The Aurum Institute, Johannesburg.
Department of Medicine, Case Western Reserve University, Cleveland.
NEJM Evid. 2024 Sep;3(9):EVIDoa2300332. doi: 10.1056/EVIDoa2300332. Epub 2024 Aug 27.
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 (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.
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.).
结核病仍然是全球关注的健康问题，一半的治愈患者存在永久性肺部损伤。N-乙酰半胱氨酸（NAC）在临床前结核病模型中表现出有益的抗菌、抗氧化和免疫调节作用。我们研究了它对结核病治疗结果的影响。
这项前瞻性、随机、对照试验嵌套在 TB SEQUEL 队列研究中，纳入了 140 名患有中度或晚期肺结核的成年人。参与者被随机分配 1:1 接受标准治疗加或不加每日两次口服 1200mg NAC 治疗 112 天。在第 168 天进行临床评估、痰培养和肺活量测定，此后参与者返回 TB SEQUEL 队列。主要结局是培养转换。次要结局包括全血谷胱甘肽水平和肺功能。
参与者主要是年轻、男性和人类免疫缺陷病毒 1 阴性，并且痰液中结核分枝杆菌（MTB）感染负担很重。NAC 增加了谷胱甘肽水平（NAC×天数交互作用，8.48；95%置信区间 [CI]，1.93 至 15.02），但并未增加稳定的培养转换（危险比，0.84；95%CI，0.59 至 1.20；P=0.33）。NAC 治疗与肺功能的恢复有关（NAC×月，0.49[95%CI，0.02 至 0.95]和 0.42[95%CI，-0.06 至 0.91]，分别为用力肺活量和第一秒用力呼气量占预计值的百分比）。在基线肺功能严重受损的参与者中，NAC 对肺功能的影响最大，并且似乎在 NAC 治疗期结束后仍持续存在。两组之间严重或 3 至 4 级非严重不良事件的发生率没有差异。
尽管全血谷胱甘肽水平升高，但 NAC 并未影响中重度肺结核成人中 MTB 感染的消除。肺功能的次要结局显示出值得进一步研究的变化。（由德国联邦教育和研究部 01KA1613 号 TB SEQUEL 赠款、健康非洲项目和德国感染研究中心、ClinicalTrials.gov 编号 NCT03702738 资助）。
