Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Background

Persistent airflow limitation (PAL) occurs in a subset of patients with asthma. Previous studies of PAL in asthma have included relatively small populations, mostly limited to severe asthma, or have not included longitudinal data. The objective of this post-hoc analysis was to investigate the determinants, clinical implications and outcomes of PAL in asthmatic patients 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 spectrum of asthma severity. The study population included patients aged 18 to 65 who had been diagnosed with asthma at least 6 months before inclusion. We defined PAL as post-bronchodilator FEV11/forced vital capacity (FVC) below the lower limit of normal at recruitment. Asthma severity was defined according to the Global Initiative for Asthma. We used the Mann-Whitney U test, you test, or χ2 test to analyze differences in baseline characteristics between patients with and without PAL. Logistic regression was used for multivariate analysis of associations between PAL and baseline data. Cox regression was used to analyze exacerbation risk relative to PAL, and a linear mixed-effects model was used to analyze change in FEV11 over time in patients with compared to patients without PAL. The results were validated in the U-BIOPRED cohort.

Results

Between June 30, 2014 and March 3, 2017, 773 patients were included in the ATLANTIS study, of whom 760 (98%) had a post-bronchodilator FEV11/FVC data available. Among the patients included with available data, the mean age was 44 years (SD 13), 441 (58%) of 760 were women, 578 (76%) had never smoked and 248 (33%) had a PAL. ALP was not only present in patients with severe asthma, but also in 21 (16%) of 133 patients with GINA stage 1 and 24 (29%) of 83 patients with GINA stage 2. PAL was independently associated with older age at baseline (46 years in the PAL group
versus 43 years in the non PAL group), longer duration of asthma (24 years versus 12 years old), male (51% versus 38%), higher blood eosinophil count (median 0 27 × 109 cells per L versus 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 have been validated in the U-BIOPRED cohort, whereas associations with gender, duration of asthma and risk of exacerbations have not been 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, ALP is associated with eosinophilic inflammation and a higher risk of exacerbations. Our results are important because they suggest that increasing treatment intensity should be considered in patients with mild asthma and ALP.

Funding

Chiesi Farmaceutici and Dutch Ministry of Economic Affairs and Climate Policy (through the public-private partnership program).

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