Benefits of three consecutive sputum inductions using nebulized racemic salbutamol versus hypertonic saline in smear-negative or sputum-scarce pulmonary tuberculosis patients: a prospective randomized, double-blind study

Although, sputum induction (SI) with hypertonic saline increases the diagnostic yield for suspected pulmonary tuberculosis (PTB) in patients with smear-negative microscopy, but, it carries adverse effects (AEs), particularly bronchospasm. This study assessed and compared the diagnostic yields and safety profiles of three consecutive SI procedures using nebulized salbutamol vs conventional 3% sodium chloride (NaCl) in patients with suspected PTB and initially negative sputum smears. A randomized, double-blind study was conducted at Songklanagarind Hospital, Thailand, between 2016 and 2019. Three hundred forty-five adults with suspected smear-negative or sputum-scarce PTB were randomized to undergo 3 consecutive days of SI with either nebulized salbutamol ( n = 172) or 3% NaCl ( n = 173). Diagnostic yields were assessed using acid-fast bacilli (AFB) smear and culture for Mycobacterium tuberculosis . Nebulized salbutamol produced a significantly higher overall diagnostic yield by AFB smear or culture than 3% NaCl (18.0% vs 9.2%, P = 0.043). For culture, both cumulative and incremental yields were consistently higher in the salbutamol group across all three samples (all P < 0.050). The 3% NaCl group experienced significantly more overall SI-related AEs than the salbutamol group (28.3% vs 9.8%, P = 0.034). Specifically, chest tightness (8.1% vs 2.3%, P = 0.031) and bronchospasm requiring rescue bronchodilators (13.3% vs 0.0%, P < 0.001) were more frequent in the 3% NaCl group. Three consecutive SI using nebulized salbutamol provide higher overall and cumulative diagnostic yields than conventional hypertonic saline, primarily driven by culture positivity, while offering a superior safety profile by eliminating bronchospasm risk. Nebulized salbutamol should, therefore, be considered the preferred induction agent for SI, particularly in high-risk patients such as those with airway diseases.

IMPORTANCE

Delays in diagnosing pulmonary tuberculosis or initiating treatment without bacteriological confirmation increase mortality, often because of inadequate sputum samples or negative acid-fast bacilli smears from self-expectoration. Sputum induction with hypertonic saline can improve diagnostic yield in patients with scanty sputum or smear-negative disease, but it is associated with adverse effects—particularly bronchospasm—which may require stopping the procedure. We demonstrated that three consecutive sputum inductions using nebulized racemic salbutamol produced significantly higher overall diagnostic yields by acid-fast bacilli smear and Mycobacterium tuberculosis culture compared with 3% NaCl. For culture, both cumulative and incremental yields were consistently superior in the salbutamol group. Regarding safety, 3% NaCl caused more chest tightness and symptomatic bronchospasm. These findings highlight the diagnostic benefit and favorable safety profile of three consecutive salbutamol-induced sputum procedures, supporting its use as the preferred agent for sputum induction.