Obstructive Airway Disorders Research Articles

In mouse model of mixed granulocytic asthma with corticosteroid refractoriness, Bronchom mitigates airway hyperresponsiveness, inflammation and airway remodeling

BackgroundAsthma is a heterogeneous, inflammatory disease with several phenotypes and endotypes. Severe asthmatics often exhibit mixed granulocytosis with reduced corticosteroid sensitivity. Bronchom is a newly developed Ayurvedic prescription medicine, indicated for the treatment of obstructive airway disorders. The purpose of the present study was to evaluate the in-vivo efficacy of Bronchom in mouse model of mixed granulocytic asthma with steroidal recalcitrance.MethodsHigh-performance thin layer chromatography (HPTLC) and Ultra-high performance liquid chromatography (UHPLC) were employed to identify and quantitate the phytometabolites present in Bronchom. The preclinical effectiveness of Bronchom was assessed in house dust mite (HDM) and Complete Freund’s adjuvant (CFA)-induced mixed granulocytic asthma model in mice. High dose of dexamethasone was tested parallelly. Specific-pathogen-free C57BL/6 mice were immunized with HDM and CFA and nineteen days later, they were intranasally challenged with HDM for four consecutive days. Then the mice were challenged with nebulized methacholine to evaluate airway hyperresponsiveness (AHR). Inflammatory cell influx was enumerated in the bronchoalveolar lavage fluid (BALF) followed by lung histology. Additionally, the concentrations of Th2 and pro-inflammatory cytokines was assessed in the BALF by multiplexed immune assay. The mRNA expression of pro-inflammatory cytokines and Mucin 5AC (MUC5AC) was also evaluated in the lung.ResultsHPTLC fingerprinting and UHPLC quantification of Bronchom revealed the presence of bioactive phytometabolites, namely, rosmarinic acid, gallic acid, methyl gallate, piperine, eugenol and glycyrrhizin. Bronchom effectively reduced AHR driven by HDM-CFA and the influx of total leukocytes, eosinophils and neutrophils in the BALF. In addition, Bronchom inhibited the infiltration of inflammatory cells in the lung as well as goblet cell metaplasia. Further, it also suppressed the elevated levels of Th2 cytokines and pro-inflammatory cytokines in the BALF. Similarly, Bronchom also regulated the mRNA expression of pro-inflammatory cytokines as well as MUC5AC in mice lungs. Reduced effectiveness of a high dose of the steroid, dexamethasone was observed in the model.ConclusionsWe have demonstrated for the first time the robust pharmacological effects of an herbo-mineral medicine in an animal model of mixed granulocytic asthma induced by HDM and CFA. The outcomes suggest the potential utility of Bronchom in severe asthmatics with a mixed granulocytic phenotype.

Comparison of Forced Oscillation Technique, Lung Volumes by Body Plethysmography, and Spirometry in Moderate Persistent Adult Asthma.

Spirometry is used extensively, but airway oscillometry is gaining acceptance for evaluating obstructive airway disorders. Moderate persistent asthma requires daily treatment with inhaled corticosteroids (ICS). We aimed to examine the relationship between airway oscillometry and lung volumes, which are the markers of lung physiology in obstructive airway disease and spirometry in the real-world clinical setting. A total of 72 adults with moderate persistent asthma followed up in our outpatient department from November 2021 to August 2022, and their clinical details and tests of spirometry, forced oscillation technique (FOT), and lung volumes by body plethysmography (BP) performed before and after bronchodilator administration were analyzed. The mean age of the study population was 40 years, and the majority (57%) were females. FOT detected airflow limitation in 12 of the 31 patients with normal spirometry. BP detected abnormalities in more patients than both spirometry and FOT (91.6 vs 73.6%, p < 0.001). Respiratory resistance 5 (R5) had a negative correlation with functional residual capacity (FRC) and total lung capacity (TLC). Reactance 5 (X5) correlated positively with inspiratory capacity (IC) and TLC and negatively with reserve volume (RV)/TLC ratio. A positive correlation was found between IC/TLC% and postbronchodilator X5 and between R5 and 19 and RV/TLC. R5 had a negative and X5 had a positive correlation with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, and maximal mid expiratory flow rates (MMEF). ∇X5 had a negative correlation with FEV1, MMEF, and FEV1/FVC. Spirometry detected postbronchodilator responsiveness in more patients than FOT when only the R5 criterion was used and in a comparable number when the X5 criterion was added. ∇X5 and R5-R19/R5 declined significantly after bronchodilators. We concluded that there is a moderate correlation between FOT and spirometry and lung volumes by BP. FOT and spirometry should be used together to identify airflow obstruction and postbronchodilator responsiveness in asthma. Lung volumes by BP identify more abnormalities in adults with asthma than both spirometry and FOT. Thresholds to define postbronchodilator responsiveness (PBDR) for ∇X5 and R5-R19 need to be defined.

