Protocol for a double-blind crossover randomised controlled trial to investigate inhalation challenge to assess inducible laryngeal obstruction: CH-ILO
Author(s)
Type
Journal Article
Abstract
Introduction
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.
Methods and analysis
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.
Conclusion
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.
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.
Methods and analysis
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.
Conclusion
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.
Date Issued
2025-04-14
Date Acceptance
2024-10-16
Citation
ERJ Open Research, 2025, 11 (2)
ISSN
2312-0541
Publisher
European Respiratory Society
Journal / Book Title
ERJ Open Research
Volume
11
Issue
2
Copyright Statement
Copyright ©The authors 2025 This version is distributed under the terms of the Creative Commons Attribution Non- Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40230432
PII: 00774-2024
Subjects
CHRONIC COUGH
HEALTH
Life Sciences & Biomedicine
QUESTIONNAIRE
Respiratory System
Science & Technology
STATEMENT
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 007742024
Date Publish Online
2025-03-01