Asthma
Conditions
Keywords
Exhaled hydrogen sulphide
Brief summary
The purpose of this study will be to determine whether there is any role for measuring Hydrogen Sulphide (H2S) in the exhaled breath in terms of management of the patient with asthma. The investigators will recruit patients with a range of severity of asthma and health volunteers. Levels of Hydrogen Sulphide will be measured in exhaled breath and blood. Also exhaled Nitric Oxide, Spirometry and asthma symptom scores will be measured at each study visit. Participants will attend either 2 or 4 separate visits. The investigators will determine whether there is a relationship between exhaled Hydrogen Sulphide and asthma severity.
Detailed description
Objectives: 1. Perform a cross-sectional study in non-asthmatic subjects and asthmatic subjects of varying severities of the levels of Hydrogen Sulphide in exhaled breath in relation to the severity and control of asthma 2. Compare the levels of exhaled Hydrogen Sulphide with exhaled Nitric Oxide. We will recruit 30 health volunteers and 90 patients with a range of severity of asthma. Particpants will attend for either 2 or 4 visits. At these visits the following measurements will be taken: 1. Exhaled Hydrogen Sulphide 2. Serum Hydrogen Sulphide 2\. Exhaled Nitric Oxide 3. Spirometry 4. Asthma Symptom Score (ACQ) The investigators will use a Hydrogen Sulphide UV fluorescent machine Model T101 (0-50 ppb to 0-20 ppm) (Cal-Bay Control Inc, USA) to measure directly on line exhaled breath Hydrogen Sulphide. This method has been used previously in normal people, but we will first determine whether there is an exhaled flow-dependence on the measurement of H2S levels. The investigators will use a hand-held Nitric Oxide machine (NO Breath) to measure Nitric Oxide in exhaled breath. Subjects must have asthma according to one or more of the following criteria documented in the last 12 months: 1. Improvement in FEV1 (forced expiratory volume at one second) ≥ 12% and 200ml predicted after inhalation of 400 mcg salbutamol 2. Airway hyper-responsiveness (PC20 \<8mg/ml) 3. Diurnal variation in PEF (peak expiratory flow): amplitude % mean of twice daily PEF \> 8% 4. Decrease in pre-bronchodilator FEV1 \>12% and \>200mls within 4 weeks after tapering treatment with one or more of the following drugs: inhaled corticosteroids, oral corticosteroids, long-acting beta-agonists, long-acting beta-agonists and short-acting beta-agonists. PLUS A history of wheeze occurring spontaneously or on exertion
Interventions
None listed
Sponsors
Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
All patients must be able to give informed consent. The definition of the severity of their asthma will be according to the GINA (Global Initiative for Asthma) guidelines dependent on the amount of therapy needed to control asthma. The investigators will also include at least 45 patients with severe asthma defined on the basis of: Uncontrolled asthma: three or more of the following features present in any week in the previous 4 weeks: * Daytime symptoms more than twice per week * Any limitation of activities * Nocturnal symptoms once or more per week * Need for reliever treatment more than twice per week * Pre bronchodilator FEV1 \<80% predicted or personal best OR * Frequent severe exacerbations (≥2 per year) OR * Require prescription of daily or alternate day oral corticosteroids (OCS) to achieve asthma control despite the prescription of high dose inhaled corticosteroids (\>1000mcg fluticasone propionate daily or equivalent) or maintenance oral corticosteroids plus a long acting beta agonist or one other controller medication (for example anti-cholinergics, leukotriene receptor antagonists or theophylline). Diagnosis of asthma for the asthma cohort: Subjects must have asthma according to one or more of the following criteria documented in the last 12 months * improvement in FEV1 ≥ 12% and 200ml predicted after inhalation of 400 mcg salbutamol * airway hyper-responsiveness (PC20 \<8mg/ml) * diurnal variation in PEF: amplitude % mean of twice daily PEF \> 8% * decrease in pre bronchodilator FEV1 \>12% and \>200mls within 4 weeks after tapering treatment with one or more of the following drugs: inhaled corticosteroids, oral corticosteroids, long-acting beta-agonists, long-acting beta-agonists and short-acting beta-agonists. PLUS a history of wheeze occurring spontaneously or on exertion
Exclusion criteria
