Azithromycin prophylaxis after lung transplantation is associated with improved overall survival

Li, David; Duan, Qiuli; Weinkauf, J.; Kapasi, A.; Varughese, Rhea; Hirji, A.; Lien, Dale; Meyer, Steven; Laing, Bryce; Nagendran, Jayan; Halloran, K.

doi:10.1016/j.healun.2020.09.006

Cited by 20 publications

(16 citation statements)

References 30 publications

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“…At our center, we observed a decreased incidence of lymphocytic bronchitis since the introduction of azithromycin for CLAD prophylaxis (89). However, data are mixed regarding the effectiveness of azithromycin on improving CLAD-free survival or overall survival when used prophylactically (90)(91)(92). Additionally, the mechanism whereby azithromycin reduces airway inflammation remains unclear.…”

Section: Acute Cellular Rejection Pathologies and The Significance Of...mentioning

confidence: 93%

Lymphocytic Airway Inflammation in Lung Allografts

2022

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Lung transplant remains a key therapeutic option for patients with end stage lung disease but short- and long-term survival lag other solid organ transplants. Early ischemia-reperfusion injury in the form of primary graft dysfunction (PGD) and acute cellular rejection are risk factors for chronic lung allograft dysfunction (CLAD), a syndrome of airway and parenchymal fibrosis that is the major barrier to long term survival. An increasing body of research suggests lymphocytic airway inflammation plays a significant role in these important clinical syndromes. Cytotoxic T cells are observed in airway rejection, and transcriptional analysis of airways reveal common cytotoxic gene patterns across solid organ transplant rejection. Natural killer (NK) cells have also been implicated in the early allograft damage response to PGD, acute rejection, cytomegalovirus, and CLAD. This review will examine the roles of lymphocytic airway inflammation across the lifespan of the allograft, including: 1) The contribution of innate lymphocytes to PGD and the impact of PGD on the adaptive immune response. 2) Acute cellular rejection pathologies and the limitations in identifying airway inflammation by transbronchial biopsy. 3) Potentiators of airway inflammation and heterologous immunity, such as respiratory infections, aspiration, and the airway microbiome. 4) Airway contributions to CLAD pathogenesis, including epithelial to mesenchymal transition (EMT), club cell loss, and the evolution from constrictive bronchiolitis to parenchymal fibrosis. 5) Protective mechanisms of fibrosis involving regulatory T cells. In summary, this review will examine our current understanding of the complex interplay between the transplanted airway epithelium, lymphocytic airway infiltration, and rejection pathologies.

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Section: Acute Cellular Rejection Pathologies and The Significance Of...mentioning

confidence: 93%

Lymphocytic Airway Inflammation in Lung Allografts

2022

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“…Azithromycin is a broad-spectrum antibacterial that is used to prevent exacerbations or delay progression in lung diseases not traditionally considered microbe-driven, including COPD, asthma, and chronic lung allograft dysfunction following transplantation (152,153). Recently, several studies investigated whether azithromycin might act by modifying lung microbiome communities, but results on community composition have been inconclusive (154)(155)(156).…”

Section: From Microbiome Association To Functionmentioning

confidence: 99%

The lung microbiome: progress and promise

Whiteside¹,

McGinniss²,

Collman³

2021

Journal of Clinical Investigation

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“…Among available treatments, the most evidence exists for azithromycin [74][75][76][77][78][79][80][81], including data from a randomised, placebo-controlled trial [82]. In observational studies, azithromycin was associated with a FEV 1 increase of 16-18% predicted [74,75,78], and an absolute FEV 1 increase of 0.11-0.86 L [74,[78][79][80].…”

Section: Clad-bosmentioning

confidence: 99%

“…The most frequent adverse effects were gastrointestinal disorders. The recent ISHLT consensus states that azithromycin should be initiated as early as possible, even before any definite BOS diagnosis has been made [ 3 ], based on its effects on lung function [ 76 , 77 , 81 ]. The optimal dosage and duration of azithromycin have not been established [ 78 , 80 , 81 ].…”

Section: Current Treatment Approachesmentioning

confidence: 99%

Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions

et al. 2022

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Bronchiolitis obliterans syndrome (BOS) may develop after either lung or haematopoietic stem cell transplantation (HSCT), with similarities in histopathological features and clinical manifestations. However, there are differences in the contributory factors and clinical trajectories between the two conditions. BOS after HSCT occurs due to systemic graft-versus-host-disease (GVHD), whereas BOS after lung transplantation is limited to the lung allograft. BOS diagnosis after HSCT is more challenging, as the lung function decline may occur due to extrapulmonary GVHD, causing sclerosis or inflammation in the fascia or muscles of the respiratory girdle. Treatment is generally empirical with no established effective therapies. This review provides rare insights and commonalities of both conditions, that are not well elaborated elsewhere in contemporary literature, and highlights the importance of cross disciplinary learning from experts in other transplant modalities. Treatment algorithms for each condition are presented, based on the published literature and consensus clinical opinion. Immunosuppression should be optimised, and other conditions or contributory factors treated where possible. When initial treatment fails, the ultimate therapeutic option is lung transplantation (or re-transplantation in the case of BOS after lung transplantation) in carefully selected candidates. Novel therapies under investigation include aerosolised liposomal cyclosporine, Janus kinase inhibitors, antifibrotic therapies, and (in patients with BOS after lung transplantation) B-cell–directed therapies. Effective novel treatments that have a tangible impact on survival and thereby avoid the need for lung transplantation or re-transplantation are urgently required.

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Azithromycin prophylaxis after lung transplantation is associated with improved overall survival

Cited by 20 publications

References 30 publications

Lymphocytic Airway Inflammation in Lung Allografts

Lymphocytic Airway Inflammation in Lung Allografts

The lung microbiome: progress and promise

Bronchiolitis obliterans syndrome after lung or haematopoietic stem cell transplantation: current management and future directions

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