The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms

Mustafa Abdo; Frederik Trinkmann; Anne-Marie Kirsten; Heike Biller; Frauke Pedersen; Benjamin Waschki; Erika Von Mutius; Matthias Kopp; Gesine Hansen; Klaus F Rabe; Thomas Bahmer; Henrik Watz; ALLIANCE study group

doi:10.2147/JAA.S313572

The Relevance of Small Airway Dysfunction in Asthma with Nocturnal Symptoms

J Asthma Allergy. 2021 Jul 13:14:897-905. doi: 10.2147/JAA.S313572. eCollection 2021.

Authors

Mustafa Abdo¹, Frederik Trinkmann^{2

3}, Anne-Marie Kirsten⁴, Heike Biller¹, Frauke Pedersen^{1

4}, Benjamin Waschki¹, Erika Von Mutius⁵, Matthias Kopp^{6

7}, Gesine Hansen⁸, Klaus F Rabe¹, Thomas Bahmer^#^{1

9}, Henrik Watz^#⁴; ALLIANCE study group

Affiliations

¹ LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
² 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.
³ Department of Biomedical Informatics, Heinrich-Lanz-Center, University Medical Center Mannheim, Heidelberg University, Heidelberg, Germany.
⁴ Pulmonary Research Institute at the LungenClinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Grosshansdorf, Germany.
⁵ 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, Both Munich, Germany.
⁶ Department of Pediatric Respiratory Medicine, Inselspital, University Children's Hospital of Bern, University of Bern, Bern, Switzerland.
⁷ 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 University Hospital Schleswig-Holstein-Campus Kiel, department for Internal Medicine I, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Kiel, Germany.

^# Contributed equally.

Abstract

Rationale: 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.

Objective: To study the association between the severity of SAD and frequency of nocturnal symptoms compared to conventional lung function testing.

Methods: 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.

Results: 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).

Conclusion: 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.

Keywords: air trapping; nocturnal asthma; small airway dysfunction; ventilation heterogeneity.

Grants and funding

The ALLIANCE infrastructure is provided by the participating sites of the German Centre for Lung Research (DZL) and associated study centers and hospitals. Direct costs of the ALLIANCE Cohort are being paid by project grants from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF), grant number “82DZL001A4“.