Exhaled Hydrogen Sulphide as a Biomarker of Airways Disease in Asthma

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 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 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.