Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol

Официальное название

Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol in Individuals With Cough Variant Asthma and Chronic Cough

Обзор

The objectives of this study are to determine the sensory-mechanical responses to Eucapneic Voluntary Hyperventilation (EVH) and Mannitol in individuals with cough variant asthma (CVA) and methacholine-induced cough with normal airway sensitivity (COUGH) and compare these responses to a control group of healthy individuals without asthma or chronic cough. We hypothesize: 1. EVH and Mannitol cause dyspnea, cough, small airway obstruction with resultant dynamic hyperinflation, gas trapping and autoPEEP in individuals with CVA and COUGH, but not healthy controls. 2. The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).

Подробное описание

Asthma is a chronic respiratory condition characterized by eosinophilic airway inflammation. Individuals with classic asthma experience paroxysmal symptoms including cough, wheeze, shortness of breath and chest tightness. Cough variant asthma (CVA) is asthma in which chronic cough (cough lasting eight weeks or more) is the sole or predominant symptom of asthma. The pathophysiologic mechanisms which differentiate asthma, CVA, and eosinophilic bronchitis without asthma are not fully understood. We have recently identified individuals with chronic cough who cough during methacholine but have normal airway sensitivity (ie. do not have asthma or CVA) (COUGH) and may or may not have eosinophilic bronchitis. The purpose of this research is to further explore the pathophysiologic basis for cough in these conditions using two 'indirect' inhalation challenge tests: eucapneic voluntary hyperventilation (EVH) and Mannitol), which induce osmotic and/or temperature changes in airway. Specifically, this study will collect preliminary data on the sensory-mechanical responses of individuals with CVA, COUGH and healthy controls to EVH and Mannitol Challenges.

Вмешательства

• Препарат Methacholine (MCh) Challenge Testing
  Visit 1: Informed consent, Baseline screening and pulmonary function tests and Low-dose methacholine challenge testing using partial and full flow-volume loops.
• Диагностический тест Eucapneic Voluntary Hyperventilation (EVH)
  Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.
• Препарат Mannitol Inhalation Kit
  Visit 2 or 3: Will be conducted in random order and subjects will perform one of the two challenge tests at either visit.

Первичные конечные точки

• Mid expiratory flows [Срок оценки: Time frame of the methacholine challenge varies between individuals. At provocative dose/ventilation causing a 20% decline in FEV1 (PD20 and PC20 respectively). On average, these occur about 15-25 minutes into the challenge test]

Вторичные конечные точки (5)

• Respiratory System Reactance (X5) [Срок оценки: After dose administration; will occur 2-5 minutes after dose]
• Peripheral Resistance (R5-R20) [Срок оценки: After dose administration; will occur 2-5 minutes after dose]
• Central Airway Resistance [Срок оценки: After dose administration; will occur 2-5 minutes after dose]
• Forced Vital Capacity (FVC) [Срок оценки: After dose administration; will occur 2-5 minutes after dose]
• FEV1/FVC [Срок оценки: After dose administration; will occur 2-5 minutes after dose]

Критерии участия

Критерии включения

• Individuals aged 18-65 years of age with CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:

• CVA: chronic cough (≥8 weeks) is the sole or predominant symptom and positive methacholine challenge (PC20 ≤ 16 mg/mL) and history of cough responding to specific asthma treatment (such as inhaled steroid or 1 week trial of bronchodilator);
• Methacholine-induced cough but normal airway sensitivity: chronic cough (≥8 weeks) is the sole or predominant symptom and negative methacholine challenges (PC20 > 16 mg/mL).
• Individuals aged 18-65 years of age with no history of asthma or chronic cough.

Критерии исключения

• an exacerbation necessitating a change in medication, emergency department visit or hospitalizations within the previous 4 weeks
• inability to perform acceptable spirometry
• medical contraindications to methacholine challenge testing
• smoking history in excess of 10 pack years Note: Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion; medication use will be recorded and examined in the analysis.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Канада · 1 центр

• Kingston Health Sciences Centre — Kingston

Идентификаторы

NCT: NCT03105843 · 2023-17

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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