clinical responses, 23.9% showed partial responses, and 10.9% showed no response. An effectivity rate of 89.1% was observed, and the median survival duration of all patients was 5 months. Conclusion The use of CZTS appears to be safe and feasible for the palliative treatment of ERFs, BPFs, and TMFs. Airway stent placement is recommended for patients with ERF. In the event that airway stents fail, esophageal stents should be given. Airway bifurcation stents were observed to be especially suitable for the sealing of fistulas near the trachea carina.

Airway Clearance Techniques (ACTs)

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

Nonstent Combination Interventional Therapy for Treatment of Benign Cicatricial Airway Stenosis.

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Qiu, Xiao-Jian; Zhang, Jie; Wang, Ting; Pei, Ying-Hua; Xu, Min

2015-08-20

Benign cicatricial airway stenosis (BCAS) is a life-threatening disease. While there are numerous therapies, all have their defects, and stenosis can easily become recurrent. This study aimed to investigate the efficacy and complications of nonstent combination interventional therapy (NSCIT) when used for the treatment of BCAS of different causes and types. This study enrolled a cohort of patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other origins. The patients were assigned to three groups determined by their type of stenosis: Web-like stenosis, granulation stenosis, and complex stenosis, and all patients received NSCIT. The efficacy and complications of treatment in each group of patients were observed. The Chi-square test, one-factor analysis of variance (ANOVA), and the paired t -test were used to analyze different parameters. The 10 patients with web-like stenosis and six patients with granulation stenosis exhibited durable remission rates of 100%. Among 41 patients with complex stenosis, 36 cases (88%) experienced remission and 29 cases (71%) experienced durable remission. When five patients with airway collapse were eliminated from the analysis, the overall remission rate was 97%. The average treatment durations for patients with web-like stenosis, granulation stenosis, and complex stenosis were 101, 21, and 110 days, respectively, and the average number of treatments was five, two, and five, respectively. NSCIT demonstrated good therapeutic efficacy and was associated with few complications. However, this approach was ineffective for treating patients with airway collapse or malacia.

Phosphodiesterases regulate airway smooth muscle function in health and disease.

Science.gov (United States)

Krymskaya, Vera P; Panettieri, Reynold A

2007-01-01

On the basis of structure, regulation, and kinetic properties, phosphodiesterases (PDEs) represent a superfamily of enzymes divided into 11 subfamilies that catalyze cytosolic levels of 3',5'-cyclic adenosine monophosphate (cAMP) or 3',5'-cyclic guanosine monophosphate (cGMP) to 5'-AMP or 5'-GMP, respectively. PDE4 represents the major PDE expressed in inflammatory cells as well as airway smooth muscle (ASM), and selective PDE4 inhibitors provide a broad spectrum of anti-inflammatory effects such as abrogating cytokine and chemokine release from inflammatory cells and inhibiting inflammatory cell trafficking. Due to cell- and tissue-specific gene expression and regulation, PDEs modulate unique organ-based functions. New tools or compounds that selectively inhibit PDE subfamilies and genetically engineered mice deficient in selective isoforms have greatly enhanced our understanding of PDE function in airway inflammation and resident cell function. This chapter will focus on recent advances in our understanding of the role of PDE in regulating ASM function.

Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure

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Zychowski, Katherine E.; Lucas, Selita N.; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J., E-mail: mcampen@salud.unm.edu

2016-08-15

Ozone (O{sub 3})-related cardiorespiratory effects are a growing public health concern. Ground level O{sub 3} can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O{sub 3}-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O{sub 3} pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O{sub 3} exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O{sub 2}) or hypoxia (10.0% O{sub 2}), followed by a 4-h exposure to either 1 ppm O{sub 3} or filtered air (FA). As an additional experimental intervention fasudil (20 mg/kg) was administered intraperitoneally prior to and after O{sub 3} exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O{sub 3} exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O{sub 3} exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O{sub 3}-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability. - Highlights: • Environmental exposures can exacerbate chronic obstructive

Extraglottic airway devices: technology update

Directory of Open Access Journals (Sweden)

Sharma B

2017-08-01

Full Text Available Bimla Sharma, Chand Sahai, Jayashree Sood Department of Anaesthesiology, Pain and Perioperative Medicine, Sir Ganga Ram Hospital, New Delhi, India Abstract: Extraglottic airway devices (EADs have revolutionized the field of airway management. The invention of the laryngeal mask airway was a game changer, and since then, there have been several innovations to improve the EADs in design, functionality, safety and construction material. These have ranged from changes in the shape of the mask, number of cuffs and material used, like rubber, polyvinylchloride and latex. Phthalates, which were added to the construction material in order to increase device flexibility, were later omitted when this chemical was found to have serious adverse reproductive outcomes. The various designs brought out by numerous companies manufacturing EADs resulted in the addition of several devices to the airway market. These airway devices were put to use, many of them with inadequate or no evidence base regarding their efficacy and safety. To reduce the possibility of compromising the safety of the patient, the Difficult Airway Society (DAS formed the Airway Device Evaluation Project Team (ADEPT to strengthen the evidence base for airway equipment and vet the new extraglottic devices. A preuse careful analysis of the design and structure may help in better understanding of the functionality of a particular device. In the meantime, the search for the ideal EAD continues. Keywords: extraglottic airway devices, laryngeal mask airway, other extraglottic airway devices, safety, technology update

Role of IL-4 receptor α-positive CD4(+) T cells in chronic airway hyperresponsiveness.

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Kirstein, Frank; Nieuwenhuizen, Natalie E; Jayakumar, Jaisubash; Horsnell, William G C; Brombacher, Frank

2016-06-01

TH2 cells and their cytokines are associated with allergic asthma in human subjects and with mouse models of allergic airway disease. IL-4 signaling through the IL-4 receptor α (IL-4Rα) chain on CD4(+) T cells leads to TH2 cell differentiation in vitro, implying that IL-4Rα-responsive CD4(+) T cells are critical for the induction of allergic asthma. However, mechanisms regulating acute and chronic allergen-specific TH2 responses in vivo remain incompletely understood. This study defines the requirements for IL-4Rα-responsive CD4(+) T cells and the IL-4Rα ligands IL-4 and IL-13 in the development of allergen-specific TH2 responses during the onset and chronic phase of experimental allergic airway disease. Development of acute and chronic ovalbumin (OVA)-induced allergic asthma was assessed weekly in CD4(+) T cell-specific IL-4Rα-deficient BALB/c mice (Lck(cre)IL-4Rα(-/lox)) and respective control mice in the presence or absence of IL-4 or IL-13. During acute allergic airway disease, IL-4 deficiency did not prevent the onset of TH2 immune responses and OVA-induced airway hyperresponsiveness or goblet cell hyperplasia, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. In contrast, deficiency of IL-13 prevented allergic asthma, irrespective of the presence or absence of IL-4Rα-responsive CD4(+) T cells. Importantly, chronic allergic inflammation and airway hyperresponsiveness were dependent on IL-4Rα-responsive CD4(+) T cells. Deficiency in IL-4Rα-responsive CD4(+) T cells resulted in increased numbers of IL-17-producing T cells and, consequently, increased airway neutrophilia. IL-4-responsive T helper cells are dispensable for acute OVA-induced airway disease but crucial in maintaining chronic asthmatic pathology. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Role of Continuous Positive Airway Pressure Therapy in the Management of Respiratory Distress in Extremely Premature Infants

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Sekar, Kris

2006-01-01

The use of mechanical ventilation for the treatment of respiratory distress syndrome (RDS) in low birth weight infants may cause barotrauma, volutrauma, and chronic lung disease. Different continuous positive airway pressure (CPAP) delivery systems exist, each with its own practical and clinical advantages and disadvantages. CPAP can be used as either a primary or an adjunctive respiratory support for RDS. Research demonstrates that CPAP decreases the incidence of respiratory failure after ex...

Gender disparity of changes in heart rate during the six-minute walk test among patients with chronic obstructive airway disease

Directory of Open Access Journals (Sweden)

Esmaeil Alibakhshi

2017-07-01

Full Text Available Background Chronic obstructive pulmonary disease (COPD is a major cause of chronic morbidity and mortality worldwide. Clarify; COPD is the fifth leading cause of death and disease burden globally. Aims The purpose of this study is to compare the gender disparity of changes in heart rate during 6-minute walk test (6MWT among patients with chronic obstructive airway disease (COPD. We also aimed to assess the relationship between change in heart rate and body mass index (BMI. Methods We randomly selected 59 elderly subjects with COPD (made up of 45 men and 14 women. The selected patients all had Medical Research Council (MRC dyspnea index of ≥3. All patients in this study had informed written consent and carried out the 6 minute walk tests (6MWT according to standards. Data analysis was carried out with SPSS version 21.0 software and Excel 2016 with level of significance taken as p<0.05. We used of ANOVA to identify difference in the means among three or more groups. Results As the BMI range is 15–50 while the mean BMI was 26±00 include the standard deviation has been observed overweight in all patients with COPD. There was significant difference in the distance covered during the 6MWT between men and women (Men=397.00, Women=375.00 at p<0.001. Also, we can be seeing lowest significant different in heart rate basic (Mean Square=0.0 and oxygen saturation at rest (Mean Square=2.0 in value p<0.00 between men and women. Conclusion In this study, distance, SPO2, resting heart rate and 1-minute heart rate variables were evaluated for assessing exercise capacity and then the amount of breathlessness and exercise in patients with COPD.

