Imaging Study of the Lungs During an Allergic Asthma Attack

Asthma is a disease of rapidly increasing incidence that already affects more than 17 million people in the United States alone. It is of major importance to understand the mechanisms responsible for underlying mechanical and physiological changes that occur during asthma exacerbations. The effect of asthma on the pulmonary vasculature is virtually unknown. It has long been known that areas of severely reduced airflow occur in asthma and contribute significantly to the impairment of gas exchange in this disease. However, the extent to which local blood flow changes during an asthmatic attack is unclear. This proposal is designed to evaluate the relevance of potential mechanisms responsible for the blood flow defects seen in our Positron Emission Tomography studies of subjects with asthma and identify factors modifying that perfusion distribution. With this knowledge, it is hoped that a more focused basic research is motivated to understand the fundamental mechanisms behind these processes ultimately targeted to improved asthma therapy. Comparing these measures in healthy subjects and asthmatics patients may lead to methods to improve patient care.

Inclusion criteria

• Mild asthma is defined in the National Institutes of Health 2002 guidelines for the Diagnosis and Management of Asthma. Briefly, people with mild asthma are defined as those with symptoms greater than 2 times a week but less than once per day with normal Forced Expired Volume in 1 second (> 80% predicted)
• Clinical history of allergic symptoms to cat or dust mite allergen and demonstrated skin reactivity
• Life-long absence of cigarette smoking (defined as a lifetime total of less than 5 pack-years); none in 5 years
• Willing and able to give informed consent
• Expressed the desire to participate in an interview with the principal investigator

Exclusion criteria

• Women of childbearing potential who are documented to be pregnant (based on blood testing) or who are nursing.
• The presence of spontaneous asthmatic episode or clinical evidence of upper respiratory tract infection within the previous 6 weeks.
• Participation in research study involving a drug or biologic during the 30 days prior to the study.
• Intolerance to albuterol, atropine, or lidocaine.
• Antihistamines within 7 days of the screening visit.
• Known exposure to agents that are associated with pulmonary disease (i.e. asbestos, silica).
• Presence of other known pulmonary disease, coronary disease, congestive heart failure, ventricular arrhythmias, history of a cerebrovascular accident, renal failure (or creatinine > 1.5, if known), history of anaphylaxis, cirrhosis or presence of a significant disease, which in the opinion of the principal investigator, would pose a significant risk for the subject or confound the results of the study.
• Use of systemic steroids, increased use of inhaled steroids, beta blockers and mono-amine oxidase inhibitors or a visit for an asthma exacerbation within

1 month of the screening visit.

• A history of asthma-related respiratory failure requiring intubation.
• A history of hospitalization for asthma.
• Subjects with a high possibility of poor compliance with the study as judged by the principal investigator.
• History of contrast dye allergy.
• Unresponsive to bronchodilator agents.
• Quantitative skin prick test at or below a dilution level of standardized cat allergen extract of 1:2048 (4.88 bioequivalent allergy unit/ml)for subjects being challenged with cat allergen.
• Quantitative skin prick test at or below a dilution level of standardized mite allergen extract of 1:2048 (4.88 bioequivalent allergy unit/ml)for subjects being challenged with either mite allergen.
• Subjects who, by participating in one of these studies, will have a cumulative radiation dose exceeding the maximum yearly recommended dose for a research subject (50 milliSieverts).
• Previous participation in one of the protocols in this proposal.
• Contraindication to methacholine challenge testing (Forced Expired Volume in 1 second < 50% predicted or < 1L, heart attack or stroke in last 3 months, uncontrolled hypertension, or known aortic aneurysm).
• Body Mass Index > 32