The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms.

Small airway dysfunction (SAD) is a frequent feature of asthma that has been linked to disease severity and poor symptom control. However, little is known about the role of SAD in nocturnal asthma. To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing. We assessed the frequency of self-reported nocturnal symptoms through the asthma control test. We studied the impact of nocturnal asthma using the Asthma Quality of Life Questionnaire (AQLQ) and the Multidimensional Fatigue Inventory (MFI-20). We assessed the lung function using spirometry, body plethysmography, impulse oscillometry, single and multiple inert gas washout and measured markers of T2-inflammation (blood and sputum eosinophils; fractional exhaled nitric oxide (FeNo)). We stratified the patients according to the presence and frequency of nocturnal asthma. A total of 166 asthma patients were enrolled in the analysis. Eighty-seven patients (52%) reported to have nocturnal symptoms at least once in the last four weeks. The odds ratio of nocturnal asthma correlated with the severity of all non-spirometric measures of SAD, yet neither with airflow obstruction (FEV1 and FEV/FVC) nor with large airway resistance (R20). Patients with frequent nocturnal asthma (n = 29) had a numerical increase of T2 markers and more severe SAD, as indicated by all non-spirometric measures of SAD (all p-values < 0.05), worse overall asthma control, increased fatigue and reduced quality of life (all p-values < 0.01) compared to patients with infrequent nocturnal asthma (n = 58) or patients without nocturnal asthma (n = 79). We identified 63 patients without airflow obstruction, nearly 43% of them (n = 27) had nocturnal asthma. In this subgroup, only markers of air trapping and ventilation heterogeneity were significantly elevated and correlated with the frequency of nocturnal symptoms: LCI (Spearman's coefficient = -0.42, p < 0.001), RV% (-0.32, p = 0.02). SAD is closely associated to asthma with nocturnal symptoms. Spirometry might underestimate the broad spectrum of distal lung function impairments in this population of patients.

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© 2021 Abdo et al.

Déclaration de conflit d'intérêts

Mustafa Abdo reports no conflict of interest. Frederik Trinkmann received travel support from Actelion, Berlin Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma and TEVA as well as speaker or consultation fees from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Novartis and Roche, Sanofi aventis, all outside the submitted work. Anne-Marie Kirsten, Heike biller and Frauke Pedersen report no conflict of interest. Erika von Mutius reports personal fees from Pharmaventures, personal fees from OM Pharma S. A., personal fees from Springer-Verlag GmbH, personal fees from Elsevier GmbH and Elsevier Ltd., personal fees from Peptinnovate Ltd., personal fees from Turun Yliopisto, personal fees from Tampereen Yliopisto, personal fees from Helsingin Yliopisto, personal fees from European Respiratory Society, personal fees from Deutsche Pharmazeutische Gesellschaft e. V., personal fees from Massachusetts Medical Society, personal fees from Chinese University of Hongkong, personal fees from European Commission, personal fees from Böhringer Ingelheim International GmbH, personal fees from Universiteit Utrecht, Faculteit Diergeneeskunde, personal fees from Universität Salzburg, personal fees from Georg Thieme Verlag, personal fees from Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI), outside the submitted work; In addition, Dr. von Mutius has a patent LU101064 - Barn dust extract for the prevention and treatment of diseases pending, a patent EP2361632: Specific environmental bacteria for the protection from and/or the treatment of allergic, chronic inflammatory and/or autoimmune disorders with royalties paid to ProtectImmun GmbH, a patent EP 1411977: Composition containing bacterial antigens used for the prophylaxis and the treatment of allergic diseases licensed to ProtectImmun GmbH, a patent number EP1637147: Stable dust extract for allergy protection licensed to ProtectImmun GmbH, and a patent EP 1964570: Pharmaceutical compound to protect against allergies and inflammatory diseases licensed to ProtectImmun GmbH. Matthias V. Kopp, Gesine Hansen, Benjamin Waschki, Klaus F. Rabe and Henrik Watz reports no relevant conflict of interest. Thomas Bahmer reports grants from BMBF: Unrestricted research grant for the German Center for Lung Research (DZL), during the conduct of the study; personal fees from AstraZeneca, personal fees from GlaxoSmithKline, personal fees from Novartis, and personal fees from Roche, outside the submitted work. The authors report no other conflicts of interest in this work.