BAL neutrophilia in azithromycin-treated lung transplant recipients: Clinical significance

作者：Vandermeulen Elly; Verleden Stijn E; Ruttens David; Moelants Eva; Mortier Anneleen; Somers Jana; Bellon Hannelore; Piloni Davide; Dupont Lieven J; Van Raemdonck Dirk E; Proost Paul; Schols Dominique; Vos Robin; Verleden Geert M; Vanaudenaerde Bart M^*

来源：Transplant Immunology, 2015, 33(1): 37-44.

DOI：10.1016/j.trim.2015.07.001

• Lung transplantation
• Chronic lung allograft dysfunction
• Azithromycin therapy
• BAL neutrophilia

Background: Azithromycin decreases airway neutrophilia and can prevent chronic lung allograft dysCLAD) after lung transplantation (LTx). It also can be used to treat lymphocytic bronchiolitis, as it decreases the submucosal infiltrating IL-17 positive lymphocytes. Some patients, while receiving azithromycin, (re)develop increased airway neutrophilia, which we hypothesize to result in worse outcome and to be regulated by an IL-17-independent mechanism.
Methods: LTx recipients, transplanted between 2001 and 2012, were investigated and categorized in a study group of patients with increased broncho-alveolar lavage (BAL) neutrophilia (>= 15%) and a matched control group with low BAL neutrophilia (<15%), both groups while already being on azithromycin treatment. CLAD-free and overall survival were compared between groups. Cell differentials and 33 proteins in BAL were analyzed to identify underlying mechanisms.
Results: The study group (n = 72) demonstrated a significantly lower CLAD-free (p = 0.015) and overall survival (p = 0.041) compared to the control group (n = 37). Absolute BAL neutrophils and eosinophils were increased in the study group, which was paralleled by elevated inflammatory cytokines (IL-1 beta/IL-1Ra, IL-4 and IL-6) and chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL3/MIP-1 alpha, CCL4/MIP-1 beta, CCL11/eotaxin) concentrations compared to the control group (all p < 0.05).
Conclusion: Patients with elevated airway neutrophilia despite azithromycin, experience worse CLAD-free and overall survival. In these patients, IL-1 beta might play a central role giving rise to neutrophils, eosinophils, macrophages and B-cells. This provides an opportunity to further investigate the modulation of this pathway.

• 出版日期2015-9
• 单位河北医科大学