Prognosis of Patients with COPD Not Eligible for Major Clinical Trials

Rationale: Randomised controlled trials only include a subset of patients with chronic obstructive pulmonary disease(COPD) fulfilling strict inclusion criteria. Thus, most patients with COPD in a real-world setting do not have the necessary evidence to support treatment effectiveness. Objective: To test the hypotheses that most individuals with COPD in the general population are not represented in major clinical trials despite clinically significant disease with exacerbations and early death. Methods: In 105,630 adults from a Danish contemporary population-based cohort, we defined COPD as age≥40 years, chronic respiratory symptoms, history of smoking exposure, and airflow limitation with forced expiratory volume in 1 second(FEV1)/forced vital capacity(FVC)<0.70. Outcomes included acute exacerbations and all-cause mortality. Symptomatic smokers without COPD were used as a reference group. Measurements and Main Results: Of all, 7,516(7%) and 16,079(15%) were symptomatic smokers with and without COPD. Only 44% of those with COPD were eligible for major clinical trials when applying FEV1<80% predicted, smoking history≥10 pack-years, and no comorbid asthma as common inclusion criteria. During median 8.9 years follow-up, we observed 2,130 acute exacerbations and 3,973 deaths in symptomatic smokers. Compared to symptomatic smokers without COPD, multivariable adjusted hazard ratios(HRs) for exacerbations were 7.45(95% confidence interval:5.41-10.3) and 29.0(21.1-39.8) in those with COPD respectively excluded and eligible for clinical trials. Corresponding HRs for all-cause mortality were 1.21(1.11-1.31) and 1.67(1.54-1.81), respectively. Conclusion: More than half of individuals with COPD in the general population are excluded from major clinical trials; however, these individuals have clinically significant disease with exacerbations and early death compared to symptomatic smokers without COPD.