Effects of Flavin7 on allergen induced hyperreactivity of airways

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Franova S

2009-12-01

Full Text Available Abstract Some studies have suggested that the polyphenolic compounds might reduce the occurrence of asthma symptoms. The aim of our experiments was to evaluate the effects of 21 days of the flavonoid Flavin7 administration on experimentally induced airway inflammation in ovalbumin-sensitized guinea pigs. We assessed tracheal smooth muscle reactivity by an in vitro muscle-strip method; changes in airway resistance by an in vivo plethysmographic method; histological picture of tracheal tissue; and the levels of interleukin 4 (IL-4, and interleukin 5 (IL-5 in bronchoalveolar lavage fluid (BALF. Histological investigation of tracheal tissue and the concentrations of the inflammatory cytokines IL-4 and IL-5 in BALF were used as indices of airway inflammation. Administration of Flavin7 caused a significant decrease of specific airway resistance after histamine nebulization and a decline in tracheal smooth muscle contraction amplitude in response to bronchoconstricting mediators. Flavin7 minimized the degree of inflammation estimated on the basis of eosinophil calculation and IL-4 and IL-5 concentrations. In conclusion, administration of Flavin7 showed bronchodilating and anti-inflammatory effects on allergen-induced airway inflammation.

[Management of malignant and benign airway stenosis by stent implantation].

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Gyulai, Márton; Slavei, Krisztina; Pénzes, István; Strausz, János

2006-11-12

In the last few decades the different bronchoscopic procedures have gained an important role in the treatment of airway stenosis, and the number of implanted airway stents has also greatly increased. Between 1998 and 2004 the authors implanted altogether 108 airway prosthesis in 90 patients at the Institute of Pulmonology of Pest County. 58% of the patients were males, 42% females, the average age was 57.5 years, the average follow-up time was 7 months. On the basis of different etiology the patients were separated into two main groups. In 57% the airway stenosis was caused by malignant illnesses, in these cases stents can be used only with palliative purpose. However, in case of benign lesions they can offer a long-term solution and require an adequate follow-up of the patients. The authors' main aim was to get an overall picture of the interventions they had done by processing the data, with the help of the measurable characteristics that make possible to follow the airways' permeability and its changes. Analysing the results of the respiratory function and blood gas examinations they didn't find a significant difference inspite of the subjective improvement.

VIRTUAL 3-D MODELLING OF AIRWAYS IN CONGENITAL HEART DEFECTS

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Simone Speggiorin

2016-10-01

Full Text Available The involvement of the airway is not uncommon in the presence of complex cardiovascular malformations. In these cases, a careful inspection of the relationship between the airway and the vasculature is paramount to plan the surgical procedure. Three-dimentional printing enhanced the visualization of the cardio-vascualr structure. Unfortunately IT does not allow to remove selected anatomy to improve the visualization of the surrounding ones. Computerized modelling (CM of has the potential to fill this gap by allowing a dynamic handling of different anatomies, increasing the exposure of vessels or bronchi to show their relationship.. We started to use this technique to plan the surgical repair in these complex cases where the airway is affected. This technique is routinely used in our Institution as an additional tool in the pre-surgical assessment. We report 4 cases in which the airways were compressed by vascular structures : ascending aorta in 1, left pulmonary artery sling in 1, Patent ductus arteriosus (PDA in 1 and major aorto-pulmonary collateral artery in 1. We believe this technique can enhance the understanding of the causes of airway involvement and facilitate the creation of an appropriate surgical plan.

Respiratory health of elite athletes – preventing airway injury: a critical review

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Kippelen, Pascale; Fitch, Kenneth D; Anderson, Sandra Doreen; Bougault, Valerie; Boulet, Louis-Philippe; Rundell, Kenneth William; Sue-Chu, Malcolm; McKenzie, Donald C

2012-01-01

Elite athletes, particularly those engaged in endurance sports and those exposed chronically to airborne pollutants/irritants or allergens, are at increased risk for upper and lower airway dysfunction. Airway epithelial injury may be caused by dehydration and physical stress applied to the airways during severe exercise hyperpnoea and/or by inhalation of noxious agents. This is thought to initiate an inflammatory cascade/repair process that, ultimately, could lead to airway hyperresponsiveness (AHR) and asthma in susceptible athletes. The authors review the evidence relating to prevention or reduction of the risk of AHR/asthma development. Appropriate measures should be implemented when athletes exercise strenuously in an attempt to attenuate the dehydration stress and reduce the exposure to noxious airborne agents. Environmental interventions are the most important. Non-pharmacological strategies can assist, but currently, pharmacological measures have not been demonstrated to be effective. Whether early prevention of airway injury in elite athletes can prevent or reduce progression to AHR/asthma remains to be established. PMID:22522585

Temporal and Spatial Expression of Transforming Growth Factor-β after Airway Remodeling to Tobacco Smoke in Rats

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Hoang, Laura L.; Nguyen, Yen P.; Aspeé, Rayza; Bolton, Sarah J.; Shen, Yi-hsin; Wang, Lei; Kenyon, Nicholas J.; Smiley-Jewell, Suzette

2016-01-01

Airway remodeling is strongly correlated with the progression of chronic obstructive pulmonary disease (COPD). In this study, our goal was to characterize progressive structural changes in site-specific airways, along with the temporal and spatial expression of transforming growth factor (TGF)-β in the lungs of male spontaneously hypertensive rats exposed to tobacco smoke (TS). Our studies demonstrated that TS-induced changes of the airways is dependent on airway generation and exposure duration for proximal, midlevel, and distal airways. Stratified squamous epithelial cell metaplasia was evident in the most proximal airways after 4 and 12 weeks but with minimal levels of TGF-β–positive epithelial cells after only 4 weeks of exposure. In contrast, epithelial cells in midlevel and distal airways were strongly TGF-β positive at both 4 and 12 weeks of TS exposure. Airway smooth muscle volume increased significantly at 4 and 12 weeks in midlevel airways. Immunohistochemistry of TGF-β was also found to be significantly increased at 4 and 12 weeks in lymphoid tissues and alveolar macrophages. ELISA of whole-lung homogenate demonstrated that TGF-β2 was increased after 4 and 12 weeks of TS exposure, whereas TGF-β1 was decreased at 12 weeks of TS exposure. Airway levels of messenger RNA for TGF-β2, as well as platelet-derived growth factor-A, granulocyte-macrophage colony–stimulating factor, and vascular endothelial growth factor-α, growth factors regulated by TGF-β, were significantly decreased in animals after 12 weeks of TS exposure. Our data indicate that TS increases TGF-β in epithelial and inflammatory cells in connection with airway remodeling, although the specific role of each TGF-β isoform remains to be defined in TS-induced airway injury and disease. PMID:26637070

Airway management in neuroanesthesiology.

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Aziz, Michael

2012-06-01

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

[Function and modulation of type Ⅱ innate lymphoid cells and their role in chronic upper airway inflammatory diseases].

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Liu, Y; Liu, Z

2017-02-07

Type Ⅱ innate lymphoid cells (ILC2) is a family of innate immune lymphocytes, which provide effective immune responses to cytokines. ILC2 are regulated by the nuclear transcription factor ROR alpha and GATA3, secreting cytokines IL-5 and IL-13, etc. Animal models have shown that ILC2 are involved in allergic diseases, such as asthma and atopic dermatitis, and also play a very important role in the metabolic balance. In addition, recent reports suggest that ILC2 not only play a role in the initial stages of the disease, but also can lead to chronic pathological changes in the disease, such as fibrosis, and may have an effect on acquired immunity. This paper mainly focus in the role and regulation of ILC2 cells, and review the research status of ILC2 in the field of chronic upper airway inflammatory diseases including allergic rhinitis and chronic rhinosinusitis.

Fatal Airway Obstruction in a Man With a Cystic Hygroma.

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Wygant, Cassandra Maria; Cohle, Stephen D

2018-05-03

We describe a 24-year-old man with a cystic hygroma of the left side of the lower neck that led to sudden death. Cystic hygroma (cystic lymphangioma) is a congenital malformation of the lymphatic system. The patient, who had a tracheostomy because of airway obstruction from the cystic hygroma, was found dead with his tracheostomy tube on the floor next to him. Complications of cystic hygroma include infiltration of the neck causing airway obstruction, dysphagia, pain, and obstructive sleep apnea.

Physiologic correlates of airspace size and airway remodeling in the smoke exposed guinea pig model

NARCIS (Netherlands)

Wright, J. L.; Postma, D. S.; Kerstjens, H. A. M.; Timens, W.; Whittaker, P.; Churg, A.

