Persistent Airflow Limitation in Asthma: Clinical Characteristics, Risk Factors, and Long−term Outcomes from a Multicenter Cohort Study

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Background: Persistent airflow limitation (PAL) is an increasingly recognized asthma phenotype, but its prevalence, determinants, and prognostic significance in real-world settings remain unclear. This study evaluated the clinical characteristics and long-term outcomes associated with PAL and its severity in asthma. Methods: Multicenter analysis of combined retrospective and prospective cohorts in South Korea. PAL was defined as post-bronchodilator FEV 1 /FVC < 0.70; severity was graded by STaging of Airflow obstruction by Ratio classification (STAR stage). Outcomes included subsequent exacerbations and longitudinal lung function change. Results: Among 849 patients with asthma, 640 (75.4%) had PAL. PAL was associated with older age, male sex, lower body mass index, higher smoking intensity, lower FEV 1 , history of tuberculosis, and less frequent allergic rhinitis. Optimal predictors of PAL were FEV 1 ≤ 83.7% predicted, age ≥ 63.5 years, and smoking intensity ≥ 9.5 pack-years. During follow-up, severe exacerbations occurred more frequently in the PAL group (13.0% vs 5.7%) with a 1.8-fold higher incidence (IRR 1.77, 95% CI 1.13– 2.79). Risk increased with PAL severity, particularly at STAR stage 4 vs stage 0 (aHR 3.32, 95% CI 1.60– 6.89). Longitudinally, annual FEV 1 decline was slower in PAL than in non-PAL (− 28.1 vs − 42.5 mL/year, P = 0.028), but within PAL, STAR stage 4 showed relatively faster declines in both FEV 1 and FVC. Conclusion: PAL and its severity independently predict the risk of severe exacerbations and progressive lung function decline in asthma, underscoring PAL as a key marker of disease progression and a potential target for early intervention. Keywords: asthma, persistent airflow limitation, exacerbation, lung function

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