Stable inflammatory phenotype in smokers and smokers with COPD
Rationale: COPD is a chronic inflammatory disease. It appears, that a single parameter or the cellular composition within the airways alone is not sufficient to characterize the degree of airway inflammation. Aim: Definition of a robust inflammatory phenotype using multiple sputum markers with a better reproducibility as compared to sputum neutrophils alone. Methods: 24 COPD patients (GOLD II) and 23 age and gender matched healthy controls were included (current smokers with 10 pack-years). Blood, bronchial biopsies, bronchoalveolar lavage (BAL), and induced sputum were collected on two occasions within 6 weeks. Cell composition and a broad panel of proteins were analyzed. Results: The top 4 most reproducible (r>0.7) sputum inflammatory markers (A1AT, IL6, MMP7, HSA) and the percentage of sputum neutrophils (r=0.52) were combined to define the inflammatory phenotype (IP) independently for both visits. The IP showed a better reproducibility (r=0.70; p<0.001) between visits as compared to the percentage of sputum neutrophils and correlated significantly with BAL (r=0.55, p<0.001) but not with serum calprotectin levels (r=0.25). Correlations with other serum markers were weak, being best for WBC count (r=0.5, p=0.002). No relationship to biopsy neutrophils was found. Conclusion: Using a combination of neutrophil cell counts and fluid phase inflammatory mediators we defined an inflammatory phenotype that was shown to be reproducible and more robust than sputum neutrophils alone. The approach to use a combination of inflammatory markers could be helpful in studies that try to relate persistent airway inflammation to exacerbation rates, to long term changes in disease severity and prognosis, especially in the field of COPD research and for ongoing large cohort trials.