Reversible Airflow Obstruction Research Articles

Can Oscillometry Replace Spirometry as a Major Tool for Lung Function Testing? – An Overview

Abstract Developing countries face a huge challenge in managing obstructive lung disorders due to frequency, severity, management, and economic impact. Spirometry has been the popular choice to assess the severity and reversibility of airflow obstruction, but the success of evaluation depends on the practitioner’s skills and the patient’s cooperation. Impulse oscillometry (IOS), a variant of forced oscillation technique is preferred over spirometry since it can be performed without forced respiratory maneuvers. The objective of this review is to evaluate IOS techniques and weigh its benefits against spirometry. Publications from international electronic databases such as PubMed, Scopus, and Web of Science were searched using relevant keywords for 5 years (2018–2023). A total of 416 articles were filtered, and of these, 70 were selected which specifically discussed the principles, procedures, parameters, and interpretations of spirometry and oscillometry. From the full-text articles included, we have reflected on the history, defined, explained, compared, and contrasted spirometry and oscillometry methods to establish the versatility of oscillometry technique to identify small airway functions and its application in special clinical conditions. This review presents an easily comprehensible synthesis of oscillometry and spirometry bringing out the principles, advantages, and limitations that are suitable for a larger spectrum of healthcare and research community.

Biologic therapies for severe asthma with persistent type 2 inflammation.

Asthma is a chronic inflammatory airways disease with reversible airflow obstruction, characterised in the majority by type 2 airway inflammation. Type 2 inflammation results in secretion of interleukin-4, -5 and -13 in the airways, recruitment of inflammatory cells (especially eosinophils and mast cells), and airway changes such as mucus hypersecretion and increased airway reactivity. Approximately 5 to 10% of people with asthma, despite optimal therapy and adherence to treatment with inhaled corticosteroids and long-acting beta2 agonists, are unable to obtain good symptom control and continue to experience exacerbations requiring oral corticosteroids; this is known as 'severe asthma'. In many cases, this is associated with persistent type 2 inflammation, indicated by the persistent elevation of blood eosinophils or fractional exhaled nitric oxide. In people with severe asthma and persistent type 2 inflammation, biologic (monoclonal antibody) therapy is indicated. Biologic therapies currently available in Australia for asthma are benralizumab, dupilumab, mepolizumab and omalizumab. They are administered subcutaneously and are generally well tolerated. Biologic asthma therapies are very effective in improving symptoms, and reducing the rate of exacerbations and use of oral corticosteroids, in people with severe asthma and persistent type 2 inflammation. Inhaled corticosteroid treatment should be continued in people using a biologic therapy.

Epidemiology of Osteoporosis in Patients with Chronic Obstructive Pulmonary Disease in Taiwan

BackgroundChronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic condition characterized by progressive, partially reversible airflow obstruction. Osteoporosis represents a significant comorbidity in individuals with COPD. However, the incidence and prevalence of osteoporosis among the COPD population remain unclear in Taiwan. Therefore, our objective is to investigate the incidence and prevalence of osteoporosis in patients with COPD.MethodsIn this cross-sectional study, we enrolled a COPD population retrieved from the Taiwan National Health Insurance Research Database (NHIRD) spanning the years 2003 to 2016. Osteoporosis patients were identified using diagnosis codes. The study included newly diagnosed COPD patients from 2003 to 2016. The case group comprised patients who developed osteoporosis or osteoporotic fractures after their COPD diagnosis. We calculated the prevalence and incidence of osteoporosis in individuals with COPD and conducted trend tests.ResultsA total of 1,297,579 COPD patients were identified during the period from 2003 to 2016, with 275,233 of them in the osteoporosis group. The average prevalence of osteoporosis among individuals with COPD was 21.21% from 2003 to 2016 in Taiwan. The number of osteoporosis cases increased from 6,727 in 2003 to 24,184 in 2016. The prevalence of osteoporosis among COPD patients increased from 3.62% in 2003 to 18.72% in 2016. The number of osteoporosis cases among individuals with COPD continued to rise over the years, reaching its highest point in 2016 with 24,184 new cases. The incidence of osteoporosis fluctuated during the study period but generally remained around 3,000 cases per 100,000 person-years. Notably, there was a significant upward trend in incidence from 2003 to 2006, after which the trend stabilized and remained relatively constant.ConclusionsOur study highlights an increase in both the prevalence and incidence of osteoporosis in individuals with COPD. Given the significant medical, economic, and social implications associated with osteoporosis, a comprehensive and robust assessment of its healthcare burden can offer valuable insights for healthcare system planning and policymaking.