2007-01-01

Although small airway remodeling (SAR) leading to airflow obstruction is a common consequence of human cigarette smoking, the airways have been largely ignored in animal models of chronic obstructive pulmonary disease ( COPD). We examined lung structure in a guinea pig model of chronic cigarette

Airway wall thickness of allergic asthma caused by weed pollen or house dust mite assessed by computed tomography.

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Liu, Liping; Li, Guangrun; Sun, Yuemei; Li, Jian; Tang, Ningbo; Dong, Liang

2015-03-01

Little was known about Airway wall thickness of asthma patients with different allergen allergy. So we explored the possible difference of Airway wall thickness of asthma patients mono-sensitized to weed pollen or HDM using high-resolution computed tomography. 85 severe asthma patients were divided into weed pollen group and HDM group according to relevant allergen. 20 healthy donors served as controls. Airway wall area, percentage wall area and luminal area at the trunk of the apical bronchus of the right upper lobe were quantified using HRCT and compared. The values of pulmonary function were assessed as well. There were differences between HDM group and weed pollen group in WA/BSA,WA% and FEF25-75% pred, and no significant difference in FEV1%pred, FEV1/FVC and LA/BSA. In weed pollen group, WA/BSA was observed to correlate with the duration of rhinitis, whereas in HDM group, WA/BSA and LA/BSA was observed to correlate with the duration of asthma. In weed pollen group, FEV1/FVC showed a weak but significant negative correlation with WA%, but in HDM group FEV1/FVC showed a significant positive correlation with WA% and a statistical negative correlation with LA/BSA. FEV1/FVC and FEF25-75% pred were higher and WA/BSA and LA/BSA were lower in healthy control group than asthma group. FEV1%pred and WA% was no significant difference between asthma patients and healthy subjects. There are differences between HDM mono-sensitized subjects and weed pollen mono-sensitized subjects, not only in airway wall thickness, but also small airway obstruction. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Airway Microbiome in Severe Asthma: Associations with Disease Features and Severity

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Huang, Yvonne J.; Nariya, Snehal; Harris, Jeffrey M.; Lynch, Susan V.; Choy, David F.; Arron, Joseph R.; Boushey, Homer

2015-01-01

Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions

BLOCKADE OF TRKA OR P75 NEUROTROPHIN RECEPTORS ATTENUATES DIESEL PARTICULATE-INDUCED ENHANCEMENT OF ALLERGIC AIRWAYS RESPONSES IN BALB/C MICE

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Neurotrophins, including nerve growth factor (NGF) partially mediate many features of allergic airways disease including airway resistance. Exposure to diesel exhaust particles (DEP) associated with the combustion of diesel fuel exacerbates allergic airways responses. We tested t...

Paediatric airway management: basic aspects

DEFF Research Database (Denmark)

Holm-Knudsen, R J; Rasmussen, L S

2009-01-01

Paediatric airway management is a great challenge, especially for anaesthesiologists working in departments with a low number of paediatric surgical procedures. The paediatric airway is substantially different from the adult airway and obstruction leads to rapid desaturation in infants and small...... children. This paper aims at providing the non-paediatric anaesthesiologist with a set of safe and simple principles for basic paediatric airway management. In contrast to adults, most children with difficult airways are recognised before induction of anaesthesia but problems may arise in all children...

Changes in Upper Airway Volume Following Orthognathic Surgery.

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Marcussen, Lillian; Stokbro, Kasper; Aagaard, Esben; Torkov, Peter; Thygesen, Torben

2017-01-01

Reduced volume of the internal skeletal dimensions of the face is 1 of the main causes of obstructive sleep apnea, and attention to patients' airways is necessary when planning orthognathic treatment. This study aims to describe changes in upper airway volume following virtually planned orthognathic surgery.A retrospective pilot study was designed with 30 randomly selected patients (10 men and 20 women, aged 23.1 ± 6.8 years, molar-relations: 15 neutral, 8 distal, and 7 mesial). Cone-beam computed tomography scans were performed before surgery and 1 week following surgery. The authors did total upper airway volume measurements and obtained 1-mm slices at vertical levels in the velo-, oro-, and hypopharynx and at the smallest visible cross-section.Measurements before and after surgery were compared using Student t test.After orthognathic surgery, the minimum cross-sectional area at the vertical level increased from 83 mm ± 33 before surgery to 102 mm ± 36 after surgery (P = 0.019). In patients with neutral and distal occlusions, the minimum cross-sectional slice volume increased in 87% but in only 57% with mesial occlusion.The present findings suggest that orthognathic surgery increases upper airway volume parameters, but a few patients have continued impairment of the airways following orthognathic surgery. Further studies are needed to confirm an individual surgical planning approach that potentially could bring the minimum cross sectional area out of the risk zone.

[Electrocautery and bronchoscopy as a first step for the management of central airway obstruction and associated hemoptysis].

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Jalilie, Alfredo; Carvajal, Juan Carlos; Aparicio, Rodrigo; Meneses, Manuel

2016-11-01

Central airway obstruction caused by malignant or benign lesions, associated in some cases with hemoptysis, is a condition with high morbidity and mortality. The use of electrocautery by flexible bronchoscopy is an initial treatment option with immediate improvement of obstruction symptoms. It is as effective as Nd: YAG laser. To describe the usefulness of electrocautery in the management of central obstruction of the airway and hemoptysis. A retrospective, descriptive study of patients referred for management of central airway obstruction or associated hemoptysis. Diagnoses, symptoms (dyspnea, cough, and hemoptysis) and radiology before and after the procedures were analyzed. Eighteen patients aged 59 ± 12 years (66% males) were evaluated, registering 25 endoscopic procedures. Three conditions were found: partial or complete airway obstruction, hemoptysis and post lung transplant bronchial stenosis. Seventy two percent presented with dyspnea, 61% with cough and 33% with hemoptysis. Sixty six percent of patients had airway obstruction caused by malignant metastatic lesions. After electrocautery, 17 patients (94.4%) improved their symptoms and achieved complete airway clearing. Three patients had significant bronchial stenosis after lung transplant achieving subsequent clearing after electrocautery. Electrocautery during flexible bronchoscopy is an effective and safe procedure for the management of central airway obstruction and associated hemoptysis.

Gefitinib, an EGFR Tyrosine Kinase inhibitor, Prevents Smoke-Mediated Ciliated Airway Epithelial Cell Loss and Promotes Their Recovery.

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Monica Valencia-Gattas

Full Text Available Cigarette smoke exposure is a major health hazard. Ciliated cells in the epithelium of the airway play a critical role in protection against the noxious effects of inhaled cigarette smoke. Ciliated cell numbers are reduced in smokers which weakens host defense and leads to disease. The mechanisms for the loss of ciliated cells are not well understood. The effects of whole cigarette smoke exposure on human airway ciliated ciliated cells were examined using in vitro cultures of normal human bronchial epithelial cells and a Vitrocell® VC 10® Smoking Robot. These experiments showed that whole cigarette smoke causes the loss of differentiated ciliated cells and inhibits differentiation of ciliated cells from undifferentiated basal cells. Furthermore, treatment with the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor, Gefitinib, during smoke exposure prevents ciliated cell loss and promotes ciliated cell differentiation from basal cells. Finally, restoration of ciliated cells was inhibited after smoke exposure was ceased but was enhanced by Gefitinib treatment. These data suggest that inhibition of EGFR activity may provide therapeutic benefit for treating smoke related diseases.

Airway management in trauma.

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Langeron, O; Birenbaum, A; Amour, J

2009-05-01

Maintenance of a patent and prevention of aspiration are essential for the management of the trauma patient, that requires experienced physicians in airway control techniques. Difficulties of the airway control in the trauma setting are increased by the vital failures, the risk of aspiration, the potential cervical spine injury, the combative patient, and the obvious risk of difficult tracheal intubation related to specific injury related to the trauma. Endotracheal intubation remains the gold standard in trauma patient airway management and should be performed via the oral route with a rapid sequence induction and a manual in-line stabilization maneuver, to decrease the risks previously mentioned. Different techniques to control the airway in trauma patients are presented: improvement of the laryngoscopic vision, lighted stylet tracheal intubation, retrograde technique for orotracheal intubation, the laryngeal mask and the intubating laryngeal mask airways, the combitube and cricothyroidotomy. Management of the airway in trauma patients requires regular training in these techniques and the knowledge of complementary techniques allowing tracheal intubation or oxygenation to overcome difficult intubation and to prevent major complications as hypoxemia and aspiration.

Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats.

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Wang, T; Liu, Y; Chen, L; Wang, X; Hu, X-R; Feng, Y-L; Liu, D-S; Xu, D; Duan, Y-P; Lin, J; Ou, X-M; Wen, F-Q

2009-05-01

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3',5'-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined. Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production. The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia. In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3',5'-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.

The effect of body weight on distal airway function and airway inflammation.

