Small Airway Dysfunction Research Articles

Metabolic syndrome, small airway dysfunction and the mediating role of inflammation

Our study examined how metabolic syndrome (MetS) affects the risk of small airway dysfunction (SAD) and its progression to chronic obstructive pulmonary disease (COPD). We also investigated the role of inflammation in mediating these effects. We included 13,948 non-COPD participants, aged 40 years and with a pulmonary function test, from multiple communities (Longquan, Mianzhu, and Pidu), and subsequently followed up the Longquan community after 3 years. Logistic models estimated the association between MetS and SAD risk, adjusted for confounders. Furthermore, a mediation analysis approach was employed to estimate the proportion of effect mediated by each marker of inflammation (e.g., the low-grade inflammation index) on the observed association. In West China Natural Population Cohort Study(WCNPCS), compared to the non-MetS group, individuals with MetS showed a significantly higher prevalence of SAD (odds ratio [OR] = 1.12, 1.02–1.22); however, this was not significant in women. For MetS components, high triacylglycerols(HTG), low high-density lipoprotein cholesterol (LHDL-C) and abdominal obesity (AO) were independent risk factors for SAD, which is consistent with men (OR = 1.09–1.33). In addition, the more metabolic disorder components, the higher the prevalence of SAD (P < 0.05). Further, when MetS as well as SAD outcomes were considered together, the incidence of COPD in individuals with both these irregularities was considerably higher (9-fold). Inflammation (the proportion of effect mediated: 14.3–28.6%) played a substantial mediating role in the observed association in Chinese participants. MetS is consistently linked to SAD and may facilitate progression from SAD to COPD; its components, HTG, LHDL-C and AO, were associated with a significantly increased risk of COPD. The observed associations were partly mediated by inflammation. Treating MetS may be an effective strategy for the prevention of the development of COPD.

Oscillometry-defined Small Airway Dysfunction in Tobacco-exposed Adults with Impaired or Preserved Airflow.

Small airway dysfunction (SAD) is a key feature of COPD and might present in tobacco-exposed adults with normal spirometry. So far, the role of oscillometry-defined SAD in this population is largely unexplored. To investigate the prevalence of oscillometry-defined SAD and its associations with airway structural changes, quality of life (QoL), metabolic and cardiovascular disease (CVD) in tobacco-exposed adults with impaired or preserved airflow. In a sub-cohort (n=1628) nested within a lung cancer screening trial, we assessed airway disease using preBD-spirometry, oscillometry, and AI-powered CT. Impaired airflow included airflow obstruction (AFO) and preserved ratio impaired spirometry (PRISm). Subjects with preserved airflow (PA), defined as FEV1 and FEV1/FVC > LLN, were further stratified as PA with SAD (PA-SAD) or normal lung function. SAD was defined as the frequency dependence of resistance (R5-19) or reactance area (AX) > ULN. CT biomarkers included airway wall thickness (AWT-Pi10), lumen diameter, branch count, and emphysema. QoL was measured using the EQ-5D-5L. The overall prevalence of SAD was 39%. SAD was present in 26% of subjects with PA and in 60% of those with impaired airflow. The frequency of AFO, PRISm and PA-SAD was 21%, 15% and 16%, respectively. Similar to impaired airflow, subjects with PA-SAD had lower EQ-5D-5L score, greater AWT-Pi10, narrower lumen, lower branch count, and higher rate of metabolic and CVD than those with normal lung function, (all p-values <0.01). However, they had minimal emphysema and significantly higher branch count than those with AFO. Subjects with AFO or PRISm and concurrent SAD had greater structural changes and more frequent CVD than those with AFO or PRISm alone. SAD was associated with CVD, OR: 1.91 (95% CI: 1.55 - 2.36), even after adjusting for confounders and metabolic disease. SAD is highly prevalent among tobacco-exposed adults and is associated with airway structural changes, impaired QoL, and increased rate of CVD, even in those with PA. PA-SAD is distinct from AFO by its preserved airway count and minimal emphysema. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Associations of small airway dysfunction assessed by impulse oscillometry with lung function decline and exacerbations in participants with Chronic Obstructive Pulmonary Disease: a prospective cohort study in China.

Associations of small airway dysfunction assessed by impulse oscillometry with lung function decline and exacerbations in participants with Chronic Obstructive Pulmonary Disease: a prospective cohort study in China.

Head-To-Head Comparison of Biologic Efficacy in Asthma: What Have We Learned?