Research on the Impact of Breathing Exercises and Aerobic Exercises on Quality of Life in Patients with Bronchial Asthma: A Comparative Study

Background: Asthma is defined as a chronic inflammatory disorder of airways characterized by reversible airflow obstruction causing cough, wheeze, chest tightness and shortness of breath Crompton et al7Asthmatic attacks are set up by exposure to specific allergens such as house dust mite, pollen and animal dander. Some other factors are exercise particularly running, dyes, air pollution, infection, cigarette smoke, dry inhaled air, certain foods such as fish, eggs, yeast, and wheat which presumably reach the bronchi via blood stream. There is noticeable increase in healthcare burden from asthma in several areas of world .The most frequently mentioned aims of breathing exercises are to ‘normalize’ breathing pattern by adopting a slower respiratory rate with longer expiration and reduction of hyperventilation and hyperinflation. Training also frequently involves encouraging nasal breathing and a diaphragmatic breathing pattern.AQLQ AND SF36 questionnaire was used as outcome measure.Methods: The sample size of this study was 30 subjects with 15 subjects in each group. The group A was given breathing exercises interventions and group B was given aerobic exercises intervention. A written consent was taken from each before their participation into the study. Asthma Quality of Life Questionnaire (AQLQ) and SF-36 quality of life Questionnaire of both the groups were taken in 0 week and both groups were assigned treatment interventions and after 3 weeks the AQLQ and SF-36 quality of life questionnaire has been repeated.The independent variables in the study were Aerobic Exercises and Breathing Exercises.Conclusion: The breathing exercise intervention was effective in improving the quality of life in asthmatic patients.The aerobic exercise intervention was also effective in improving the quality of life in asthmatic patients.However, the quantum of reduction in lung obstruction and therefore, the overall improvement in quality of life found to be more significant with the aerobic exercise intervention than breathing exercise intervention. Thus,a combination of the breathing exercises and aerobic exercise should be incorporated into the pulmonary rehabilitation program of the asthmatic patients.

Pharmacology and non-pharmacology treatment in a way of well controlled childhood asthma

Introduction and purpose: Asthma is a chronic disease of air pathways which is characterized by episodic or persistent reversible airflow obstruction with chronic inflammation of respiratory tract and increased bronchial reactivity. Our aim is to broaden patients’ knowledge concerning suitable diet and exercises which can help in controlling asthma symptoms. Description of the state of knowledge: A diet rich in vegetables and fruit contains a huge amount of fiber and anti-inflammatory flavonoids. introducing plant products into the diet of children with asthma improves parameters such as FEV1, FVC and PEF. Dairy products, on the other hand, are associated with worsening of these parameters and are not recommended for patients with asthma. The aforementioned effects are related to the presence of cow's milk protein and increased activity of interleukin 17. The Western diet being rich in animal fats and low in fiber is not recommended for patients with asthma. This is primarily due to resulting difficulty in maintaining a healthy body weight and the pro-inflammatory properties of animal fats. Conclusions: In light of the impact of a suitable diet on the reduction of asthma symptoms, it is recommended to increase the share of vegetables and fruit in the daily menu of asthmatics and to limit their consumption of animal fats. In addition, young patients are encouraged to undertake physical activity adapted to their individual abilities.

Asthma Management in Children

Asthma is a common, complex heterogeneous disease often beginning in early life and is characterized by reversible airflow obstruction. The phenotypic differences that exist in children with asthma may impact underlying comorbid conditions and pharmacologic treatment choices. Prenatal factors for increased risk of asthma could include maternal diet and the maternal microbiome. Evidence also suggests that postnatal microbial exposures and colonization contribute to the risk of allergic diseases and asthma. After confirming the diagnosis, asthma management in children centers on 3 broad areas: pharmacologic treatment, treatment of underlying comorbidities, and education of the patient and caregivers on the importance of adherence and device technique. Moreover, social determinants of health significantly impact on symptom burden and treatment response.

Anti-inflammatory effect of N-(trifluoromethylphenyl)- 2-cyano-3-hydroxy-crotonic acid amide and gluconic acid on allergic rhinitis and asthma controlling.

