Microglia Activation in Asthma

Inclusion criteria

• Individuals with no health concerns that might affect the outcome of the study.
• Age 18-75 years of age.
• 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). Mild asthma will be defined as asthma that is well controlled with low-intensity treatment, e.g., SABA alone, as-needed low-dose ICS-LABA, or low-dose ICS plus as-needed SABA.
• An increase in FEV1 > 10% predicted after up to 8 puffs of albuterol OR positive methacholine defined as PD20 ≤ 400 mcg. (Historical data that is approved by the investigator is acceptable).
• FEV1 ≥ 75% predicted at screening Visit 0a.FEV1 ≥ 70% predicted at baseline.
• Positive immediate skin test for allergies to cat hair and reports asthma symptoms to cats, house dust mite and reports asthma symptoms to dust, or ragweed and reports asthma symptoms to ragweed (historical data documented within the last 5 years with our research group is acceptable).
• Ability to tolerate a simulated MRI 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 PIs 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 allergen immunotherapy
• 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)
• Inability to hold medications detailed in the medication hold schedule
• Needle phobia or claustrophobia
• Major health problems such any of the following in the last 6 months: stroke/TIA, myocardial Infarction, stent placement, or acute coronary syndrome are definitively exclusionary. Decisions regarding other major health problems, such as autoimmune disease, history of carotid stenosis, heart disease, uncontrolled hypertension, lung diseases other than asthma, history of significant arrhythmias, etc. will be based upon the judgement of the PI/Co-I.
• Use of biologic medication that might affect signaling pathways under investigation (at the discretion of the PI/Co-I)
• Pre-existing chronic infectious disease
• Scheduled use of non-selective beta-blockers prior to each study visit
• Current use of beta-1 selective blockers (e.g., metoprolol, atenolol, acebutolol, betaxolol, esmolol, bisoprolo, and nebivolol)
• Use of an investigational drug within 30 days of entering the study. This criterion will be reviewed on a case by case basis by the PI or Co-I 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 most current MRI screening form
• 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
• 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
• Ever intubated due to asthma and has not had a severe exacerbation requiring an ER visit or hospitalization in the past year.
• Participants with well-controlled asthma at enrollment using ICS for their asthma will undergo a supervised step-down of therapy. This step-down aligns with the 2020 Focused Updates to the Management of Asthma Guidelines: Clinician Guide. Participants who undergo the supervised step-down will not proceed to V0a unless their asthma remains well-controlled for 6 weeks using PRN SABA only. Subjects will be monitored remotely during the supervised step-down. If the subject experiences any of the following during the supervised step-down, they will not be eligible to continue in the MAIA study:

• Use of SABA > 2 days a week for symptom relief (not for exercise-induced bronchoconstriction)
• PEF < 80% of baseline PEF for > 2 days in a row
• Use of systemic corticosteroids for asthma symptoms
• ACT < 20