Assessment of working conditions and features of respiratory disorders in modern refractory manufacturing

Introduction. Broad prospects for development of refractory manufacturing in Russia necessitate studies of the work environment, especially of the indoor air quality, and respiratory health effects of adverse occupational factors. &#x0D; The purpose of our study was to conduct a general hygienic assessment of working conditions of the core personnel engaged in contemporary refractory manufacturing for more than 10 years and establish their respiratory functional status.&#x0D; Materials and methods. We assessed working conditions of press operators of a Ural refractory manufacturing plant in compliance with Russian Guidelines &#x0D; R 2.2.2006–05. The respiratory functional status was established by the results of clinical instrumental testing of refractory production workers who were examined and/or treated at the occupational health clinic of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers &#x0D; in 2015–2021.&#x0D; Results. We gave a general assessment of working conditions of press operators engaged in the production of spinel periclase-carbon and fireclay-dinas molded refractories in the first refractory workshop, aluminosilicate refractories at the molding site, and corundum-graphite products in the second refractory workshop. &#x0D; We analyzed the results of instrumental testing and established characteristics of clinical disorders of the respiratory system.&#x0D; Limitations. The study has regional (Sverdlovsk Region) and occupational (workers of a refractory manufacturing plant) limitations.&#x0D; Conclusion. Occupational risk factors for refractory production workers include silica-containing aerosols, which levels exceed maximum allowable concentrations (Class 3.1), aerosols of disintegration of aluminum oxides (in refractory workshop No. 2), iron in concentrations below MACs (Class 2), higher concentrations of volatile products of phenol formaldehyde resins (Class 3.1 in terms of phenol and up to 3.4 in terms of formaldehyde), increased noise levels for all jobs (Class 3.2), and heavy physical labour (Classes 3.1–3.3). Features of clinical respiratory disorders in the core personnel (press operators) were scarcity of complaints and physical data, absence of pronounced coniotic (respirable dust-related) X-ray findings and inflammatory (septic and allergic) blood changes. Moderate obstructive airway disorders were observed in 30 % of the examined cases.

Role of Therapeutic Bronchoscopy in Comparison to Standards of Care in Critically Ill Patients with Acute Respiratory Failure

