Abstract
BackgroundNon-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation.MethodsTh17 pathway cytokines were quantified in bronchoalveolar lavage fluid (BALF), and gene expression of IL-17A, IL-1β, IL-8 and IL-23 determined from endobronchial biopsies (EBx) in 41 stable bronchiectasis subjects and 20 healthy controls. Relationships between IL-17A levels and infection status, important clinical measures and subsequent Pseudomonas aeruginosa infection were determined.ResultsBALF levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p<0.0001) and IL-23 (9.48 (4.79, 15.75) vs. 0.70 (0.43, 1.79), 95% CI 4.68 to 11.21, p<0.0001). However, BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection. Furthermore, gene expression of IL-17A in bronchiectasis EBx did not differ from control. In contrast, gene expression (relative to medians of controls) in bronchiectasis EBx was significantly higher than control for IL1β (4.12 (1.24, 8.05) vs 1 (0.13, 2.95), 95% CI 0.05 to 4.07, p = 0.04) and IL-8 (3.75 (1.64, 11.27) vs 1 (0.54, 3.89), 95% CI 0.32 to 4.87, p = 0.02) and BALF IL-8 and IL-1α levels showed significant relationships with clinical measures and airway microbiology. P. aeruginosa infection was associated with increased levels of IL-8 while Haemophilus influenzae was associated with increased IL-1α.Conclusions and Clinical RelevanceEstablished adult non-CF bronchiectasis is characterised by luminal Th17 pathway activation, however this pathway may be relatively less important than activation of non-antigen-specific innate neutrophilic immunity.
Highlights
Bronchiectasis is a condition characterised by permanent bronchial dilatation which can result from a myriad of underlying aetiologies, most cases are idiopathic [1]
bronchoalveolar lavage fluid (BALF) levels of all Th17 cytokines (median (IQR) pg/mL) were significantly higher in bronchiectasis than control subjects, including IL-17A (1.73 (1.19, 3.23) vs. 0.27 (0.24, 0.35), 95% CI 1.05 to 2.21, p
BALF IL-17A levels were not associated with clinical measures or airway microbiology, nor predictive of subsequent P. aeruginosa infection
Summary
Bronchiectasis is a condition characterised by permanent bronchial dilatation which can result from a myriad of underlying aetiologies, most cases are idiopathic [1]. Recent data suggest that the co-existence of bronchiectasis in COPD subjects is independently associated with a more than doubling in the risk of death [4]. Airway inflammation in bronchiectasis is characterised by neutrophil-dominated inflammation associated with elevated levels of proinflammatory cytokines and chemokines such as IL-8, IL-6 and TNF-α in bronchoalveolar lavage fluid (BALF)[5]. The major product of Th17 cells, IL-17A, stimulates local cytokine (eg IL-1β, TNF-α and IL-6) and chemokine (eg CXCL1, CXCL2, CXCL5 and CXCL8/IL-8) secretion by other cells, inducing neutrophil recruitment and activation [9]. Non-cystic fibrosis (CF) bronchiectasis is characterised by chronic airway infection and neutrophilic inflammation, which we hypothesised would be associated with Th17 pathway activation
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