We performed an in-depth appraisal of indirect head-to-head comparisons of biologics approved for asthma, including anti-IL5/5Rα (mepolizumab, benralizumab), anti-IL4Rα (dupilumab), anti-TSLP (tezepelumab) and anti-IgE (omalizumab), which was neither a systematic review nor a meta-analysis. A crude evaluation of 95% CI's for rate ratios which excluded unity revealed greater overall reductions in annualised exacerbations with dupilumab versus either mepolizumab or benralizumab and also with tezepelumab versus benralizumab. Furthermore in patients with eosinophils ≥ 300/μL exacerbation rates were lower for tezepelumab, dupilumab and mepolizumab versus benralizumab; and with eosinophils< 150/μL for tezepelumab versus dupilumab. For lung function, no overall differences in FEV1 response were observed between drugs where there was considerable heterogeneity of overlapping 95% CI's. Dupilumab was superior to benralizumab for oscillometry-derived peripheral lung resistance and compliance, as well as for attenuation of mannitol airway hyperresponsiveness. There were no differences in asthma control or quality of life scores where the effect sizes were small, along with wide overlaps in 95% CI's. There is an unmet need for prospective pragmatic randomised controlled trials to directly compare biologics, especially to assess clinical remission in both type 2 high and low asthma patients. Real-life studies might also evaluate complete remission with different biologics to include outcomes such as inhaled corticosteroid sparing, small airways dysfunction using oscillometry, abolition of airway hyperresponsiveness and to assess mucus plugging and remodelling as wall thickening with imaging.

Oscillometry and spirometry derived ratios to assess small airways dysfunction in severe asthma patients taking tezepelumab.

Oscillometry and spirometry derived ratios to assess small airways dysfunction in severe asthma patients taking tezepelumab.

The Canadian Lung Outcomes in Users of Vaping Devices (CLOUD) Study: protocol for a prospective, observational cohort study

IntroductionThe rapid growth in popularity of e-cigarettes over the past decade has prompted concerns about their impact on long-term respiratory health. Small airway injury is suspected to be a direct...

Physiological Small Airways Dysfunction and the Bronchodilator Response in Adults With Asthma and Its Risk Factors: A Retrospective Analysis.

Physiological evidence of small airways dysfunction (SAD) is present in some patients with asthma and is associated with poor disease control. It is unclear if this represents a distinct phenotype of asthma or if it is an early manifestation of the disease. The study aimed to evaluate SAD in asthma and its clinical associations. A retrospective analysis of routinely collected health data obtained from adults referred for routine spirometric assessment as part of their clinical management. The Maximal Mid-Expiratory Flow (MMEF) z-scores were used to assess the prevalence and association factors for SAD. Pre- and post-bronchodilator data of MMEF and FEV1 in patients with and without SAD or airflow obstruction (AO) were analysed. A total of 1094 patients were included. 366 (33.5%) had evidence of SAD of whom 261 (71.3%) also had AO. Current smokers were at an increased risk of having SAD (OR: 2.05; 95% CI: 1.43-2.93). 214 patients had Bronchodilator response (BDR) data with 157 (73.4%) demonstrating BDR for MMEF and 121 (56.5%) for FEV1. SAD at baseline was associated with a significant BDR for FEV1 (OR of 3.59 (95% CI: 1.77-7.57)) and MMEF (OR of 2.89 (95% CI: 1.41-5.95)). Males were less likely to have a positive BDR for MMEF than females (OR of 0.46; 95% CI: 0.24-0.89). SAD is common in asthma and is related to the presence of AO, cigarette smoking and is associated with increased BDR for both FEV1 and MMEF. The assessment of SAD in routine clinical practice may help identify airway impairment early for the initiation of targeted therapies.

The Impact of Age and Disease Entity on Small Airway Dysfunction in Obstructive Airway Diseases.

Small airway dysfunction (SAD) is prevalent in asthma and chronic obstructive pulmonary disease (COPD). Aging is acknowledged to be associated with the loss of small airway structures. However, the impact of aging and pathophysiological changes on SAD in asthma and COPD remains unclear. We aimed to investigate the impact of aging and disease entity on pathophysiological change-related SAD in asthma and COPD assessed by spirometry and impulse oscillometry (IOS). We retrospectively reviewed adult patients diagnosed with asthma or COPD between May 2017 and August 2021 in Taipei Veterans General Hospital. Treatment-naïve COPD patients aged ≥60 years were enrolled, along with age- and gender-matched elderly asthmatics (EA), and younger asthmatics aged <60 years (YA) for comparison. All participants underwent spirometry and IOS with a bronchodilator test. Blood eosinophil counts (BECs) and immunoglobulin E(IgE) levels were documented if blood tests were conducted at the time of diagnosis. The mean age of YA, EA, and COPD were 44, 73, and 73 years, respectively. The FEV1, FEV1/FVC and FEF25-75% were higher in the YA followed by EA and COPD groups. The spirometric values were significantly correlated with IOS parameters in both asthmatic and COPD groups. No significant differences were observed in baseline IOS parameters among the three groups for participants with FEV1 ≥80% predicted. However, in patients with FEV1< 80% predicted, COPD patients exhibited significantly worse spirometric values and most IOS parameters (except R5-R20) compared to asthmatics. Additionally, asthmatics with AX reduction ≥35% exhibited significantly higher levels of blood eosinophil counts and IgE. Aging process contributes to more impact on small airway reactance in asthma, while disease entity in COPD exhibits worse spirometric and IOS parameters compared to the age- and gender-matched EA.