Allergic rhinitis and asthma are the main airway diseases with a higher prevalence. Eosinophilic inflammation, airway hyperresponsiveness, mucus hypersecretion, and reversible airflow obstruction are immunopathogenesis symptoms of rhinitis and asthma. Crotonic acid has bio-activity on the inflammation, and gluconic acid as chelator may protect crotonic acid activity in airway and together may control allergic rhinitis and asthma.Allergic rhinitis and asthma mice models were treated with crotonic and gluconic acids. The total IgE, histamine, IL-4, IL-5, and IL-13 levels were measured. In lung tissues, goblet cell hyperplasia, mucus hypersecretion, and inflammation were evaluated.The level of IL-5, goblet cell hyperplasia, and perivascular and peribronchial inflammation were controlled by crotonic acid in asthma and allergic rhinitis groups. But, total IgE, hista-mine, IL-4, and IL-13 levels, and mucus hypersecretion had no significant changes between treated and nontreated asthma and rhinitis groups.

Management of asthma (ḌĪQ Al-Nafas) in Unani system of medicine

Numerous functions within the human body have been conducted throughout time without anyone being aware of them or interfering with their functioning. One of them is breathing. Thus, when a person develops trouble breathing and must exert considerable effort to inhale and exhale, it becomes an argument for a will condition. Asthma is a chronic inflammatory airway disorder that is often characterized by reversible airflow obstruction and chest tightness, wheezing, coughing, and dyspnea, all of which are signs of airway obstruction. They can occur spontaneously, most frequently at night or early in the morning, the following activity or responding to an allergy. This potentially severe chronic disease places a significant financial burden on individuals and their families. The development of bronchodilators and corticosteroids simplified the management of bronchial asthma in modern medicine. In modern medicine, bronchial asthma is treated through bronchodilators and corticosteroids. Apart from this invention, comprehensive treatment of asthma is still a long way off. The Unani medical system takes a holistic approach to prevent and treating Asthma (Ḍīq al-Nafas). This article aims to describe Asthma (Ḍīq al-Nafas) and find a comprehensive and safe method of managing asthma through a holistic approach to the Unani system of medicine.

Extracellular Traps: A Novel Therapeutic Target for Severe Asthma.

Asthma is a complicated disease defined by a combination of clinical symptoms and physiological characteristics. Typically, asthma is diagnosed by the presence of episodic cough, wheezing, or dyspnea triggered by variable environmental factors (allergens and respiratory infections), and reversible airflow obstruction. To date, the majority of asthmatic patients have been adequately controlled by anti-inflammatory/bronchodilating agents, but those with severe asthma (SA) have not been sufficiently controlled by high-dose inhaled corticosteroids-long-acting beta-agonists plus additional controllers including leukotriene modifiers. Accordingly, these uncontrolled patients provoke a special issue, because they consume high healthcare resources, requiring innovative precision medicine solutions. Recently, phenotyping based on biomarkers of airway inflammation has led to elucidating the pathophysiological mechanism of SA, where emerging evidence has highlighted the significance of eosinophil or neutrophil extracellular traps contributing to the development of SA. Here, we aimed to provide current findings about extracellular traps as a novel therapeutic target for asthma to address medical unmet needs.

Clinical and genomic characteristics of lung cancer concomitant chronic obstructive pulmonary disease (COPD).

e15131 Background: Lung cancer and chronic obstructive pulmonary disease (COPD) often coexist. Lots of clinical and genomic descriptions related lung cancer have been investigated. However, the clinical and genomics characteristics of lung cancer coexisting COPD are still unclear. Herein, we explored the clinical characteristics and somatic mutational landscape of lung cancer coexisting COPD (COPD-LC) and compared with non-COPD Lung cancer (non-COPD-LC). Methods: We retrospectively collected total COPD-LC and non-COPD-LC patients who performed next generation sequencing (NGS) simultaneously from The Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University during December 2018 to August 2021. And collected COPD-LC data from TCGA to further analysis. COPD was defined as incompletely reversible airflow obstruction associated with post-bronchodilator forced expiratory volume in one second (FEV1) and its ratio to forced vital capacity (FEV1/FVC) < 0.7. Results: Of the 139 patients enrolled in the study, 51 were categorized as COPD and 88 as non-COPD. In our clinical cohort, compared with non-COPD-LC, amount of male gender, older age and smoking patients were significantly higher than non-COPD in term of clinical data (all P < 0.01). As for somatic mutation in our cohort, compared with non-COPD-LC, COPD-LC had higher mutation frequency of LRP1B (43% vs 9%, P = 0.001), EPHA5 (24% vs 1%, P = 0.002), PRKDC (14% vs 1%, P = 0.039) and PREX2 (14% vs 0%, P = 0.012), which had relationship with improved tumor immunity. Immunotherapy biomarker of PD-L1 positive expression (62.5% vs 52.0%, P = 0.397) and TMB (P = 0.004) also were higher in COPD group. Whereas, COPD-LC had lower frequency of EGFR (19% vs 50%, P = 0.013). And survival analysis showed in EGFR mutant patients with targeted therapy, COPD-LC had worse PFS than non-COPD-LC (HR = 3.52, 95%CI: 1.27-9.80, P = 0.01). TCGA cohort mutation data differed from the results of our cohort. In addition, RNA data from TCGA indicated COPD-LC increased tumor immunity. Conclusions: In our research, COPD-LC had unique clinical and molecular features. High PD-L1 expression and TMB indicated these patients may benefit from immunotherapy. Notably, mutation difference between Chinese and TCGA cohort and COPD-LC immunotherapy efficacy need prospective further study.

