Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality

Abstract

Background: The long-term natural history of chronic obstructive pulmonary disease (COPD) in terms of successive severe exacerbations and mortality is unknown.

Methods: The authors formed an inception cohort of patients from their first ever hospitalisation for COPD during 1990-2005, using the healthcare databases from the province of Quebec, Canada. Patients were followed until death or 31 March 2007, and all COPD hospitalisations occurring during follow-up were identified. The hazard functions of successive hospitalised COPD exacerbations and all-cause mortality over time were estimated, and HRs adjusted for age, sex, calendar time and comorbidity.

Results: The cohort included 73 106 patients hospitalised for the first time for COPD, of whom 50 580 died during the 17-year follow-up, with 50% and 75% mortality at 3.6 and 7.7 years respectively. The median time from the first to the second hospitalised exacerbation was around 5 years and decreased to <4 months from the 9th to the 10th. The risk of the subsequent severe exacerbation was increased threefold after the second severe exacerbation and 24-fold after the 10th, relative to the first. Mortality after a severe exacerbation peaked to 40 deaths per 10 000 per day in the first week after admission, dropping gradually to 5 after 3 months.

Conclusions: The course of COPD involves a rapid decline in health status after the second severe exacerbation and high mortality in the weeks following every severe exacerbation. Two strategic targets for COPD management should include delaying the second severe exacerbation and improving treatment of severe exacerbations to reduce their excessive early mortality.

Figure 1

Flowchart of cohort formation. COPD, chronic obstructive pulmonary disease.

Figure 2

Kaplan–Meier survival function for the cohort of 73 106 patients from the time of their first ever hospitalisation for a chronic obstructive pulmonary disease exacerbation over the 17-year follow-up period.

Figure 3

Hazard function of successive hospitalised chronic obstructive pulmonary disease (COPD) exacerbations (per 10 000 per day) for the cohort of 73 106 patients from the time of their first ever hospitalisation for a COPD exacerbation over the follow-up period, with the time between successive exacerbations estimated using: (A) the median inter-exacerbation times, conditional on survival with death as a competing risk; and (B) the median inter-exacerbation times as time to the next exacerbation or death, whichever occurs first.

Figure 4

Hazard function of a subsequent hospitalised chronic obstructive pulmonary disease exacerbation (per 10 000 per day) in the 1-year period after discharge from the previous one.

Figure 5

Daily rates of death (per 10 000 per day) in the 90-day period after onset of severe chronic obstructive pulmonary disease exacerbation.