Delineating excess comorbidities in idiopathic pulmonary fibrosis: an observational study

Abstract

Background: Our study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD.

Methods: IPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status.

Results: Across 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001). In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43-1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10-1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02-1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09-1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7-10 years prior to IPF diagnosis.

Interpretation: The mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.

Keywords: Chronic obstructive pulmonary disease; Comorbidities; Idiopathic pulmonary fibrosis.

Fig. 1

Graphs demonstrating the cumulative incidence of each of the fifteen selected prevalent comorbidities in patients with idiopathic pulmonary fibrosis (IPF; blue) or chronic obstructive pulmonary disease (COPD; red) matched for age, gender and smoking history, or control subjects (green) matched for age, gender and pack-year smoking history. The x-axis indicates years prior to IPF or COPD diagnosis or equivalent age in matched controls

Fig. 2

Multivariable Cox regression analyses displayed in a Forest Plot showing hazard ratios, 95% confidence intervals and p-values for the 15 most common comorbidities in IPF patients (n = 3885). IPF subjects are compared with COPD patients (n = 3885) and matched controls (n = 3885), with all models adjusted for patient age, gender and smoking status. IPF = idiopathic pulmonary fibrosis; COPD = chronic obstructive pulmonary disease

Fig. 3

Kaplan Meier curves comparing survival in each of the three matched groups (IPF, COPD, Matched Controls) with increasing numbers of comorbidities. IPF = idiopathic pulmonary fibrosis; COPD = chronic obstructive pulmonary disease

Fig. 4

Numbers of subjects in each of the three matched groups (IPF, COPD, Matched Controls) with multiple comorbidities. IPF = idiopathic pulmonary fibrosis; COPD = chronic obstructive pulmonary disease