Summary
Background
Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous
studies on PAL in asthma have included relatively small populations, mostly restricted
to severe asthma, or have no included longitudinal data. The aim of this post-hoc
analysis was to investigate the determinants, clinical implications, and outcome of
PAL in patients with asthma who were included in the ATLANTIS study.
Methods
In this post-hoc analysis of the ATLANTIS study, we assessed the prevalence, clinical
characteristics, and implications of PAL across the full range of asthma severity.
The study population included patients aged 18–65 years who had been diagnosed with
asthma at least 6 months before inclusion. We defined PAL as a post-bronchodilator
FEV1/forced vital capacity (FVC) of less than the lower limit of normal at recruitment.
Asthma severity was defined according to the Global Initiative for Asthma. We used
Mann-Whitney U test, t test, or χ2 test to analyse differences in baseline characteristics between patients with and
without PAL. Logistic regression was used for multivariable analysis of the associations
between PAL and baseline data. Cox regression was used to analyse risk of exacerbation
in relation to PAL, and a linear mixed-effects model was used to analyse change in
FEV1 over time in patients with versus patients without PAL. Results were validated in
the U-BIOPRED cohort.
Findings
Between June 30, 2014 and March 3, 2017, 773 patients were enrolled in the ATLANTIS
study of whom 760 (98%) had post-bronchodilator FEV1/FVC data available. Of the included patients with available data, mean age was 44
years (SD 13), 441 (58%) of 760 were women, 578 (76%) were never-smokers, and 248
(33%) had PAL. PAL was not only present in patients with severe asthma, but also in
21 (16%) of 133 patients with GINA step 1 and 24 (29%) of 83 patients with GINA step
2. PAL was independently associated with older age at baseline (46 years in PAL group
vs 43 years in non-PAL group), longer duration of asthma (24 years vs 12 years), male sex (51% vs 38%), higher blood eosinophil counts (median 0·27 × 109 cells per L vs 0·20 × 109 cells per L), more small airway dysfunction, and more exacerbations during 1 year
of follow-up. Associations between PAL, age, and eosinophilic inflammation were validated
in the U-BIOPRED cohort, whereas associations with sex, duration of asthma, and risk
of exacerbations were not validated.
Interpretation
PAL is not only present in severe disease, but also in a considerable proportion of
patients with milder disease. In patients with mild asthma, PAL is associated with
eosinophilic inflammation and a higher risk of exacerbations. Our findings are important
because they suggest that increasing treatment intensity should be considered in patients
with milder asthma and PAL.
Funding
Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (by
means of the public–private partnership programme).
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Article Info
Publication History
Published: July 27, 2022
Identification
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© 2022 Elsevier Ltd. All rights reserved.
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Access this article on ScienceDirectLinked Articles
- Correction to Lancet Respir Med 2022; published online July 27. https://doi.org/10.1016/S2213-2600(22)00185-0
- Kole TM, Vanden Berghe, Kraft M, et al. Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study. Lancet Respir Med 2022; published online July 27. https://doi.org/10.1016/S2213-2600(22)00185-0—In this Article, Klaus F Rabe's affiliation should have been “LungenClinic Grosshansdorf, Airway Research Center North in the German Center for Lung Research, Grosshansdorf, Germany”. This correction has been made to the online version as of Oct 21, 2022, and will be made to the printed version.
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