Effectiveness of Nebulized Bronchodilator-Enhanced Sputum Induction in Thai Patients With Presumed Pulmonary Tuberculosis: A Randomized Controlled Trial (NeB-TB Trial).

Abstract

Delayed pulmonary tuberculosis (PTB) diagnosis, especially with limited bronchoscopy resources, worsens outcomes and increases transmission risks. Sputum induction offers a noninvasive and effective alternative. We investigated whether adding nebulized bronchodilators improves sputum induction effectiveness for presumed PTB. In a randomized controlled trial at King Chulalongkorn Memorial Hospital, Thailand, 204 adults with presumed PTB and negative Xpert MTB/RIF Ultra results or inadequate sputum production were enrolled between July and October 2024. Participants were randomly assigned to conventional sputum induction (3% hypertonic saline alone; n = 101) or bronchodilator-enhanced induction (nebulized bronchodilator plus 3% hypertonic saline; n = 103). The primary outcome was TB diagnosis by Xpert MTB/RIF assay. Tuberculosis detection rates by Xpert MTB/RIF were significantly higher in the bronchodilator-enhanced group (30.1%; number needed to diagnose [NND] = 4) versus the conventional group (17.8%; NND = 6), with a 12.3% difference (relative risk [RR], 1.68; 95% confidence interval [CI] 1.01-2.80). The group receiving bronchodilator co-administration showed a trend toward higher mycobacterial culture positivity (RR 1.49; 95% CI .93-2.41) and a lower need for bronchoscopy (RR 0.41; 95% CI .15-1.12). They also experienced fewer adverse events and required fewer induction attempts, significantly assisting us to be able to provide early treatment to the patients (median 4.5 vs 14 days; P < .01). Subgroup analysis revealed a significant benefit among outpatients (RR 1.86; 95% CI 1.00-3.48). Bronchodilator-enhanced sputum induction demonstrated superiority over conventional induction, with higher diagnostic yield, fewer adverse events, fewer invasive procedures, and significantly earlier TB treatment initiation, supporting its potential as a new standard for TB diagnosis. Thai Clinical Trials Registry (TCTR20240709001), registered on 9 July 2024.