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van de Kant, Kim D G; Paredi, Paolo; Meah, Sally; Kalsi, Harpal S; Barnes, Peter J; Usmani, Omar S

Obesity is a global health problem that adversely influences the respiratory system. We assessed the effects of body mass index (BMI) on distal airway function and airway inflammation. Impulse oscillometry (IOS) as a measure of distal airway function, together with spirometry, were assessed in adults with a range of different BMIs. Airway inflammation was assessed with the fraction of exhaled nitric oxide (FeNO) and participants exhaled at various exhalation flows to determine alveolar and bronchial NO. In total 34 subjects were enrolled in the study; 19 subjects had a normal BMI (18.50-24.99), whilst 15 subjects were overweight (BMI 25.00-29.99), or obese (BMI ≥30). All subjects had normal spirometry. However, IOS measures of airway resistance (R) at 5Hz, 20Hz and frequency dependence (R 5-20 ) were elevated in overweight/obese individuals, compared to subjects with a normal BMI (median (interquartile range)); 5Hz: 0.41 (0.37, 0.45) vs. 0.32 (0.30, 0.37)kPa/l/s; 20Hz: 0.34 (0.30, 0.37) vs. 0.30 (0.26, 0.33)kPa/l/s; R 5-20 : 0.06 (0.04, 0.11) vs. 0.03 (0.01, 0.05)kPa/l/s; plimitation) and FeNO inflammatory measures, did not differ between groups (p>0.05). Being overweight has significant effects on distal and central airway function as determined by IOS, which is not detected by spirometry. Obesity does not influence airway inflammation as measured by FeNO. IOS is a reliable technique to identify airway abnormalities in the presence of normal spirometry in overweight people. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway epithelium.

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Manunta, Maria D I; McAnulty, Robin J; Tagalakis, Aristides D; Bottoms, Stephen E; Campbell, Frederick; Hailes, Helen C; Tabor, Alethea B; Laurent, Geoffrey J; O'Callaghan, Christopher; Hart, Stephen L

2011-01-01

Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy. The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by electrostatic interactions to form a receptor-targeted nanocomplex (RTN) of approximately 150 nm with a cationic surface charge of +50 mV. The aerodynamic properties of aerosolised nanocomplexes produced with three different nebulisers were compared by determining aerosol deposition in the different stages of a Next Generation Pharmaceutical Impactor (NGI). We also investigated the yield of intact plasmid DNA by agarose gel electrophoresis and densitometry, and transfection efficacies in vitro and in vivo. RTNs nebulised with the AeroEclipse II BAN were the most effective, compared to other nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical properties of the nanocomplexes were unchanged after nebulisation while the deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 µm-1.4 µm cut off (NGI stages 3-6) compatible with deposition in the central and lower airways. RTNs showed their ability at delivering genes via nebulisation, thus suggesting their potential applications for therapeutic interventions of cystic fibrosis and other respiratory disorders.

Nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway epithelium.

Directory of Open Access Journals (Sweden)

Maria D I Manunta

Full Text Available Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy.The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by electrostatic interactions to form a receptor-targeted nanocomplex (RTN of approximately 150 nm with a cationic surface charge of +50 mV. The aerodynamic properties of aerosolised nanocomplexes produced with three different nebulisers were compared by determining aerosol deposition in the different stages of a Next Generation Pharmaceutical Impactor (NGI. We also investigated the yield of intact plasmid DNA by agarose gel electrophoresis and densitometry, and transfection efficacies in vitro and in vivo.RTNs nebulised with the AeroEclipse II BAN were the most effective, compared to other nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical properties of the nanocomplexes were unchanged after nebulisation while the deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 µm-1.4 µm cut off (NGI stages 3-6 compatible with deposition in the central and lower airways.RTNs showed their ability at delivering genes via nebulisation, thus suggesting their potential applications for therapeutic interventions of cystic fibrosis and other respiratory disorders.

Chronic pulmonary disease - a multifacted disease complex in the horse

International Nuclear Information System (INIS)

Clarke, A.F.

1987-01-01

This paper reviews chronic pulmonary disease (CPD) as an insidiously developing disease capable of being manifest in many degrees. Horses may suffer mild, sub-clinical degrees of lower respiratory tract inflammation or small airway disease withouth showing symptoms at rest. This form of disease becomes manifest as poor performance when these horses take part in athletic competition. Factors relating to the aetiology, diagnosis, treatment and prevention of all degrees of small airway disease of horses are discussed. 30 refs

Efficacy of a Conservative Weight Loss Program in the Long-Term Management of Chronic Upper Airway Obstruction

Directory of Open Access Journals (Sweden)

Ryan C. Case

2009-01-01

Full Text Available Objective. Obesity is a significant contributor to oxygen demand and dynamic airway obstruction. The objective of the current study is to determine the long-term success of conservative measures directed toward weight reduction on airway management without respect to specific airway disease etiology. Methods. Patients with chronic airway obstruction secondary anatomic lesions or obstructive sleep apnea were recruited and followed prospectively. Demographics, initial and final weights, diagnosis, and followup information were recorded. Patients were referred to a registered dietician, provided counseling, and started on a weight-loss regimen. Outcome measures were change in body mass index (BMI and rate of decannulation from weight loss alone. Results. Of fourteen patients, ten remained tracheostomy-dependent and four had high-grade lesions with the potential for improvement in oxygen demand and dynamic airway collapse with weight loss. The mean follow up period was 25 months. The mean change in BMI was an increase of 1.4 kg/m2 per patient. Conclusions. Conservative measures alone were not effective in achieving weight reduction in the population studied. This may be due to comorbid disease and poor compliance. The promise of decannulation was an insufficient independent motivator for weight loss in this study. Although the theoretical benefits of weight loss support its continued recommendation, the long-term success rate of conservative measures is low. More aggressive facilitated interventions including pharmacotherapy or bariatric surgery should be considered early in the course of treating airway disease complicated by obesity.

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

Endocrine causes of nonalcoholic fatty liver disease.

Science.gov (United States)

Marino, Laura; Jornayvaz, François R

2015-10-21

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

Airway malacia in children with achondroplasia.

Science.gov (United States)

Dessoffy, Kimberly E; Modaff, Peggy; Pauli, Richard M

2014-02-01

This study was undertaken to assess the frequency of airway malacia in infants and young children with achondroplasia, a population well known to be at risk for a variety of respiratory problems. We also wished to evaluate what, if any, contribution airway malacia makes to the complex respiratory issues that may be present in those with achondroplasia. Retrospective chart review of all infants and young children with achondroplasia who were assessed through the Midwest Regional Bone Dysplasia Clinics from 1985 through 2012 (n = 236) was completed. Records of comprehensive clinical examinations, polysomnographic assessments, and airway visualization were reviewed and abstracted using a data collection form. Analyses were completed comparing the group with and those without evidence for airway malacia. Thirteen of 236 patients (5.5%) were found to have airway malacia. Most of those affected had lower airway involvement (9/13). The presence of airway malacia was correlated with an increased occurrence of obstructive sleep apnea as well as need for oxygen supplementation, airway surgeries and tracheostomy placement. Although estimates of the frequency of airway malacia in the general population are limited, its frequency in children with achondroplasia appears to be much higher than any published general population estimate. The presence of airway malacia appears to confound other breathing abnormalities in this population and results in the need for more invasive airway treatments. © 2013 Wiley Periodicals, Inc.

Old dilemma : asthma with irreversible airway obstruction or COPD

NARCIS (Netherlands)

Fattahi, Fatemeh; Vonk, Judith M.; Bulkmans, Nicole; Fleischeuer, Ruth; Gouw, Annette; Grunberg, Katrien; Mauad, Thais; Popper, Helmut; Felipe-Silva, Aloisio; Vrugt, Bart; Wright, Joanne L.; Yang, Hui-Min; Kocks, Janwillem W. H.; Hylkema, Machteld N.; Postma, Dirkje S.; Timens, Wim; ten Hacken, Nick H. T.

2015-01-01

Older asthmatic patients may develop fixed airway obstruction and clinical signs of chronic obstructive pulmonary disease (COPD). We investigated the added value of pathological evaluation of bronchial biopsies to help differentiate asthma from COPD, taking into account smoking, age, and inhaled

Anaesthetic management in a case of large plunging ranula with difficult airway: A case report

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Surendra Kumar Sethi

2017-04-01

Full Text Available Plunging ranula is a mucous retention cyst found on the floor of mouth which arises from the submandibular and sublingual salivary glands extending to lateral aspect of neck, which may often cause potential airway obstruction leading to difficulty in airway management. A forty year old female patient was admitted to our hospital with large, painless swelling in the floor of mouth extending to the lateral part of body of mandible and neck. This intraoral swelling distorted the normal airway anatomy thus making airway management difficult as the patient was planned for excision of swelling under general anaesthesia. So we present a case of successful management of a difficult airway by using awake fibre optic intubation in a patient posted for excision of a large plunging ranula under general anaesthesia.

Relationship between airway pathophysiology and airway inflammation in older asthmatics

DEFF Research Database (Denmark)

Porsbjerg, Celeste M; Gibson, Peter G; Pretto, Jeffrey J

2013-01-01

-dose ratio (%fall in forced expiratory volume in 1 s (FEV1 )/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). RESULTS...

Computed tomography dose and variability of airway dimension measurements: how low can we go?

