Tezepelumab on Airway Structure and Function in Patients With Uncontrolled Moderate-to-severe Asthma

Inclusion Criteria: * General * Able and willing to provide written informed consent. * Able and willing to comply with the study protocol. * Males and females ≥ 18 years of age. * Asthma-related * Asthma diagnosed by a respiratory physician ≥12 months prior to study enrolment based on the Global Initiative for Asthma (GINA) 2021 guidelines. * ACQ ≥1.5 at screening. * Methacholine PC20 ≤ 4 mg/mL OR ≥15% decrease in FEV1 during saline inhalation for sputum induction OR ≥15% improvement in FEV1 after bronchodilator during the screening period. * Criteria met for moderate or severe asthma defined by GINA 2021 guidelines, i.e. treatment with low, medium or high dose ICS (\<250 mcg, 251 - 500 mcg, \>500 mcg of fluticasone equivalent/day respectively) plus another controller. Patients on prednisone would not be excluded, as long as they meet the rest of the inclusion criteria. * FeNO \>25 ppb OR ≥3% sputum eosinophils (preferred) OR blood eos ≥300/µL during the screening period. * History of ≥1 exacerbation in the previous year. Exclusion Criteria: * General \-- Participation in any clinical trial of an investigational agent or procedure within six months prior to screening or during the study. * Medical conditions and treatment history * History of anaphylaxis to any previous biologic therapy received. * Receipt of live attenuated vaccine within 30 days, receipt of COVID vaccine within 28 days, known or suspected COVID infection at the time of enrollment. * Acute or chronic parasitic, bacterial, fungal or viral infections that required, or currently requires, hospitalization or antimicrobial treatment during the last four weeks. * Acute asthma exacerbation event treated with increased doses of oral, or any dose of intramuscular (IM) or intravenous (IV) corticosteroids within six weeks prior to screening. * Other relevant pulmonary diseases (e.g. chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension, tuberculosis) requiring treatment within 12 months prior to screening. * Alcohol or substance abuse within 12 months prior to screening. * Current smoker defined as having smoked at least one cigarette (or pipe, cigar, or marijuana) per day for ≥ 30 days within the three months prior to screening. * Ex-smokers with ≥ 10 pack-year smoking history. * Pregnancy. * Treatment with anti-IgE, anti-IL-4, anti-IL-5, or anti-IL-13 targeted therapy currently or within three months prior to screening. * MRI-related * Patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist). * In the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.