Association between COPD exacerbations and lung function decline during maintenance therapy

Marjan Kerkhof, Jaco Voorham, Paul Dorinsky, Claudia Cabrera, Patrick Darken, Janwillem WH Kocks, Mohsen Sadatsafavi, Don D. Sin, Victoria Carter, David B. Price* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
6 Downloads (Pure)


Background: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. Methods: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-­ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms.ResultsL Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1mL/ year (6.6 to 23.6) to 4.3mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. Conclusion: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.
Original languageEnglish
Pages (from-to)744-753
Number of pages10
Issue number9
Early online date12 Jun 2020
Publication statusPublished - 30 Sep 2020


  • COPD exacerbations
  • COPD pharmacology
  • eosinophil biology
  • lung physiology


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