Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma
Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma
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.
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
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.