International Nuclear Information System (INIS)

Jong, Pim A. de; Long, Frederick R.; Nakano, Yasutaka

2006-01-01

Quantitative CT shows promise as an outcome measure for cystic fibrosis (CF) lung disease in infancy, but must be accomplished at a dose as low as reasonably achievable. To determine the feasibility of ultra-low-dose CT for quantitative measurements of airway dimensions. Two juvenile pigs were anesthetized and their lungs scanned at 25 cm H 2 O face-mask pressure in apnoea using beam currents of 5, 10, 20, 40 and 100 mAs. The lumen diameters and wall thicknesses of matched airways (n=22) at each dose were measured by two observers using validated software. Measurement variability at each dose was compared to that at 100 mAs (reference dose) for large and small airways (lumen diameter <2.5 mm). Lowering CT dose (mAs) affected measurement variability for lumen diameter of small and large airways (P<0.001) and for wall thickness of small (P<0.001), but not large (P=0.63), airways. To obtain the same measurement variability at 5 mAs as at 100 mAs, four to six small airways or one to three large airways have to be measured and averaged. Quantitative airway measurements are feasible on images obtained at as low as 5 mAs, but more airways need to be measured to compensate for greater measurement variability. (orig.)

Exposure to environmental tobacco smoke from husband more strongly impacts on the airway obstruction of nonsmoking women.

Science.gov (United States)

Suyama, Kazuaki; Kozu, Ryo; Tanaka, Takako; Ishimatsu, Yuji; Sawai, Terumitsu

2018-01-01

The impact of airway obstruction of nonsmoking women caused by their husband's smoking is unclear, despite the association between environmental tobacco smoke (ETS) exposure at home and obstructive pulmonary diseases among nonsmoking women. The aim of this study was to provide evidence that ETS exposure from the husband at home has a more significant influence on the airway obstruction of nonsmoking women than other housemates. Nonsmoking women aged 40 years or older were recruited from the health checkup during May 2015-December 2016, Japan. They answered structured questionnaires, including ETS exposure from their husbands and other housemates (parents, siblings and dependants), and performed spirometry. We categorized the women with any history of ETS exposure from housemates into three groups (A = husband, B = others and C = both of husband and others) and defined the control group as those with no ETS exposure from housemates. A total of 811 nonsmoking women completed questionnaires and spirometry. The proportion of nonsmoking women who had airway obstruction (forced expiratory volume in 1 second [FEV 1 ]/forced vital capacity [FVC] <70%) among Group A (7.5%) was significantly higher than those in the control group (1.1%, p <0.01) and Group B (0.8%, p <0.01). The proportion of airway obstruction in Group C (6.4%) was also higher than that in the control group ( p <0.05) and Group B ( p <0.05). ETS exposure from husband (odds ratio [OR], 3.53; 95% confidence interval [CI], 1.48-8.42) remained strongly associated with airway obstruction after multiple logistic regression analysis, adjusting for age, housemate's smoking habits, family history and ETS exposure in childhood and at work. Nonsmoking women who were exposed to ETS from their husband had the lowest FEV 1 /FVC, and a higher proportion of them had airway obstruction when compared to nonsmoking women who experienced ETS from housemates other than their husbands. The findings suggest that tobacco control in

Effect of inhaled formyl-methionyl-leucyl-phenylalanine on airway function.

Science.gov (United States)

Berend, N; Peters, M J; Armour, C L; Black, J L; Ward, H E

1988-01-01

Formyl-methionyl-leucyl-phenylalanine (FMLP), a synthetic, acylated tripeptide analogous to bacterial chemotactic factors, has been shown to cause bronchoconstriction in guinea pig, rabbit, and human airways in vitro. To determine whether FMLP causes bronchoconstriction in man in vivo, a preliminary study was undertaken in which five non-smokers (mean age 35 years, FEV1 94% (SEM 5%) predicted) and five smokers (mean age 34 years, FEV1 93% (6%) predicted) inhaled aerosols of FMLP. None of the subjects showed airway hyperresponsiveness to histamine (the provocative concentrations of histamine causing a fall of greater than or equal to 20% in FEV1 (PC20) were over 8 mg/ml). FMLP dissolved in 50% dimethylsulphoxide and 50% saline in concentrations of 0, 0.06, 0.12, 0.25, 0.5, 1.0, 2.0, and 4.0 mg/ml was administered to the subjects by means of a French-Rosenthal dosimeter, FEV1 being recorded after inhalation of each concentration. Dose dependent falls in FEV1 occurred in five non-smokers (geometric mean 1.76, 95% confidence limits 0.87-3.53 mg/ml) and three smokers (0.23, 0.07-0.78 mg/ml), with two smokers not responding by 20% to the highest concentration of FMLP. On a separate day the FMLP dose-response curves were repeated after nebulisation of 500 micrograms of ipratropium bromide. The PC20 FMLP in the responders more than doubled. In six additional normal subjects a histamine inhalation test was performed before and four and 24 hours after inhalation of FMLP. All subjects remained unresponsive to histamine. These results show that FMLP is a potent bronchoconstrictor in some non-asthmatic individuals in vivo and this may be important in bronchoconstriction related to infection in patients with chronic obstructive lung disease.

Multiple hypothesis tracking based extraction of airway trees from CT data

DEFF Research Database (Denmark)

Raghavendra, Selvan; Petersen, Jens; de Bruijne, Marleen

Segmentation of airway trees from CT scans of lungs has important clinical applications, in relation to the diagnosis of chronic obstructive pulmonary disease (COPD). Here we present a method based on multiple hypothesis tracking (MHT) and template matching, originally devised for vessel...... segmentation, to extract airway trees. Idealized tubular templates are constructed and ranked using scores assigned based on the image data. Several such regularly spaced hypotheses are used in constructing a hypothesis tree, which is then traversed to obtain improved segmentation results....

The clinical utility of long-term humidification therapy in chronic airway disease.

Science.gov (United States)

Rea, Harold; McAuley, Sue; Jayaram, Lata; Garrett, Jeffrey; Hockey, Hans; Storey, Louanne; O'Donnell, Glenis; Haru, Lynne; Payton, Matthew; O'Donnell, Kevin

2010-04-01

Persistent airway inflammation with mucus retention in patients with chronic airway disorders such as COPD and bronchiectasis may lead to frequent exacerbations, reduced lung function and poor quality of life. This study investigates if long-term humidification therapy with high flow fully humidified air at 37 degrees C through nasal cannulae can improve these clinical outcomes in this group of patients. 108 patients diagnosed with COPD or bronchiectasis were randomised to daily humidification therapy or usual care for 12 months over which exacerbations were recorded. Lung function, quality of life, exercise capacity, and measures of airway inflammation were also recorded at baseline, 3 and 12 months. Patients on long-term humidification therapy had significantly fewer exacerbation days (18.2 versus 33.5 days; p = 0.045), increased time to first exacerbation (median 52 versus 27 days; p = 0.0495) and reduced exacerbation frequency (2.97/patient/year versus 3.63/patient/year; p = 0.067) compared with usual care. Quality of life scores and lung function improved significantly with humidification therapy compared with usual care at 3 and 12 months. Long-term humidification therapy significantly reduced exacerbation days, increased time to first exacerbation, improved lung function and quality of life in patients with COPD and bronchiectasis. Clinical trial registered with www.actr.org.au; Number ACTRN2605000623695. Copyright 2010 Elsevier Ltd. All rights reserved.

Metabolomics diagnostic approach to mustard airway diseases: a preliminary study

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BiBi Fatemeh Nobakht Mothlagh Ghoochani

2018-01-01

Full Text Available Objective(s: This study aims to evaluate combined proton nuclear magnetic resonance (1H NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS metabolic profiling approaches, for discriminating between mustard airway diseases (MADs and healthy controls and for providing biochemical information on this disease. Materials and Methods: In the present study, analysis of serum samples collected from 17 MAD subjects and 12 healthy controls was performed using NMR. Of these subjects, 14 (8 patients and 6 controls were analyzed by GC-MS. Then, their spectral profiles were subjected to principal component analysis (PCA and orthogonal partial least squares regression discriminant analysis (OPLS-DA. Results: A panel of twenty eight metabolite biomarkers was generated for MADs, sixteen  NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline, dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate, cholesterol, alanine, and lipid (mainly VLDL and twelve GC-MS-derived metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric acid, linoleic acid, and oleic acid. This composite biomarker panel could effectively discriminate MAD subjects from healthy controls, achieving an area under receiver operating characteristic curve (AUC values of 1 and 0.79 for NMR and GC-MS, respectively. Conclusion: In the present study, a robust panel of twenty-eight biomarkers for detecting MADs was established. This panel is involved in three metabolic pathways including aminoacyl-tRNA biosynthesis, arginine, and proline metabolism, and synthesis and degradation of ketone bodies, and could differentiate MAD subjects from healthy controls with a higher accuracy.

Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

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Di Jiang

Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

Clinical review: Management of difficult airways

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Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

2006-01-01

Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway. PMID:17184555

Clinical review: management of difficult airways.