Abstract Background Acute respiratory failure (ARF) is a sudden failure of oxygenation, carbon dioxide clearance or both, Hypoxic ARF is most commonly caused by pneumonia, cardiogenic or noncardiogenic pulmonary edema, or pulmonary haemorrhage, while the underlying causes of hypercapnic ARF include drug overdose, neuromuscular disease, chest wall abnormalities and severe obstructive airway disorders. Treatment for respiratory failure includes clearing the airways by suction, use of bronchodilators, tracheostomy and endotracheal tube with ventilator support. Additionally, the treatment regimen includes antibiotics for infections, anticoagulants for pulmonary thromboembolism, and electrolyte replacement for fluid imbalance. Objective To evaluate difference between use of therapeutic bronchoscope to standards of care, including open and closed suctioning (no bronchoscopy) regarding patient outcome. Patients and Methods Study included 80 patients who were divided by alternation into two groups: Group A: 40 patients were subjected to traditional standards of care including chest percussion, closed and open suctioning. Group B: 40 patients were subjected to therapeutic bronchoscope (fibreoptic bronchoscopy) with endobronchial washing and suctioning in addition to traditional standards of care. Results Regarding ABG significant improvements were observed, (in terms of PaCO2, PaO2 and PaO2/FiO2 ratio) in group B (fibreoptic bronchoscopy) in comparison with group A (traditional standards of care) at all follow up periods (P &amp;lt; 0.05). Regarding the radiological improvement, in this study we observed significant improvement after 3 days, after 8 days and total improvement were observed in group B (fibreoptic bronchoscopy) compared to group A (traditional standards of care) (P &amp;lt; 0.05). Regarding the patient’s ICU length of stay, both groups demonstrated insignificant differences (8.24±3.06 in group A versus 6.78±4.09 in group B) (P &amp;gt; 0.05). Conclusion The current study revealed that fibreoptic bronchoscopy was associated with significant improvement compared to traditional standards of care, in ARF cases in terms of ABG parameters as well as radiological findings. However, ICU length of stay and duration of mechanical ventilation seemed to be comparable.

ERS International Congress 2021: highlights from the Clinical Techniques, Imaging and Endoscopy Assembly.

This article summarises the highlights from the European Respiratory Society's “Clinical techniques, imaging and endoscopy” Assembly 14 presented at the virtual 2021 European Respiratory Society International Congress. Cutting-edge innovative developments in both diagnostic approaches and therapeutic strategies in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases were presented on this year's interactive congress platform. In this article, the Assembly 14 subgroups summarise the key take home messages given new research outcomes and place them in the context of the current knowledge.

Drug prescribing pattern in obstructive airway disorders in a tertiary care hospital, Chengalpattu, Tamil Nadu: A cross-sectional and observational study

Background: The term obstructive airway disorder comprises of bronchial asthma and chronic obstructive airway disease (COPD). Asthma is a chronic inflammatory disorder of airways while COPD is disease of alveoli. Asthma is characterized by recurrent episodes of wheezing, breathlessness, and nocturnal cough while patients of COPD present with chronic progressive breathlessness and wheezing. International guidelines are established for the management of obstructive airway disorders. Aims and Objectives: The aim of the study was to evaluate drug prescribing pattern in bronchial asthma and COPD patients at a tertiary care hospital. Materials and Methods: After obtaining permission from hospital authority and permission from the Institutional Ethics Committee, 54 admitted patients’ prescription were screened between period of June 2021 to December 2021. Informed consent taken from the patients and were interviewed for collection of basic data such as name, age, and occupation. The purpose of the observational study was to see whether there is adherence to current practice guidelines of obstructive airway disorders. Data were compiled and tabulated using excel sheet and were presented using percentages and frequencies with necessary graphs and charts. Results: Short acting β2 agonist (91%) and corticosteroids (59%) were the most prescribed agents in bronchial asthma while corticosteroids (75%) and short acting antimuscarinic agents (78.57%) were most common prescription in COPD patients. The most common antibiotic used for in obstructive airway disease was beta lactam antibiotic-cefotaxime. Conclusion: In obstructive airway disorders, inhalation route was most preferred route as compared to oral, intramuscular, or intravenous route. The preferred antibiotic was cefotaxime.

Changes in Airway Dimensions After Face-Mask Therapy in Cleft Lip and Palate and Non-cleft Patients: Systematic Review and Meta-Analysis

