Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease

Rationale: Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities. Objectives: To test the hypothesis that elevated levels of three inflammatory biomarkers are associated with increased risk of comorbidities in COPD. Methods:We examined 8,656 patients withCOPDfrom two large Danish population studies andduringa median 5 years' follow-up recorded hospital admissions due to major comorbidities as endpoints. Measurements and Main Results: We measured baseline C-reactive protein (CRP), fibrinogen,and leukocyte count,andrecorded admissions due to ischemic heart disease, myocardial infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary embolism, hip fracture, and depression for all participants. Multifactorially adjusted risk of ischemic heart disease was increased by a factor of 2.19 (95% confidence interval, 1.48-3.23) in individuals with three biomarkers elevated (CRP > 3mg/L, fibrinogen > 14 mmol/L, and leukocyte count > 9×10⁹/L) versus individuals with all three biomarkers at or below these limits. Corresponding hazard ratios were 2.32 (1.34-4.04) formyocardial infarction, 2.63 (1.71-4.04) for heart failure, 3.54 (2.03-6.19) for diabetes, 4.00 (2.12-7.54) for lung cancer, and 2.71 (2.03-3.63) forpneumonia.Therewerenoconsistentdifferences in risk of pulmonary embolism, hip fracture, or depression as a function of these three biomarkers. Conclusions: Simultaneously elevated levels of CRP, fibrinogen, and leukocyte count are associated with a two-to four fold increased risk of major comorbidities in COPD. These biomarkersmay be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.