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.

  • Review
  • Published:

Macrolides in the treatment of bronchiolitis obliterans in allograft recipients

Abstract

Bronchiolitis obliterans (BO) is a serious complication of hematopoietic SCT (HSCT). The condition is believed to be the result of an inflammatory part of the GVHD. Although many BO patients receive immunosuppressive therapy, there is no clear evidence that therapeutic interventions have a positive impact. In the last 20 years, it has been recognized that macrolides have immunomodulatory effects beyond their antibiotic effect. Recent data suggest also that the use of macrolides in BO post HSCT may halt disease progression. Our objectives are to give the readers information on the background of BO post HSCT, to review the immunomodulatory properties of macrolides in general and specifically in pulmonary diseases, and to summarize the current knowledge of macrolide benefits in BO therapy. Research into macrolide immunomodulation for chronic pulmonary disorders, such as diffuse panbronchiolitis and cystic fibrosis, shows consistent positive effects. The use of macrolides for other types of pulmonary inflammatory complications is yet to be proved. The benefit for BO post HSCT was shown only in a small non-randomized trial. Additional in vivo research is needed before developing any firm conclusions.

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. Chan CK, Hyland RH, Hutcheon MA . Pulmonary complications following bone marrow transplantation. Clin Chest Med 1990; 11: 323–332.

    CAS  PubMed  Google Scholar 

  2. Chan CK, Hyland RH, Hutcheon MA, Minden MD, Alexander MA . Small-airways disease in recipients of allogeneic bone marrow transplants. An analysis of 11 cases and a review of the literature. Medicine (Baltimore) 1987; 66: 327–340.

    Article  CAS  Google Scholar 

  3. Bryant D . Pulmonary complications. 2004 In: Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner MK, (eds) Clinical Bone Marrow and Blood Stem Cell Transplantation, 3rd edn. Cambridge, Cambridge University Press, pp 1466.

    Google Scholar 

  4. Marras T, Chan C . Obliterative bronchiolitis complicating bone marrow transplantation. Semin Respir Crit Care Med 2003; 24: 531–541.

    Article  Google Scholar 

  5. Afessa B, Litzow MR, Tefferi A . Bronchiolitis obliterans and other late onset non infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 28: 425–431.

    Article  CAS  Google Scholar 

  6. Cooke KR, Krenger W, Hill G, Martin TR, Kobzik L, Brewer J et al. Host reactive donor T-cells are associated with lung injury after experimental allogeneic bone marrow transplantation. Blood 1998; 92: 2571–2580.

    CAS  PubMed  Google Scholar 

  7. Krebs R, Tikkanen JM, Nykanen AI, Krebs R, Tikkanen JM, Nykänen AI et al. Dual role of vascular endothelial growth factor in experimental obliterative bronchiolitis. Transplantation 2004; 78: 541–544.

    Article  Google Scholar 

  8. Ratanatharathorn V, Ayash L, Lazarus HM, Fu J, Uberti JP . Chronic graft-versus-host disease: clinical manifestations and therapy. Bone Marrow Transplant 2001; 28: 121–129.

    Article  CAS  Google Scholar 

  9. Egan J . Obliterative bronchiolitis after lung transplantation. Am J Respir Crit Care Med 2004; 170: 931–932.

    Article  Google Scholar 

  10. 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  Google Scholar 

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

    Article  CAS  Google Scholar 

  12. Kurdowska A, Noble JM, Griffith DE . The effects of azithromycin and clarithromycin on ex vivo interleukin-8 (IL-8) release from whole blood and IL-8 production by human alveolar macrophages. J Antimicrob Chemother 2001; 47: 867–870.

    Article  CAS  Google Scholar 

  13. Koch CC, Esteban DJ, Chin AC, Olson ME, Read RR, Ceri H et al. Apoptosis, oxidative metabolism and interleuken-8 production in human neutrophils exposed to azithromycin: effects of Streptoccus pneumoniae. J Antimicrob Chemother 2000; 46: 19–26.

    Article  CAS  Google Scholar 

  14. Milojkovic D, Mufti JG . Extending the role of allogenic stem cell transplantation. Lancet 2001; 357: 652–654.

    Article  CAS  Google Scholar 

  15. Kotloff RM, Ahya VN, Crawford SW . Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2004; 170: 22–48.

    Article  Google Scholar 

  16. Beinert T, Dull T, Wolf K, Behr J, Kolb H . Late pulmonary impairment following allogeneic bone marrow transplantation. Eur J Med Res 1996; 1: 343–348.