Context: Maxillary deficiency can lead to the reduction of airway space and increase the chances of development of obstructive airway disorders. Facemask therapy is one of the main treatment protocols in developing maxillary deficient patients. Objectives: The purpose of this systematic review and meta-analysis was to assess the changes in the airway dimensions after face-mask therapy in both cleft lip and palate and non-cleft patients. Methods: A systematic search in different electronic databases (EMBASE, Pubmed, Cochrance Central register of controlled trials), IADR proceedings and a hand search by October 2020 were conducted and a meta-analysis and systematic review was performed. Results: In patients without cleft lip and palate, upper pharyngeal width was significantly increased by mean of 2.05 mm (CI = 95%, 0.61 - 3.50) following facemask therapy in comparison to patients who did not receive the treatment. Other upper pharyngeal (nasopharyngeal) measurements also showed a statistically significant improvement after therapy: S-PNS by 4.64 mm (CI = 95%, 3.34 - 5.94), AD1-PNS by 3.81 mm (CI = 95%, 2.40 - 5.21), AD2-PNS by 2.90 mm (CI = 95%, 0.13 - 5.67) and Pm’-SPL by 2.53 (CI = 95%, 0.54 - 4.51). Lower pharyngeal measurments did not show any significant changes after the treatment (P &gt; 0.05). In the analysis of studies with 3D imaging modalities, upper pharyngeal volume was also significantly increased by 499.29 mm3 (CI = 95%, 69.58-929.00) after the treatment. In addition, a review of articles that included cleft lip and palate patients also showed after the treatment, the upper pharyngeal measurements all showed a significant improvement (P &lt; 0.05), whereas the oropharyngeal region was relatively stable. Conclusions: In maxillary deficient patients with or without an orofacial cleft, facemask therapy can improve the nasopharyngeal area dimensions; however, this treatment protocol appears not to have an effect on the oropharyngeal area of the airway tract.

ERS International Congress 2020: highlights from the Clinical Techniques, Imaging and Endoscopy assembly.

The European Respiratory Society congress in the year 2020, a year dominated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, was the first virtual congress planned with an innovative and interactive congress programme upfront. It was a large, novel platform for scientific discussion and presentations of cutting-edge innovative developments. This article summarises a selection of the scientific highlights from the Clinical Techniques, Imaging and Endoscopy assembly (assembly 14). In addition to presentations on the important role of bronchoscopy, imaging and ultrasound techniques in the field of SARS-CoV-2 infection, novel diagnostic approaches and innovative therapeutic strategies in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases were discussed.

Upregulation of neuropeptides and obstructive airway disorder in infancy: A review with focus on post-RSV wheezing and NEHI.

Obstructive airway disorders, common in infancy and early childhood, include some entities that are recognized to have neuro immune mediators as their underlying pathogenetic mechanisms. The best characterized example amongst post-viral wheezing phenotypes is the disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P. Neuroendocrine hyperplasia of infancy (NEHI), while a less common entity, is a disorder characterized by more severe and long-term obstructive airway disease. NEHI is pathophysiologically characterized by abundance of neuroendocrine cells in the airways containing the neuroimmune mediator bombesin, the release of which is presumed to be the driver of the persistent small airway obstruction and functional air-trapping. Here we review the NANC and neuroendocrine cells, the neurotransmitter systems and their studied roles in pulmonary diseases with a focus on their role in lung development, and subsequent various pediatric lung diseases. We focus on the juxtaposition of the separate neuroimmune mechanisms underlying the pathogenesis of post-RSV recurrent wheezing and NEHI's persistent small airway obstruction. We finally propose a unifying concept of neuropeptides in obstructive disorders that may encompass these two entities and possibly others.

The Differences in the Levels of Oxidative Status Marker and Soluble CD95 in Patients with Moderate to Severe COPD during an Exacerbation and a Stable Period.

