Transitions to and reversion from a persistent frequent exacerbator state in COPD

Background Preventing acute exacerbations in COPD (AECOPD) is key in striving for disease stability. To investigate the differential impact of risk factors across AECOPD phenotypes, we identified baseline health determinants and comorbidities associated with transitions from non-exacerbator (NE) to persistent frequent-exacerbator (FE) and reversion. Methods Patients ≥45 years with ≥3 months treatment for obstructive airway diseases or hospital-labelled COPD without (concomitant) asthma were identified in Belgian nationwide data between January 2017-February 2018. Factors associated with disease worsening (transitioning from NE to persistent FE), reversion (from FE to stable NE) or transition to death were investigated using multinomial logistic regression. Results Among 183 762 patients (mean age 68.6 years, 48.0% female), 11.5% (21 072) never experienced AECOPDs and 11.6% (21 375) exacerbated frequently in each of three consecutive years. Among 56 933 NE at baseline (31.0%), 4.1% transitioned to persistent FE, whereas among 80 502 FE (43.8%), 7.3% reversed to stable NE. Transitions from NE towards persistent FE were associated with having lung cancer (aOR: 3.67, 95%CI 2.33–5.78), being an ever smoker (aOR: 2.09, 95% CI 1.94–2.43) or having neuropsychiatric or musculoskeletal comorbidity. Overuse of short-acting bronchodilators (aOR: 0.57, 95%CI 0.46–0.49), ever smoking or having overuse of maintenance therapy were factors most strongly associated with lower odds of reversion. Cardiovascular comorbidities were significantly associated with increased mortality odds, but not with disease worsening. Conclusions The results of this cohort study support addressing smoking and inhaler overuse to promote reversion to stable NE while managing lung cancer and neuropsychiatric or musculoskeletal comorbidities to reduce worsening.