Systematic review of lung transplantation in cystic fibrosis with nontuberculous mycobacteria infectionLung Transplant for Cystic Fibrosis Patients with NTM Infection: What New Data Reveals

Rationale Cystic fibrosis (CF) is an inherited multi‐organ disorder. People with CF (pwCF) experience recurrent and chronic lung infections and a progressive loss of lung function. PwCF with poor and rapidly declining lung function may be considered for lung transplantation (LTx), which may improve their quality of life and survival. Nontuberculous mycobacteria (NTM) can cause pulmonary disease in pwCF, and NTM infection is a poor prognostic factor in LTx. Guidelines recommend NTM infection should not automatically preclude LTx. It is important to evaluate the evidence base for LTx in pwCF and NTM pulmonary disease. Objectives To evaluate clinical outcomes in pwCF and with NTM infection (NTM infection alone or with NTM pulmonary disease) who undergo LTx by comparing: 1. pwCF with current NTM lung infection who undergo LTx versus those with NTM infection who do not undergo LTX; 2. pwCF with current NTM lung infection who undergo LTx versus those without NTM undergoing LTx. Search methods We searched the Cochrane Cystic Fibrosis Trials Register, CENTRAL, MEDLINE, Embase, and PubMed as well as two ongoing trials registries. We checked references. The latest search date was 17 February 2026. Eligibility criteria We considered non‐randomised studies of pwCF (any age) with or without NTM lung infection or disease being considered for LTx as well as studies of pwCF and NTM who either did or did not undergo LTx. Outcomes Our critical outcomes were mortality, disseminated NTM infection post‐LTx, time to chronic lung allograft dysfunction (CLAD), and quality of life at any time points reported. We additionally planned to report lung function, hospitalisations for pulmonary exacerbations, and nutritional parameters in the review. Risk of bias We assessed the risk of bias in three studies using ROBINS‐I and in one study using the Joanna Briggs Institute checklist for case series. Synthesis methods We could only report results narratively. We used GRADE to assess the certainty of the evidence. Included studies We included four single‐centre retrospective studies (388 adults). Sample sizes ranged from nine to 177 participants. Mycobacteria abscessus was the most common NTM species identified, and all studies reported infection with other pathogens. All studies compared pwCF and NTM infection to pwCF without NTM infection, all undergoing LTx. Each study reported mortality and disseminated NTM infection post‐LTx; two studies recorded CLAD. No study reported quality of life, specific lung function measures (although one study commented briefly on lung function in general), hospitalisations for pulmonary exacerbations, or nutritional parameters. Synthesis of results We analysed all NTM infections together for practical reasons and were not able to undertake a planned subgroup analysis by subspecies, but acknowledge that the prognosis and clinical trajectory of pwCF infected with different NTM may not be similar. We downgraded the certainty of the evidence due to non‐randomised study design and serious risk of bias across all studies. We assessed all identified evidence as of very low certainty, such that lung transplant may have little to no effect on any of the outcomes listed below, but the evidence is very uncertain. Mortality Two studies (18 participants with NTM) reported similar survival data between NTM‐positive LTx recipients and matched controls without NTM. Another study (9 participants) reported that two of five participants NTM‐positive at LTx died within a few months post‐LTx, whilst one of four NTM‐negative participants died three years post‐LTx due to chronic rejection. One study (177 participants) found that pwCF who had positive NTM cultures pre‐LTx had a longer median survival duration than those who had negative cultures. This study additionally reported on survival of participants with post‐LTx NTM infection, finding that the five participants who had post‐LTx NTM disease had a longer mean survival duration than the 141 participants without post‐LTx NTM disease. Disseminated NTM infection post‐LTx In the largest study, of the 18 pwCF with NTM at the time of LTx, seven had at least one positive NTM culture, and four developed NTM disease post‐LTx. Conversely, 79 of the 89 pwCF without NTM remained so post‐LTx; 10 participants recorded a positive NTM culture, but none developed NTM disease. For the 39 participants without a baseline NTM culture, three participants recorded positive NTM cultures post‐LTx, and one developed NTM disease. Of the remaining small studies, one reported that NTM was isolated in four of 13 participants at LTx and in three of these post‐LTx. A second study reported that one out of five pwCF had NTM infection post‐LTx (all were positive at LTx). The third study reported that five out of nine participants had NTM disease at LTx, and two of these five remained NTM‐positive post‐LTx. CLAD Two studies assessed CLAD. One study reported that none of the five NTM‐positive LTx recipients developed CLAD, stating that the risk of CLAD appeared to be similar between the NTM and the comparator group. The second study stated that three out of nine LTx recipients with NTM disease developed chronic rejection or graft dysfunction. Authors' conclusions There are no randomised trials to guide clinicians and patients or their families when making decisions regarding LTx in pwCF with NTM. The available data come from observational studies and registry data, often with few people with NTM reported. It has not been possible to pool the available data in meta‐analysis, and we are very uncertain of the effect of NTM on pwCF undergoing LTx on the risk of developing NTM disease post‐LTx, survival after LTx, and the development of CLAD. The studies were small and at times contradictory. In the era of highly effective modulator treatments, as some centres do not offer LTx to people with a history of NTM, there is an urgent need for more data to guide decision‐making. Funding This review is part of a suite of reviews on NTM funded jointly by the CF Foundation and the CF Trust. Registration Protocol registration (2024): www.crd.york.ac.uk/PROSPERO/view/562682 PICOs PICOs Population Intervention Comparison Outcome