Mustafa Abdo1, Frauke Pedersen2, Anne-Marie Kirsten3, Vera Veith4, Heike Biller4, Frederik Trinkmann5, Erika von Mutius6, Matthias Kopp7, Gesine Hansen8, Klaus F Rabe4, Thomas Bahmer9, Henrik Watz3. 1. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. Electronic address: m.abdo@lungenclinic.de. 2. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; Pulmonary Research Institute at the LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. 3. Pulmonary Research Institute at the LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. 4. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany. 5. Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany; Department of Biomedical Informatics, Center for Preventive Medicine and Digital Health Baden-Württemberg (CPD-BW), University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany. 6. Dr von Hauner Children's Hospital, Ludwig Maximilians University of Munich, Comprehensive Pneumology Center Munich, German Center for Lung Research (DZL), and Institute of Asthma and Allergy Prevention, Helmholtz Centre, Munich, Germany. 7. Department of Pediatric Respiratory Medicine, Inselspital, University Children's Hospital of Bern, University of Bern, Bern, Switzerland; Division of Pediatric Pneumology & Allergology, University Hospital Schleswig-Holstein-Campus Luebeck, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Luebeck, Germany. 8. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover, Germany. 9. LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany; Department for Internal Medicine I, University Hospital Schleswig-Holstein-Campus Kiel, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Kiel, Germany.
Abstract
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.
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.
Authors: Mustafa Abdo; Frauke Pedersen; Frederik Trinkmann; Felix J F Herth; Klaus F Rabe; Anne-Marie Kirsten; Henrik Watz Journal: Int J Chron Obstruct Pulmon Dis Date: 2022-06-17