A Comprehensive Evaluation of the Impact of ATP on Laryngeal Symptoms, Hypersensitivity and Function

Bispebjerg Hospital30 enrolled

Overview

OBJECTIVES * To deliver a comprehensive model of laryngeal assessment, evaluating both the sensory and motor components of upper airway control and to relate this to symptom disturbance. * Determine if laryngeal control is altered by coughing and the impact of repeated coughing on overall laryngeal control and relaxation to its baseline state. * Evaluate if cell damage and tissue inflammation (including exposure to ATP) modulates laryngeal hypersensitivity and function, by using a comprehensive array of test modalities. AIM To utilise state-of-the-art comprehensive assessment tools to evaluate laryngeal hypersensitivity and function in a cohort of individuals with chronic refractory cough and control subjects. The test modalities utilise direct stimulation of the laryngeal adductor reflex, measurement of laryngeal EMG and assessment of functional laryngeal response to an inhalational challenge with laryngoscopic techniques. HYPOTHESIS Physiological markers of laryngeal hypersensitivity and dysfunction are highly prevalent in patients with chronic refractory cough and manifestations are driven by ATP stimulation. OUTCOME MEASURES Measurements of laryngeal symptomatology will be measured over a run-in period and during challenge testing. Laryngeal relaxation will be studied using our novel tracking software capability, combining endoscopic imaging and physiological measurements of diaphragm activation.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Chronic Refractory Cough

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria (controls) * Age ≥ 18 years * Healthy - with no history of any medical conditions * No history of asthma / allergies * Normal spirometric indices * Non smoker Inclusion criteria (patients) * Age ≥ 18 years * Chronic cough as per ATS definition (\>8 weeks duration) * High symptom burden (i.e. Cough VAS \>= 40 mm at the screening visit) * Chest radiograph or CT within 3 years of the screening visit with no abnormalities considered to contribute to chronic cough * For patients with asthma: a confirmed diagnosis of asthma on the basis of asthma symptoms and reversible airflow obstruction (BDR 200mls + 12% change post bronchodilator and/or positive bronchoprovocation test). Exclusion criteria * Current smoker or a smoking history of \>10 pack years * Asthma that is not well-controlled, as per international asthma guidelines as specified by Global Initiative for Asthma (GINA) * Recent exacerbation of cough or asthma within 4 weeks of inclusion * Pregnancy or childbearing potential and no contraceptive treatment * Respiratory tract infection within 4 weeks of inclusion * Currently taking any of the following medications: * ACE inhibitors and within 3 months of inclusion * Antitussives (opioids, pregabalin, gabapentin, amitriptyline, nortriptyline or over-the-counter medications) within 2 weeks of inclusion * Medical treatments for GORD, eosinophilic bronchitis or other cough related conditions, initiated or changed (i.e. not in a stable regimen) for 4 weeks prior to inclusion. * Medical history of COPD or chronic bronchitis * Medical conditions/history or other circumstances which, in the judgement of the investigator, could increase the risk of adverse events or bias the study results

Outcomes

Primary Outcomes

Maximal decrease in glottic anterior angle (degrees) during challenge testing

The maximal decrease in glottic anterior angle during challenge testing

Time frame: Baseline measurement is taken immediately before beginning the challenge test. Minimal value is taken from continuously measured glottic anterior angle, from immediately after baseline measurement and until immediately after challenge testing

Maximal increase in glottic anterior angle (degrees) after challenge testing

The difference between the minimal glottic anterior angle observed during challenge testing and the maximal glottic anterior angle observed from immediately after challenge testing and until 5 minutes after challenge testing

Time frame: During challenge testing and from immediately after challenge testing until 5 minutes after challenge testing

Maximal laryngeal relaxation time (seconds)

Maximum time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

Time frame: At baseline, during challenge testing and from immediately after challenge testing until 5 minutes after challenge testing

Change in laryngeal relaxation time (seconds) during challenge testing

Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

Time frame: At baseline and immediately after challenge testing

Change in laryngeal relaxation time (seconds) in recovery

Change in time for glottic angle to normalise (i.e. achieve a value equal to or above the value prior to sensory stimulus)

Time frame: Immediately after challenge testing and at 5 minutes after challenge testing

Secondary Outcomes

Cough VAS (0-100 mm)

This is a descriptive delineation of the ATP/Cough VAS dose/response relationship. The measure is taken at multiple times (see Time Frame) and visualised graphically.

Time frame: At baseline, during challenge testing at minutes 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 3:30 and 4:00 (from immediately after an administered dose of ATP and until 15 seconds after an administered dose) and immediately after challenge testing

Cough count and frequency

This is a descriptive delineation of the ATP/Cough count dose/response relationship. The measure is taken at multiple times (see Time Frame) and visualised graphically.