Redox Determinants of Severe Asthma (a Substudy of the Severe Asthma Research Program)

Redox Determinants of Severe Asthma: A Substudy of the NHLBI Severe Asthma Research Program

Hypotheses: 1) Airway pH regulation is abnormal in severe asthma; 2) In severe asthma, there is formation of cytotoxic nitrogen oxides and loss of beneficial nitrogen oxides in the airways

Specific Aim 1:Test hypothesis that airway pH regulation is abnormal in severe asthma.

1a) Determine the effects of systemic corticosteroids on breath pH in children with severe and mild to moderate asthma.

1b) Examine whether breath condensate pH and other biomarkers of oxidant stress can predict clinical outcomes in children with severe and mild to moderate asthma.

1c) Identify whether increased Th1/Th2 cytokine ratio, and abnormalities in airway glutaminase, G-SNO-reductase, VATPase, and carbonic anhydrase are associated with airway pH disturbance in children with severe asthma.

1d) Test whether rhinovirus infections, which reduce airway pH, persist longer or are more frequent in children with severe asthma than in children with mild to moderate asthma.

1e) Examine the relationship between gastroesophageal reflux and proximal airway pH in children with severe asthma and mild to moderate asthma.

Inclusion Criteria:

• At least 6 years old
• Asthma diagnosis by physician
• Current treatment with an inhaled corticosteroid medication

Exclusion criteria:

• Bronchiectasis
• Cystic Fibrosis
• Chronic Obstructive Pulmonary Disease