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Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD^*

^* From the Academic Unit of Respiratory Medicine (Drs. Donaldson, Seemungal, Patel, Bhowmik, Wilkinson, Hurst, and Wedzicha), Institute of Preventive Medicine (Dr. MacCallum), St. Bartholomew’s and the Royal London Hospital School of Medicine and Dentistry, London, UK.

Correspondence to: Jadwiga A. Wedzicha, MD, Academic Unit of Respiratory Medicine, Dominion House, St. Bartholomew’s Hospital, London, EC1A 7BE, UK; e-mail: j.a.wedzicha{at}qmul.ac.uk

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 10⁶ cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations ( 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.

Key Words: airway • COPD • inflammatory markers • systemic

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