Science.gov (United States)

Langeron, Olivier; Amour, Julien; Vivien, Benoît; Aubrun, Frédéric

2006-01-01

Difficulties or failure in airway management are still important factors in morbidity and mortality related to anesthesia and intensive care. A patent and secure airway is essential to manage anesthetized or critically ill patients. Oxygenation maintenance during tracheal intubation is the cornerstone of difficult airway management and is always emphasized in guidelines. The occurrence of respiratory adverse events has decreased in claims for injuries due to inadequate airway management mainly at induction of anesthesia. Nevertheless, claim reports emphasize that airway emergencies, tracheal extubation and/or recovery of anesthesia phases are still associated with death or brain damage, indicating that additional educational support and management strategies to improve patient safety are required. The present brief review analyses specific problems of airway management related to difficult tracheal intubation and to difficult mask ventilation prediction. The review will focus on basic airway management including preoxygenation, and on some oxygenation and tracheal intubation techniques that may be performed to solve a difficult airway.

Overlap Syndrome in Respiratory Medicine: Asthma and Chronic Obstructive Pulmonary Disease

OpenAIRE

Alexandru Corlateanu; Valeria Pripa; Gloria Montanari; Victor Botnaru

2014-01-01

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic diseases in the general population. Both are characterized by similar mechanisms: airway inflammation, airway obstruction, and airway hyperresponsiveness. However, the distinction between the two obstructive diseases is not always clear. Multiple epidemiological studies demonstrate that in elderly people with obstructive airway disease, as many as half or more may have overlapping diagnoses of asthma and COPD...

Antithetic regulation by β-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway β-agonist paradox

OpenAIRE

McGraw, Dennis W.; Almoosa, Khalid F.; Paul, Richard J.; Kobilka, Brian K.; Liggett, Stephen B.

2003-01-01

β-adrenergic receptors (βARs) relax airway smooth muscle and bronchodilate, but chronic β-agonist treatment in asthma causes increased sensitivity to airway constriction (hyperreactivity) and is associated with exacerbations. This paradox was explored using mice with ablated βAR genes (βAR–/–) and transgenic mice overexpressing airway smooth muscle β2AR (β2AR-OE) representing two extremes: absence and persistent activity of airway βAR. Unexpectedly, βAR–/– mice, lacking these bronchodilating ...

Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

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Maria Galluzzo

2015-01-01

Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

The influence of upper airways diameter on the intensity of obstructive sleep apnea

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Jolanta Szymańska

2014-03-01

Full Text Available Introduction and Objective. Obstructive sleep apnea (OSA is characterized by at least 5 ten-second-long episodes of apnea or hypopnea, per hour of sleep. This disease may lead to severe, life-threatening complications. Therefore, risk analysis and its influence on disease intensity is crucial for proper implementation of preventive treatments. Objective. To determine the relation between the intensity of OSA expressed in Apnea-Hypopnea Index (AHI, and the anterior-posterior diameter of upper airways at the levels of soft palate and tongue base. Material and Method. Medical records of 41 patients with sleep apnea (AHI>4 diagnosed through polysomnographic examination obstructive were used for the study. The data consisted of: age and gender, polysomnographic examination results (AHI, lateral cephalogram with cephalomertic analysis, together with measurements of the upper and lower pharyngeal depth according to McNamara. Statistical analysis was carried out in accordance with Pearson’s r correlation coefficient test (Statistica 8.0 software package. Results. Analysis of the influence of upper airways diameter on the intensity of OSA showed that the value of upper Airways diameter at the tongue base level had no statistically significant impact on the value of AHI (p=0.795. However, a statistically significant impact of the value of upper airways diameter on the AHI value (p=0.008 at the soft palate level was observed. Patients with OSA have narrowed upper airways diameter. The value of AHI increases with the decrease of upper diameter and is not dependent on a lower diameter value. Patients with a decreased upper airways diameter should be informed about potential breathing disorders during sleep.

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

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Konrad Urbanek

Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

Different Labelling of Obstructive Airway Diseases in Estonia, Finland, and Sweden

International Nuclear Information System (INIS)

Pallasaho, Paula; Meren, Mari; Raukas-Kivioja, Aet; Roenmark, Eva

2005-01-01

Large differences in prevalence of asthma have been reported between westernised countries and the former Eastern European countries, and still no consensus about the reasons for the differences exists. The aim of this study was to assess diagnostic labelling of obstructive airway diseases, comparing subjects with respiratory symptoms and the diagnoses obtained in Estonia, Finland, and Sweden. A postal questionnaire was sent to population-based random samples, and 44,483 (76%) answers were obtained from the 58,661 invited in 1996. Among men, current smoking was most common in Estonia, 60%, followed by Finland, 39%, and Sweden, 28%. In all three countries, 30% of women were current smokers. Most respiratory symptoms including wheezing were most common in Estonia, also among non-smokers. The prevalence of asthma was 2.0% and chronic bronchitis 10.7% in Estonia, while the opposite was found in Sweden with an asthma prevalence of 7.8% and a chronic bronchitis prevalence of 3.1%. The pattern in Finland was similar to that of Sweden. The same differences between the three countries were found also among young subjects. The total proportion of diagnosed obstructive lung diseases in subjects with respiratory symptoms was similar, but the diagnosis of asthma was considerably more common in Finland and Sweden. Chronic bronchitis was favoured in Estonia, also among young adults irrespectively of what symptoms were present. In a multivariate model with correction for confounders, the risk (OR) for having a diagnosis of asthma was 5.65 (95% CI: 4.86-6.56) when living in Sweden, and 3.51 (95% CI: 3.00-4.12) in Finland, whereas risk for chronic bronchitis was 0.28 (0.25-0.31) and 0.22 (0.19-0.25), respectively, compared to Estonia. The study indicates differences in diagnostic practices of obstructive lung diseases between the three countries

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

Science.gov (United States)

Freund-Michel, Véronique; Frossard, Nelly

2008-10-01

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

Effect of chlorhexidine on oral airway biofilm formation of Staphylococcus epidermidis

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Ünase Büyükkoçak

2015-12-01

Full Text Available Objective: Biofilm formation of microorganisms on the surface of airways may lead to supraglottic colonization that may cause lower respiratuar tract infections. Studies searching the efficiency of local disinfectants on biofilm formation are limited. The aim of this study was to investigate the effects of chlorhexidine coated airways on biofilm formation of Staphylococcus epidermidis. Methods: Culture and electron microscopy methods were used for biofilm assessment. Airways were divided into two groups to investigate the effects of chlorhexidine on number of bacteria attached to the airway and biofilm formation. Group 1(control: naive material, S. epidermidis, Group 2: chlorhexidine coated material, S. epidermidis. No process was applied in Group 1. Chlorhexidine gluconate (0.2% was sprayed on the surface of naive material for four seconds and then left to dry in air, in Group to. Number of bacteria attached to the airway were counted by microbiological methods and biofilm formation was shown by Scanning Electron Microscope (SEM. Mann-Whitney u test was performed for statistical analyses. Results: In Group 2, bacteria numbers were 1x102-8x102 cfu/ml, whereas they were 3x103-1x104 cfu/ml in Group 1. Chlorhexidine decreased number of microorganisms attached to the airways with statistical significance (p=0.04. The results of the electron microscopic evaluation were in accordance with the acteriological findings. Conclusion: This study has shown that chlorhexidine coating can successfully reduce the number of adhered bacteria and biofilm formation on airways. J Microbiol Infect Dis 2015;5(4: 162-166

Vessel-guided airway tree segmentation

DEFF Research Database (Denmark)

Lo, Pechin Chien Pau; Sporring, Jon; Ashraf, Haseem

2010-01-01

This paper presents a method for airway tree segmentation that uses a combination of a trained airway appearance model, vessel and airway orientation information, and region growing. We propose a voxel classification approach for the appearance model, which uses a classifier that is trained to di...

Critical Airway Team: A Retrospective Study of an Airway Response System in a Pediatric Hospital.

Science.gov (United States)

Sterrett, Emily C; Myer, Charles M; Oehler, Jennifer; Das, Bobby; Kerrey, Benjamin T

2017-12-01

Objective Study the performance of a pediatric critical airway response team. Study Design Case series with chart review. Setting Freestanding academic children's hospital. Subjects and Methods A structured review of the electronic medical record was conducted for all activations of the critical airway team. Characteristics of the activations and patients are reported using descriptive statistics. Activation of the critical airway team occurred 196 times in 46 months (March 2012 to December 2015); complete data were available for 162 activations (83%). For 49 activations (30%), patients had diagnoses associated with difficult intubation; 45 (28%) had a history of difficult laryngoscopy. Results Activation occurred at least 4 times per month on average (vs 3 per month for hospital-wide codes). The most common reasons for team activation were anticipated difficult intubation (45%) or failed intubation attempt (20%). For 79% of activations, the team performed an airway procedure, most commonly direct laryngoscopy and tracheal intubation. Bronchoscopy was performed in 47% of activations. Surgical airway rescue was attempted 4 times. Cardiopulmonary resuscitation occurred in 41 activations (25%). Twenty-nine patients died during or following team activation (18%), including 10 deaths associated with the critical airway event. Conclusion Critical airway team activation occurred at least once per week on average. Direct laryngoscopy, tracheal intubation, and bronchoscopic procedures were performed frequently; surgical airway rescue was rare. Most patients had existing risk factors for difficult intubation. Given our rate of serious morbidity and mortality, primary prevention of critical airway events will be a focus of future efforts.

