The Long-term Burden of COPD Exacerbations during Maintenance Therapy and Lung Function Decline

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
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Introduction: Early identification of preventable risk factors of COPD progression is important. Whether exacerbations have a negative impact on disease progression is largely unknown. We investigated whether the long-term occurrence of exacerbations is associated with lung function decline at early stages of COPD.
Methods: Patients diagnosed with mild/moderate COPD (obstruction and FEV1% predicted 50– 90%), aged ≥ 35 years, and a smoking history, who had ≥ 6 years of UK electronic medical records after initiation of maintenance therapy were studied. Multilevel mixed-effect linear regression was performed to determine the association between the count of any year in which the patient had ≥ 1 exacerbation over a 6-year period and FEV1 decline, adjusted for sex, age, anthropometrics and smoking habits. Exacerbations were defined as any prescription for an acute oral corticosteroid course and/or lower respiratory-related antibiotics and/or any COPD-related emergency or inpatient hospitalization.
Results: Of 11,337 patients included (mean age 65 years; 49% female) 31.6%, 23.3%, 16.6%, 11.6%, 8.1%, 5.3% and 3.4% had 0, 1, 2, 3, 4, 5 and 6 years with ≥ 1 exacerbation. The mean annual FEV1 decline accelerated by 1.50 mL/year (95% Confidence Interval 1.02; 1.98) with every additional year with ≥ 1 exacerbation from 31.0 mL/year in subjects without any exacerbation to 40.0 mL/year in patients experiencing ≥ 1 exacerbation every year. Patients with more years with ≥ 1 exacerbation had a lower mean FEV1 at first diagnosis: 14.7 mL (11.7; 17.8) lower with every additional year with exacerbations. When counting years with ≥ 2 exacerbations, greater effects were observed (2.19 [1.50; 2.88]  mL/year excess decline per year with ≥ 2 exacerbations; 16.5 mL [12.1; 20.8] lower FEV1 at diagnosis).
Conclusion: Patients who experienced a greater exacerbation burden after initiation of maintenance therapy had worse lung function at diagnosis and a more rapid lung function decline thereafter, which emphasizes the need for better treatment strategies.
Original languageEnglish
Pages (from-to)1909-1918
Number of pages10
JournalInternational journal of chronic obstructive pulmonary disease
Publication statusPublished - 6 Aug 2020

Bibliographical note

Data Sharing Statement
The dataset supporting the conclusions of this article was derived from the Clinical Practice Research Datalink ( and the Optimum Patient Care Research Database ( The CPRD has broad National Research Ethics Service Committee (NRES) ethics approval for purely observational research using the primary care data and established data linkages. The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymized research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymized Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD, and the Independent Scientific Advisory Committee (ISAC) for the CPRD. The authors do not have permission to give public access to the study dataset; researchers may request access to CPRD or OPCRD data for their own purposes.
Access to CPRD can be made via the CPRD website ( or via the inquiries email Access to OCPRD can be made via the OCPRD website ( or via the inquiries email

This study is funded by AstraZeneca. AstraZeneca participated in the study design and reporting.


  • COPD
  • Exacerbations
  • Spirometry
  • Inhalation Therapy
  • Observational Study
  • inhalation therapy
  • spirometry
  • exacerbations
  • observational study
  • Observational study
  • Inhalation therapy


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