Imaging Study of the Lungs During an Allergic Asthma Attack

Not Applicable

Completed

Conditions: Atopy
Asthma

Interventions: Biological: Standardized Cat Allergen Extract and Standardized Dust Mite Allergen
Radiation: Computed Tomography imaging, functional Positron Emission Tomography imaging
Drug: Nebulized methacholine inhalation

Registration Number: NCT01547286

Lead Sponsor: Massachusetts General Hospital

Brief Summary: Asthma is a disease of rapidly increasing incidence that already affects more than 17 million people in the United States alone. 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. The purpose of this study is using Positron Emission Tomography - Computed Tomography imaging to evaluate how the blood flow changes in the lungs during an asthma attack induced by allergens.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allergic asthmatic	Standardized Cat Allergen Extract and Standardized Dust Mite Allergen	-
Allergic asthmatic	Computed Tomography imaging, functional Positron Emission Tomography imaging	-
Allergic asthmatic	Nebulized methacholine inhalation	-

Primary Outcome Measures

Name	Time	Method
Percentage Change in the Ratio of Mean-normalized Perfusion Within Ventilation Defective Regions Relative to Outside	7 hours after allergen administration	Blood flow relative to the mean blood flow of the lung (mean normalized perfusion) inside areas that have reduced ventilation (Vdefs) relative to outside the Vdefs. Or, another way of writing this is: (Blood flow inside Vdefs/mean blood flow of the lung)/(Blood flow outside Vdefs/mean blood flow of the lung).

Secondary Outcome Measures

Name	Time	Method
Coefficient of Variation Squared of Perfusion	7 hours after allergen administration	Coefficient of variation squared of the perfusion in the imaged lung. This measures the overall heterogeneity of perfusion in the imaged lung.