Association between small airway dysfunction and cardiac conditions: a Swiss urban population cross-sectional study

Association between small airway dysfunction and cardiac conditions: a Swiss urban population cross-sectional study

Asthma With Fixed Obstruction Displays a Similar Small Airway Dysfunction to That Observed in Asthma-COPD Overlap.

The clinical characteristics of asthma patients with fixed airflow obstruction were compared with those with asthma-COPD overlap. Asthma patients with fixed airflow obstruction had comparable small airway dysfunction to asthma-COPD overlap patients.

The effects of temperature variation on obstructive pulmonary dysfunction and small airway dysfunction in asthmatic children: A continuous eight-year study in Jinan, China.

The effects of temperature variation on obstructive pulmonary dysfunction and small airway dysfunction in asthmatic children: A continuous eight-year study in Jinan, China.

Dupilumab Produces Clinically Relevant Improvement in Small Airway Dysfunction in Patients With Moderate-to-Severe Asthma: Results From the Phase 4 VESTIGE Study

Dupilumab Produces Clinically Relevant Improvement in Small Airway Dysfunction in Patients With Moderate-to-Severe Asthma: Results From the Phase 4 VESTIGE Study

Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis.

Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis.

Clinical Characteristics of 31 Patients with Chest Pain Variant Asthma.

Asthma is a major public health challenge in China. Although chest pain variant asthma (CPVA) is not common in clinical practice, there are still a few people who only or mainly manifest as chest pain. Here, we aim to introduce the characteristics of their symptoms, lung function and chest imaging features to arouse the attention of physicians to know better of the disease. We retrospectively analyzed thirty-one patients who had been diagnosed with CPVA based on clinical data and positive bronchial provocation tests (BPTs). The mean age of all enrolled patients was forty-seven years, and females accounted for 64.5%. Main features of chest pain manifested as dull pain and mild pain with unfixed location, and several patients were presented with distending pain, pinprick pain, chest pain related to breathing, chest pain position-related and chest pain like angina pectoris. The median duration of their chest pain was four months, and 77.4% of the patients did not find any trigger. Among the 31 patients, 10 were with normal lung function, 14 were with mild obstructive ventilation dysfunction, 6 were with small airway dysfunction and 1 was with mild restrictive ventilation dysfunction. The predicted values of forced expiratory volume in 1 s (FEV1) were greater than 80% in 29 out of 31 patients, and the values of other two patients were 74% and 79%, respectively. Additionally, 35.5% of the patients meanwhile had allergic rhinitis, and 64.5% of the patients exhibited type 2 inflammation. Among the 31 patients, 22 (71.0%) showed abnormalities on inspiratory computed tomography (CT) scans, including bronchiolar (38.7%), bronchial (25.8%) or pulmonary parenchyma abnormalities (32.3%). Only 7 patients (22.6%) had normal inspiratory CT scans. CPVA is relatively rare in clinical practice. Understanding its manifestations, lung function, chest CT features and comorbidities is helpful for diagnosis and evaluation of patients with such symptoms.

Oscillometry-defined small airways dysfunction as a treatable trait in asthma.

Oscillometry-defined small airways dysfunction as a treatable trait in asthma.

Evaluation of Small Airways Dysfunction with Dupilumab using Airway Oscillometry in Uncontrolled Severe Asthma

Evaluation of Small Airways Dysfunction with Dupilumab using Airway Oscillometry in Uncontrolled Severe Asthma

Small airways dysfunction in severe asthma: Current treatment approaches and future directions.

Small airways dysfunction in severe asthma: Current treatment approaches and future directions.

Changes in Small Airway Physiology Measured by Impulse Oscillometry in Subjects with Allergic Asthma Following Methacholine and Inhaled Allergen Challenge.