Fetal tracheolaryngeal airway obstruction: prenatal evaluation by sonography and MRI

Energy Technology Data Exchange (ETDEWEB)

Courtier, Jesse; Poder, Liina; Wang, Zhen J.; Westphalen, Antonio C.; Yeh, Benjamin M.; Coakley, Fergus V. [University of California San Francisco, Department of Radiology, San Francisco, CA (United States)

2010-11-15

We reviewed the sonographic and MRI findings of tracheolaryngeal obstruction in the fetus. Conditions that can cause tracheolaryngeal obstruction include extrinsic causes such as lymphatic malformation, cervical teratoma and vascular rings and intrinsic causes such as congenital high airway obstruction syndrome (CHAOS). Accurate distinction of these conditions by sonography or MRI can help facilitate parental counseling and management, including the decision to utilize the ex utero intrapartum treatment (EXIT) procedure. (orig.)

Relationship between airway colonization, inflammation and exacerbation frequency in COPD.

Science.gov (United States)

Tumkaya, Munir; Atis, Sibel; Ozge, Cengiz; Delialioglu, Nuran; Polat, Gurbuz; Kanik, Arzu

2007-04-01

To evaluate bacterial colonization and the airway inflammatory response, and its relationship to the frequency of exacerbation in patients with stable chronic obstructive pulmonary disease (COPD). Quantitative bacteriologic cultures, neutrophil elastase, myeloperoxidase (MPO), tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-8 were measured in bronchoalveoler lavage (BAL) in 39 patients with stable COPD [19 with frequent exacerbation (> or = 3/year), and 20 with infrequent] and in 18 healthy controls (10 smokers and 8 non-smokers). BAL revealed the microorganisms with potential pathogenicity above the established threshold (> or = 10(3)cfu/ml) in 68.4% of patients with frequent exacerbation, 55% of infrequent exacerbation, 40% of smokers and 12.5% of non-smokers controls (P=0.05). BAL MPO, IL-8 and TNF-alpha levels were found to be significantly higher in COPD as compared to controls (P=0.001). However, only IL-8 level was significantly higher in COPD patients with frequent exacerbation as compared to infrequent (P=0.001). Airway bacterial load correlated with levels of airway inflammation markers in COPD (P<0.05). The bacterial load and airway inflammation contributes to each other in stable COPD. However, there is a link only between interleukine (IL)-8 and frequent exacerbations. Clearly, the relationship between bacterial colonization, airway inflammation and frequent exacerbations is of major importance in understanding of the COPD pathogenesis.

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

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Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

2016-07-15

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

International Nuclear Information System (INIS)

Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

2016-01-01

A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

Effects of condensate in the exhalation limb of neonatal circuits on airway pressure during bubble CPAP.

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Youngquist, Tiffany M; Richardson, C Peter; Diblasi, Robert M

2013-11-01

Bubble CPAP is frequently used in spontaneously breathing infants with lung disease. Often bubble CPAP systems lack pressure alarms and pressure-release valves. We observed a large volume of condensate in the exhalation limb of a patient circuit and conducted a series of experiments to test the hypothesis that accumulated condensate could affect delivered pressures. An anatomically accurate nasal airway model of a preterm infant was attached to a spontaneously breathing lung model. A bubble CPAP system was attached to the nasal airway with bi-nasal short prongs, and the rate of fluid condensation was measured. Next, tracheal pressures were monitored digitally to detect changes in airway pressure related to condensate accumulation. Measurements were obtained with volumes of 0, 5, 10, 15, and 20 mL of water in the exhalation limb, at flows of 4, 6, 8, and 10 L/min. Measurements with 20 mL in the exhalation limb were recorded with and without a pressure-relief valve in the circuit. The rate of condensate accumulation was 3.8 mL/h. At volumes of ≥ 10 mL, noticeable alterations in the airway pressure waveforms and significant increases in mean tracheal pressure were observed. The pressure-relief valve effectively attenuated peak tracheal pressure, but only decreased mean pressure by 0.5-1.5 cm H2O. Condensate in the exhalation limb of the patient circuit during bubble CPAP can significantly increase pressure delivered to the patient. The back and forth movement of this fluid causes oscillations in airway pressure that are much greater than the oscillations created by gas bubbling out the exhalation tube into the water bath. We recommend continuously monitoring pressure at the nasal airway interface, placing an adjustable pressure-relief valve in the circuit, set to 5 cm H2O above the desired mean pressure, and emptying fluid from the exhalation limb every 2-3 hours.

Simulation of deposition and activity distribution of radionuclides in human airways

International Nuclear Information System (INIS)

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

2002-01-01

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

IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

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Amniai, L.; Biet, F.; Marquillies, P.; Locht, C.; Pestel, J.; Tonnel, A.-B.; Duez, C.

2007-01-01

Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D20–22) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation. PMID:18299704

The human airway epithelial basal cell transcriptome.

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Neil R Hackett

2011-05-01

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

Airway remodelling and inflammation in asthma are dependent on the extracellular matrix protein fibulin-1c.

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Liu, Gang; Cooley, Marion A; Nair, Prema M; Donovan, Chantal; Hsu, Alan C; Jarnicki, Andrew G; Haw, Tatt Jhong; Hansbro, Nicole G; Ge, Qi; Brown, Alexandra C; Tay, Hock; Foster, Paul S; Wark, Peter A; Horvat, Jay C; Bourke, Jane E; Grainge, Chris L; Argraves, W Scott; Oliver, Brian G; Knight, Darryl A; Burgess, Janette K; Hansbro, Philip M

2017-12-01

Asthma is a chronic inflammatory disease of the airways. It is characterized by allergic airway inflammation, airway remodelling, and airway hyperresponsiveness (AHR). Asthma patients, in particular those with chronic or severe asthma, have airway remodelling that is associated with the accumulation of extracellular matrix (ECM) proteins, such as collagens. Fibulin-1 (Fbln1) is an important ECM protein that stabilizes collagen and other ECM proteins. The level of Fbln1c, one of the four Fbln1 variants, which predominates in both humans and mice, is increased in the serum and airways fluids in asthma but its function is unclear. We show that the level of Fbln1c was increased in the lungs of mice with house dust mite (HDM)-induced chronic allergic airway disease (AAD). Genetic deletion of Fbln1c and therapeutic inhibition of Fbln1c in mice with chronic AAD reduced airway collagen deposition, and protected against AHR. Fbln1c-deficient (Fbln1c -/- ) mice had reduced mucin (MUC) 5 AC levels, but not MUC5B levels, in the airways as compared with wild-type (WT) mice. Fbln1c interacted with fibronectin and periostin that was linked to collagen deposition around the small airways. Fbln1c -/- mice with AAD also had reduced numbers of α-smooth muscle actin-positive cells around the airways and reduced airway contractility as compared with WT mice. After HDM challenge, these mice also had fewer airway inflammatory cells, reduced interleukin (IL)-5, IL-13, IL-33, tumour necrosis factor (TNF) and CXCL1 levels in the lungs, and reduced IL-5, IL-33 and TNF levels in lung-draining lymph nodes. Therapeutic targeting of Fbln1c reduced the numbers of GATA3-positive Th2 cells in the lymph nodes and lungs after chronic HDM challenge. Treatment also reduced the secretion of IL-5 and IL-13 from co-cultured dendritic cells and T cells restimulated with HDM extract. Human epithelial cells cultured with Fbln1c peptide produced more CXCL1 mRNA than medium-treated controls. Our data show

Woodstove exposure as a risk factor for airway obstruction

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Alexandros Mpagordakis

2015-06-01

Full Text Available Background: The recent financial crisis in Greece has significantly increased woodstove use and therefore the indoor air pollution of the household atmosphere. Related studies have shown that indoor air pollution is associated with the onset of obstructive airway diseases, especially in women who are occupied with household duties. Aim: To investigate whether the woodstove exposure is a risk factor of obstructive airway disease especially in nonsmoking women. Methods: In this cross-sectional study participated 410 individuals (51.7% women, mean age 56,1 ± 13,0 years, ranging from 40 to 93 years old who visited eight Primary Health Care Settings on the island of Crete, Greece. A spirometry testing was performed to assess the degree of airflow limitation setting criteria the fixed ratio of spirometry values (FEV1 / FVC 17] were establish in non-smoker women who were exposed for 30.2 years to woodstove smoke compared to non-COPD non-smoker women (11.8 years exposure, despite the fact that interactions terms (female gender, smoking, woodstove use, cough with sputum production were not associated with COPD development. Conclusion: The present study confirms that woodstove exposure (about 30 years is associated with Airway Obstruction in non-smoker women. Also, a greater woodstove exposure is indicative of a greater prevalence of airflow limitation and a greater COPD-related symptoms.