Studying the features of changes in markers of oxidative stress (OS) and inflammation indicators in COPD patients depending on the degree of bronchial obstruction is one of the priority directions for improving the prognosis and monitoring of the course of this pathology. We conducted a comparative investigation of changes in markers of OS and apoptosis at the systemic and local levels in patients with moderate to severe COPD during exacerbation and stable phase. 105 patients with COPD aged 46-67 and 21 healthy nonsmoking volunteers comparable in age were examined. COPD patients were divided into four groups: moderate COPD (GOLDII) during the exacerbation (GOLDIIex, n = 25) and in the stable phase (GOLDIIst, n = 27), severe COPD (GOLDIII) during the exacerbation (GOLDIIIex, n = 29), and in the stable phase (GOLDIIIst, n = 24). We studied the levels of such lipid peroxidation (LPO) products as diene conjugates (DC) and Schiff bases (SB) and parameters of induced chemiluminescence (Imax, total light sum-S, Imax/S) in blood serum, as well as sCD95 concentration in blood and exhaled breath condensate (EBC). The relationship between the values of the OS system indicators with sCD95, as well as with the parameters of lung function, was investigated. Multidirectional changes in OS indicator levels in COPD patients depending on the severity of obstructive airway disorders have been established. The maximum values of DC (0.26 ± 0.046 RU), Imax (0.265 ± 0.19 RLU), and Imax/S (0.13 ± 0.05) were typical for patients with moderate COPD, while the highest SB level (5.7 ± 2.3 RU) was observed in severe COPD during an exacerbation. The exacerbation of the disease was characterized by an increase in DC concentration in both GOLDIIex (0.26 ± 0.046 RU) and GOLDIIIex (0.209 ± 0.02 RU) compared to the stable moderate and severe COPD (0.202 ± 0.028 RU and 0.19 ± 0.03 RU, respectively, p < 0.05). The established decrease in high values of DC, Imax, Imax/S, and sCD95 and an increase in SB concentration in GOLD III can serve as quantitative indicators of the prognosis of the severity of the disease. The serum concentration of sCD95 in GOLDIIex (366.4 ± 70.5 U/ml) and GOLDIIst (361.4 ± 72.8 U/ml) did not differ from the control group (393.7 ± 80.9 U/ml, p > 0.05). In patients with FEV1 < 49% during the exacerbation and stable phase, the serum levels of Imax/S (0.058 ± 0.01 and 0.062 ± 0.01) and sCD95 (318.2 ± 66.3 U/ml and 321.4 ± 42.5 U/ml) were lower than the values of healthy volunteers (0.08 ± 0.01 and 393.7 ± 80.9 U/ml, respectively, p < 0.05). A positive correlation between sCD95 concentration and airway obstruction degree in all examined COPD patients was established. The revealed numerous associations between sCD95 and OS marker levels in GOLDIII indicate a relationship between systemic radical stress and apoptosis processes both in the respiratory tract and the whole body under conditions of severe inflammation. The established correlations between the values of DC, Imax, and sCD95 in the blood serum and the lung function parameters in all studied patients allow us to consider these indicators as additional prognostic indicators of disease intensification. Our work results help clarify the participation and detail of FRO and apoptosis processes in developing pathophysiological features in moderate to severe COPD in different periods and, accordingly, improve the efficiency of diagnosis and treatment of the disease.

Diagnostic practices for patients with shortness of breath and presumed obstructive airway disorders: a cross-sectional analysis.

Dyspnea is a common symptom that has many causes, including obstructive airway disorders. We sought to examine previous diagnosis of obstructive airway disorders and other conditions in patients receiving treatment with inhaled medications for shortness of breath in a community setting. This cross-sectional study included consecutive patients aged 18 years and older receiving treatment for shortness of breath with inhaled medications for a minimum of 6 months. Study participants were recruited through community pharmacies in Edmonton and Saskatoon, Canada, between February 2009 and February 2012. Previous diagnosis of obstructive airway disorders by a primary care provider was assessed by patient self-report and review of health records. We conducted an assessment (as per guidelines from the American Thoracic Society and the European Respiratory Society), including pulmonary function tests; diagnoses were adjudicated by an expert physician panel (2 respirologists and 1 emergency physician). The agreement between diagnoses derived from pulmonary function tests and diagnoses from primary care providers was evaluated. A total of 328 patients (median age 50 yr, 57.3% female) underwent assessment; 134 (40.9%) of patients reported ever having a pulmonary function test performed. After adjudication, 138 (42.1%) were diagnosed with asthma only, 86 (26.2%) with chronic obstructive pulmonary disease only and 11 (3.4%) with both. Some patients (93, 28.4%) had no evidence of obstructive airway disorders and 20 (6.1%) had evidence of other conditions that cause shortness of breath, such as heart failure and pulmonary hypertension. Overall, 62 (18.9%) patients could not be assigned a diagnosis. In a group of community-based patients with shortness of breath being treated with inhalers, less than half ever had pulmonary function tests performed, and a considerable proportion had no evidence of lung disease or other conditions. These findings highlight the need for confirmatory testing, including pulmonary function tests, before prescribing inhalers for patients with presumed obstructive airway disorders.

