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.
- Abdo, M.
- Trinkmann, F.
- Kirsten, A. M.
- Biller, H.
- Pedersen, F.
- Waschki, B.
- Von Mutius, E.
- Kopp, M.
- Hansen, G.
- Rabe, K. F.
- Bahmer, T.
- Watz, H.
Keywords
- air trapping
- nocturnal asthma
- small airway dysfunction
- ventilation heterogeneity
- 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.
