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Correspondence |

Azithromycin in Posttransplant Bronchiolitis Obliterans Syndrome FREE TO VIEW

Robin Vos, MD, PhD; Bart M. Vanaudenaerde, PhD; Stijn E. Verleden, MSc; Dirk E. Van Raemdonck, MD, PhD, FCCP; Lieven J. Dupont, MD, PhD; Geert M. Verleden, MD, PhD
Author and Funding Information

From the Laboratory of Pneumology (Drs Vos and Vanaudenaerde and Mr Verleden), the Laboratory of Experimental Thoracic Surgery (Dr Van Raemdonck), and the Lung Transplantation Unit (Drs Vos, Vanaudenaerde, Van Raemdonck, and Dupont, and Mr Verleden), Katholieke Universiteit Leuven and University Hospital Gasthuisberg.

Correspondence to: Geert M. Verleden, MD, PhD, University Hospital Gasthuisberg, Lung Transplantation Unit, 49 Herestraat, B-3000 Leuven, Belgium; e-mail: geert.verleden@uzleuven.be


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Verleden receives an annual research grant from GlaxoSmithKline (GSK) Belgium, and is holder of the GlaxoSmithKline Chair in Respiratory Pharmacology at the Katholieke Universiteit Leuven, Leuven, Belgium. The remaining authors have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):1246. doi:10.1378/chest.10-2944
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To the Editor:

In their excellent review of chronic macrolide therapy in inflammatory airways diseases in a recent issue of CHEST (November 2010), Friedlander and Albert1 only briefly discuss its importance in posttransplant bronchiolitis obliterans syndrome (BOS). However, some important information is missing regarding this topic. First, we believe their review should include our retrospective cohort study, which is in fact the largest study (N = 107) with the longest duration of azithromycin treatment (mean 3.1 ± 1.9 years) in lung transplant recipients with established BOS thus far.2 This study confirmed that long-term azithromycin improves FEV1 ≥ 10% after 3 to 6 months of treatment in 40% of patients with BOS (so-called responders), of which 33% later may nevertheless redevelop BOS, as seen in the Hannover study.3 Responders demonstrated higher pretreatment BAL neutrophilia compared with nonresponders (median 29.3% vs 11.5%, P = .025), which decreased to a median of 4.2% (P = .041) after 3 to 6 months of azithromycin. Perhaps even more important, responders demonstrated better overall long-term survival compared with nonresponders after a mean follow-up of 6.3 ± 3.8 years posttransplantation (P = .050), a fact that was previously observed in the study by Jain et al4 comparing with a historical BOS cohort.

Moreover, there is currently also grade A evidence that azithromycin prophylaxis actually may prevent BOS. We recently published a randomized controlled trial of patients given azithromycin, 250 mg (n = 40), or placebo (n = 43) initiated at discharge and given thrice weekly for 2 years after lung transplantation (ClinicalTrials.gov, identifier: NCT01009619).5 This study demonstrated that prophylactic azithromycin treatment not only interacts with the innate immune system, since it attenuated airway neutrophilia (P = .015) and systemic C-reactive protein levels (P = .050) over time after transplantation, but also effectively improves FEV1 (P = .028) and BOS-free survival after transplantation (hazard ratio, 4.06; 95% CI, 1.55-7.72; P = .0025).

Serious adverse events were not noted in our retrospective or our prospective studies. Azithromycin, indeed, generally displays a good tolerability and is associated with a lower incidence of laboratory abnormalities, adverse events, or drug-drug interactions compared with other macrolides. In patients with subjective intolerance (mainly due to stimulation of gut motility) or rare drug interactions to oral azithromycin, aerosolized administration may perhaps represent a potential strategy to minimize adverse effects while maximizing drug delivery to the target site of disease, although this remains to be further investigated.6 Another consideration in long-term low-dose azithromycin therapy is the potential selection of antibiotic-resistant organisms, for which we currently have no evidence in our center, but which may become more prevalent with increased and generalized use of azithromycin in inflammatory airways diseases.

Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest. 2010;1385:1202-1212. [CrossRef] [PubMed]
 
Vos R, Vanaudenaerde BM, Ottevaere A, et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer? J Heart Lung Transplant. 2010;2912:1358-1368. [CrossRef] [PubMed]
 
Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2008;851:36-41. [CrossRef] [PubMed]
 
Jain R, Hachem RR, Morrell MR, et al. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2010;295:531-537. [CrossRef] [PubMed]
 
Vos R, Vanaudenaerde BM, Verleden SE, et al. A randomized placebo-controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J. 2011;371:164-172. [CrossRef] [PubMed]
 
Hickey AJ, Lu D, Ashley ED, Stout J. Inhaled azithromycin therapy. J Aerosol Med. 2006;191:54-60. [CrossRef] [PubMed]
 

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References

Friedlander AL, Albert RK. Chronic macrolide therapy in inflammatory airways diseases. Chest. 2010;1385:1202-1212. [CrossRef] [PubMed]
 
Vos R, Vanaudenaerde BM, Ottevaere A, et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer? J Heart Lung Transplant. 2010;2912:1358-1368. [CrossRef] [PubMed]
 
Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2008;851:36-41. [CrossRef] [PubMed]
 
Jain R, Hachem RR, Morrell MR, et al. Azithromycin is associated with increased survival in lung transplant recipients with bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2010;295:531-537. [CrossRef] [PubMed]
 
Vos R, Vanaudenaerde BM, Verleden SE, et al. A randomized placebo-controlled trial of azithromycin to prevent chronic rejection after lung transplantation. Eur Respir J. 2011;371:164-172. [CrossRef] [PubMed]
 
Hickey AJ, Lu D, Ashley ED, Stout J. Inhaled azithromycin therapy. J Aerosol Med. 2006;191:54-60. [CrossRef] [PubMed]
 
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