Background
Patients with structural lung disease and immunocompromised status are at increased
risk of pulmonary non-tuberculous mycobacteria (NTM) infection. However, literature
on NTM in lung transplant recipients (LTR) is limited. We sought to systematically
review the literature and perform a meta-analysis to examine associations with NTM
disease and isolation in LTRs and their influence on mortality and chronic lung allograft
dysfunction (CLAD).
Methods
A literature search of MEDLINE and Embase was performed on February 23, 2022. NTM
disease was defined according to international guidelines. Isolation was defined as
any growth of NTM in culture. Odds ratios (OR) were pooled for risk factors of NTM
disease or isolation, and hazard ratios (HR) were pooled for mortality or CLAD.
Results
Eleven studies totaling 3,371 patients were eligible for inclusion, 10 of which underwent
meta-analysis. Cystic fibrosis (OR 1.84, 95% confidence interval [CI] 1.03-3.30; I2 = 0%) and pre-transplant NTM isolation (OR 2.40, 95% CI 1.20-4.83; I2 = 0%) were associated with NTM disease. Only male sex was associated with NTM isolation
(OR 1.45, 95% CI 1.01-2.10; I2 = 0%). NTM disease was associated with increased mortality (HR 2.69, 95% CI 1.70-4.26;
I2 = 0%) and CLAD (HR 2.11, 95% CI 1.03-4.35; I2 = 44%). NTM isolation was not associated with mortality in pooled analysis or CLAD
in 1 included study.
Conclusions
NTM disease, but not isolation, is associated with worse outcomes. Several factors
were associated with development of NTM disease, including cystic fibrosis and pretransplant
NTM isolation. Strategies to optimize prevention and treatment of NTM disease in lung
transplant recipients are needed.
Keywords
Abbreviations:
AFB (Acid-fast bacilli), ATS/IDSA (American Thoracic Society/Infectious Diseases Society of America), BOS (Bronchiolitis obliterans syndrome), CF (Cystic fibrosis), CI (Confidence interval), CLAD (Chronic lung allograft dysfunction), CMV (Cytomegalovirus), HR (Hazard ratio), ILD (Interstitial lung disease), LTR (Lung transplant recipient), MAC (Mycobacterium avium complex), NOS (Newcastle-Ottawa scale), NTM (Non-tuberculous mycobacteria), OLD (Obstructive lung disease), OR (Odds ratio)To read this article in full you will need to make a payment
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References
- Update on pulmonary disease due to non-tuberculous mycobacteria.Int J Infect Dis. 2016; 45: 123-134https://doi.org/10.1016/j.ijid.2016.03.006
- Mycobacterium abscessus disease in lung transplant recipients: Diagnosis and management.J Clin Tuberc Other Mycobact Dis. 2017; 9: 10-18https://doi.org/10.1016/j.jctube.2017.08.002
- Mycobacteria: Selection of transplant candidates and post-lung transplant outcomes.Semin Respir Crit Care Med. 2021; 42: 460-470https://doi.org/10.1055/s-0041-1727250
- Mycobacterium abscessus Infections in lung transplant recipients: The International Experience.J Hear Lung Transplant. 2006; 25: 1447-1455https://doi.org/10.1016/j.healun.2006.09.003
- Mycobacterium abscessus infection in transplant recipients.Transplant Proc. 2010; 42: 3058-3060https://doi.org/10.1016/j.transproceed.2010.08.004
- Rapidly growing mycobacteria infection in patients with cancer.Clin Infect Dis. 2010; 51: 422-434https://doi.org/10.1086/655140
- Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case-control study.Transpl Infect Dis. 2014; 16: 76-83https://doi.org/10.1111/tid.12170
- Non-tuberculous mycobacterial infections after solid organ transplantation: a survival analysis.Clin Microbiol Infect. 2015; 21: 43-47https://doi.org/10.1016/j.cmi.2014.07.001
- The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.BMJ. 2009; : 339https://doi.org/10.1136/bmj.b2700
- Meta-analysis of observational studies: a proposal for reporting.J Am Med Assoc. 2000; 283: 2008-2012https://doi.org/10.1007/978-94-007-3024-3_10
- Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline.Clin Infect Dis. 2020; 71: e1-e36https://doi.org/10.1093/cid/ciaa241
- An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases.Am J Respir Crit Care Med. 2007; 175: 367-416https://doi.org/10.1164/rccm.200604-571ST
- Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment―a consensus report from the Pulmonary Council of the ISHLT.J Hear Lung Transplant. 2019; 38: 493-503https://doi.org/10.1016/j.healun.2019.03.009
- An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome.Eur Respir J. 2014; 44: 1479-1503https://doi.org/10.1183/09031936.00107514
Wells G, Shea B, O'Connell D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Accessed September 13, 2021. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
Guyatt G, Busse J. Methods Commentary: Risk of Bias in Cohort Studies. Evidence partners. Accessed February 20, 2021. https://www.evidencepartners.com/resources/methodological-resources/risk-of-bias-in-cohort-studies/
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188https://doi.org/10.1016/0197-2456(86)90046-2
- Quantifying heterogeneity in a meta-analysis.Stat Med. 2002; 21: 1539-1558https://doi.org/10.1002/sim.1186
