Utilizing CT Based Imaging Parameters of Body Composition to Understand Heterogeneity of Response to Biologic Therapies in Severe Asthma Cohorts

University of Michigan233 enrolled

Overview

This study will utilize University of Michigan EMR data to form a retrospective cohort of severe asthma patients on biologic therapies for asthma with computed tomography (CT) imaging and known outcomes on therapy. These images will then be analyzed using morphomics, a combination of high-throughput image analysis and deep learning techniques, to derive imaging biomarkers that will be able to predict therapeutic response to biologics. These biomarkers will then be tested in a second cohort from the National Jewish Health to assess for validity.

The two arms for this study represent the two cohorts: the University of Michigan cohort, and the National Jewish Health cohort. The cohorts were split into arms, as the National Jewish Health cohort was intended to act as a validator group for results derived from participants in the University of Michigan cohort.

Study Type

OBSERVATIONAL

Enrollment

233

Conditions

Asthma

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Asthma diagnosis defined as a positive methacholine test, supportive PFTs, or clinician diagnosis with appropriate supporting clinical context * Prescribed and taking an FDA-approved biologic medication for severe asthma (mepolizumab, benralizumab, reslizumab, omalizumab, or dupilumab) * Chest computerized tomography (CT) images taken for any clinical purpose Exclusion Criteria: * 10-year history of smoking * Evidence of emphysema on CT imaging * Severe bronchiectasis secondary to other causes (subjects with scattered bronchiectasis secondary to severe asthma will not excluded) * Lack of accessible adequate follow-up information (4 or more months from drug initiation with clear documentation of response) will be excluded from final analysis due to inability to assess response but will be included in the initial cluster identification

Outcomes

Primary Outcomes

Chest Wall Muscle Size

Muscle size was measured as the skeletal muscle cross-sectional area in centimeters squared (cm2) measured at the level of the T10 vertebra to determine the cutoff value in chest wall muscle size that optimally classified patients that had and did not have any reduction in pre-treatment baseline exacerbation frequency (binary).

Time frame: 28 months

Chest Wall Muscle Quality

Muscle quality was measured as the skeletal muscle density in Hounsfield Units (HU) to determine the cutoff value in chest wall muscle quality that optimally classified patients that had and did not have any reduction in pre-treatment baseline exacerbation frequency (binary).

Time frame: 28 months

Exacerbation Reduction - Muscle Size

Muscle size was measured as the skeletal muscle cross-sectional area in centimeters squared (cm2) measured at the level of the T10 vertebra to assess whether skeletal muscle size area could be used to predict exacerbation frequency. Results reflect the average muscle sizes when frequency could be predicted.

Time frame: 28 months

Exacerbation Reduction - Muscle Quality

Muscle quality was measured as the skeletal muscle density in Hounsfield Units (HU) to determine the cutoff value in chest wall muscle quality to assess whether skeletal muscle quality could be used to predict exacerbation frequency. Results reflect the average muscle sizes when frequency could be predicted.

Time frame: 28 months

Exacerbations

The number of exacerbations post-biologic were compared to the the number of baseline exacerbations. Baseline measurements were counted in the year prior to biologic initiation. Any exacerbation recorded between 4 to 28 months after biologic initiation was recorded as a post-biologic exacerbation. Any reduction in between the pre- and post-biologic was counted as an exacerbation reduction. Results reflect the number of participants who experienced (True) or did not experience (False) a reduction in exacerbations.

Time frame: pre-biologic at baseline (looking back 1 year), post-biologic (4-18 months after biologic)

Secondary Outcomes

FEV1 Improvement

Muscle size was used to investigate body composition measures associated with a 5% or greater improvement in forced expiratory volume in one second (FEV1). Muscle size was measured as the skeletal muscle cross-sectional area in centimeters squared (cm2) measured at the level of the T10 vertebra to determine the cutoff value in chest wall muscle size that optimally classified participants who had and did not have improvement in FEV1. Participants with ≥5% improvement in FEV1 during the 4 to 18-month period following initiation of biologics were classified as responders. Any participant who did not achieve a ≥5% improvement from baseline in that timeframe was classified as a non-responder.

Time frame: pre-biologic at baseline (looking back 1 year), post-biologic (4-18 months after biologic)

Reduction in Oral Corticosteroid (OCS)

Muscle size was used to investigate body composition measures associated with any reduction in maintenance OCS use when compared to baseline OCS use. Subjects with any OCS reduction in use during the 4- to 18-month period following initiation of biologics were classified as responders.

Time frame: pre-biologic at baseline (looking back 1 year), post-biologic (4-18 months after biologic)

Utilizing CT Based Imaging Parameters of Body Composition to Understand Heterogeneity of Response to Biologic Therapies in Severe Asthma Cohorts

Overview

Conditions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes