Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.

Autor:	Wallis RS; The Aurum Institute, Johannesburg.; Department of Medicine, Case Western Reserve University, Cleveland.; Department of Medicine, Vanderbilt University, Nashville., Sabi I; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Lalashowi J; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Bakuli A; Institute of Infectious Diseases and Tropical Medicine, Ludwig Maximilian University Hospital, Munich, Germany., Mapamba D; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Olomi W; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Siyame E; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Ngaraguza B; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Chimbe O; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Charalambous S; The Aurum Institute, Johannesburg.; Department of Medicine, Vanderbilt University, Nashville., Rachow A; Institute of Infectious Diseases and Tropical Medicine, Ludwig Maximilian University Hospital, Munich, Germany.; German Centre for Infection Research, Partner Site Munich, Munich, Germany.; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany., Ivanova O; Institute of Infectious Diseases and Tropical Medicine, Ludwig Maximilian University Hospital, Munich, Germany.; German Centre for Infection Research, Partner Site Munich, Munich, Germany.; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany., Zurba L; Education for Health Africa, Durban, South Africa., Myombe B; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Kunambi R; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Hoelscher M; Institute of Infectious Diseases and Tropical Medicine, Ludwig Maximilian University Hospital, Munich, Germany.; German Centre for Infection Research, Partner Site Munich, Munich, Germany.; Unit Global Health, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany.; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP; Immunology, Infection and Pandemic Research, Munich, Germany., Ntinginya N; National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania., Churchyard G; The Aurum Institute, Johannesburg.; Department of Medicine, Vanderbilt University, Nashville.
Jazyk:	angličtina
Zdroj:	NEJM evidence [NEJM Evid] 2024 Sep; Vol. 3 (9), pp. EVIDoa2300332. Date of Electronic Publication: 2024 Aug 27.
DOI:	10.1056/EVIDoa2300332
Abstrakt:	Background: Tuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes. Methods: This prospective, randomized, controlled trial nested within the TB SEQUEL cohort study enrolled 140 adults with moderate or far-advanced tuberculosis. Participants were randomly assigned 1:1 to standard therapy with or without 1200 mg of oral NAC twice daily for days 1 to 112. Clinical evaluations, sputum culture, and spirometry were performed at specified intervals through day 168, after which participants returned to the TB SEQUEL cohort. The primary outcome was culture conversion. Secondary outcomes included whole-blood glutathione levels and lung function. Results: Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum Mycobacterium tuberculosis (MTB) infection burdens. NAC increased glutathione levels (NAC × day interaction, 8.48; 95% confidence interval [CI], 1.93 to 15.02) but did not increase stable culture conversion (hazard ratio, 0.84; 95% CI, 0.59 to 1.20; P=0.33). NAC treatment was associated with improved recovery of lung function (NAC × month, 0.49 [95% CI, 0.02 to 0.95] and 0.42 [95% CI, -0.06 to 0.91] for forced vital capacity and forced expiratory volume in the first second, respectively, as percentages of predicted values). The effects of NAC on lung function were greatest in participants with severe baseline lung impairment and appeared to persist beyond the period of NAC administration. Rates of serious or grade 3 to 4 nonserious adverse events did not differ between the groups. Conclusions: Despite increasing whole-blood glutathione levels, NAC did not affect eradication of MTB infection in adults with pulmonary tuberculosis that was moderate to far advanced. Secondary outcomes of lung function showed changes that merit further investigation. (Funded by TB SEQUEL grant 01KA1613 of the German Ministry for Education and Research, the Health Africa Project, and the German Center for Infection Research; ClinicalTrials.gov number, NCT03702738.).
Databáze:	MEDLINE
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