- Non-tuberculous mycobacteria in lung transplant recipients: prevalence, risk factors, and impact on survival and chronic lung allograft dysfunction.Transpl Infect Dis. 2020; 22: 1-7https://doi.org/10.1111/tid.13229
- Epidemiology and outcomes of nontuberculous mycobacterial infections in solid organ transplant recipients at a midwestern center.Transplantation. 2016; 100: 1073-1078https://doi.org/10.1097/TP.0000000000001123
- P61 Pulmonary nontuberculous mycobacterial (NTM) culture is common following lung transplantation, and NTM lung disease is associated with poor prognosis.Thorax. 2010; 65 (-A103): A103https://doi.org/10.1136/thx.2010.150979.12
- Outcomes of nontuberculous mycobacteria isolation among lung transplant recipients: A matched case-control with retrospective cohort study.Am J Heal Pharm. 2022; 79: 338-345https://doi.org/10.1093/ajhp/zxab389
- Outcomes in lung transplant recipients with mycobacterium abscessus infection: a 15-year experience from a large tertiary care center.Transplant Proc. 2019; 51: 2035-2042https://doi.org/10.1016/j.transproceed.2019.02.028
- Non-tuberculous mycobacterium infection after lung transplantation is associated with increased mortality.J Hear Lung Transplant. 2011; 30: 790-798https://doi.org/10.1016/j.healun.2011.02.007
- Nontuberculous mycobacterial pulmonary infection among lung transplant recipients.Exp Clin Transpl. 2021; 19: 1076-1081https://doi.org/10.6002/ect.2021.0177
- Non-tuberculous mycobacterial infection among lung transplant recipients: a 15-year cohort study.Transpl Infect Dis. 2012; 14: 452-460https://doi.org/10.1111/j.1399-3062.2012.00753.x
- Nontuberculous mycobacterial infection after lung transplantation: a single-center experience in South Korea.J Microbiol Immunol Infect. 2022; 55: 123-129https://doi.org/10.1016/j.jmii.2020.08.021
- Analysis of pulmonary non-tuberculous mycobacterial infections after lung transplantation.Transpl Infect Dis. 2016; 18: 585-591https://doi.org/10.1111/tid.12546
- Impact of azithromycin prophylaxis in lung transplant recipients on the risk of nontuberculous mycobacterial infections.Open Forum Infect Dis. 2018; 5: S288
- Susceptibility to nontuberculous mycobacterial lung disease.Eur Respir J. 2008; 31: 1322-1333https://doi.org/10.1183/09031936.00140007
- Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients.Clin Infect Dis. 2004; 38: 1428-1439https://doi.org/10.1086/420746
- Nontuberculous mycobacteria infections in immunosuppressed hosts.Clin Chest Med. 2015; 36: 91-99https://doi.org/10.1016/j.ccm.2014.11.002
- Markers indicating deterioration of pulmonary Mycobacterium avium-intracellulare infection.Am J Respir Crit Care Med. 1999; 160: 1851-1855https://doi.org/10.1164/ajrccm.160.6.9902019
- Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype.Eur Respir J. 2017; 501602503https://doi.org/10.1183/13993003.02503-2016
Ramos AL, Carvalho T, Guimarães JT. The importance of multiple samples in mycobacterial recovery: a 10-year retrospective study. Int J mycobacteriol. 8:175-179. doi:10.4103/ijmy.ijmy_68_19
- Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis.Respir Med. 2009; 103: 743-749https://doi.org/10.1016/j.rmed.2008.11.015
- Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome.Transplantation. 2008; 85: 771-774https://doi.org/10.1097/TP.0b013e31816651de
- Lung microbiota predict chronic rejection in healthy lung transplant recipients: a prospective cohort study.Lancet Respir Med. 2021; 9: 601-612https://doi.org/10.1016/S2213-2600(20)30405-7
- Lung-enriched organisms and aberrant bacterial and fungal respiratory microbiota after lung transplant.Am J Respir Crit Care Med. 2012; 186: 536-545https://doi.org/10.1164/rccm.201204-0693OC
- The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-eighth adult lung transplantation report — 2021; Focus on recipient characteristics.J Hear Lung Transpl. 2021; 40: 1060-1072https://doi.org/10.1016/j.healun.2021.07.021
- The spectrum of mycobacterial infection after lung transplantation.Am J Respir Crit Care Med. 1999; 160: 1611-1616https://doi.org/10.1164/ajrccm.160.5.9808113
- Gastroesophageal reflux disease, acid suppression, and mycobacterium avium complex pulmonary disease.Chest. 2007; 131: 1166-1172https://doi.org/10.1378/chest.06-1906
- Nontuberculous mycobacterial infections in heart transplant recipients: a seventeen-year experience.J Heart Transplant. 1990; 9: 357-363http://www.ncbi.nlm.nih.gov/pubmed/2398429Date accessed: April 16, 2022
- Lung transplant referral for individuals with cystic fibrosis: Cystic Fibrosis Foundation consensus guidelines.J Cyst Fibros. 2019; 18: 321-333https://doi.org/10.1016/j.jcf.2019.03.002
- International Society for Heart and Lung Transplantation consensus statement for the standardization of bronchoalveolar lavage in lung transplantation.J Hear Lung Transpl. 2020; 39: 1171-1190https://doi.org/10.1016/j.healun.2020.07.006
Article Info
Publication History
Published online: October 11, 2022
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