Effect of inhaled anticholinergics on bronchial secretions: a systematic review

Background: Inhaled anticholinergics are commonly used in chronic respiratory diseases with the intention of reducing bronchial secretions in addition to their bronchodilatory effects. However, evidence regarding their direct influence on mucus production and clearance remains limited and fragmented. This study aimed to identify, evaluate, and synthesize the available evidence on the effects of inhaled and nebulized anticholinergics on mucus volume, rheological properties, mucociliary clearance, cough, and pulmonary function in adults. Methods: A systematic review was conducted following PRISMA 2020 guidelines and registered in PROSPERO (CRD42024575999). Comprehensive searches were performed in PubMed, OVID, Embase, SciELO, EBSCO, ScienceDirect, and Cochrane Library without date restrictions. Randomized and non-randomized studies assessing inhaled or nebulized anticholinergics were included. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Results: Out of 2,449 records identified, eight studies comprising 403 participants met the inclusion criteria. Under stable clinical conditions, inhaled ipratropium and tiotropium showed no significant changes in sputum volume, viscosity, or mucociliary clearance compared with placebo. In acute or procedural settings, such as bronchoscopy, nebulized ipratropium was associated with a reduction in bronchial secretion grade and cough frequency. Tiotropium treatment demonstrated decreases in sputum solid fraction and mucin content (MUC5AC and MUC5B). None of the included studies reported impairment of mucociliary clearance or serious adverse events related to treatment. Conclusion: Current evidence does not demonstrate a consistent effect of inhaled or nebulized anticholinergics on sustained reduction of bronchial secretions. However, their use does not appear to cause adverse changes in mucus production or clearance and may induce transient effects during acute cholinergic stimulation. Overall, the findings support a favorable safety profile of these agents regarding airway secretion management. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024575999.