    CAS  PubMed  Google Scholar 

  17. Chien JW, Martin PJ, Gooley TA, Nichols WG, Clark JG . Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2003; 168: 146–147.

    Article  Google Scholar 

  18. Nagai H, Shishido H, Yoneda R, Yamaguchi E, Tamura A, Kurashima A . Long-term low-dose administration of erythromycin to patients with diffuse panbronchiolitis. Respiration 1991; 58: 145–149.

    Article  CAS  Google Scholar 

  19. Rubin BK, Druce H, Ramirez OE, Palmer R . Effect of clarithromycin on nasal mucus properties in healthy subjects and in patients with purulent rhinitis. Am J Respir Crit Care Med 1997; 155: 2018–2023.

    Article  CAS  Google Scholar 

  20. Koh YY, Lee MH, Sun YH, Sung KW, Chae JH . Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Eur Respir J 1997; 10: 994–999.

    Article  CAS  Google Scholar 

  21. Jaffe A, Francis J, Rosenthal M, Bush A . Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 1998; 351: 420.

    Article  CAS  Google Scholar 

  22. Spector S, Katz F, Farr R . Troleandomycin: effectiveness in steroid-dependent asthma and bronchitis. J Allergy Clin Immunol 1974; 54: 367–379.

    Article  Google Scholar 

  23. Ordonez CL, Stulbarg M, Grundland H . Effect of clarithromycin on airway obstruction and inflammatory markers in induced sputum in cystic fibrosis: a pilot study. Pediatr Pulmonol 2001; 32: 29–37.

    Article  CAS  Google Scholar 

  24. Koch CC, Esteban DJ, Chin AC, Ceri H . Apoptosis, oxidative metabolism and interleuken-8 production in human neutrophils exposed to azithromycin: effects of Streptoccus pneumoniae. J Antimicrob Chemother 2000; 46: 19–26.

    Article  CAS  Google Scholar 

  25. Ianaro A, Ialenti A, Maffa P, Sautebin L, Rombolà L, Carnuccio R . Anti-inflammatory activity of macrolide antibiotics. J Pharmacol Exp Ther 2000; 292: 156–163.

    CAS  PubMed  Google Scholar 

  26. Culic O, Erakovic V, Cepelak I, Barisić K, Brajsa K, Ferencić Z . Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur J Pharmacol 2002; 450: 277–289.

    Article  CAS  Google Scholar 

  27. Culic O, Erakovic V, Parnham MJ . Anti-inflammatory effects of macrolide antibiotics. Eur J Pharmacol 2001; 429: 209–229.

    Article  CAS  Google Scholar 

  28. Siracusa A, Brugnami G, Fiordi T, Areni S, Severini C, Marabini A . Troleandomycin in the treatment of difficult asthma. J Allergy Clin Immunol 1993; 92: 677–682.

    Article  CAS  Google Scholar 

  29. Simpson JL, Powell H, Boyle MJ . Clarithromycin targets neutrophilic airway inflammation in refractory asthma. Am J Respir Crit Care Med 2008; 177: 148–155.

    Article  CAS  Google Scholar 

  30. Ball BD, Hill MR, Brenner M . Effect of low-dose troleandomycin on glucocorticoid pharmacokinetics and airway hyper-responsiveness in severely asthmatic children. Ann Allergy 1990; 65: 37–45.

    CAS  PubMed  Google Scholar 

  31. Tamaoki J, Takeyama K, Tagaya E, Konno K . Effect of clarithromycin on sputum production and its rheological properties in chronic respiratory tract infections. Antimicrob Agents Chemother 1995; 39: 1688–1690.

    Article  CAS  Google Scholar 

  32. Shimizu T, Shimizu S, Hattori R Gabazza EC, Majima Y . In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells. Am J Respir Crit Care Med 2003; 168: 581–587.

    Article  Google Scholar 

  33. Gerhardt SG, McDyer JF, Girgis RE, Orens JB . Maintenance azithromycin therapy for bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2003; 168: 121–125.

    Article  Google Scholar 

Download references

Acknowledgements

NM was supported by grants from Princes Margaret Hospital Foundation, Toronto, Canada, and SACTA-RASHI Foundation, Israel.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J H Lipton.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maimon, N., Lipton, J., Chan, C. et al. Macrolides in the treatment of bronchiolitis obliterans in allograft recipients. Bone Marrow Transplant 44, 69–73 (2009). https://doi.org/10.1038/bmt.2009.106

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.106

Keywords

This article is cited by

Search

Quick links