Bronchodilating and Bronchoprotective Effects of Deep Inspirations in Asthma, Cough Variant Asthma and Chronic Cough With Normal Airway Sensitivity and Sensory-Mechanical Responses to High-Dose Methacholine in Healthy Normal Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 2
- 主要终点
- Mid expiratory flows
研究概览
简要总结
The objectives of this research are to compare (i) the bronchodilating and (ii) the bronchoprotective effects of deep inspirations (DIs) in individuals with: (a) asthma, (b) CVA, (c) methacholine-induced cough but normal airway sensitivity and .
(d) in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).
Hypotheses:
i. The bronchodilating effect of a DI will be: (a) absent or impaired in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in individuals with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).
ii. The bronchoprotective effect of a DI will be: (a) absent in individuals with classic asthma; (b) impaired in individuals with CVA; (c) preserved in those with methacholine-induced cough but normal airway sensitivity; and (d) preserved in healthy individuals (without asthma, chronic cough or asymptomatic airway hyperresponsiveness).
iii. Healthy individuals without asthma, chronic cough, or asymptomatic airway hyperresponsiveness, will not cough, or develop significant dyspnea, small airways obstruction or dynamic hyperinflation during high-dose methacholine bronchoprovocation.
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) and may or may not have eosinophilic bronchitis. The purpose of this research is to examine the pathophysiologic differences between three causes of chronic cough: asthma, cough variant asthma and methacholine-induced cough with normal airway sensitivity. The responses in healthy normal subjects are crucial to understand the clinical relevance of methacholine-induced cough with normal airway sensitivity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 asthma, CVA and individuals with methacholine-induced cough but normal airway sensitivity. The following definitions will be used:
- •asthma: episodic respiratory symptoms occurring in association with variable airflow obstruction (Canadian Asthma Consensus Report definition);
- •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
- •Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
- •Heart attack or stroke in last 3 months;
- •Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
- •Known aortic aneurysm;
- •Moderate airflow limitation <60% predicted or 1.5) is a relative contraindication;
- •Inability to perform acceptable quality spirometry;
- •Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
- •Pregnant or nursing mothers.
- •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
Asthma
Individuals diagnosed with asthma.
干预措施: Methacholine(MCh) Challenge Testing (Other)
Cough Variant Asthma
Individuals diagnosed with cough variant asthma.
干预措施: Methacholine(MCh) Challenge Testing (Other)
Mch-induced cough w/normal airway sensitivity
Individuals with chronic cough normal PC20 MCh(>16 mg/mL) & who cough during Mch challenge testing.
干预措施: Methacholine(MCh) Challenge Testing (Other)
Normal
Individuals with no history of asthma or chronic cough
干预措施: Methacholine(MCh) Challenge Testing (Other)
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 concentration of methacholine causing a 20% and 50% decline in FEV1 (PC20 and PC50 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 high-dose methacholine challenge testing (Visit 1) 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 PC20 and PC50 with that recorded at baseline.
次要结局
- percent fall in FEV1(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)
- peripheral resistance (R5-R20)(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)
- respiratory system reactance (X5)(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)
- Central airway resistance(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)
- Forced vital capacity (FVC)(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)
- FEV1/FVC(After methacholine administration; will occur 2-5 minutes after 1 dose of methacholine.)