Protocol for a double-blind crossover randomised controlled trial to investigate inhalation challenge to assess...

Inducible laryngeal obstruction (ILO) remains a poorly understood condition in part due to lack of understanding about the underlying neuronal mechanisms. Many suffer delayed confirmed diagnosis as no standardised assessment exists. Based on previous work, we propose citric acid (CA) is the most appropriate inhalation agent for inducing upper airway reflex responses, with a view to developing an inhalation challenge test for ILO.

This is a single-centre, double-blind crossover study. The primary objective is to identify if CA inhalation challenge provokes laryngeal obstruction in patients with confirmed ILO. We will recruit 10 participants with ILO, 10 with refractory chronic cough (RCC) and 10 healthy controls. Each participant will undergo two inhalation challenges during laryngoscopy, with ascending concentrations of CA or saline control; they will be randomised sequentially by a computer-generated schedule to determine order of delivery. Follow-up is a telephone consultation. Randomisation and preparation of challenge agents will be by an unblinded study team member not involved in data analysis. Challenge agents will only be unblinded on study completion. Log₁₀ concentration of CA evoking ILO will be compared between patient groups using a one-way ANOVA, comparing participants with ILO and participants with RCC to healthy controls.

This will be the first randomised controlled trial to investigate the role of inhalation challenge as an assessment tool to evoke laryngeal obstruction in patients with confirmed ILO. If results prove CA inhalation challenge agent provokes ILO, it will provide new insights into neuronal mechanisms and support development of a standardised diagnostic test.