Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV 1 . There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV 1 .A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1–4.8). At recruitment, median age was 68.5 years (IQR, 62.5–73.6) and FEV 1 as percentage of predicted (FEV 1 %Pred) was 38.5% (IQR, 27.7–50.3).During the study, the patients experienced 1389 exacerbations, a median of 2.52/yr (IQR, 1.48–3.96) and FEV 1 declined by 40.2mL/yr or as FEV 1 %Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9pg/mL/yr, sputum neutrophil count rose by 1.64×10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10g/L/yr (all P<0.05). Patients with frequent exacerbations (> or=2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063g/L/yr (P=0.046, n=130) and 29.5pg/mL/yr (P<0.001, n=98), respectively, compared to patients with infrequent exacerbations (<2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV 1 %Pred decline of 0.42%/yr (P=0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV 1 %Pred decline of 0.97%/yr (P=0.001) and 0.40%/yr (P=0.014), respectively.In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.