Rationale: Patients with chronic obstructive pulmonary disease (COPD) have an ongoing systemic inflammation, which can be assessed by measuring serum C-reactive protein (CRP). Objective: To determine whether increased serum CRP in individuals with airway obstruction predicts future hospitalization and death from COPD. Methods: We performed a cohort study with a median of 8-yr follow-up of 1,302 individuals with airway obstruction selected from the ongoing Copenhagen City Heart Study. Measurements and Main Results: We measured serum CRP at baseline, and recorded COPD admissions and deaths as outcomes. During follow-up, 185 (14%) individuals were hospitalized due to COPD and 83 (6%) died of COPD. Incidences of COPD hospitalization and COPD death were increased in individuals with baseline CRP > 3 mg/L versus ⩽ 3 mg/L (log rank: p < 0.001). After adjusting for sex, age, FEV₁% predicted, tobacco consumption, and ischemic heart disease, the hazard ratios for hospitalization and death due to COPD were increased at 1.4 (95% confidence interval, 1.0–2.0) and 2.2 (1.2–3.9) in individuals with baseline CRP > 3 mg/L versus ⩽ 3 mg/L. After close matching for FEV₁% predicted and adjusting for potential confounders, baseline CRP was, on average, increased by 1.2 mg/L (analysis of variance: p = 0.002) and 4.1 mg/L (p = 0.001) in those who were subsequently hospitalized or died of COPD, respectively. The absolute 10-yr risks for COPD hospitalization and death in individuals with CRP above 3 mg/L were 54 and 57%, respectively, among those older than 70 yr with a tobacco consumption above 15 g/d and an FEV₁% predicted of less than 50. Conclusions: CRP is a strong and independent predictor of future COPD outcomes in individuals with airway obstruction.

Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease (COPD) are of major importance because of their profound and long-lasting adverse effects on patients.^1,2 Frequent episodes accelerate loss of lung function,³ affect the quality of life of the patients,^4,5 and are associated with poor survival.^6-8 In general, exacerbations become more frequent with increasing disease severity, but the single best 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.⁹ However, when predicting risk of future exacerbations based on previous events, the positive predictive value remains low,⁹ indicating that additional determinants of exacerbation susceptibility remain to be identified.

Rationale: The new Global Initiative for Obstructive Lung Disease (GOLD) stratification of chronic obstructive pulmonary disease (COPD) into categories A, B, C, and D is based on symptoms, level of lung function, and history of exacerbations. Objectives: To investigate the abilities of this stratification to predict the clinical course of COPD. Methods: Two similar population studies were performed in an area of Copenhagen including 6,628 individuals with COPD. Measurements and Main Results: The patients were monitored for an average period of 4.3 years regarding COPD exacerbations, hospital admissions, and mortality. The percentages of individuals experiencing a COPD exacerbation during the first year of observation were 2.2% in group A, 5.8% in group B, 25.1% in group C, and 28.6% in group D. One- and 3-year mortality rates were 0.6 and 3.8%, respectively, in group A, 3.0 and 10.6% in group B, 0.7 and 8.2% in group C, and 3.4 and 20.1% in group D. Groups B and D, characterized by a higher degree of dyspnea than groups A and C, had five to eight times higher mortality from cardiovascular disease and cancer than did groups A and C. Conclusions: The new stratification performs well by identifying individuals at risk of exacerbations. Surprisingly, subgroup B, characterized by more severe dyspnea, had significantly poorer survival than group C, in spite of a higher FEV₁ level. This subgroup warrants special attention, as the poor prognosis could be caused by cardiovascular disease or cancer, requiring additional assessment and treatment.

Rationale: Low body mass index (BMI) is a marker of poor prognosis in chronic obstructive pulmonary disease (COPD). In the general population, the harmful effect of low BMI is due to the deleterious effects of a low fat-free mass index (FFMI; fat-free mass/weight²). Objectives: We explored distribution of low FFMI and its association with prognosis in a population-based cohort of patients with COPD. Methods: We used data on 1,898 patients with COPD identified in a population-based epidemiologic study in Copenhagen. FFM was measured using bioelectrical impedance analysis. Patients were followed up for a mean of 7 yr and the association between BMI and FFMI and mortality was examined taking age, sex, smoking, and lung function into account. Main Results: The mean FFMI was 16.0 kg/m² for women and 18.7 kg/m² for men. Among subjects with normal BMI, 26.1% had an FFMI lower than the lowest 10th percentile of the general population. BMI and FFMI were significant predictors of mortality, independent of relevant covariates. Being in the lowest 10th percentile of the general population for FFMI was associated with a hazard ratio of 1.5 (95% confidence interval, 1.2–1.8) for overall mortality and 2.4 (1.4–4.0) for COPD-related mortality. FFMI was also a predictor of overall mortality when analyses were restricted to subjects with normal BMI. Conclusions: FFMI provides information in addition to BMI and assessment of FFM should be considered in the routine assessment of COPD.

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 with COPD from two large Danish population studies and during a 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, and recorded 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 > 3 mg/L, fibrinogen > 14 μmol/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) for myocardial 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) for pneumonia. There were no consistent differences 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 fourfold increased risk of major comorbidities in COPD. These biomarkers may be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.

Many human epidemiologic studies demonstrate that maternal asthma confers greater risk of asthma to offspring than does paternal disease. However, a handful have shown the opposite. Given this disparity, a meta-analysis is necessary to determine the veracity and magnitude of the “maternal effect.” We screened the medical literature from 1966 to 2009 and performed a meta-analysis to compare the effect of maternal asthma vs. paternal asthma on offspring asthma susceptibility. Aggregating data from 33 studies, the odds ratio for asthma in children of asthmatic mothers compared with non-asthmatic mothers was significantly increased at 3.04 (95% confidence interval: 2.59–3.56). The corresponding odds ratio for asthma in children of asthmatic fathers was increased at 2.44 (2.14–2.79). When comparing the odds ratios, maternal asthma conferred greater risk of disease than did paternal asthma (3.04 vs. 2.44, p = 0.037). When analyzing the studies in which asthma was diagnosed by a physician the odds ratios were attenuated and no significant differences were observed (2.85 vs. 2.48, N = 18, p = 0.37). Similarly, no significant differences were observed between maternal and paternal odds ratios when analyzing the studies in which the patient population was 5 years or older (3.15 vs. 2.60, p = 0.14). However, in all cases the trend remained the same, that maternal asthma was a greater risk factor for asthma than paternal. The results show that maternal asthma increases offspring disease risk to a greater extent than paternal disease.