A Cross-sectional Study to Measure Cough in Severe Asthma
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Cough Frequency Measurement
研究概览
简要总结
This study aims to characterise cough in severe asthma through an observational cross-sectional analysis of patients stratified by inflammatory biomarker profile using a number of subjective and objective cough measurement tools.
详细描述
This study will use a combination of subjective and objective cough measures to assess the frequency of cough as well as its related morbidity in severe asthmatics. Comparisons will be made between T2-High, T2-Low and T2-intermediate patients defined using a composite biomarker profile (blood eosinophil count and FeNO) to assess the role of cough in each and these results will be compared to the transcriptomic and proteomic measurements in the RASP-UK where the same biomarker profiling is being used to define clinical sub-groups of severe asthma. This study aims to also improve characterisation of the T2-Low population and identify possible mechanisms for the pathophysiology of this group.
60 patients are expected to be recruited to the study. Patients will be provided with an information sheet and have a telephone follow-up after at least 24 hours to ask if they remain interested in participation and if so, they will then be asked back for a baseline visit.
Three groups of severe asthmatics will be recruited (as described in appropriate section) and undergo the following procedures:
-
Demographic details, height, weight, spirometry, FeNO and vital signs
-
Patient reported outcomes:
-
Asthma Mini-Asthma Quality of Life Questionnaire (mini-AQLQ) - abbreviated version of Juniper AQLQ
-
Asthma Control Questionnaire (ACQ-5 (5 questions);
-
Leicester Cough Questionnaire, the Cough-specific quality-of-life Questionnaire and Cough Hypersensitivity Questionnaire will be used to assess the impact of cough;
-
Visual analogue scales (VAS) for cough (VASc) and urge to cough (VASu) will be used as a measure of cough severity.
-
Blood samples - a sample of blood will be taken for whole blood transcriptomic and serum analyses
-
Citric acid cough challenge test will be used to measure cough reflex sensitivity in each phenotype.
-
Spontaneous sputum sample - if patients produce a sputum sample during spirometry or citric acid challenge, this will be recorded and the sample will be retained for sputum differential cell count and storage of processed soluble components.
-
On completing the above procedures, patients will be asked to wear a validated ambulatory cough monitor (Leicester Cough Monitor) for a 24-hour period to assess the frequency of cough and if they agree, will be fully instructed in its use.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Baseline FEV1 ≤50% of predicted or ≤ 1.0L
- •Asthma exacerbation within 28 days before the time of informed consent or during screening
- •Major episode of infection requiring any of the following:
- •Admission to hospital for ≥24 hours within the 28 days before the time of informed consent
- •Treatment with intravenous antibiotics within the 28 days before the time of informed consent or during Screening
- •Treatment with oral antibiotics within the 14 days before the time of informed consent or during Screening
- •For adults: Active tuberculosis (TB) requiring treatment within the 12 months before the time of informed consent (patients are also required to have no recurrence of symptoms in the 12 months following completion of TB treatment), or
- •Known history of severe clinically significant immunodeficiency, including, but not limited to, human immunodeficiency virus infection and/or currently receiving or have historically received intravenous Ig for treatment for immunodeficiency Note: Immunodeficiency encompasses a wide spectrum of human conditions and/or diseases. A relative IgG deficiency that is thought, but not proven, to be a feature of severe asthma would not be exclusionary for the study.
- •Diagnosis or history of malignancy, or current investigation for possible malignancy
- •Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or affect the ability to participate in the study
- •History of alcohol, drug, or chemical abuse that would impair or risk the patient's full participation in the study, in the opinion of the investigator
- •Current smoker or former smoker with a smoking history of >15 pack-years A current smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥30 days within the 24 months before the time of informed consent and for whom cotinine testing is positive.
- •A former smoker is defined as someone who has smoked one or more cigarettes per day (or marijuana or pipe or cigar) for ≥30 days in his or her lifetime (as long as the 30-day total did not include the 24 months before the time of informed consent) and for whom cotinine testing is negative.
- •A pack-year is defined as the average number of packs per day times the number of years of smoking.
