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Background: Diagnostic and therapeutic options for asthma have improved with asthma control and remission being of central importance. The RELEVANT study aimed for a nationwide snapshot of current asthma diagnosis and treatment in general practice and specialty care for identification of further aspects for optimization., Method: RELEVANT is a nationwide cross-sectional study using a structured questionnaire. This comprised 14 questions on asthma-related topics covering diagnostics and therapy. Participants were general practitioners/internal medicine specialists and pulmonologists., Results: A total of 1,558 persons took part in the survey. Regarding relevant specific diagnostic procedures for asthma, GPs/internists almost exclusively mentioned pulse oximetry. Among the pulmonologists, fractional exhaled nitric oxide (FeNO) measurement was mentioned, among others. FeNO and blood eosinophils were only mentioned by the pulmonologists as diagnostic and treatment-relevant markers. A total of more than 60% of the GPs/internists surveyed stated that only around 25% or fewer of their patients would voluntarily report restrictions in their everyday lives. Regarding drug treatment, the majority stated that they recognized differences between various ICS/LABA combination therapies., Conclusions: The results indicate a need for optimization, particularly regarding asthma control. This involves both a better assessment by patients' everyday life restrictions and modern ways of assessing asthma control in cooperation between GPs/internal medicine specialists and pulmonologists. One fifth of respondents do not see any differences between various ICS/LABA combinations in daily practice, although there are pharmacodynamic and pharmacokinetic differences., (© 2024. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Impulse oscillometry (IOS) allows an effort-independent evaluation of small airway function in asthma. Unfortunately, well-determined minimal clinically important differences (MCIDs) for IOS measures are lacking. Here, we provide MCIDs for frequently used IOS measures, namely frequency dependence of resistance (FDR) and area of reactance (AX), in patients with asthma., Methods: We performed IOS at baseline and 1 year later in adult patients with mild-to-severe asthma (n=235). In a two-step approach, we first applied a distribution-based method to statistically determine the MCID. Next, we validated the proposed MCID according to patient-reported outcome measures (PROMs): Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire-7 (ACQ-7) and Asthma Control Test (ACT). We used multivariable analyses to investigate the proposed MCIDs as predictors for improvements in PROMs compared with the established MCID of forced expiratory volume in 1 s (FEV 1 )., Results: The proposed MCID was a decline of ≥0.06 kPa·L -1 ·s -1 and ≥0.65 kPa·L -1 for FDR and AX, respectively. Patients who had changes beyond the MCIDs for both FDR and AX showed greater improvements in all PROMs than those who had not. The mean improvements in PROMs were beyond the established MCIDs for ACQ-7 and AQLQ, and approximated the MCID for ACT. Multivariable analyses demonstrated the MCIDs for both FDR and AX as independent predictors for the MCIDs of all PROMs. The MCID for FDR was a stronger predictor of all PROMs than the MCID for FEV 1 ., Conclusions: This study provides MCIDs for IOS-derived measures in adult patients with asthma and emphasises that small airway function is a distinguished end-point beyond the conventional measure of FEV 1 ., Competing Interests: Conflicts of interest: M. Abdo received travel support from Chiesi and consulting fees from AstraZeneca, all outside the submitted work. E. von Mutius reports personal fees from Pharmaventures, OM Pharma SA, Springer-Verlag GmbH, Elsevier GmbH, Elsevier Ltd, Peptinnovate Ltd, Turun Yliopisto, Tampereen Yliopisto, Helsingin Yliopisto, European Respiratory Society, Deutsche Pharmazeutische Gesellschaft eV, Massachusetts Medical Society, Chinese University of Hongkong, Boehringer Ingelheim, ProtectImmun GmbH, Faculteit Diergeneeskunde, Universität Salzburg, Georg Thieme Verlag, Japanese Society of Pediatric Allergy and Clinical Immunology, and Universiteit Utrecht, all outside the submitted work. K.F. Rabe reports grants from Boehringer Ingelheim and AstraZeneca, as well as personal fees from Boehringer Ingelheim, AstraZeneca, Novartis, Roche, Chiesi Pharmaceuticals, Regeneron, Sanofi and Berlin-Chemie. F. Trinkmann received travel support from Actelion, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma, TEVA, AstraZeneca, Berlin-Chemie, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Novartis, Roche and Sanofi-Aventis, all outside the submitted work. T. Bahmer reports grants from Bundesministerium für Bildung und Forschung (BMBF) (an unrestricted research grant for the German Center for Lung Research (DZL)), during the conduct of the study, and personal fees from AstraZeneca, GlaxoSmithKline, Novartis and Roche, outside the submitted work. The remaining authors report no relevant conflicts of interest., (Copyright ©The authors 2023.)

