REverse LuNg Airway and Vascular RemOdeling in Asthma ReMission (ReNORM)

Summary

In this program of research, the investigators aim to answer the question: In patients with asthma aged 18-80, how do the lung airways and vessels respond to biologic therapy and what role does age and asthma duration have in this response? While about 4.6 million Canadians live with asthma, \~5-10% of patients have severe asthma meaning that multiple inhaled and systemic oral corticosteroid treatments have failed to improve symptoms and exacerbations, leading to lost work and school days and substantially diminished ability to participate in normal life. For such people, the vast majority of whom are middle aged and remember asthma as part of their entire lifespan, biologic immunomodulator therapies, which block the function of asthma inflammatory pathways, provide a final step-up therapy option. There is emerging evidence that prescribed in the right patient at the right time, the right biologic can result in clinical remission of asthma. While spontaneous clinical remission of asthma is rare, it has been documented in children in whom lung growth and remodeling is still possible. It remains unknown whether clinical remission in adults is accompanied by the reversal of pathologic remodeling, at the level of the airways and pulmonary vessels. This is critical to elucidate as investigators and physicians move forward with currently proposed criteria for "complete asthma remission". The inconvenient truth about asthma and age is that in older adult lungs, exposed to years of infection, exacerbations, smooth muscle remodeling and pulmonary vascular shunt, the mechanisms by which complete pathologic remission may be achieved are complex and poorly understood.

To address this knowledge gap, the investigators will evaluate 150 patients (Vancouver, Ottawa, Hamilton, London) (in three age tertiles 18-29; 30-59; 60-80) with severe asthma and 50 age- and sex matched healthy volunteers over 2-years using chest CT, MRI and pulmonary function tests. The investigators will use the pulmonary imaging measurements to generate an imaging-index of normal airway structure and function which will be compared with and significantly correlate with MR-guided bronchoscopic sample measurements made before and after 1-/2-years of treatment. The investigators will reveal the pathobiologic relationship between age, asthma duration, clinical remission and imaging normalization with direct comparison to histology-based airway measurements.

Conditions

• Asthma; Eosinophilic

Interventions

BIOLOGICAL

Biologic Therapy

Participants with severe asthma (GINA 5) who are eligible to begin biologic therapy. Participants will undergo serial assessment with pulmonary imaging (CT, MRI), lung function testing, sputum collection, and symptom questionnaires. A subset of participants (\~15%) will be randomized to undergo MRI-guided bronchoscopy with airway sampling at baseline and 2 years.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Western University, Canada

  lead OTHER

Principal Investigators

• Grace Parraga, PhD · Robarts Research Institute, The University of Western Ontario

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-10-31

Primary Completion

2030-10-31

Completion

2030-10-31

Countries

• Canada

Study Locations