APPLICATION OF EXERCISE COMBINED WITH LUNG REHABILITATION IN RESPIRATORY DISEASE

ABSTRACT Introduction: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by incomplete reversibility of airflow obstruction and persistent respiratory symptoms. Objective: To explore the therapeutic effect of physical exercise on patients with chronic obstructive pulmonary disease in pulmonary rehabilitation. Methods: Forty-eight experimental subjects were divided into control group, experimental group 1, and experimental group 2 for research. The control group received normal medical-related treatment without any other means of intervention. In addition to normal medical-related treatment, experimental group 1 received breathing training and educational interventions and experimental group 2 received exercise, breathing training and educational interventions. Results: The vital capacity of female subjects before and during the experiment ranged from 2.23±0.01 to 2.26±0.04, the FVC ranged from 2.00±0.02 to 2.01±0.03, the FEV1 ranged from 1.03±0.01 to 1.03±0.01,the FEV1% ranged from 55.50±1.29 to 55.25±1.71,the FEV1/FVC ranged from 51.44±0.24 to 50.84±1.00, andthe heart rate ranges from 65.00±0.82 to 65.50±1.29. Conclusions: Exercise training can increase the exercise tolerance of patients with COPD, relieve dyspnea, and improve the quality of life. Level of evidence II; Therapeutic studies - investigation of treatment results.

Pulmonary function tests in extremely low gestational age infants at one year of age.

Identifying neonatal and post-discharge exposures among extremely low gestational age newborns (ELGANs) that drive increased pulmonary morbidity and abnormal lung function at 1 year of age proves challenging. The NIH-sponsored Prematurity and Respiratory Outcomes Program (PROP), evaluated infant pulmonary function tests (iPFTs) at 1 year corrected age to determine which demographic and clinical factors are associated with abnormal lung function. iPFTs were performed on a PROP subcohort of 135 participants following Institutional Review Board (IRB)-approved written consent. Demographic data, Neonatal Intensive Care Unit (NICU) clinical care, and post-NICU exposures were analyzed for association with iPFTs. A significant decrease in forced expiratory volume at 0.5 s (FEV0.5 ) and/or forced expiratory flows at 75% of forced vital capacity (FEF75 ), were associated with male sex and African American race. Clinical factors including longer duration of ventilatory support, exposure to systemic steroids, and weight less than the 10th percentile at 36 weeks postmenstrual age were also associated with airflow obstruction, whereas supplemental oxygen requirement and bronchopulmonary dysplasia were not. Additionally, the need for respiratory medications, technology, or hospitalizations during the first year, ascertained by a quarterly survey, were the only post-NICU factors associated with decreased FEV0.5 and FEF75 . Only 7% of infants had reversible airflow obstruction. Neonatal demographic factors, respiratory support in the NICU, and a history of greater post-NICU medical utilization for respiratory disease had the strongest association with lower lung function at 1 year in ELGANs.

