Overview

The primary purpose of this study is to provide preliminary data to determine if an acute increase in airway inflammation, provoked by an inhaled allergen challenge, is associated with an increase in microglial activation and may inform whether individuals with asthma, in the long-term, are at increased risk for neurodegeneration, cognitive decline, and forms of dementia. Though in the long-term airway inflammation may be associated with neurodegenerative processes, these changes reflect the accumulation over a lifetime of allergen exposures and disease-related changes. This relationship between peripheral inflammation and microglial activation is analogous to the impact of sleep loss. No single night of poor sleep will lead to long-term change in brain structure, function, or cognitive function, but the accumulation of frequent and repeated sleep loss over a lifetime has been shown to have a major impact. These data will be used for a larger scale study to determine if asthma is a risk factor for neurodegeneration, and will inform brain health issues in asthma more broadly.

Eligibility

Inclusion Criteria:

• Male or female with no health concerns that might affect the outcome of the study
• Physician diagnosis of asthma for at least six months prior to screening (can be determined at the discretion of an asthma/allergy physician member of the study team)
• At least a 20% decrease in forced expiratory volume (FEV1) during the immediate response following inhaled allergen challenge
• FEV1 > 70% at baseline
• Positive immediate skin test for allergies to ragweed, cat dander, or house dust mite (historical data documented within the last 5 years is acceptable)
• Women of child-bearing potential (WCBP) must have a negative urine pregnancy test for human chorionic gonadotropin (hCG) at screening and within 48 hours of the inhaled allergen challenge(s) and the positron emission tomography (PET) scans. WCBP must agree to use a medically-acceptable form of birth control for the duration of the study (medically-acceptable birth control methods can include: abstinence, barrier methods, oral contraceptives, injection contraceptives or skin absorption contraceptives).
• Asthma medications consisting of only inhaled beta-agonists taken as needed or leukotriene inhibitors
• Ability to tolerate a simulated functional magnetic resonance imaging (fMRI) brain scanning session
• In the opinion of the investigator, capable and willing to grant written informed consent and cooperate with study procedures and requirements
• High-affinity TSPO-binding genotype. Mixed (high/low) binding-affinity genotype may be included at principal investigator's (PI) discretion.

Exclusion Criteria:

• Current smoker (defined as more than 0.5 pack per week for the past 6 months and any smoking within two weeks of study procedures) or has a smoking history exceeding 5 pack years within the last 10 years
• Currently receiving immunotherapy
• Not able to withhold medication(s) as outlined by the study
• Use of psychotropic medication that might affect function of neurocircuitry implicated in the investigator's hypotheses at the discretion of the PI or Co-Investigator (Co-I)
• Needle phobia or claustrophobia
• Major health problems such as autoimmune disease, heart disease, uncontrolled hypertension or lung diseases other than asthma. The listed health problems are definitively exclusionary, but decisions regarding major health problems not listed will be based upon the judgment of the investigator.
• Pre-existing chronic infectious disease
• Use of inhaled corticosteroids or oral corticosteroids within 1 month of screening
• Use of an investigational drug within 30 days of entering the study. This criteria will be reviewed on a case by case basis by the principal investigators or co-investigator to determine appropriate washout period. Appropriate wash out period may be greater than 30 days depending on the half-life of the investigational drug. Participants may be eligible for study participation after completing the washout period designated by the PI or Co-I (physician only).
• Any MRI incompatibility as determined by WIMRs most current MRI screening form
• Does not fit in the MRI scanner
• History of a diagnosed Bipolar Disorder, Schizophrenia, or Schizoaffective Disorder
• History of serious head trauma or seizure disorder (can be included at the discretion of the PI or Co-I)
• Unable, in the judgement of the investigator, to comply with directions and/or tolerate the procedures required for participation in this study
• Pregnant or breast-feeding or has a planned pregnancy during the course of the study
• History of positive COVID-19 test (nasal swab or antibody test)
• Have corrected vision and are not able to wear contacts or see sufficiently well to read without glasses or contacts, as glasses will not fit in the PET/MR head coil
• Any other medical condition or disease that would impact subject safety or data integrity in the opinion of the PIs