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Nebulized Bronchodilator-Enhanced Sputum Induction in
Presumed Smear-Negative Pulmonary TB: A Randomized
Controlled Trial (NeB-TB)
Pichanon Mingchay1, Kamon Kawkitinarong2, Pattama Torvorapanit1,3, Gompol Suwanpimolkul1,3*
1 Division of Infectious Diseases, Department of Medicine, Faculty of Medicine, Chulalongkorn University
2 Division of Pulmonary Medicine and Pulmonary Critical Care, Department of Medicine, Faculty of
Medicine, Chulalongkorn University
3 Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital
*Corresponding Author E-mail: sgompol@gmail.com
Background: Abstract
Delayed diagnosis of pulmonary tuberculosis (TB), especially in settings with limited
bronchoscopy resources, worsens clinical outcomes and increases transmission risks.
Sputum induction is a non-invasive and effective alternative, but improvements in the induction
method could further enhance TB diagnostic yield. We investigated whether adding
nebulized bronchodilators could enhance sputum induction effectiveness in patients with
clinically presumed smear-negative pulmonary TB.
Methods: In this randomized controlled trial conducted at King Chulalongkorn Memorial Hospital,
Thailand, 204 adults with clinically presumed pulmonary TB and negative Xpert MTB/RIF
Ultra results or insufficient sputum production were enrolled between June and September
2024. Participants were randomly assigned to either conventional sputum induction
using 3% hypertonic saline alone (n=101), or the novel sputum induction using nebulized
bronchodilator combined with 3% hypertonic saline (n=103). The primary outcome was the
proportion of confirmed TB diagnoses via Xpert MTB/RIF assay.
Results: TB diagnosis rates by Xpert MTB/RIF were significantly higher in the novel group (30.1%;
number needed to diagnose [NND]=4) compared to the conventional group (17.8%;
NND=6), with a difference of 12.3% (95% CI: 0.1–23.9%, p=0.04). The novel sputum
induction method increased mycobacterial culture positivity (31.1% vs. 20.8%) and reduced
the need for bronchoscopy (4.8% vs. 11.9%). Participants in the novel group reported fewer
adverse reactions, greater comfort, required fewer induction rounds, and initiated TB
treatment significantly sooner (4.5 vs. 14 days; p<0.01). The method was particularly
beneficial for outpatients (p=0.04) and showed promising trends in patients with chronic
obstructive pulmonary disease. Detection rates of non-tuberculous mycobacteria also
improved.
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