Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity.

Background: Patients with chronic obstructive pulmonary disease (COPD) have raised serum levels of C reactive protein (CRP). This may be related directly to COPD and its associated systemic inflammation or secondary to other factors such as concomitant ischaemic heart disease (IHD) or smoking status. The aim of this study was to evaluate IHD and smoking as potential causes of raised CRP levels in COPD and to test the association between inhaled corticosteroid (ICS) use and serum CRP levels. Methods: Cross sectional analyses comparing cohorts of 88 patients with COPD, 33 smokers (S), and 38 non-smoker (NS) controls were performed. Clinical assessments included a complete medical history, pulmonary function, 6 minute walk test (6MWT), cardiopulmonary exercise test, and high sensitivity serum CRP measurements. Results: Serum CRP levels were significantly higher in patients with COPD (5.03 (1.51) mg/l) than in controls (adjusted odds ratio 9.51; 95% confidence interval 2.97 to 30.45) but were similar in the two control groups (S: 2.02 (1.04) mg/l; NS: 2.24 (1.04) mg/l). There was no clinical or exercise evidence of unstable IHD in any of the subjects. CRP levels were lower in COPD patients treated with ICS than in those not treated (3.7 (3.0) mg/l v 6.3 (3.6) mg/l); this association was confirmed in an adjusted regression model (p<0.05). Conclusion: CRP levels are raised in COPD patients without clinically relevant IHD and independent of cigarette smoking, and reduced in patients with COPD using ICS. CRP may be a systemic marker of the inflammatory process that occurs in patients with COPD.

Chronic obstructive pulmonary disease (COPD) exacerbations are associated with increased airway and systemic inflammation, though relationships between exacerbation recovery, recurrent exacerbation and inflammation have not been previously reported. In the present study, inflammatory changes at COPD exacerbations were related to clinical nonrecovery and recurrent exacerbations within 50 days.Serum interleukin (IL)-6, C-reactive protein (CRP), sputum IL-6 and IL-8 were measured in 73 COPD patients when stable, at exacerbation and at 7, 14 and 35 days post-exacerbation.In 23% of patients, symptoms did not recover to baseline by day 35. These patients had persistently higher levels of serum CRP during the recovery period. A total of 22% of the patients who had recurrent exacerbations within 50 days had significantly higher levels of serum CRP at day 14, compared with those without recurrences: 8.8 mg·L⁻¹versus3.4 mg·L⁻¹. Frequent exacerbators had a smaller reduction in systemic inflammation between exacerbation onset and day 35 compared with infrequent exacerbators.Nonrecovery of symptoms at chronic obstructive pulmonary disease exacerbation is associated with persistently heightened systemic inflammation. The time course of systemic inflammation following exacerbation is different between frequent and infrequent exacerbators. A high serum C-reactive protein concentration 14 days after an index exacerbation may be used as a predictor of recurrent exacerbations within 50 days.

Rationale: Depression is prevalent in patients with chronic obstructive pulmonary disease (COPD); however, its etiology and relationship to the clinical features of COPD are not well understood. Objectives: Using data from a large cohort, we explored prevalence and determinants of depression in subjects with COPD. Methods: The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study is an observational 3-year multicenter study that enrolled smokers with and without COPD and nonsmoker controls. At baseline, several patient-reported outcomes were measured including the Center for Epidemiologic Studies of Depression Scale. For the purposes of this analysis, depression was defined as a score of 16 and higher on this scale, which reflects a high load of depressive symptoms and has a good correspondence with a clinical diagnosis of major depression. Measurements and Main Results: The study cohort consisted of 2,118 subjects with COPD; 335 smokers without COPD (smokers); and 243 nonsmokers without COPD (nonsmokers). A total of 26%, 12%, and 7% of COPD, smokers, and nonsmokers, respectively, suffered from depression. In subjects with COPD, higher depression prevalence was seen in females, current smokers, and those with severe disease (Global Initiative for Obstructive Lung Disease [GOLD]-defined). Multivariate modeling of depression determinants in subjects with COPD revealed that increased fatigue, higher St. George's Respiratory Questionnaire for COPD patients score, younger age, female sex, history of cardiovascular disease, and current smoking status were all significantly associated with depression; physiologic and biologic measures were weak or nonsignificant descriptors. Conclusions: Depression is more prevalent in subjects with COPD compared with smokers and nonsmokers without COPD. Clinical and biologic measures were less important determinants of depression in COPD than disease symptoms and quality-of-life. Clinical trial registered with www.clinicaltrials.gov (NCT 00292552).