Inhalation challenge to assess inducible laryngeal obstruction (ILO)

INTERVENTION: On the first two visits, participants will be asked to complete a standard cough challenge (where an increasing amount of challenge solution is inhaled through a mouth piece) at the same time as having a laryngoscopy (a small flexible tube passed through a nostril to rest just above the voice box). Participants will wear two bands around their chest to monitor breathing movements and a microphone to record sounds. The challenge agent given on each visit will be determined by randomisation and the person doing the test and the participant will not know which is being administered. Before and after the challenge simple breathing tests and questionnaires will be completed. After each dose challenge questions will be asked about throat and breathing symptoms. On the final visit some questionnaires and a simple breathing test will be performed. This is a crossover study, so the participants will be randomised to either a citric acid cough challenge or placebo challenge and will then have the other intervention on the next visit. The influences of gender and age on the ILO threshold will be assessed as will correlations with sensations evoked by the challenge, ILO symptoms (VCDQ), cough responses and flow volume loop changes. Comparisons will also be made between the subject groups for the different sensations experienced during the challenge, the coughing evoked and parameters extracted from the video and acoustic recordings using Linear Mixed Effects models. Correlations between the sensations will be analysed using within‐subject Bland Altman analyses. The level of citric acid evoking laryngeal obstruction in the ILO subjects is determined by the speech and language therapist who is viewing the larynx via the laryngoscope throughout testing. Laryngeal narrowing measures will be calculated at the glottic and supraglottic aperture. Image stills will be taken from the continuous recording, at end inspiration and end expiration. Breathing cycle will be verified by corre CONDITION: Chronic idiopathic cough and inducible laryngeal obstruction (ILO) ; Respiratory ; Chronic idiopathic cough, inducible laryngeal obstruction PRIMARY OUTCOME: The level of citric acid evoking laryngeal obstruction in the ILO subjects, as determined by the speech and language therapist who is viewing the larynx via the laryngoscope throughout testing SECONDARY OUTCOME: 1. Spirometry performed pre and post inhalation and flow volume loops; 2. Sensation: the following will be recorded on a 100 mm visual analogue scale after each inhalation challenge:; 2.1. Intensity of sense of taste ; 2.2. Intensity of symptoms in throat/upper chest; 2.3. Intensity of something in throat unable to clear; 2.4. Intensity of breathing difficulty ; 3. Objective cough monitoring measured throughout the inhalation challenge. Measurements will be recorded specifically 10 seconds after each incremental dose; 4. The VCDQ (acute) questionnaire and the Leicester Cough Questionnaire (acute) will be administered post inhalation challenge INCLUSION CRITERIA: All participants: 1. Aged >18 years 2. Non‐smoker for at least 6 months 3. No evidence of active asthma Healthy volunteers: 4. In good general health with no clinically relevant abnormalities based on the medical history, physical examination, vital signs 5. Aged >45 years to broadly age‐match to patient groups 6. No history of current or significant past respiratory disease, specifically a previous diagnosis of asthma ILO patients: 7. An established diagnosis of ILO based on clinical evaluation AND visualisation of laryngeal obstruction during a symptomatic episode Chronic cough patients: 8. Refractory/idiopathic chronic cough as defined by BTS guidelines (i.e. normal radiology, no airflow obstruction on spirometry and have asthma, gastro‐oesophageal reflux disease and nasal disease excluded based on symptoms/investigations and trials of treatment where appropriate)