Quantitative CT Characteristics of Cluster Phenotypes in the Severe Asthma Research Program Cohorts

From the Division of Pulmonary, Critical Care, and Sleep Medicine, Rush University Medical Center, Chicago, Ill (A.P.T.); Division of Pulmonary and Critical Care Medicine, University of Kansas School of Medicine, Kansas City, KS 66103-2937 (C.H., M.C.); Division of Biostatistics (C.W.G., D.L., K.B.S.), Division of Pulmonary and Critical Care Medicine (J.G.K., M.C.M., M.S.), Washington University School of Medicine, St Louis, Mo; Department of Radiology, University of Iowa, Iowa City, Iowa (J.P.S., J.M.R., J.D.N., E.A.H.); Department of Medicine, University of Arizona, Tucson, Ariz (H.L., E.R.B., D.A.M.); VIDA Diagnostics, Coralville, Iowa (J.S., S.M., S.P.); Section of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest University School of Medicine, Winston-Salem, NC (W.C.M.); Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Mass (E.I., G.R.W., B.D.L.); Department of Radiology (J.K.L.) and Division of Pulmonary, Allergy and Critical Care Medicine (S.E.W.), University of Pittsburgh, Pittsburgh, Pa; Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, Calif (J.V.F.); Department of Radiology (M.L.S., S.B.F.) and Division of Allergy, Pulmonary and Critical Care Medicine (N.N.J.), University of Wisconsin, Madison, Wis; Department of Public Health Sciences, Penn State Eberly College of Science, University Park, Pa (D.T.M.); and Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Tex (A.S.).
Address correspondence to M.C. (email: [email protected]).

Published Online:Apr 26 2022https://doi.org/10.1148/radiol.210363

See editorial byJohny A. Verschakelen

Abstract

Background

Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes.

Purpose

To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes.

Materials and Methods

A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models.

Results

A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001).

Conclusion

Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study.

Online supplemental material is available for this article.

See also the editorial by Verschakelen in this issue.

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Article History

Received: Feb 25 2021
Revision requested: Apr 7 2021
Revision received: Dec 27 2021
Accepted: Feb 17 2022
Published online: Apr 26 2022

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Abbreviations

Abbreviations:
ADI	anisotropic deformation index
DPM	disease probability map
FEV₁	forced expiratory volume in 1 second
FRC	functional residual capacity
fSAD	functional small airway disease
Pi10	square root of bronchial wall area for a theoretical airway with an internal perimeter of 10 mm
qCT	quantitative CT
SARP	Severe Asthma Research Program
TLC	total lung capacity

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