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Risk of Exacerbations in COPD Associated with Inflammatory Biomarkers
Patients with chronic obstructive pulmonary disease (COPD) who experience exacerbations of respiratory symptoms may have lasting adverse effects. Frequent episodes of COPD exacerbations may accelerate loss of lung function, affect quality of life, and are associated with poor survival.
Exacerbations become more frequent as the disease progresses; however, according to researchers, the most reliable predictor of exacerbations in all grades of COPD is a previous exacerbation, suggesting the existence of a phenotype susceptible to exacerbations independent of degree of airflow limitation. However, the researchers noted, the positive predictive value of basing estimates of future exacerbations on previous events is low, suggesting that “additional determinants of exacerbation susceptibility remain to be identified.”
The researchers recently conducted a study to test the hypothesis that elevated levels of inflammatory biomarkers in patients with stable COPD are associated with an increased risk of experiencing exacerbations. They reported study results in JAMA [2012;309(22):2352-2361].
The prospective cohort study examined 61,650 patients with spirometry measurements from the Copenhagen City Heart Study (2001-2003) and the Copenhagen General Population Study (2003-2008) to identify 6574 patients who had COPD (defined as a ratio between forced expiratory volume in 1 second FEV1 and forced vital capacity <0.7).
Patients’ levels of C-reactive protein (CRP) and fibrinogen and leukocyte count were measured when the patient was not experiencing symptoms of exacerbations (baseline measurement). Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or hospital admission for COPD. Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L, 14mµmol/L, and 9×109/L, respectively.
Among the 6574 participants in the study cohort, 3083 exacerbations were recorded during a median of 4 years of follow-up. In the year prior to examination, 4% (n=244) of the study participants had ³1 exacerbations; 1% (n=85) had their most recent exacerbation within 2 months of the date of examination.
During year 1 of follow-up, 129 participants had frequent exacerbations, defined as ³2, and the number of participants with frequent exacerbations increased stepwise according to groups of inflammatory biomarkers. The numbers of events per 1000 person-years were 17 for those with 1 high biomarker, 32 for those with 2 high biomarkers, and 81 for those with 3 high biomarkers; participants with no elevated biomarkers experienced 9 events per 1000 person-years.
There was a stepwise increase in the absolute 1-, 3-, and 5-year risk of frequent exacerbations, from none through 3 high inflammatory biomarkers, in all strata for Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades A-D, history of frequent exacerbations, and GOLD grades 1-4. The highest 5-year absolute risks of frequent exacerbations in those with 3 high biomarkers (compared with those with no high biomarkers) were 62% (vs 24%) for those with GOLD grades C-D (n=558), 98% (vs 64%) in those with a history of frequent exacerbations (n=127), and 52% (vs 15%) for those with GOLD grades 3-4 (n=465).
In summary, the researchers stated, “Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations, even in those with milder COPD and in those without previous exacerbations. Further investigation is needed to determine the clinical value of these biomarkers for risk stratification.”
