Long-Term Azithromycin Use for Treatment of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients

Shitrit, David; Daniele, Bruno; Sahar, Gul; Sauté, Milton; Bakal, Ilana; Kramer, Mordechai R.

doi:10.1016/j.healun.2004.08.006

Cited by 94 publications

(71 citation statements)

References 15 publications

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“…Beneficial effects have been reported for approximately 35-40% of lung transplant recipients treated with azithromycin [25,26,[110][111][112][113][114][115][116]. Complete reversal of FEV1 decline may occur in some patients, and patients with BAL neutrophilia appear to represent a subset of patients that are particularly likely to respond to azithromycin therapy [25,26,114].…”

Section: Azithromycinmentioning

confidence: 99%

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

et al. 2014

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Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS.A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations.The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of posttransplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS.The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention. Executive summaryMany lung transplant recipients develop delayed allograft dysfunction that has been traditionally referred to as bronchiolitis obliterans syndrome (BOS), which is thought to be caused by inflammation, destruction and fibrosis of small airways in the lung allograft that leads to obliterative bronchiolitis (OB). Because a definitive diagnosis of OB is difficult to make without a surgical lung biopsy, a decrease in the forced expiratory volume in 1 s (FEV1) has been used as a surrogate marker to identify patients who develop a syndrome of significant and persistent loss of lung allograft function with onset three or more months following transplantation. However, it is now recognised that numerous factors apart from OB can lead to a delayed onset, significant decline in lung function, and these causes of delayed onset graft dysfunction must be carefully excluded when a diagnosis of BOS is made. In general, BOS responds poorly to therapeutic interventions but may stabilise, and some patients may have a significant improvement in FEV1 with certain ther...

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Section: Azithromycinmentioning

confidence: 99%

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

et al. 2014

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“…Several small studies (maximum 20 patients) have examined the potential benefit of azithromycin in the treatment of post-transplant obliterative bronchiolitis (table 5). Five prospective open-label studies have been undertaken, with four showing significant improvements in FEV1 with azithromycin treatment [61,62,65,66] and one showing no significant effect [63]. One retrospective study also showed a significant increase in FEV1 with azithromycin treatment [64].…”

Section: Post-transplant Obliterative Bronchiolitismentioning

confidence: 99%

Long-term macrolide therapy in chronic inflammatory airway diseases

Crosbie¹,

Woodhead²

2009

European Respiratory Journal

119

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In addition to direct antibacterial actions, 14-and 15-member-ring macrolides have immune modulating effects that appear to be the reason for clinical benefit in diffuse panbronchiolitis.A literature search was conducted for studies of the clinical effectiveness of macrolides in other chronic lung conditions.A number of studies were identified that showed short-term beneficial outcomes or the potential for such outcomes in cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, asthma and post-transplant obliterative bronchiolitis. The studies were limited by small patient numbers, different outcome measures and short-term follow-up, and were not designed to assess potentially harmful effects.Further large prospective and long-term studies are required in order to identify potential benefit and harm before these agents can be recommended routinely for these conditions.

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“…Those authors, however, reported that there was a change in the natural history of bronchiolitis obliterans, since the disease did not progress during the assessment period. (37) This result is in contrast with the findings of another group of authors, (36) whose patients developed bronchiolitis obliterans regardless of treatment with a macrolide (clarithromycin), there being no change in the natural history of the disease. Therefore, the role of the use of macrolides in patients with post-transplant bronchiolitis obliterans has yet to be well defined.…”

Section: Bronchiolitis Obliteransmentioning

confidence: 61%

“…(36,37) One study, involving 146 lung transplant recipients with a survival of more than 180 days (102 of whom were treated with clarithromycin and 44 of whom received standard postoperative care), demonstrated that clarithromycin did not reduce the incidence of bronchiolitis obliterans (76 patients treated with clarithromycin developed bronchiolitis obliterans, whereas 7 receiving standard care developed the disease) or the incidence of respiratory complications (35 patients treated with clarithromycin vs. 18 receiving standard care). (36) One study, (37) assessing forced expiratory volume in 11 patients over 10 months of unblinded treatment with azithromycin (250 mg, 3 times a week), demonstrated that there was no improvement in pulmonary function. Those authors, however, reported that there was a change in the natural history of bronchiolitis obliterans, since the disease did not progress during the assessment period.…”

Section: Bronchiolitis Obliteransmentioning

confidence: 99%

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

et al. 2012

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Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.Keywords: Macrolides; Asthma; Cystic Fibrosis; Bronchiolitis. ResumoOs macrolídeos são fármacos com efeitos antimicrobianos especialmente contra patógenos intracelulares. Vários estudos têm demonstrado possíveis efeitos anti-inflamatórios dos macrolídeos. Esses medicamentos inibem a produção de algumas interleucinas e podem reduzir a inflamação neutrofílica pulmonar. Ensaios clínicos têm demonstrado efeitos benéficos dos macrolídeos em diversas doenças pulmonares crônicas. O objetivo deste estudo foi revisar os dados recentes da literatura médica sobre os efeitos anti-inflamatórios dos macrolídeos nas doenças respiratórias da infância, através da pesquisa da base de dados Medline (PubMed) dos seguintes termos em inglês: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; e "macrolide and acute bronchiolitis" Foram selecionados artigos publicados em revistas científicas internacionais entre 2001 e 2012. Estudos clínicos e evidências in vitro comprovam o efeito anti-inflamatório dos macrolídeos em doenças respiratórias. Alguns ensaios clínicos demonstram benefícios na administração de macrolídeos em pacientes com fibrose cística; porém, o risco de resistência bacteriana deve ser considerado na análise desses benefícios. Tais benefícios são controversos em outras doenças respiratórias, e seu uso rotineiro não está indicado. Mais estudos clínicos controlados são necessários para avaliar a eficácia desses medicamentos como anti-inflamatórios. Dessa forma, poderemos d...

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Long-Term Azithromycin Use for Treatment of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients

Cited by 94 publications

References 15 publications

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

Long-term macrolide therapy in chronic inflammatory airway diseases

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

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