Effect of OPEP on Mucus Plugging and Airflow Obstruction in Patients with Moderate-to-severe Asthma

Inclusion Criteria:

1. Able and willing to provide written informed consent.

2. Able and willing to comply with the study protocol.

3. Males and females ≥ 18 years of age.

4. Asthma diagnosed by a respiratory physician ≥12 months prior to study enrolmentbased on the Global Initiative for Asthma (GINA) 2014 guidelines - GINA 4 or 5.

5. ICS dose ≥500 mcg of fluticasone equivalent/day. Patients on prednisone or biologicfor ≥3 months would not be excluded as long as they meet the rest of the inclusioncriteria.

6. ACQ ≥1.5 during the screening period.

7. CT mucus score ≥4 during the screening period.

Exclusion Criteria:

1. Acute or chronic parasitic, bacterial, fungal or viral infections that required, orcurrently requires, hospitalization or antimicrobial treatment during the last fourweeks.

2. Acute asthma exacerbation event treated with increased doses of oral, or any dose ofintramuscular (IM) or intravenous (IV) corticosteroids within six weeks prior toscreening.

3. 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.

4. Alcohol or substance abuse within 12 months prior to screening.

5. Current smoker defined as having smoked at least one cigarette (or pipe, cigar, orcannabis) per day for ≥ 30 days within the three months prior to screening.

6. Ex-smokers with ≥ 15 pack-year smoking history.

7. Patient has an implanted mechanically, electrically, or magnetically activateddevice or any metal in their body which cannot be removed, including but not limitedto pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysmclips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt,surgical staples (including clips or metallic sutures and/or ear implants) (at thediscretion of the MRI Technologist).

8. In the investigator's opinion, subject suffers from any physical, psychological, orother condition(s) that might prevent performance of the MRI, such as severeclaustrophobia.

9. Pregnant or breastfeeding

10. Participation in any clinical trial of an investigational agent or procedure withinthree months prior to screening or during the study.