ERS International Congress, Madrid, 2019: highlights from the Clinical Techniques, Imaging and Endoscopy Assembly

This manuscript summarises the highlights from Assembly 14, “Clinical techniques, imaging and endoscopy”, which were presented at the 2019 European Respiratory Society (ERS) International Congress in Madrid, Spain. Novel diagnostic approaches and innovative therapeutic strategies in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases are discussed. The authors from the different Assembly 14 subgroups focus on the key take-home messages given new study results, and place them in the context of current knowledge in these areas.At the 2019 ERS International Congress, encouraging results of numerous trials in the field of interventional pulmonology, imaging and ultrasound were presented. Key topics included novel diagnostic and therapeutic approaches in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases.

Routine use of post-bronchodilator testing in pulmonary function testing labs.

Pulmonary function tests (PFTs), including spirometry with and without post-bronchodilator (post-BD) testing, are frequently performed in the assessment of asthma, along with other obstructive airway disorders. Multiple publications over the past 15 years have noted that one in three physician-diagnosed asthma cases are not in fact asthma. In this quality assurance project, we assess whether PFT labs in Alberta have policies on post-BD testing, as extraneous and unnecessary use of post-BD testing can lead to wasted staff and patient time and unnecessary expenses to the health care system. We reviewed, in collaboration with the College of Physicians and Surgeons of Alberta and Alberta Medical Association, all PFT labs in the province of Alberta (hospital-based private not-for-profit [NFP] and private for-profit [FP] labs). This health policy study of PFT labs involved identifying the proportions and regional distribution of NFP and private FP labs in the province of Alberta while assessing post-BD policies. Each PFT lab was asked for their policy regarding spirometry and asthma diagnosis from May 1 to August 31, 2017. A total of 92 PFT labs were identified in Alberta, 74 of which were private FP (independent) labs, while 18 were private NFP (public) hospital-based labs. Policies were as follows: (i) post-BD policy existed (and if so routinely performed / not routinely done); (ii) no post-BD policy; and (iii) lab chose not to participate. All 18 hospital labs responded: 10 had no policy; six had a policy or algorithm; one did not perform post-BD testing (exercise testing) and one had multiple testing sites. Of the private FP labs, three had relevant policies and/or algorithm and 10 had none. No information was provided from 61 labs. Access to PFT labs in Northern Alberta was limited. Lab policies surrounding post-BD testing were found to be heterogeneous in Alberta. Low response rates, despite the use of a systems approach and requests in writing and in person from FP labs, were notable. Development of a standardized policy across the province would be beneficial. Further higher-level review of the appropriateness of post-BD use in both FP and NFP PFT labs is needed.

Pulmonary mycosis in asthma-chronic obstructive pulmonary disease overlap syndrome

Background: Chronic obstructive pulmonary disease (COPD) and asthma are the two most commonly seen obstructive airway disorders, affecting millions of people across the world. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) includes the patients having features of both COPD and asthma. Objectives: The objectives of the study were to evaluate spectrum of fungal infection in sputum/induced sputum/bronchoalveolar lavage (BAL) samples of ACOS patients. Materials and Methods: Our prospective study conducted on 80 patients diagnosed ACOS, in exacerbation, of either sex attending the Department of Respiratory Medicine, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, after taking permission from the ethical committee. Sputum or induced sputum or BAL sample was collected in sterile vials and sent to the microbiology department for the examination for fungal species. In microbiology, sputum/BAL samples were subjected to direct microscopic examination using KOH and cultured on Sabouraud Dextrose Agar. The culture was observed daily until 21 days for any fungal growth. Results: Out of 80 patients of ACOS, 43 were males and 37 were females. Culture results were positive for fungal species in 33 patients out of 80 patients (41.2%). Different species of fungi were cultured such as Candida (22.6%), Aspergillus flavus (5%), Aspergillus fumigatus (2.5%), Aspergillus niger (2.5%), Penicillium non-marneffei (3.8%), Trichosporon spp. (3.8%), and Geotrichum spp. (1.3%). Conclusion: Our observations show that a wide spectrum of fungal species is prevalent in respiratory tract in ACOS patients. Determination of pulmonary mycosis in ACOS is required to detect, and treat the coinfection with fungus well in time and decrease morbidity and mortality due to ACOS.

