Sensory-Mechanical Responses to Eucapneic Voluntary Hyperventilation and Mannitol in Individuals With Cough Variant Asthma and Chronic Cough
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Mid expiratory flows
研究概览
简要总结
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:
- 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.
- The sensory-mechanical responses to both hyperosmolar challenges (EVH and Mannitol) are comparable within groups (CVA, COUGH and healthy controls).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Cough Variant Asthma
Individuals diagnosed with Cough variant asthma
干预措施: Eucapneic Voluntary Hyperventilation (EVH) (Diagnostic Test)
Cough Variant Asthma
Individuals diagnosed with Cough variant asthma
干预措施: Methacholine (MCh) Challenge Testing (Drug)
Methacholine-induced cough
Individuals with chronic cough and negative methacholine challenge
干预措施: Methacholine (MCh) Challenge Testing (Drug)
Methacholine-induced cough
Individuals with chronic cough and negative methacholine challenge
干预措施: Eucapneic Voluntary Hyperventilation (EVH) (Diagnostic Test)
Control
Individuals with no history of asthma or chronic cough
干预措施: Eucapneic Voluntary Hyperventilation (EVH) (Diagnostic Test)
Control
Individuals with no history of asthma or chronic cough
干预措施: Methacholine (MCh) Challenge Testing (Drug)
Control
Individuals with no history of asthma or chronic cough
干预措施: Mannitol Inhalation Kit (Drug)
Cough Variant Asthma
Individuals diagnosed with Cough variant asthma
干预措施: Mannitol Inhalation Kit (Drug)
Methacholine-induced cough
Individuals with chronic cough and negative methacholine challenge
干预措施: Mannitol Inhalation Kit (Drug)
结局指标
主要结局
Mid expiratory flows
时间窗: 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
The bronchodilating effect of a DI will be examined using responses to the challenge testing (Visit 2/3) in these subgroups by comparing the mid-expiratory flow difference between the partial (PEF) and full maximal flow-volume (MEF) loops at 40% above Residual Volume (RV) from the forced vital capacity (FVC) (PEF40 and MEF40 respectively) at provocative dose of 4.5% saline causing a 20% decline in FEV1 (PD20 (HS)) and provocative minute ventilation causing a 20% decline in FEV1 (PC20 (EVH)) with that recorded at baseline.
次要结局
- Respiratory System Reactance (X5)(After dose administration; will occur 2-5 minutes after dose)
- Peripheral Resistance (R5-R20)(After dose administration; will occur 2-5 minutes after dose)
- Central Airway Resistance(After dose administration; will occur 2-5 minutes after dose)
- Forced Vital Capacity (FVC)(After dose administration; will occur 2-5 minutes after dose)
- FEV1/FVC(After dose administration; will occur 2-5 minutes after dose)
研究者
Dr. Diane Lougheed
Professor of Medicine
Queen's University