Importance of Functional Airway Surgery in Orthognathic Surgery Performed Patients

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Erkan Yüce

2017-06-01

Full Text Available Le Fort I osteotomy is usually combined with mandibular ramus procedures (sagittal split in order to correct dentofacial deformities that cause malocclusion. Patients who have dentofacial anomalies involving the maxilla carry a higher risk of difficulty in breathing due to septal deviation and inferior turbinate hypertrophy. If these conditions are ignored preoperatively, severe airway problems may come up after orthognathic surgery. A detailed examination regarding nasal airway should be conducted in such patients, and they should be informed about their condition which may require an additional intervention during or after their main surgery.

Foreign bodies in the lactant airway, Report of a case

International Nuclear Information System (INIS)

Arango L, Magnolia

1999-01-01

We report the case of a lactant who aspired (popcorn) fragments of popcorn into his airway. Immediately the patient developed respiratory difficulty, he was remitted to a specialized hospital until 72 hours after. In this hospital the fragments of popcorn were removed by bronchoscopic procedure with posterior improvement. The aspiration of foreign bodies into the airway is a frequent accident in the early childhood. The clinical picture may be confounded specially with asthma attacks or simple acute respiratory infections. It is very important to recognize this condition because of the foreign bodies can cause severe complications and sequels, and occasionally the death

Computer simulation of airflow through a multi-generation tracheobronchial conducting airway

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Fan, B.; Cheng, Yung-Sung; Yeh, Hsu-Chi

1995-12-01

Knowledge of airflow patterns in the human lung is important for an analysis of lung diseases and drug delivery of aerosolized medicine for medical treatment. However, very little systematic information is available on the pattern of airflow in the lung and on how this pattern affects the deposition of toxicants in the lung, and the efficacy of aerosol drug therapy. Most previous studies have only considered the airflow through a single bifurcating airway. However, the flow in a network of more than one bifurcation is more complicated due to the effect of interrelated lung generations. Because of the variation of airway geometry and flow condition from generation to generation, a single bifurcating airway cannot be taken as a representative for the others in different generations. The flow in the network varies significantly with airway generations because of a redistribution of axial momentum by the secondary flow motions. The influence of the redistribution of flow is expected in every generation. Therefore, a systematic information of the airflow through a multi-generation tracheobronchial conducting airway is needed, and it becomes the purpose of this study. This study has provided information on airflow in a lung model which is necessary to the study of the deposition of toxicants and therapeutic aerosols.

Computer simulation of airflow through a multi-generation tracheobronchial conducting airway

International Nuclear Information System (INIS)

Fan, B.; Cheng, Yung-Sung; Yeh, Hsu-Chi.

1995-01-01

Knowledge of airflow patterns in the human lung is important for an analysis of lung diseases and drug delivery of aerosolized medicine for medical treatment. However, very little systematic information is available on the pattern of airflow in the lung and on how this pattern affects the deposition of toxicants in the lung, and the efficacy of aerosol drug therapy. Most previous studies have only considered the airflow through a single bifurcating airway. However, the flow in a network of more than one bifurcation is more complicated due to the effect of interrelated lung generations. Because of the variation of airway geometry and flow condition from generation to generation, a single bifurcating airway cannot be taken as a representative for the others in different generations. The flow in the network varies significantly with airway generations because of a redistribution of axial momentum by the secondary flow motions. The influence of the redistribution of flow is expected in every generation. Therefore, a systematic information of the airflow through a multi-generation tracheobronchial conducting airway is needed, and it becomes the purpose of this study. This study has provided information on airflow in a lung model which is necessary to the study of the deposition of toxicants and therapeutic aerosols

Obstetric airway management

African Journals Online (AJOL)

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

Relationships between respiratory and airway resistances and activity-related dyspnea in patients with chronic obstructive pulmonary disease

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Plantier L

2012-03-01

Full Text Available Bruno Mahut1,2, Aurore Caumont-Prim3,4, Laurent Plantier1,5, Karine Gillet-Juvin1,6, Etienne Callens1, Olivier Sanchez5,6, Brigitte Chevalier-Bidaud3, Plamen Bokov1, Christophe Delclaux1,5,71Assistance Publique – Hôpitaux de Paris (AP-HP, Hôpital Européen Georges Pompidou, Service de Physiologie – Clinique de la Dyspnée, F-75015 Paris, France; 2Cabinet La Berma, 4 avenue de la Providence; F-92160 Antony, France; 3AP-HP, Hôpital Européen Georges Pompidou, Unité d'Épidémiologie et de Recherche Clinique, F-75015 Paris, France; 4INSERM, Centre d'Investigation Épidémiologique 4, F-75015 Paris, France; 5Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, F-75015 Paris, France; 6AP-HP, Hôpital Européen Georges Pompidou, Service de Pneumologie; F-75015 Paris, France; 7CIC 9201 Plurithématique, Hôpital Européen Georges Pompidou, F-75015 Paris, FranceBackground: The aims of the study were: (1 to compare numerical parameters of specific airway resistance (total, sRawtot, effective, sRaweff and at 0.5 L • s-1, sRaw0.5 and indices obtained from the forced oscillation technique (FOT: resistance extrapolated at 0 Hz [Rrs0 Hz], mean resistance [Rrsmean], and resistance/frequency slope [Rrsslope] and (2 to assess their relationships with dyspnea in chronic obstructive pulmonary disease (COPD.Methods: A specific statistical approach, principal component analysis that also allows graphic representation of all correlations between functional parameters was used. A total of 108 patients (mean ± SD age: 65 ± 9 years, 31 women; GOLD stages: I, 14; II, 47; III, 39 and IV, 8 underwent spirometry, body plethysmography, FOT, and Medical Research Council (MRC scale assessments.Results: Principal component analysis determined that the functional parameters were described by three independent dimensions (airway caliber, lung volumes and their combination, specific resistance and that resistance parameters of the two techniques

Pediatric Trainees Managing a Difficult Airway: Comparison of Laryngeal Mask Airway, Direct, and Video-Assisted Laryngoscopy

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Art Ambrosio MD

2017-05-01

Full Text Available Objective Difficult airway management is a key skill required by all pediatric physicians, yet training on multiple modalities is lacking. The objective of this study was to compare the rate of, and time to, successful advanced infant airway placement with direct laryngoscopy, video-assisted laryngoscopy, and laryngeal mask airway (LMA in a difficult airway simulator. This study is the first to compare the success with 3 methods for difficult airway management among pediatric trainees. Study Design Randomized crossover pilot study. Setting Tertiary academic medical center. Methods Twenty-two pediatric residents, interns, and medical students were tested. Participants were provided 1 training session by faculty using a normal infant manikin. Subjects then performed all 3 of the aforementioned advanced airway modalities in a randomized order on a difficult airway model of a Robin sequence. Success was defined as confirmed endotracheal intubation or correct LMA placement by the testing instructor in ≤120 seconds. Results Direct laryngoscopy demonstrated a significantly higher placement success rate (77.3% than video-assisted laryngoscopy (36.4%, P = .0117 and LMA (31.8%, P = .0039. Video-assisted laryngoscopy required a significantly longer amount of time during successful intubations (84.8 seconds; 95% CI, 59.4-110.1 versus direct laryngoscopy (44.9 seconds; 95% CI, 33.8-55.9 and LMA placement (36.6 seconds; 95% CI, 24.7-48.4. Conclusions Pediatric trainees demonstrated significantly higher success using direct laryngoscopy in a difficult airway simulator model. However, given the potential lifesaving implications of advanced airway adjuncts, including video-assisted laryngoscopy and LMA placement, more extensive training on adjunctive airway management techniques may be useful for trainees.

Randomized crossover comparison of the laryngeal mask airway classic with i-gel laryngeal mask airway in the management of difficult airway in post burn neck contracture patients

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Jeevan Singh

2012-01-01

Full Text Available Purpose: The objective of the study was to compare the performance of i-gel supraglottic airway with cLMA in difficult airway management in post burn neck contracture patients and assess the feasibility of i-gel use for emergency airway management in difficult airway situation with reduced neck movement and limited mouth opening. Methods: Prospective, crossover, randomized controlled trial was performed amongst forty eight post burn neck contracture patients with limited mouth opening and neck movement. i-gel and cLMA were placed in random order in each patient. Primary outcome was overall success rate. Other measurements were time to successful ventilation, airway leak pressure, fiberoptic glottic view, visualization of square wave pattern. Results: Success rate for the i-gel was 91.7% versus 79.2% for the cLMA. i-gel required shorter insertion time (19.3 seconds vs. 23.5 seconds, P=0.000. Airway leak pressure difference was statistically significant (i-gel 21.2 cm H20; cLMA 16.9 cm H 2 0; P=0.00. Fiberoptic view through the i-gel showed there were less epiglottic downfolding and better fiberoptic view of the glottis than cLMA. Overall agreement in insertion outcome for i-gel was 22/24 (91.7% successes and 2/24(8.3% failure and for cLMA, 19/24 (79.16% successes and 5/24 (16.7% failure in the first attempt. Conclusion: The i-gel is cheap, effective airway device which is easier to insert and has better clinical performance in the difficult airway management of the airway in the post burn contracture of the neck. Our study shows that i-gel is feasible for emergency airway management in difficult airway situation with reduced neck movement and limited mouth opening in post burn neck.

Corals diseases are a major cause of coral death

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