Cholesterol modulates the signaling of chemosensory bitter taste receptor T2R14 in human airway cells.

Bitter taste receptors (T2Rs) are a group of 25 chemosensory receptors expressed at significant levels in the human airways. In human airways, bitter taste receptor 14 (T2R14)-mediated physiological response in ameliorating obstructive airway disorders is an active area of investigation. Therefore, understanding various factors regulating the structure and function of T2R14 will be beneficial. We hypothesize that membrane lipids like cholesterol play a regulatory role in T2R14 signaling in airway cells. We confirmed the expression and signaling of T2R14 in primary human airway smooth muscle (HASM) cells and the human airway epithelial cell line (NuLi-1) using immunoblot analysis and intracellular calcium concentration mobilization experiments, respectively. Next, T2R14 signaling was examined in membrane cholesterol-altered environments by methyl-β-cyclodextrin or cholesterol oxidase treatments. In the cells analyzed, cholesterol depletion affected the agonist-induced T2R14 signaling, and cholesterol replenishment rescued its efficacy. An alternative approach for cholesterol depletion (with cholesterol oxidase pretreatment) also negatively affected the agonist potency at T2R14 in HASM cells. To understand the molecular mechanism of interaction between cholesterol and T2R14, we used site-directed mutagenesis coupled with functional assays and examined the role of putative cholesterol-binding motifs (CRAC and CARC) in T2R14. Functional characterization of wild-type and mutant T2R14 receptors suggests that amino acid residues K110, F236, and L239 are crucial in T2R14-cholesterol functional interaction. In conclusion, our results show that cholesterol influences the T2R14 signaling efficacy by forming direct interactions with the receptor and consequently plays a regulatory role in T2R14-mediated signaling in human airway cells.

Geometric Validation of Continuous, Finely Sampled 3-D Reconstructions From aOCT and CT in Upper Airway Models.

Identification and treatment of obstructive airway disorders (OADs) are greatly aided by imaging of the geometry of the airway lumen. Anatomical optical coherence tomography (aOCT) is a promising high-speed and minimally invasive endoscopic imaging modality for providing micrometer-resolution scans of the upper airway. Resistance to airflow in OADs is directly caused by the reduction in luminal cross-sectional area (CSA). It is hypothesized that aOCT can produce airway CSA measurements as accurate as that from computed tomography (CT). Scans of machine hollowed cylindrical tubes were used to develop methods for segmentation and measurement of airway lumen in CT and aOCT. Simulated scans of virtual cones were used to validate 3-D resampling and reconstruction methods in aOCT. Then, measurements of two segments of a 3-D printed pediatric airway phantom from aOCT and CT independently were compared to ground truth CSA. In continuous unobstructed regions, the mean CSA difference for each phantom segment was 2.2 ± 3.5 and 1.5 ± 5.3 mm2 for aOCT, and -3.4 ± 4.3 and -1.9 ± 1.2 mm2 for CT. Because of the similar magnitude of these differences, these results support the hypotheses and underscore the potential for aOCT as a viable alternative to CT in airway imaging, while offering greater potential to capture respiratory dynamics.

