The Effect of a Cold Air Eucapnic Hyperventilation Test on Lower Respiratory Airways in Healthy Volunteers and Patients With Asthma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- KU Leuven
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Proportional change in FEV1 after hyperventilation challenge
研究概览
简要总结
In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory phenotype induced by cold air inhalation differs between subjects with asthma and healthy subjects. Furthermore, we want to evaluate whether the CAEH test is more robust over time compared to the EVH test. Previously, our lab has demonstrated that submaximal exercise at subfreezing temperatures in a climate chamber (-5°C) induces an acute respiratory response in patients with asthma and in healthy subjects who have been exposed to high PM10 (unpublished data). Finally, This study will serve as a preliminary study for a subsequent prospective study in which the results and optimized protocol obtained in this study will be used to further evaluate the feasibility of using this CAEH as a diagnostic tool in asthma compared to EIB (CLARINET2). The present study is required to develop a standardized CAEH test in a safe and feasible manner. This study will also help to identify appropriate endpoints (FEV1, multiple breath washout test, biomarkers…) of the subsequent studies.
详细描述
In this study, we aim to develop a safe and feasible cold air (-15°C) eucapnic hyperventilation (CAEH) test protocol in which we can compare the lower airway responses between healthy volunteers and subjects with asthma. Consequently, we want to evaluate the effect of cold air inhalation on FEV1, respiratory symptoms, airway integrity, and local and systemic inflammation.
Primary endpoints
The primary endpoint of this study is to compare proportional change in FEV1, (% decrease) after a CAEH test in healthy volunteers and patients with mild to moderate asthma. Post-exposure will be calculated as a time-weighted average over the 30 min after the CAEH test. At each time point (pre-, 5, 10, 15, and 30 minutes post-exposure), FEV1 will be measured in triplicate.
Secondary endpoints
We want to evaluate whether and to what extent the inhalation of cold air during this CAEH test can induce changes in respiratory symptoms (including dyspnea, cough, mucus production, etc.), affects lower airway integrity (airway obstruction (FEV1/FVC), small airway dysfunction (FEF 25/75, lung ventilation inhomogeneity (LCI), bronchial hyperreactivity (PC20 AMP)) and whether it induces (local or systemic) inflammation (different biomarkers in sputum and blood, as defined in section 5.2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Age between 18 and 65 years old at time of signing informed consent
- •BMI between 18 and 28 kg/cm2
- •Ability to give informed consent and to comply with study protocol, in the investigator's judgement
- •Non-smoking or ex-smokers for at least 12 months with less than 10 pack years
- •Normal spirometry
- •Group specific:
- •Histamine positive healthy controls: histamine bronchial challenge test (< 8 mg/ml) at screening Healthy controls: histamine bronchial challenge test (≥ 8 mg/ml) at screening
- •Patients with asthma:
- •Physician-diagnosed asthma for at least 6 months
- •Post-bronchodilator FEV1 of ≥ 80% at screening
- •Documented airway reversibility either by means of post-bronchodilator reversibility of ≥ 12.% and ≥ 200 ml or in the previous 6 months or by means of documented airway hyperresponsiveness (histamine PC20 < 4 mg/ml) at screening
- •Asthma control questionnaire (ACQ) ≤ 1.5
- •Regular treatment with ICS with or without LABA (unchanged dose for at least 30 days) at a low or medium dose of ICS
排除标准
- •Previous history of intubation or admission to ICU due to asthma
- •Severe asthma exacerbation within one month prior to screening visit
- •Treatment with oral or systemic steroids within one month prior to screening visit
- •Previous treatment with biologics for asthma
- •Other major concurrent pulmonary (such as COPD, cystic fibrosis, sarcoidosis, interstitial lung disease, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, bronchiectasis) or cardiovascular disease
- •Pregnancy
研究组 & 干预措施
Healthy volunteers with negative histamine provocation challenge
Healthy volunteers with negative histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation
干预措施: Cold air challenge (Device)
Healthy volunteers with positive histamine provocation challenge
Healthy volunteers with positive histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation
干预措施: Cold air challenge (Device)
Patients with asthma
Patients with asthma will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation
干预措施: Cold air challenge (Device)
结局指标
主要结局
Proportional change in FEV1 after hyperventilation challenge
时间窗: After each hyperventilation challenge: pre, immediately, 3, 5, 10, 15 and 30 minutes after the challenge
The proportional change in FEV1 after hyperventilation challenges compared to baseline were measured.
次要结局
- Changes in symptoms(From the first hyperventilation challenge until 1 day after the second)
- Lung function changes(After each hyperventilation challenge)
- Inflammatory parameters(At baseline and after each hyperventilation challenge)