Background: Little is known about the relationship between airway inflammatory phenotypes and some important asthma features such as small airway dysfunction (SAD)., Objective: To describe the longitudinal impact of airway inflammatory phenotypes on SAD and asthma outcomes., Methods: We measured eosinophil and neutrophil counts in induced sputum at baseline and 1 year later to stratify 197 adult patients with asthma into 4 inflammatory phenotypes. We conducted a comprehensive assessment of lung function using spirometry, body plethysmography, impulse oscillometry, and inert gas single and multiple breath washouts. We compared lung function, asthma severity, exacerbation frequency, and symptom control between the phenotypes. We studied the longitudinal impact of persistent sputum inflammatory phenotypes and the change of sputum cell counts on lung function., Results: Patients were stratified into eosinophilic (23%, n = 45), neutrophilic (33%, n = 62), mixed granulocytic (22%, n = 43), and paucigranulocytic (24%, n = 47) phenotypes. Patients with eosinophilic and mixed granulocytic asthma had higher rates of airflow obstruction and severe exacerbation as well as poorer symptom control than patients with paucigranulocytic asthma. All SAD measures were worse in patients with eosinophilic and mixed asthma than in those with paucigranulocytic asthma (all P values <.05). Eosinophilic asthma also indicated worse distal airflow obstruction, increased ventilation inhomogeneity (all P values <.05), and higher tendency for severe exacerbation (P = .07) than neutrophilic asthma. Longitudinally, persistent mixed granulocytic asthma was associated with the worst follow-up measures of SAD compared with persistent neutrophilic, persistent paucigranulocytic, or nonpersistent asthma phenotypes. In patients with stable forced expiratory volume in 1 second (FEV1), the mean increase in small airway resistance (R5-20) was greater in patients with persistent mixed granulocytic asthma (+103%) than in patients with persistent neutrophilic (+26%), P = .040, or persistent paucigranulocytic asthma (-41%), P = .028. Multivariate models adjusted for confounders and treatment with inhaled or oral corticosteroids or antieosinophilic biologics indicated that the change of sputum eosinophil rather than neutrophil counts is an independent predictor for the longitudinal change in FEV1, forced expiratory flow at 25% to 75% of forced vital capacity, specific effective airway resistance, residual lung volume, and lung clearance index., Conclusions: In asthma, airway eosinophilic inflammation is the main driver of lung function impairment and poor disease outcomes, which might also be aggravated by the coexistence of airway neutrophilia to confer a severe mixed granulocytic asthma phenotype. Persistent airway eosinophilia might be associated with dynamic SAD even in patients with stable FEV1., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the role of small airway dysfunction (SAD) and its complex relation with asthma control and physical activity (PA)., Objective: To investigate the interrelations among SAD, risk factors for asthma severity, symptom control, and PA., Methods: We assessed SAD by impulse oscillometry and other sophisticated lung function measures including inert gas washout in adults with asthma (mild to moderate, n = 140; severe, n = 128) and 69 healthy controls from the All Age Asthma Cohort. We evaluated SAD prevalence and its interrelation with risk factors for asthma severity (older age, obesity, and smoking), type 2 inflammation (sputum and blood eosinophils, fractional exhaled nitric oxide), systemic inflammation (high-sensitivity C-reactive protein), asthma control (AC), and PA (accelerometer for 1 week). We applied a clinical model based on structural equation modeling that integrated causal pathways among these clinical variables., Results: The prevalence of SAD ranged from 75% to 90% in patients with severe asthma and from 53% to 64% in mild to moderate asthma. Severe SAD was associated with poor AC and low PA. Structural equation modeling indicated that age, obesity, obesity-related systemic inflammation, T2 inflammation, and smoking are independent predictors of SAD. Small airway dysfunction was the main determinant factor of AC, which in turn affected PA. Obesity affected AC directly and through its contribution to SAD and low PA. In addition, PA had bidirectional associations with obesity, SAD, and AC. Structural equation modeling also indicated interrelations among distal airflow limitation, air trapping, and ventilation heterogeneity., Conclusions: Small airway dysfunction is a highly prevalent key feature of asthma that interrelates a spectrum of distal lung function abnormalities with risk factors for asthma severity, asthma control, and physical activity., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Extracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited., Objective: To characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction., Methods: We measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes., Results: Patients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values < 0.05). E-DNA concentrations correlated directly with sputum neutrophils (R = 0.49, p < 0.0001) and negatively with sputum macrophages (R = - 0.36, p < 0.0001), but neither with sputum eosinophils (R = 0.10, p = 0.26), nor with FeNO (R = - 0.10, p = 0.22). We found that 29% of asthma patients (n = 39) had high e-DNA concentrations above the upper 95th percentile value in healthy controls (55.6 ng /μl). High-DNA was associated with broad lung function impairments including: airflow obstruction of the large (FEV 1 ) and small airways (FEF50%, FEF25-75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values < 0.05). We also found that high e-DNA was associated with nearly three-fold greater risk of severe exacerbations (OR 2·93 [95% CI 1.2-7.5]; p = 0·012), worse asthma control test (p = 0.03), worse asthma control questionnaire scores (p = 0.01) and higher doses of inhaled corticosteroids (p = 0.026)., Conclusion: Increased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.

Background: Multiple breath washout (MBW) became a valuable research tool assessing ventilation heterogeneity. However, routine clinical application still faces several challenges. Deriving MBW parameters from three technically acceptable measurements according to current recommendations prolongs test times. We therefore aimed to evaluate reporting only duplicate measurements in healthy adults and pulmonary disease., Methods: One hundred and fifty-three subjects prospectively underwent conventional lung function testing and closed-circuit SF 6 -MBW. Three technically acceptable MBW-measurements were obtained in 103 subjects., Results: Lung clearance index (LCI) differed significantly among 19 controls (7.4 ± 0.8), 19 patients with sarcoidosis (8.1 ± 1.2), 32 with bronchial asthma (9.2 ± 1.9) and 33 with COPD (10.8 ± 2.2, p < 0.001). Within-test repeatability was high (coefficient of variation between 2.5% in controls and 3.6% in COPD) and remained unchanged when only including the first two measurements. Likewise, LCI remained stable with mean absolute changes ranging from 0.9 ± 0.8% in controls to 1.5 ± 0.9% in COPD (p = 0.1). Mean test time reduction differed significantly between groups reaching 200 s in COPD (p = 0.01)., Conclusions: Duplicate SF 6 -MBW-measurements are sufficient in adult patients with pulmonary disease and healthy controls. LCI values and intra-test repeatability are not affected reducing total test time statistically significant. Our findings have the potential to further facilitate application of MBW in research and clinical routine., Trial Registration: NCT03176745 , June 2, 2017 retrospectively registered.