Comorbidities and burden of COPD: a population based case-control study

Abstract

COPD is associated with a relevant burden of disease and a high mortality worldwide. Only recently, the importance of comorbidities of COPD has been recognized. Studies postulated an association with inflammatory conditions potentially sharing pathogenic pathways and worsening overall prognosis. More evidence is required to estimate the role of comorbidities of COPD. Our aim was to investigate the prevalence and clustering of comorbidities associated with COPD, and to estimate their impact on clinically relevant outcomes. In this population-based case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2010 (n = 12'888'075) was analyzed using MySQL and R statistical software. Statistical methods included non-parametric hypothesis testing by means of Fisher's exact test and Wilcoxon rank sum test, as well as linear models with generalized estimating equation to account for intra-patient variability. Exploratory multivariate approaches were also used for the identification of clusters of comorbidities in COPD patients. In 2.6% (6.3% in patients aged >70 years) of all hospitalization cases an active diagnosis of COPD was recorded. In 21% of these cases, COPD was the main reason for hospitalization. Patients with a diagnosis of COPD had more comorbidities (7 [IQR 4-9] vs. 3 [IQR 1-6]; [Formula: see text]), were more frequently rehospitalized (annual hospitalization rate 0.33 [IQR 0.20-0.67] vs. 0.25 [IQR 0.14-0.43]/year; [Formula: see text]), had a longer hospital stay (9 [IQR 4-15] vs. 5 [IQR 2-11] days; [Formula: see text]), and had higher in-hospital mortality (5.9% [95% CI 5.8%-5.9%] vs. 3.4% [95% CI 3.3%-3.5%]; [Formula: see text]) compared to matched controls. A set of comorbidities was associated with worse outcome. We could identify COPD-related clusters of COPD-comorbidities.

Figure 1. Age, gender and seasonal distribution of COPD hospitalizations.

The left panel displays the age distribution stratified by gender of patients with COPD diagnosis. The right panels show the seasonal effect in the hospitalization of acute COPD patients (COPD as main diagnosis), over the 2002–2010 period (upper right panel), and further summarized over monthly fluctuations (lower right panel).

Figure 2. Principal component analysis biplot of comorbidities associated with COPD.

Hospitalization cases (PCA scores) are represented on the first 2 principal component axes using smoothed blue colored density. Comorbidities coded according to ICD-10 are depicted by framed labels (PCA loadings). Comorbidities lying in the same directions are correlated with each other. The further away from the center of the plot, the stronger is the influence of comorbidities. External explanatory variables (including age, gender, length-of-hospital stay [LOS], in-hospital death [Death], hospitalization rate, number of comorbidities and Charlson’s comorbidity score) were fitted to the PCA and displayed in the upper right box using vectors representations (red arrows). The number displayed on the upper left corner indicates the size of the grid.

Figure 3. Discrimination between emphysema, bronchitis and asthma-associated COPD patients based on comorbidities using between-group principal component analysis (axes 1–2).

Hospitalization cases are displayed in the first 2 axes of the between-group PCA (smoothed blue colored density). The ellipsoids summarize the dispersion of the 3 COPD subtypes in the factorial map. Comorbidities are coded according to ICD-10 codes and depicted by framed labels. The number displayed on the upper left corner indicates the size of the grid.