Worsening COPD Exacerbations Tied to Future Exacerbations and Mortality Risk

Pavankumar Kamat


March 23, 2022


  • In patients with chronic obstructive pulmonary disease (COPD), increasing frequency and severity of exacerbations were linked to a higher risk of future exacerbations and all-cause and COPD-related mortality.

  • Even a single moderate exacerbation significantly increased the risk of future exacerbations.

Why This Matters

  • Few studies have evaluated the effect of moderate or severe COPD exacerbations alone, their cumulative effect in triggering further exacerbations, and the incremental burden associated with an increasing number of exacerbation events.

Study Design

  • The EXAcerbations of COPD and their OutcomeS (EXACOS) study included 340,515 patients with COPD (age, >40 years), identified from the Clinical Practice Research Datalink (CPRD) Aurum UK, and Hospital Episode Statistics data.

  • Patients were classified into 7 groups based on their baseline exacerbation frequency and severity:

    • no exacerbation (n=181,176);

    • 1 moderate exacerbation (n=68,038);

    • 2 moderate exacerbations (n=31,825);

    • 3+ moderate exacerbations (n=33,780);

    • 1 severe exacerbation (n=19,194);

    • 2 severe exacerbations (n=4,094); and

    • 3+ severe exacerbations (n=2,408).

  • Funding: AstraZeneca.

Key Results

  • Increasing frequency and severity of COPD exacerbations were associated with a higher risk of future exacerbations (incidence rate ratio; 95% CI):

    • 1 moderate exacerbation (1.70; 1.66 to 1.74);

    • 2 moderate exacerbations (2.31; 2.24 to 2.37);

    • 3+ moderate exacerbations (3.52; 3.43 to 3.62);

    • 1 severe exacerbation (2.53; 2.44 to 2.63);

    • 2 severe exacerbations (3.00; 2.79 to 3.22); and

    • 3+ severe exacerbations (4.08; 3.75 to 4.43).

  • Patients with a higher frequency and severity of baseline COPD exacerbations had a higher risk of all-cause and COPD-related mortality, but the risk of CVD-related mortality was less pronounced in these patients.


  • Observational design.

Whittaker H, Rubino A, Müllerová H, Morris T, Varghese P, Xu Y, De Nigris E, Quint JK. Frequency and Severity of Exacerbations of COPD Associated with Future Risk of Exacerbations and Mortality: A UK Routine Health Care Data Study. Int J Chron Obstruct Pulmon Dis. 2022 Mar 3;17:427-437. doi: 10.2147/COPD.S346591. PMID: 35264849 View Full Text.


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