Azithromycin and the Treatment of Lymphocytic Airway Inflammation After Lung Transplantation

• Published in: American journal of transplantation Vol. 14; no. 12; pp. 2736 - 2748
• Main Authors: Vos, R., Verleden, S. E., Ruttens, D., Vandermeulen, E., Bellon, H., Neyrinck, A., Van Raemdonck, D. E., Yserbyt, J., Dupont, L. J., Verbeken, E. K., Moelants, E., Mortier, A., Proost, P., Schols, D., Cox, B., Verleden, G. M., Vanaudenaerde, B. M.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.12.2014; Wiley Subscription Services, Inc
• Subjects: acute; Adolescent; Adult; Anti-Bacterial Agents - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Azithromycin - therapeutic use; Biological and medical sciences; Bronchitis - drug therapy; Bronchitis - etiology; Bronchoalveolar Lavage; bronchoalveolar lavage (BAL); C-Reactive Protein; Clinical research; Cytokines - metabolism; dysfunction; Female; Follow-Up Studies; Graft Rejection - drug therapy; Graft Rejection - etiology; Graft Survival; Humans; immune regulation; immunobiology; immunosuppressant; Inflammation; lung (allograft) function; Lung Diseases - complications; Lung Diseases - surgery; lung transplantation; Lung Transplantation - adverse effects; Lymphocytes - drug effects; Lymphocytes - pathology; Male; Medical sciences; Middle Aged; other; Pharmacology. Drug treatments; Pneumonia - drug therapy; Pneumonia - etiology; Postoperative Complications; practice; Prognosis; Prospective Studies; Proteins; pulmonology; rejection; Respiratory Function Tests; Retrospective Studies; science; Spirometry; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; translational research; Transplantation, Homologous; Transplants & implants; Young Adult; Lung; Azithromycin; Inflammation; Transplantation; Homotransplantation; Respiratory system; Macrolide; Respiratory tract; Antibiotic; Treatment; Surgery; Graft; Protein synthesis inhibitor; Antibacterial agent; Lymphocyte; acute; lung (allograft) function; other; practice; Clinical research; immunobiology; immunosuppressant; pulmonology; immune regulation; rejection; dysfunction; science; lung transplantation; translational research; bronchoalveolar lavage (BAL)
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.12942

Lymphocytic airway inflammation is a major risk factor for chronic lung allograft dysfunction, for which there is no established treatment. We investigated whether azithromycin could control lymphocytic airway inflammation and improve allograft function. Fifteen lung transplant recipients demonstrating acute allograft dysfunction due to isolated lymphocytic airway inflammation were prospectively treated with azithromycin for at least 6 months (NCT01109160). Spirometry (FVC, FEV1, FEF25–75, Tiffeneau index) and FeNO were assessed before and up to 12 months after initiation of azithromycin. Radiologic features, local inflammation assessed on airway biopsy (rejection score, IL‐17+ cells/mm2 lamina propria) and broncho‐alveolar lavage fluid (total and differential cell counts, chemokine and cytokine levels); as well as systemic C‐reactive protein levels were compared between baseline and after 3 months of treatment. Airflow improved and FeNO decreased to baseline levels after 1 month of azithromycin and were sustained thereafter. After 3 months of treatment, radiologic abnormalities, submucosal cellular inflammation, lavage protein levels of IL‐1β, IL‐8/CXCL‐8, IP‐10/CXCL‐10, RANTES/CCL5, MIP1‐α/CCL3, MIP‐1β/CCL4, Eotaxin, PDGF‐BB, total cell count, neutrophils and eosinophils, as well as plasma C‐reactive protein levels all significantly decreased compared to baseline (p < 0.05). Administration of azithromycin was associated with suppression of posttransplant lymphocytic airway inflammation and clinical improvement in lung allograft function. This prospective, interventional, open‐label study demonstrates that treatment with azithromycin is effective in controlling posttransplant lymphocytic airway inflammation as it attenuates underlying IL‐17+ T cell–mediated airway inflammation, ameliorates lung allograft function, and improves associated radiologic abnormalities. See editorial by Glanville on page 2681.