* Current smoker, or Ex-smoker with a \>10 year pack history or having smoked within the past 6 months. * Significant alternative diagnoses that may mimic or complicate asthma, in particular dysfunctional breathing, panic attacks, and overt psychosocial problems (if these are thought to be the major problem rather than in addition to severe asthma) * Significant other primary pulmonary disorders in particular pulmonary embolism, pulmonary hypertension, interstitial lung disease and lung cancer * Subjects with emphysema and bronchiectasis should only be excluded if this is thought to be the major pulmonary disorder rather than in addition to severe asthma * Diagnosis or current investigation of occupational asthma * Any subjects currently participating, or having participated within 3 months of the first dose in a study using a new molecular entity, or the first dose in any other study investigating drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hydrogen Sulphide in Exhaled Breath | At baseline visit | Level of hydrogen sulphide in exhaled breath measured as parts per billion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 | At baseline visit | Forced expiratory volume in one second as percent of predicted value (%) |
| FVC (Forced Vital Capacity) | At 4 visits which occur during the study duration, up to 1 year | Forced vital capacity as per cent of predicted |
| Exhaled Nitric Oxide | At 4 visits which occur during the study duration, up to 1 year | Levels of nitric oxide in exhaled breath in parts per billion |
| Blood Hydrogen Sulpide Level | At 4 visits which occur during the study duration, up to 1 year | Hydrogen Sulpide level measurements from blood |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Healthy participants | 20 |
| Mild-moderate Mild-moderate asthma patients | 5 |
| Severe Severe asthma patients | 45 |
| Total | 70 |
Baseline characteristics
| Characteristic | Mild-moderate | Severe | Total | Healthy |
|---|---|---|---|---|
| Age, Continuous | 55.6 years STANDARD_DEVIATION 5.9 | 55.9 years STANDARD_DEVIATION 11.5 | 54.5 years STANDARD_DEVIATION 9.1 | 51.1 years STANDARD_DEVIATION 3.5 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 5 participants | 45 participants | 70 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 31 Participants | 47 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 14 Participants | 23 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 5 | 0 / 45 |
| other Total, other adverse events | 0 / 20 | 0 / 5 | 0 / 45 |
| serious Total, serious adverse events | 0 / 20 | 0 / 5 | 0 / 45 |
Outcome results
Primary
Hydrogen Sulphide in Exhaled Breath
Level of hydrogen sulphide in exhaled breath measured as parts per billion
Time frame: At baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Hydrogen Sulphide in Exhaled Breath | 5.0 parts per billion | Standard Error 0.6 |
| Mild-moderate | Hydrogen Sulphide in Exhaled Breath | 3.2 parts per billion | Standard Error 1 |
| Severe | Hydrogen Sulphide in Exhaled Breath | 4.9 parts per billion | Standard Error 1.3 |
p-value: >0.05t-test, 2 sided
Secondary
Blood Hydrogen Sulpide Level
Hydrogen Sulpide level measurements from blood
Time frame: At 4 visits which occur during the study duration, up to 1 year
Population: Data not collected
Secondary
Exhaled Nitric Oxide
Levels of nitric oxide in exhaled breath in parts per billion
Time frame: At 4 visits which occur during the study duration, up to 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Exhaled Nitric Oxide | 25.41 parts per billion | Standard Error 6.3 |
| Mild-moderate | Exhaled Nitric Oxide | 39.42 parts per billion | Standard Error 13.6 |
| Severe | Exhaled Nitric Oxide | 39.45 parts per billion | Standard Error 2.2 |
Secondary
FEV1
Forced expiratory volume in one second as percent of predicted value (%)
Time frame: At baseline visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | FEV1 | 98.9 per cent of predicted value | Standard Error 4.1 |
| Mild-moderate | FEV1 | 92.0 per cent of predicted value | Standard Error 11.1 |
| Severe | FEV1 | 73.6 per cent of predicted value | Standard Error 4.3 |
Secondary
FVC (Forced Vital Capacity)
Forced vital capacity as per cent of predicted
Time frame: At 4 visits which occur during the study duration, up to 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | FVC (Forced Vital Capacity) | 105.1 per cent of predicted value (%) | Standard Error 4.3 |
| Mild-moderate | FVC (Forced Vital Capacity) | 97.40 per cent of predicted value (%) | Standard Error 15.3 |
| Severe | FVC (Forced Vital Capacity) | 88.22 per cent of predicted value (%) | Standard Error 3.5 |