Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis.


Journal

NEJM evidence
ISSN: 2766-5526
Titre abrégé: NEJM Evid
Pays: United States
ID NLM: 9918317485806676

Informations de publication

Date de publication:
Sep 2024
Historique:
medline: 27 8 2024
pubmed: 27 8 2024
entrez: 27 8 2024
Statut: ppublish

Résumé

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. 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. Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum 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.).

Sections du résumé

BACKGROUND 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 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 RESULTS
Participants were predominantly young, male, and human immunodeficiency virus 1-negative and had heavy sputum
CONCLUSIONS 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.).

Identifiants

pubmed: 39189858
doi: 10.1056/EVIDoa2300332
doi:

Substances chimiques

Acetylcysteine WYQ7N0BPYC
Antitubercular Agents 0
Glutathione GAN16C9B8O

Banques de données

ClinicalTrials.gov
['NCT03702738']

Types de publication

Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

EVIDoa2300332

Auteurs

Robert S Wallis (RS)

The Aurum Institute, Johannesburg.
Department of Medicine, Case Western Reserve University, Cleveland.
Department of Medicine, Vanderbilt University, Nashville.

Issa Sabi (I)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Julieth Lalashowi (J)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Abhishek Bakuli (A)

Institute of Infectious Diseases and Tropical Medicine, Ludwig Maximilian University Hospital, Munich, Germany.

Daniel Mapamba (D)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Willyhelmina Olomi (W)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Elimina Siyame (E)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Beatrice Ngaraguza (B)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Ombeni Chimbe (O)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Salome Charalambous (S)

The Aurum Institute, Johannesburg.
Department of Medicine, Vanderbilt University, Nashville.

Andrea 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.

Olena 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.

Lindsey Zurba (L)

Education for Health Africa, Durban, South Africa.

Bahati Myombe (B)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Revocatus Kunambi (R)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Michael 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.

Nyanda Ntinginya (N)

National Institute for Medical Research-Mbeya Medical Research Center, Mbeya, Tanzania.

Gavin Churchyard (G)

The Aurum Institute, Johannesburg.
Department of Medicine, Vanderbilt University, Nashville.

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Classifications MeSH