The effects of NOX4 and TGF-βinvolved in airway remodeling of Chronic Obstructive Pulmonary Disease

To investigate the role of nicotinamide adenine dinucleotide phosphate 4 (NADPH4,NOX4) and transforming growth factor-beta (TGF-β) involve in pathogenesis of airway remodeling in chronic obstructive pulmonary disease (COPD). Lung tissues from 36 COPD patients and 19 patients with normal lung function were enrolled in this study. The volume of airway smooth muscle (ASM)mass was evaluated. The expressions of NOX4, collagen Ⅳ (Col Ⅳ) and TGF-β were tested by a semi-quantitative morphological and/or immunohistochemistry staining method and Western blot, and their correlations with pulmonary functions were analyzed. ①Index of the percentage of the thickness of ASM/external diameter of small airway (WT%) and the percentage of the area of ASM/transverse area of small airway (WA%) were significantly higher in the COPD group than those in controls(P<0.05).②In COPD patients,epithelial cells metaplasia were found and α-SMA and Col Ⅳwere expressed in a part of epithelial cells. The expressions of α-small muscle actin (α-SMA) and Col Ⅰ were increased in COPD patients in comparison with the patients without obstructive airway disorders(P<0.05).③The expression of NOX4 in ASM and epithelial cells of COPD patients was significantly higher in comparison with the patients without COPD. The expression of NOX4 in ASM of small airway were statistically different among different COPD grade (P<0.05). Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway was inversely associated with pulmonary functions. ④The expression of TGF-β in COPD was significantly higher than that in patients without COPD. ⑤ Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway, WT% and WA% were inversely associated with pulmonary functions. ①The airway remodeling of COPD is characterized by increasing hyperplasia of small airway smooth muscle.②Remodeling of airway smooth muscle associats with severity of airflow limitation in COPD patients. ③The expressions of NOX4, TGF-β and α-SMA in COPD epithelial cells and small airway smooth muscle cells are significantly enhanced. The expressions of NOX4, α-SMA and TGF-β are positively correlated with the severity of chronic obstructive pulmonary air flow, suggesting that TGF-β and NOX4 signaling may be involved in the development of chronic obstructive pulmonary disease airway remodeling.

Modeling asthma: Pitfalls, promises, and the road ahead.

Asthma is a chronic, heterogeneous, and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of type 2 T helper cell cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses, or bacteria as exacerbants. Nonetheless, differences in lung size, structure, and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource.

Validation of the Children's Sleep Habits Questionnaire in a sample of Greek children with allergic rhinitis

BackgroundObstructive respiratory disorders, such as allergic rhinitis and asthma may impair sleep quality. The aim of this study is to validate the Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14 years of age. No validated tool has been developed so far to assess sleep disturbances in Greek school-aged children. MethodsWe examined the reliability and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and a non-clinical population of parents of these children as a proxy measure of children's AR quality of life (QoL) as evaluated by the Pediatric Allergic Rhinitis Quality of Life (PedARQoL) questionnaire. ResultsThe CSHQ questionnaire Child's Form (CF) had a moderate internal consistency with a Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when correlated with the PedARQoL (CF). There was also a moderate intraclass correlation of ICC=0.505 between the responses to both questionnaires in the two visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was a high intraclass correlation of 0.643 between the responses in the two visits. ConclusionsThe Greek version of the CSHQ CF, but particularly the PF has proved to be a very reliable clinical instrument, which can be used in clinical trials for assessing sleep quality in school-aged children with sleep disturbances because of obstructive airway disorders, such as AR.

Inhalational anesthetics agents: The pharmacokinetic, pharmacodynamics, and their effects on human body

In this review article, inhalational anesthetics agents and their pharmacokinetic, pharmacodynamics and effects on the central nervous, cardiovascular, and respiratory systems are discussed. There is a wide spectrum of inhalational anesthetic agents with different characteristics. As some examples, in this study, recovery times of sevoflurane and halothane are reviewed. Overall, gas drugs have extensive usage in Intensive Care Unit. For example, a combination of oxygen and helium may be utilized in patients with obstructive airway disorders, endotracheal tubes, acute lung damage, diphtheria, respiratory distress syndrome, asthma, bronchiolitis, and chronic obstructive pulmonary disease. Xenon would be effective in reducing memories after traumatic events.