Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Post-Transplant Events

Effects of Azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT—a randomized double-blinded placebo-controlled study

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

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Soubani AO, Uberti JP . Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J 2007; 29: 1007–1019.

    Article  CAS  PubMed  Google Scholar 

  2. Dudek AZ, Mahaseth H . Hematopoietic stem cell transplant-related airflow obstruction. Curr Opin Oncol 2006; 18: 115–119.

    Article  PubMed  Google Scholar 

  3. 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.

    Article  PubMed  Google Scholar 

  4. Williams KM, Chien JW, Gladwin MT, Pavletic SZ . Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009; 302: 306–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Grossman EJ, Shilling RA . Bronchiolitis obliterans in lung transplantation: the good, the bad, and the future. Transl Res 2009; 153: 153–165.

    Article  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Crawford SW, Clark JG . Bronchiolitis associated with bone marrow transplantation. Clin Chest Med 1993; 14: 741–749.

    CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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.

    Article  CAS  PubMed  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Schultz MJ . Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. J Antimicrob Chemother 2004; 54: 21–28.

    Article  CAS  PubMed  Google Scholar 

  24. Verleden GM, Dupont LJ . Azithromycin therapy for patients with bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2004; 77: 1465–1467.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. 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.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study and the drug used in this study were sponsored by Pfizer Pharmaceuticals.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A K W Lie.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.1

Keywords

This article is cited by

Search

Quick links