- •Initiation of or change in allergen immunotherapy within three months before the time of informed consent
- •Treatment with an investigational agent within 30 days of informed consent or 5 half-lives of the investigational agent, whichever is longer
- •Female patients who are pregnant or lactating
研究组 & 干预措施
D - T2 Intermediate
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL OR high FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Leicester Cough monitor (Device)
A - T2 High Severe Asthmatics
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL andhigh FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Citric acid (Drug)
A - T2 High Severe Asthmatics
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL andhigh FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Leicester Cough monitor (Device)
A - T2 High Severe Asthmatics
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL andhigh FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: fractional exhaled nitric oxide testing (FeNO) (Other)
A - T2 High Severe Asthmatics
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL andhigh FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Patient reported outcome measures (Other)
B - T2 Low Severe Asthmatics
Severe asthmatic patients with eosinophil count ≤ 0.15x10^9/mL and low FeNO levels <20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Citric acid (Drug)
B - T2 Low Severe Asthmatics
Severe asthmatic patients with eosinophil count ≤ 0.15x10^9/mL and low FeNO levels <20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Leicester Cough monitor (Device)
B - T2 Low Severe Asthmatics
Severe asthmatic patients with eosinophil count ≤ 0.15x10^9/mL and low FeNO levels <20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: fractional exhaled nitric oxide testing (FeNO) (Other)
B - T2 Low Severe Asthmatics
Severe asthmatic patients with eosinophil count ≤ 0.15x10^9/mL and low FeNO levels <20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Patient reported outcome measures (Other)
C - Mild/Moderate Asthmatics
mild/moderate severe asthmatics (defined as step 2/3 using the GINA classification of severity) recruited from general respiratory clinics in the Belfast HSC Trust Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Citric acid (Drug)
C - Mild/Moderate Asthmatics
mild/moderate severe asthmatics (defined as step 2/3 using the GINA classification of severity) recruited from general respiratory clinics in the Belfast HSC Trust Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Leicester Cough monitor (Device)
C - Mild/Moderate Asthmatics
mild/moderate severe asthmatics (defined as step 2/3 using the GINA classification of severity) recruited from general respiratory clinics in the Belfast HSC Trust Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: fractional exhaled nitric oxide testing (FeNO) (Other)
C - Mild/Moderate Asthmatics
mild/moderate severe asthmatics (defined as step 2/3 using the GINA classification of severity) recruited from general respiratory clinics in the Belfast HSC Trust Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Patient reported outcome measures (Other)
D - T2 Intermediate
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL OR high FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Citric acid (Drug)
D - T2 Intermediate
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL OR high FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: fractional exhaled nitric oxide testing (FeNO) (Other)
D - T2 Intermediate
Severe asthmatic patients with eosinophil count ≥ 0.15x10^9/mL OR high FeNO levels ≥20 ppb.
Interventions include 24 hour ambulatory cough monitoring (Leicester Cough Monitor), citric acid cough challenge, fractional exhaled nitric oxide (FeNO) testing, patient reported outcome measures and blood, urine and sputum sampling
干预措施: Patient reported outcome measures (Other)
结局指标
主要结局
Cough Frequency Measurement
时间窗: Baseline
Objectively measure cough frequency (measured as hours per hour over a 24 hour monitoring period) in different phenotypes of severe asthma and a mild/moderate control group using a validated ambulatory cough monitor (Leicester Cough Monitor)
Cough Reflex Sensitivity (Citric Acid Cough Challenge)
时间窗: Baseline
To objectively measure cough reflex sensitivity in different phenotypes of severe asthma and a mild.moderate control group using citric acid cough challenge testing. Patients are asked to inhale increasing concentrations of citric acid solutions and the cough response to each is measured in the 15 seconds following. The final outcome endpoint is described as the concentrations needed to cause 2 coughs (C2)
次要结局
- Asthma Control Questionnaire(Baseline)
- Asthma Quality of Life Questionnaire(Baseline)
- Leceister Cough Questionnaire(Baseline)
- Cough Quality of Life Questionnaire(Baseline)
- Fractional Exhaled Nitric Oxide (FeNO)(Baseline)
- Blood Eosinophil Count(Baseline)
研究者
Liam Heaney
Professor
Queen's University, Belfast