The Potential Role of The Long non-coding RNA MEG3 in Bronchial Asthma in children

Abstract Aim and Background Asthma is an inflammatory disease affecting the airways of the lungs being characterized by reversible airflow obstruction and bronchospasm. Environmental and genetic factors play a role in the pathogenesis of the disease; these factors are controlled by epigenetic mechanisms. There is a demand of clinical biomarkers for diagnosis of asthma and monitoring the response to therapy. In this study, we aimed to evaluate the role of lnc-MEG3 expression and its downstream effector in the pathogenesis of bronchial asthma disease. Methods Based on bioinformatics analysis using online databases, the current work has been designed to study the expression status of lnc-MEG3 and GDF15 mRNA in serum and sputum of asthmatic children aiming to find its clinical significance. This study was conducted on 30 children, 15 children newly diagnosed with bronchial asthma as patient group (A) and 15 age and sex matched healthy children as control group (B). Quantitative PCR was carried out to evaluate the expression pattern of selected biomarkers in serum and sputum of asthmatic children. Results The expression of circulating lnc-MEG3 was highly significantly up-regulated in asthmatic children than in control group (p ≤ 0.01), while the expression of circulating GDF15 mRNA was highly significantly down-regulated in asthmatic children than in control group (p ≤ 0.01). The findings showed a negative significant correlation between both investigated biomarkers. Conclusion This study supports the role of lnc-MEG3 and GDF15 protein as potential biomarkers in diagnosis of bronchial asthma in children.

Asthma and Comorbid Conditions—Pulmonary Comorbidity

Pulmonary comorbidities can increase disease severity and health care costs associated with asthma management. Vocal cord dysfunction/inducible laryngeal obstruction is a common comorbidity that results from intermittent laryngeal obstruction. Patients describe distinct episodes of dyspnea that do not respond to bronchodilators. Inspiratory stridor is common. The gold standard diagnostic testing strategy is continuous laryngoscopy performed during exercise or irritant challenges. Dysfunctional breathing (DB) is an overarching term that describes conditions with a chronic change in the pattern of breathing that results in pulmonary and extrapulmonary symptoms. The prevalence of DB in asthma is up to 30%, and breathing retraining can improve symptoms and quality of life in people with DB and asthma. Asthma-chronic obstructive pulmonary disease overlap (ACO) refers to both asthmatics who develop fixed airflow obstruction after a history of exposure to smoke or biomass and patients with chronic obstructive pulmonary disease who have "asthmatic features" such as a large bronchodilator response, elevated levels of serum IgE, or peripheral eosinophil counts ≥300 per μL. Triple inhaler therapy with inhaled corticosteroid/long-acting beta-agonist/long-acting muscarinic should be considered in people with ACO and severe symptoms or frequent exacerbations. The clinical expression of bronchiectasis involves persistent mucus hypersecretion, recurrent exacerbations of infective bronchitis, incompletely reversible airflow obstruction, and lung fibrosis and can occur in up to 30% of adults with longstanding asthma. The treatable traits strategy is a useful model of care to manage the complexity and heterogeneity of asthma with pulmonarycomorbidity.

Effects of Air Pollutant Exposure on Exacerbation Severity in Asthma Patients with or without Reversible Airflow Obstruction.

BackgroundReversible airflow obstruction (RO) and fixed airflow obstruction (FO) are two important clinical phenotypes of asthma. However, the relationship between air pollutant exposure and exacerbation of the two phenotypes is unknown.ObjectiveTo study the effects of air pollutant exposure on exacerbation severity in asthma patients with or without FO.MethodsA total of 197 severe asthma patients were enrolled, and divided into two groups: the FO group (n=81) and the RO group (n=116). We collected the demographic data, laboratory parameters, pulmonary function test parameters, and the daily average concentrations of different air particles in Shenzhen on the different lag days of each subject. The receiver operating characteristic (ROC) curve was used to identify the effects of major air pollutants on the severity of asthma patients with RO.ResultsCompared with the RO group, the FO group had fewer women, lower body mass index (BMI), longer disease duration, higher smoking history rate, allergic family history rate, FeNO level, and lower levels of large airway parameters. The median exposure levels of PM10 and PM2.5 in the severe RO subgroup were both higher than those in the mild-to-moderate RO subgroup on Lag0, 1 and 3, and the median exposure level of PM1 on Lag0 in the severe RO subgroup was significantly higher than that in the mild-to-moderate RO subgroup. Logistic regression modeling indicated exposure to PM2.5 and PM1.0 on Lag0, and PM10 on Lag0-2 were the independent risk factors for hospital admissions for asthma patients with RO. By performing an ROC curve analysis, PM2.5 on Lag0 (AUC = 0.645, p = 0.027) provided a best performance to predict severe asthma exacerbations with RO, with a sensitivity of 36.0% and a specificity of 91.2%.ConclusionShort-term exposure to PM10, PM2.5 and PM1 may play a role in exacerbation severity among asthma patients with RO.

IGF1R as a Potential Pharmacological Target in Allergic Asthma.

Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. Methods: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. Results: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. Conclusions: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

Efficacy of budesonide/glycopyrronium/formoterol metered dose inhaler in patients with COPD: post-hoc analysis from the KRONOS study excluding patients with airway reversibility and high eosinophil counts

BackgroundIn the Phase III KRONOS study, triple therapy with budesonide/glycopyrronium/formoterol fumarate metered dose inhaler (BGF MDI) was shown to reduce exacerbations and improve lung function versus glycopyrronium/formoterol fumarate dihydrate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). However, whether the benefits related to the ICS component of BGF are driven by patients with high blood eosinophil counts (EOS) and/or airway reversibility has not been previously studied.MethodsKRONOS was a Phase III, double-blind, parallel-group, multicenter, randomized, controlled study of patients with moderate-to-very-severe COPD. Patients were randomized 2:2:1:1 to receive BGF 320/14.4/10 μg, GFF 14.4/10 μg, budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10 μg via a single Aerosphere inhaler, or open-label budesonide/formoterol fumarate dihydrate dry powder inhaler 400/12 μg (BUD/FORM DPI; Symbicort Turbuhaler) twice-daily for 24 weeks. Efficacy outcomes included in this post-hoc analysis were change from baseline in morning pre-dose trough FEV1 over weeks 12–24 and the rate of moderate-to-severe and severe COPD exacerbations. Adverse events in the non-reversible subgroup are also reported.ResultsOf 1896 patients analyzed, 948 (50%) were non-reversible and had EOS < 300 cells/mm3. In this group, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM (least squares mean treatment difference, 95% confidence interval [CI] 69 mL [39, 99], unadjusted p < 0.0001 and 51 mL [20, 81], unadjusted p = 0.0011, respectively) and was comparable to GFF. BGF also significantly reduced annual moderate-to-severe exacerbation rates versus GFF (rate ratio [95% CI] 0.53 [0.37, 0.76], unadjusted p = 0.0005), with numerical reductions observed versus BFF and BUD/FORM. These results were similar for the overall study population. Safety findings were generally similar between non-reversible patients with EOS < 300 cells/mm3 and the overall population.ConclusionsIn patients with moderate-to-very-severe COPD without airway reversibility and EOS < 300 cells/mm3, BGF significantly improved morning pre-dose trough FEV1 versus BFF and BUD/FORM and significantly reduced the rate of moderate-to-severe exacerbations versus GFF. These findings demonstrate that BGF can provide benefits for a broad range of patients with COPD, and that the overall findings of the KRONOS primary analysis were not driven by patients with reversible airflow obstruction or high eosinophil counts.Trial registration ClinicalTrials.gov, NCT02497001. Registered 14 July 2015, https://clinicaltrials.gov/ct2/show/NCT02497001

Extracellular Vesicles and Asthma-More Than Just a Co-Existence.

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.

Regulation of Eosinophilia in Asthma-New Therapeutic Approaches for Asthma Treatment.

Asthma is a complex and chronic inflammatory disease of the airways, characterized by variable and recurring symptoms, reversible airflow obstruction, bronchospasm, and airway eosinophilia. As the pathophysiology of asthma is becoming clearer, the identification of new valuable drug targets is emerging. IL-5 is one of these such targets because it is the major cytokine supporting eosinophilia and is responsible for terminal differentiation of human eosinophils, regulating eosinophil proliferation, differentiation, maturation, migration, and prevention of cellular apoptosis. Blockade of the IL-5 pathway has been shown to be efficacious for the treatment of eosinophilic asthma. However, several other inflammatory pathways have been shown to support eosinophilia, including IL-13, the alarmin cytokines TSLP and IL-33, and the IL-3/5/GM-CSF axis. These and other alternate pathways leading to airway eosinophilia will be described, and the efficacy of therapeutics that have been developed to block these pathways will be evaluated.

The association of trimethoprim-sulfamethoxazole with improved lung function in pediatric asthma

Asthma affects more than 300 million patients worldwide and is characterized by intermittent reversible airflow obstruction and airway inflammation. Pneumocystis, an opportunistic fungus, has recently been implicated in asthma pathogenesis. In preclinical models, Pneumocystis exposure causes goblet cell hyperplasia, bronchial hyperreactivity, and airway inflammation.1,2 From a clinical perspective, patients with severe asthma have elevated anti-Pneumocystis antibody titers compared with healthy controls, and higher levels of anti-Pneumocystis immunoglobulin G are correlated with worsened lung function.