Inclusion Criteria:
* Provision of signed and dated informed consent form
* Age ≥18 years
* A history of physician-diagnosed persistent asthma or symptoms consistent with persistent asthma based on national or international guidelines for diagnosis and management of asthma.
* Current use of controller therapy such as inhaled corticosteroid (ICS) or ICS in combination with long-acting beta agonist (LABA)
* Asthma exacerbation requiring systemic corticosteroid therapy in the past 12 months
* Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy or who have been amenorrheic for 12 months or more.
* Asthma Impairment and Risk Questionnaire (AIRQ) Score \>2
Exclusion Criteria:
* Clinical contraindications:
1. Physician diagnosis of other chronic pulmonary disease including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), chronic bronchitis, emphysema or congenital disorders of the lungs or airways.
2. History of undergoing bronchial thermoplasty.
3. Intubation for asthma in the last 12 months
4. History of malignancy except non-melanoma skin cancer within the last five years.
5. Any chronic medical condition considered by the PI as a contraindication to inclusion in the study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic or recurrent infections or immunodeficiency.
6. Mental illness or history of substance abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
7. History of smoking: i. Smoking \>1 time per week in the past year; ii. If ≥40 years old: Smoked ≥15 pack years; iii. If \<40 years old: Smoked ≥10 pack years; iv. Smoking equivalents of 1 pack cigarettes a day for 1 year: 1 cigar or pipe daily for 1 year; Hookah - 1 session per day for 1 year; E-cigarettes or vapes - 1 cartridge/tank/pod per day for 1 year; and active use of smoking/vaping marijuana, specified as once per week in the last year.
8. Allergy/sensitivity to study drugs or their formulations, including latex
9. Unwillingness to use reliable contraception if sexually active (IUD, birth control pills/patch, condoms).
10. Current participation in an interventional trial in which study administration was administered within the past 60 days or within 5 half-lives of the drug (whichever is greater)
* Pregnancy, plans to get pregnant or nursing a baby. Female volunteers will be asked to use effective birth control (stable regimen of hormonal contraceptive use for at least 6 months, intrauterine device placement, or tubal ligation for at least 6 months through at least one week after study completion) and will provide a urine sample to test for pregnancy on study days. If the test is positive or the participant has reason to believe she may be pregnant, she will be dismissed from the study. Women who have been amenorrheic for 12 months may participate. Male volunteers will be asked to use condoms for the duration of the study through at least one week after study completion.
* Usage of the following medications:
1. Use of daily systemic corticosteroid therapy for asthma control
2. Use of any immunomodulatory therapy within the preceding 12 months, including biologics that are approved for asthma.
3. Currently receiving allergen immunotherapy
4. Use of any immunosuppressant therapy within the preceding 12 months will be reviewed by the study physician.
* Laboratory: Participants who meet the following criteria will be excluded from study:
1. Positive QuantiFERON-tuberculosis (TB) gold assay. Cases of indeterminate QuantiFERON-TB test results will require a second specimen to be drawn.
2. Baseline absolute neutrophil count (ANC) \<1.0 x 109/L for participants of African descent, \<1.5 x 109/L for other participants
* Allergy/sensitivity to study drugs or their formulations, including latex.
* History of anaphylaxis requiring epinephrine treatment
* Inability or unwillingness of a participant to give written informed consent.
* Inability or unwillingness to self-administer injectable medication (anakinra or placebo).
