Assessment of airway inflammation using sputum, BAL, and endobronchial biopsies in current and ex-smokers with established COPD.

RATIONALE: Smoking effects on physiological and gross pathology in chronic obstructive pulmonary disease (COPD) are relatively well described. However, there is little known in COPD about the detailed interrelationships between lung function and inflammatory profiles in different airway compartments from the same individual and whether airway inflammation in these different compartments differs in ex- and current smokers with established COPD. OBJECTIVES: We compared sputum, bronchoalveolar (BAL), and airway wall inflammatory profiles in current versus ex-smokers and related this to smoking intensity and lung function in 17 current and 17 ex-smokers with mild to moderate COPD. RESULTS: Current smokers had more sputum mast cells (% differential and absolute numbers), whereas ex-smokers had increased sputum neutrophils. In BAL, there was a significant increase in eosinophils in current smokers, but ex-smokers had significantly increased neutrophils, lymphocytes, and epithelial cells. There were no cell profile differences observed in airway biopsies between current and ex-smokers and there were no correlations between the individual inflammatory cell populations in any of the airway compartments. In current smokers only, smoking intensity was negatively correlated with lung function, and associated with a reduction in overall cellularity of both sputum and BAL. CONCLUSION: Airway inflammation persists in ex-smokers with COPD, but differs from COPD current smokers. The impact of smoking appears to vary in different airway compartments and any direct relationships between cellularity and lung function tended to be negative, ie, worse lung function indicated the presence of fewer cells.

Bronchodilator reversibility, airway eosinophilia and anti-inflammatory effects of inhaled fluticasone in COPD are not related.

BACKGROUND AND OBJECTIVE: Bronchodilator reversibility (BDR) is common in smoking-related COPD, but the airway pathology underlying this has not been described. In particular, it is not known whether BDR is associated with underlying airway eosinophilia and whether BDR is predictive of a better response to inhaled corticosteroid (ICS) treatment. METHODS: A double-blind, placebo-controlled, randomized 2:1 study of fluticasone propionate (FP), 500 microg twice daily versus placebo over 6 months was performed in subjects with mild to moderate COPD. Subjects with a clinical history of asthma were excluded, but not on BDR criteria alone. Induced sputum, BAL and endobronchial biopsies (EBB) were performed in 36 subjects at baseline, and 30 of these provided a second full set of samples (FP, n = 19; placebo, n = 11). RESULTS: Baseline BDR was not related to airway eosinophilia and did not predict response to ICS. Post-bronchodilator FEV(1) increased in the FP group compared with the placebo group (P = 0.05), and there were within-treatment group reductions in total symptom scores with FP (P < 0.05). Compared with placebo, FP reduced macrophage numbers but increased neutrophil numbers in EBB (P = 0.01 and P = 0.003, respectively). BAL neutrophil and epithelial cell numbers were also reduced with FP (P = 0.03 for both). There were within-treatment group reductions in the numbers of EBB mast cells and CD8+ve lymphocytes with FP (P = 0.007). CONCLUSIONS: BDR was not related to any particular inflammatory phenotype or any clinical or anti-inflammatory response to ICS in these subjects with mild to moderate COPD.