Background: Small airway dysfunction (SAD) is associated with impaired asthma control, but small airway physiology is not routinely assessed in clinical practice. Previously, we demonstrated impulse oscillometry (IOS)-defined small airway dysfunction (SAD) in dual responders (DRs) upon bronchoprovocation with various allergens. Aim: To compare lung physiology using spirometry and IOS following bronchoprovocation with methacholine (M) and inhaled house dust mite (HDM) extract in corticosteroid-naïve asthmatic subjects. Methods: Non-smoking, clinically stable HDM-allergic asthmatic subjects (18-55 years, FEV1 > 70% of pred.) underwent an M and inhaled HDM challenge on two separate days. Airway response was measured by IOS and spirometry, until a drop in FEV1 ≥ 20% (PC20) from post-diluent baseline (M), and up to 8 h post-allergen (HDM). Early (EAR) and late asthmatic response (LAR) to HDM were defined as ≥20% and ≥15% fall in FEV1 from post-diluent baseline during 0-3 h and 3-8 h post-challenge, respectively. IOS parameters (Rrs5, Rrs20, Rrs5-20, Xrs5, AX, Fres) were compared between mono-responders (MRs: EAR only) and dual responders (EAR + LAR). Correlations between maximal % change from baseline after the two airway challenges were calculated for both FEV1 and IOS parameters. Results: A total of 47 subjects were included (11 MRs; 36 DRs). FEV1 % predicted did not differ between MR and DR at baseline, but DR had lower median PC20M (0.84 (range 0.07-7.51) vs. MR (2.15 (0.53-11.29)); p = 0.036). During the LAR, DRs had higher IOS values than MRs. For IOS parameters (but not for FEV1), the maximal % change from baseline following M and HDM challenge were correlated. PC20M was inversely correlated with the % change in FEV1 and the % change in Xrs5 during the LAR (r= -0.443; p = 0.0018 and r= -0.389; p = 0.0075, respectively). Conclusions: During HDM-induced LAR, changes in small airway physiology can be non-invasively detected with IOS and are associated with increased airway hyperresponsiveness and changes in small airway physiology during methacholine challenge. DRs have a small airways phenotype, which reflects a more advanced airway disease.

A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule.

A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule.

Comparing spirometry, impulse oscillometry with computed tomography for assessing small airway dysfunction in subjects with and without chronic obstructive pulmonary disease

BackgroundStudies on consistency among spirometry, impulse oscillometry (IOS), and histology for detecting small airway dysfunction (SAD) remain scarce. Considering invasiveness of lung histopathology, we aimed to compare spirometry and IOS with chest computed tomography (CT) for SAD detection, and evaluate clinical characteristics of subjects with SAD assessed by these three techniques.MethodsWe collected baseline data from the Early COPD (ECOPD) study. CT-defined SAD was defined as parametric response mapping quantifying SAD (PRMfSAD) ≥ 15%. Spirometry-defined SAD was defined as at least two of maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD was defined as peripheral airway resistance R5 − R20 > 0.07 kPa/L/s. The consistency of spirometry, IOS and CT for diagnosing SAD was assessed using Kappa coefficient. Correlations among the three techniques-measured small airway function parameters were assessed by Spearman correlation analysis.Results2055 subjects were included in the final analysis. There was low agreement in SAD assessment between spirometry and CT (Kappa = 0.126, 95% confidence interval [CI]: 0.106 to 0.146, p < 0.001), between IOS and CT (Kappa = 0.266, 95% CI: 0.219 to 0.313, p < 0.001), as well as among spirometry, IOS, and CT (Kappa = 0.056, 95% CI: 0.029 to 0.082, p < 0.001). The correlation was moderate (|r|: 0.5 to 0.7, p < 0.05) between spirometry and CT-measured small airway function parameters, and weak (|r|< 0.4, p < 0.05) between IOS and CT-measured small airway function parameters. Only spirometry-defined SAD group had more lower lung function (FEV1/FVC: adjusted difference=-10.7%, 95% CI: -13.5% to -7.8%, p < 0.001) and increased airway wall thickness (Pi 10: adjusted difference = 0.3 mm, 95% CI: 0 to 0.6 mm, p = 0.046) than only CT-defined SAD group. Only IOS-defined SAD group had better lung function (FEV1/FVC: adjusted difference = 3.9%, 95% CI: 1.9 to 5.8%, p < 0.001), less emphysema (inspiratory LAA− 950: adjusted difference=-2.1%, 95% CI:-3.1% to -1.1%, P < 0.001; PRMEmph: adjusted difference=-2.3%, 95% CI: -3.2% to -1.4%, p < 0.001), and thicker airway wall (Pi 10: adjusted difference = 0.2 mm, 95% CI: 0.1 mm to 0.4 mm, p = 0.005) than only CT-defined SAD group.ConclusionsThere was low consistency in the assessment of SAD between spirometry and CT, between IOS and CT, as well as among spirometry, IOS, and CT.Clinical trial numberNot applicable.