Survival in COPD: impact of lung dysfunction and comorbidities

Abstract

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. Recent studies investigated the impact of comorbidities on the survival in COPD, but most of them lacked a referent group of comorbidity-matched, nonobstructed individuals.We examined the 10-year mortality in a sample of 200 COPD patients and 201 nonobstructed controls. They were part of a larger cohort enrolled in a European case-control study aimed at assessing genetic susceptibility to COPD. By design, the COPD group included patients with a forced expiratory volume in 1 second (FEV1) ≤70% predicted. Cases and controls were matched on age, sex, and cumulative smoking history, and shared a nearly identical prevalence of cardiovascular and metabolic disorders. We estimated the hazard of death with Cox regression and percentiles of survival with Laplace regression. COPD was the main exposure variable of interest. Five comorbidities (hypertension, coronary artery disease, prior myocardial infarction, chronic heart failure, and diabetes) were included as covariates in multiple regression models.The all-cause mortality rate was significantly higher in cases than in controls (43% vs 16%, P < 0.001). The unadjusted hazard of death for COPD was 3-fold higher than the referent category (P < 0.001), and remained nearly unchanged after introducing the 5 comorbidities in multiple regression. Patients with COPD had significantly shorter survival percentiles than comorbidity-matched controls (P < 0.001). Notably, 15% of the nonobstructed controls died by 10.3 years into the study; the same proportion of COPD patients had died some 6 years earlier, at 4.6 years.In a separate analysis, we split the whole sample into 2 groups based on the lower tertile of FEV1 and carbon monoxide lung diffusing capacity (DLCO). The hazard of death for COPD patients with low FEV1 and DLCO was nearly 3.5-fold higher than in all the others (P < 0.001), and decreased only slightly after introducing age and chronic heart failure as relevant covariates.COPD is a strong predictor of reduced survival independently of coexisting cardiovascular and metabolic disorders. Efforts should be made to identify patients at risk and to ensure adherence to prescribed therapeutic regimens.

FIGURE 1

Number of coexisting comorbid conditions (hypertension, coronary artery disease, prior myocardial infarction, chronic heart failure, and diabetes mellitus) in 200 COPD patients and 201 nonobstructed controls. Differences between groups are not statistically significant (P > 0.10).

FIGURE 2

Causes of death in 200 COPD patients and 201 nonobstructed controls. Other cardiovascular (CV) deaths are: stroke (N = 8), irreversible cardiac arrhythmia (N = 4), intestinal infarction (N = 3), pulmonary embolism (N = 1), rupture of cardiac aneurysm (N = 1), and death during heart transplantation (N = 1). “Others” include: hemorrhagic shock (N = 3) and multiorgan failure (N = 2). With the exception of respiratory failure, differences between groups are not statistically significant (P > 0.05).

FIGURE 3

Kaplan–Meier survivor curves in 200 COPD patients (red step curve) and 201 nonobstructed controls (blue step curve). Shaded areas indicate 95% confidence intervals. P < 0.001 by log-rank test.

FIGURE 4

Laplace regression estimates of the 5th, 10th, and 15th survival percentiles in COPD patients against nonobstructed controls. For each percentile, survival is significantly shorter in cases than in controls (P < 0.001).

FIGURE 5

Laplace regression estimates of the 5th, 10th, and 15th survival percentiles in the whole study sample split in 2 groups based on the lower tertile of FEV₁ and DL_CO. For each percentile, survival is significantly shorter among patients in lower tertile of FEV₁ and DL_CO than in all the others (P < 0.001). DL_CO = lung diffusing capacity for carbon monoxide, FEV₁ = forced expiratory volume in 1 second.