Patterns of Neurocircuitry Activation In Severe Asthma

Study Overview
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Brief Summary
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The overall purpose of the study is to compare the patterns of neurocircuitry activation in severe asthmatics vs. mild to moderate and healthy controls. The Investigators hypothesize that neurocircuitry activation increases with asthma severity, producing different neurocircuitry patterns for severe asthmatics than those of mild to moderate asthmatics or non-asthmatics.

Detailed Description
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To begin to further address possible relationships of asthma and brain function, the investigators propose the following hypothesis, patients with defined characteristics of severe asthma will have distinct patterns of persistent neurocircuitry activation. The investigators further propose that the detection of ongoing neurocircuitry activation occurs because of persistent and active airway inflammation in severe asthma. Finally, the investigators propose that the intensity of specific neurocircuitry activation will relate to the severity of underlying asthma.

Official Title
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Patterns of Neurocircuitry Activation In Severe Asthma

Conditions
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Lung Diseases

Intervention / Treatment
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* Other: functional Magnetic Resonance Imaging (research grade)
* Other: Cognitive Function Testing (non-diagnostic)
* Other: Asthma and Psychological Questionnaires (non-diagnostic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently enrolled in Severe Asthma Research Program III (2012-0571) study Has severe asthma Is a male or female with no health concerns that might affect the outcome of the study Provided a negative urine pregnancy test prior to visit (Females only) Capable and willing to grant written informed consent and cooperate with study procedures and requirements (investigator discretion) Is able to tolerate a simulated functional Magnetic Resonance Imaging brain scanning session Is able to give valid informed consent to participate by signing and dating a written consent form Exclusion Criteria: Uses psychotropic medication that might affect function of neurocircuitry implicated in our hypotheses (at the discretion of a study physician or Co-Investigator) Has one or more contraindications for functional Magnetic Resonance Imaging Has needle phobia or claustrophobia Unable to distinguish specific colors used in Stroop task History of a diagnosed Bipolar Disorder, Schizophrenia, or Schizoaffective Disorder Is a pregnant or lactating female Has had an upper or lower respiratory infection within 1 month of the visit Has unstable asthma as indicated by self-report of increased symptoms or increased beta-agonist use over the 2 weeks preceding the visit Is a current smoker (defined as smoked within the last year) or a former smoker with a history of >5 pack years Any condition which, in the opinion of the investigator, might interfere with participation in the study Inability or unwillingness to perform required study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe Asthmatics<br>Individuals with severe asthma that are already enrolled in the University of Wisconsin Severe Asthma Research Program III study will fill out asthma and psychological questionnaires (non-diagnostic), will undergo Cognitive Function Testing (non-diagnostic), and will undergo a simulated and actual functional Magnetic Resonance Imaging (research grade) scan. | Other: functional Magnetic Resonance Imaging (research grade)<br>* Subjects will undergo a simulated and actual functional Magnetic Resonance Imaging scan.<br>Other: Cognitive Function Testing (non-diagnostic)<br>* Subjects will take non-diagnostic cognitive function tests<br>Other: Asthma and Psychological Questionnaires (non-diagnostic)<br>* Subjects will fill out asthma and psychological questionnaires (non-diagnostic)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measures of Neural Activity | % signal change in brain insula detected by functional Magnetic Resonance Imaging | Visit 1 (1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Airway Cellular and Molecular Inflammatory Response- White Blood Cells | Cell differential counts- Total White Blood Cell count (sum of absolute counts for: Eosinophils, Monocytes, Neutrophils, Basophils, Lymphocytes) | Visit 1 (1 day) | 
| Airway Cellular and Molecular Inflammatory Response- Eosinophils | Cell differential counts- Eosinophils | Visit 1 (1 day) | 
| Airway Cellular and Molecular Inflammatory Response- Lymphocytes | Cell differential counts- Lymphocytes (absolute lymphocyte count, percent lymphocytes) | Visit 1 (1 day) | 
| Airway Cellular and Molecular Inflammatory Response- Monocytes/Macrophages | Cell differential counts- Monocytes/Macrophages (absolute monocyte count, percent monocytes) | Visit 1 (1 day) | 
| Airway Cellular and Molecular Inflammatory Response- Neutrophils | Cell differential counts- Neutrophils (absolute neutrophil count, percent neutrophils) | Visit 1 (1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, neurocircuitry, severe asthma, mild to moderate asthma, neurocircuitry patterns