Airway and systemic inflammation and decline in lung function in patients with COPD

Abstract

Study objectives: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.

Patients and design: A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).

Results: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/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 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/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 FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.

Conclusions: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.

Figure 1

Mean stable (exacerbation-free) sputum IL-6, sputum neutrophil count, and plasma fibrinogen measured over 4-month periods, over the 7.3-year period of this study, from October 1995. Bars are 2 × SE. Lines are from a simple linear regression through these data.

Figure 2

Mean FEV₁%Pred in 4-month periods for low plasma fibrinogen and sputum IL-6 group patients (circles and thin line) and for high plasma fibrinogen and sputum IL-6 group patients (squares and thick line) against time from recruitment of each patient. Bars are 2 × SE. Error bars increase in size with time, as not all patients participated in the study for 7.33 years. No adjustment has been made for covariates.

Figure 3

Mean plasma fibrinogen levels over 4-month intervals in infrequent (circles and thin-line exacerbators (< 2.52/yr) and frequent (box and thick line) exacerbators (≥ 2.52/yr), against time from recruitment of each patient. Bars are 2 × SE. Error bars increase in size with time, as not all patients participated in the study for 7.33 years. These data are unadjusted for the presence of an exacerbation.