Which inflammatory markers in the bronchial mucosa of asthma patients are associated with decline of lung function during 14 years of prospective follow-up?To address this question, 19 mild-to-moderate, atopic asthmatic patients underwent spirometry and bronchoscopy at baseline and after 14 years of follow-up (t=14). Baseline bronchial biopsies were analysed for reticular layer thickness, eosinophil cationic protein (EG2), mast cell tryptase (AA1), CD3, CD4 and CD8. Follow-up biopsies were stained for EG2, AA1, neutrophil elastase, CD3, CD4, CD8, CD20, granzyme B, CD68, DC-SIGN, Ki67 and mucins.Decline in forced expiratory volume in 1 s (FEV1) % predicted was highest in patients with high CD8 (p=0.01, both pre- and post-bronchodilator) or high CD4 counts at baseline (p=0.04 pre-bronchodilator, p=0.03 post-bronchodilator). Patients with high CD8, CD3 or granzyme B counts at t=14 also exhibited faster decline in FEV1 (p=0.00 CD8 pre-bronchodilator, p=0.04 CD8 post-bronchodilator, p=0.01 granzyme B pre-bronchodilator, and p<0.01 CD3 pre-bronchodilator).Long-term lung function decline in asthma is associated with elevation of bronchial CD8 and CD4 at baseline, and CD8, CD3 and granzyme B at follow-up. This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes.
Copyright ©ERS 2016.