Therapeutic Relevance of Abnormal Airway Morphology in Asthma

Summary

Most individuals with asthma can effectively manage their symptoms and maintain normal lung function using inhaled medications, unfortunately, there is a subset of asthma sufferers whose symptoms, lung function, and risk of asthma attacks remain unimproved despite conventional inhaled medications. There could be several reasons for this. One possibility is that inhaled medications fail to reach the intended areas within the lungs, due to structural abnormalities within the airways themselves. Much like road conditions or closures can impede the speed and efficiency of vehicle travel, factors such as airway narrowing or mucus blockages, which are common in asthma, can obstruct the passage of inhaled medications through the airways. Our team has now optimized advanced medical imaging techniques, including magnetic resonance imaging (MRI) and computed tomography (CT), required to investigate this. This study will use these imaging methods to visually assess and measure individual patients' airways and determine whether abnormal airway structures impact how well they respond to inhaled and orally delivered medications. We anticipate finding that abnormal airway structures make inhaled medications less effective, but that they do not affect the response to oral medications.

Eligibility

Inclusion Criteria:

* 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 diagnosed by a respiratory physician.
* Airway hyperresponsiveness (defined as methacholine PC20 ≤8mg/mL) and/or bronchodilator reversibility (defined as post-bronchodilator FEV1 improvement ≥200mL and 12%) in the last 6 months
* ACQ ≥1.5 during the screening period.
* Sputum eosinophils ≥3% and/or FeNO ≥35ppb during the screening period.

Exclusion Criteria:

* Current smoker, defined as someone having smoked ≥1 cigarette/day (or vape/pipe/cigar/marijuana) for ≥30 days within 12 months prior to screening.
* Pregnant or breastfeeding
* Non-English speaking
* Oral corticosteroids in past 1-month
* Biologic therapy in past 6-months
* Unable to perform proper MDI technique during the screening period
* Other 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.
* Unable to undergo MRI. 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). Suffers from any physical, psychological, or other condition(s) that might prevent performance of the MRI, such as severe claustrophobia.

Conditions1

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