TY - JOUR T1 - Mechanistical differences of chronic lung allograft dysfunction phenotypes in lung transplantation JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - 1857 AU - Monika I. Suwara AU - Bart M. Vanaudenaerde AU - Stijn E. Verleden AU - Lee A. Borthwick AU - Robin Vos AU - Nicola J. Green AU - Chris Ward AU - Dirk E. Van Raemdonck AU - Paul A. Corris AU - Derek A. Mann AU - Geert M. Verleden AU - Andrew J. Fisher Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/1857.abstract N2 - Purpose: The neomacrolide azithromycin, is now widely used in the treatment of Bronchiolitis Oblierans Syndrome after lung transplantation. However, only a proportion of patients respond by improving their lung function. This study aimed to evaluate differences in airway microenvironment between azithromycin responsive (>10% improvement in FEV1) and azithromycin resistant BOS patients.Methods: Bronchoalveolar lavage (BAL) from recipients identified as stable n=10 (control), azithromycin responsive n=10 and azithromycin resistant n=10 were evaluated for cell differential, IL-1α, IL-1β, IL-6, IL-8, TNF-α proteins. BAL was then added to primary bronchial epithelial cells (PBEC) and tested for viability by XTT assay.Results: BAL neutrophilia (%) was increased in responders (56% p<0.0001) and non-responders (52.9% p<0.0001) compared to the control (0.8%). IL-1α, IL-1β, IL-6, IL-8, TNF-α were increased in both groups (all proteins <0.05) compared to the control. The levels of IL-1α, IL-1b and TNFa showed increasing trend in responders compared to non-responders. PBEC viability in response to BAL was reduced in non-responders (p=0.012) but not in the responders group (p=0.64). Moreover, there was a negative correlation between PBEC viability and IL-1α (p=0.042), IL-8 (p=0.0017), TNFα (p=0.039), IL-1β (p=0.045) and IL-6 (p=0.0453) concentrations.Conclusions: Unlike in responders, where azithromycin blocks IL-17 T cell mediated neutrophilia, azithromycin resistant phenotype is associated with epithelial damage, inducing IL-1α, TNFα and IL-1β release. This suggests anti-IL-1/TNFα therapies could be considered for BOS patients who develop an azithromycin resistant phenotype. ER -