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


METHODS
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.
Donaldson
Gavin C
GC
Academic Unit of Respiratory Medicine, St. Bartholomew's and Royal London Hospital School of Medicine and Dentistry, London, UK.
Seemungal
Terence A R
TA
Patel
Irem S
IS
Bhowmik
Angshu
A
Wilkinson
Tom M A
TM
Hurst
John R
JR
Maccallum
Peter K
PK
Wedzicha
Jadwiga A
JA
D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D018579:Patient Selection; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology*; D012129:Respiratory Function Tests; D013183:Sputum / Q000276:immunology
D015415:Biomarkers; D015850:Interleukin-6