Abstract
Bronchiolitis obliterans syndrome (BOS) is an important complication after hematopoietic SCT (HSCT). Recent observations suggested that azithromycin might improve lung function in BOS after HSCT. We conducted a randomized double-blinded placebo-controlled study on azithromycin in patients with BOS after HSCT. The treatment group (n=10) received oral azithromycin 250 mg daily while the control group (n=12) received placebo daily for 12 weeks. Respiratory symptoms were assessed by the St George Respiratory Questionnaires and spirometry at baseline (drug commencement), 1, 2, 3 (drug cessation) and 4 months (1 month after drug cessation). There was no significant difference in the baseline demographic characteristics between the treatment and the control groups in age, gender, time from HSCT to BOS, time since diagnosis of BOS, chronic GVHD, baseline respiratory symptom scores and baseline forced expiratory volume in 1 s (FEV1). Throughout and after 3 months of treatment, there were no significant changes in respiratory symptom scores and FEV1 measurements between the treatment and the control groups. In conclusion, there was no significant benefit of 3 months of oral azithromycin on the respiratory symptoms and lung function in patients with relatively late BOS after HSCT in this randomized placebo-controlled study.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Soubani AO, Uberti JP . Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J 2007; 29: 1007–1019.
Dudek AZ, Mahaseth H . Hematopoietic stem cell transplant-related airflow obstruction. Curr Opin Oncol 2006; 18: 115–119.
Watkins TR, Chien JW, Crawford SW . Graft versus host-associated pulmonary disease and other idiopathic pulmonary complications after hematopoietic stem cell transplant. Semin Respir Crit Care Med 2005; 26: 482–489.
Williams KM, Chien JW, Gladwin MT, Pavletic SZ . Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009; 302: 306–314.
Verleden GM, Dupont LJ, Van Raemdonck DE . Is it bronchiolitis obliterans syndrome or is it chronic rejection: a reappraisal? Eur Respir J 2005; 25: 221–224.
Grossman EJ, Shilling RA . Bronchiolitis obliterans in lung transplantation: the good, the bad, and the future. Transl Res 2009; 153: 153–165.
Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 2002; 21: 297–310.
Hopkins PM, Aboyoun CL, Chhajed PN, Malouf MA, Plit ML, Rainer SP et al. Association of minimal rejection in lung transplant recipients with obliterative bronchiolitis. Am J Respir Crit Care Med 2004; 170: 1022–1026.
Crawford SW, Clark JG . Bronchiolitis associated with bone marrow transplantation. Clin Chest Med 1993; 14: 741–749.
Fietta AM, Meloni F . Lung transplantation: the role of azithromycin in the management of patients with bronchiolitis obliterans syndrome. Curr Med Chem 2008; 15: 716–723.
Shitrit D, Bendayan D, Gidon S, Saute M, Bakal I, Kramer MR . Long-term azithromycin use for treatment of bronchiolitis obliterans syndrome in lung transplant recipients. J Heart Lung Transplant 2005; 24: 1440–1443.
Yates B, Murphy DM, Forrest IA, Ward C, Rutherford RM, Fisher AJ et al. Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2005; 172: 772–775.
Gerhardt SG, McDyer JF, Girgis RE, Conte JV, Yang SC, Orens JB . Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Am J Respir Crit Care Med 2003; 168: 121–125.
Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T . Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2008; 85: 36–41.
Porhownik NR, Batobara W, Kepron W, Unruh HW, Bshouty Z . Effect of maintenance azithromycin on established bronchiolitis obliterans syndrome in lung transplant patients. Can Respir J 2008; 15: 199–202.
Khalid M, Al Saghir A, Saleemi S, Al Dammas S, Zeitouni M, Al Mobeireek A et al. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study. Eur Respir J 2005; 25: 490–493.
Maimon N, Lipton JH, Chan CK, Marras TK . Macrolides in the treatment of bronchiolitis obliterans in allograft recipients. Bone Marrow Transplant 2009; 44: 69–73.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.
Ip MS, Ko FW, Lau AC, Yu WC, Tang KS, Choo K et al. Updated spirometric reference values for adult Chinese in Hong Kong and implications on clinical utilization. Chest 2006; 129: 384–392.
Chan SL, Chan-Yeung MM, Ooi GC, Lam CL, Cheung TF, Lam WK et al. Validation of the Hong Kong Chinese version of the St. George Respiratory Questionnaire in patients with bronchiectasis. Chest 2002; 122: 2030–2037.
Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.
Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE . Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2006; 174: 566–570.
Schultz MJ . Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. J Antimicrob Chemother 2004; 54: 21–28.
Verleden GM, Dupont LJ . Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2004; 77: 1465–1467.
Santo Tomas LH, Loberiza Jr FR, Klein JP, Layde PM, Lipchik RJ, Rizzo JD et al. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest 2005; 128: 153–161.
O′Brien KD, Hackman RC, Sale GE, Prentice R, Deeg J, Thomas ED et al. Lymphocytic bronchitis unrelated to acute graft-versus-host disease in canine marrow graft recipients. Transplantation 1984; 37: 233–238.
Taylor PM, Rose ML, Yacoub MH . Expression of MHC antigens in normal human lungs and transplanted lungs with obliterative bronchiolitis. Transplantation 1989; 48: 506–510.
Hodge G, Hodge S, Chambers D, Reynolds PN, Holmes M . Bronchiolitis obliterans syndrome is associated with absence of suppression of peripheral blood Th1 proinflammatory cytokines. Transplantation 2009; 88: 211–218.
Acknowledgements
This study and the drug used in this study were sponsored by Pfizer Pharmaceuticals.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Lam, D., Lam, B., Wong, M. et al. Effects of Azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT—a randomized double-blinded placebo-controlled study. Bone Marrow Transplant 46, 1551–1556 (2011). https://doi.org/10.1038/bmt.2011.1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2011.1
Keywords
This article is cited by
-
Diagnosis and treatment of bronchiolitis obliterans syndrome accessible universally
Bone Marrow Transplantation (2019)
-
Azithromycin versus placebo for the treatment of HIV-associated chronic lung disease in children and adolescents (BREATHE trial): study protocol for a randomised controlled trial
Trials (2017)
-
A Call to Arms: a Critical Need for Interventions to Limit Pulmonary Toxicity in the Stem Cell Transplantation Patient Population
Current Hematologic Malignancy Reports (2015)
-
The efficacy of prophylactic azithromycin on bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation
International Journal of Hematology (2015)