Quantitative CT metrics are associated with longitudinal lung function decline and future asthma exacerbations: Results from SARP-3 - 03/09/21
for the
National Heart, Lung, and Blood Institute’s Severe Asthma Research Program Investigators
Abstract |
Background |
Currently, there is limited knowledge regarding which imaging assessments of asthma are associated with accelerated longitudinal decline in lung function.
Objectives |
We aimed to assess whether quantitative computed tomography (qCT) metrics are associated with longitudinal decline in lung function and morbidity in asthma.
Methods |
We analyzed 205 qCT scans of adult patients with asthma and calculated baseline markers of airway remodeling, lung density, and pointwise regional change in lung volume (Jacobian measures) for each participant. Using multivariable regression models, we then assessed the association of qCT measurements with the outcomes of future change in lung function, future exacerbation rate, and changes in validated measurements of morbidity.
Results |
Greater baseline wall area percent (β = –0.15 [95% CI = –0.26 to –0.05]; P < .01), hyperinflation percent (β = –0.25 [95% CI = –0.41 to –0.09]; P < .01), and Jacobian gradient measurements (cranial-caudal β = 10.64 [95% CI = 3.79-17.49]; P < .01; posterior-anterior β = –9.14, [95% CI = –15.49 to –2.78]; P < .01) were associated with more severe future lung function decline. Additionally, greater wall area percent (rate ratio = 1.06 [95% CI = 1.01-1.10]; P = .02) and air trapping percent (rate ratio =1.01 [95% CI = 1.00-1.02]; P = .03), as well as lower decline in the Jacobian determinant mean (rate ratio = 0.58 [95% CI = 0.41-0.82]; P < .01) and Jacobian determinant standard deviation (rate ratio = 0.52 [95% CI = 0.32-0.85]; P = .01), were associated with a greater rate of future exacerbations. However, imaging metrics were not associated with clinically meaningful changes in scores on validated asthma morbidity questionnaires.
Conclusions |
Baseline qCT measures of more severe airway remodeling, more small airway disease and hyperinflation, and less pointwise regional change in lung volumes were associated with future lung function decline and asthma exacerbations.
Le texte complet de cet article est disponible en PDF.Key words : Asthma, severe asthma, CT imaging, asthma morbidity, asthma exacerbations, longitudinal, lung function
Abbreviations used : ACT, AQLQ, COPD, CT, DPM, FEV1%, HU, PRM, qCT, SAD, SARP-3, WA%, WT%
Plan
| Funded by grants from the National Heart, Lung, and Blood Institute to the Severe Asthma Research Program’s (SARP's) principal investigators, clinical centers, and data coordinating center, including grants U10 HL109086–04 (to D.T.M.), U10 HL109146 (to J.V.F.), U10 HL109168 (to L.C.D.), U10 HL109172 (to G.W.), U10 HL109152 (to S.E.W.), and U10 HL109257 (to M.C.). Support for SARP visits occurring beyond the third year of follow-up was provided in part by SARP’s partnerships with AstraZeneca, Boehringer-Ingelheim, Genentech, GSK, Sanofi-Genzyme-Regeneron, and TEVA. In addition, this study was supported by a Washington University Institutional Training Award (2T32HL007317-41) from the National Heart, Lung, and Blood Institute, as well as by support from the following National Center for Advancing Translational Science awards: UL1 TR000427 (University of Wisconsin), UL1 TR001102 (Harvard University), UL1TR002345 (Washington University). |
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| Disclosure of potential conflict of interest: L. B. Bacharier reports grants from the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) during conduct of the study, as well as personal fees from GlaxoSmithKline, Genentech/Novartis, AstraZeneca, WebMD/Medscape, Sanofi/Regeneron, Vectura, and Circassia and personal fees and nonfinancial support from Merck, DBV Technologies, Teva, and Boehringer Ingelheim outside the submitted work. D. T. Mauger reports grants from the NIH, Boehringer-Ingelheim, TEVA, AstraZeneca, GlaxoSmithKline, Sanofi, and Genentech during conduct of the study, as well as nonfinancial support from Vifor-Pharma and Merck outside the submitted work. A. Sheshadri reports receiving personal fees from PsiOxus, Inc. C. Hall reports receiving speaking/consulting fees from Boehringer Ingelheim and VIDA Diagnostics. J. V. Fahy reports grants from NIH/NHLBI and Boehringer Ingelheim during conduct of the study, as well as personal fees from Boehringer Ingelheim, Pieris, Arrowhead Pharmaceuticals, and Gossamer outside the submitted work; in addition, Dr Fahy has patents issued (US20110123530A1 ["Compositions and methods for treating and diagnosing asthma"] and WO2014153009A2 ["Thiosaccharide mucolytic agents"]) and the patent WO2017197360 (“CT mucus score—a new scoring system that quantifies airway mucus impaction using computed tomography lung scans”). S. B. Fain reports grants from NIH/NHLBI during conduct of the study, as well as personal fees from the COPD Gene Foundation and Sanofi/Regeneron and grants from GE Healthcare outside the submitted work; in addition, he serves as the physics chair of the Computer Tomography Lung Density Biomarker Committee within the Quantitative Imaging Biomarker Alliance. L. C. Denlinger reports grants from NHLBI, during conduct of the study, as well as grants and personal fees from AstraZeneca, and personal fees from Sanofi outside the submitted work. G. Washko reports grants from NIH, DoD, Boehringer Ingelheim, Janssen Pharmaceuticals, BTG Therapeutics, PulmonX, Lung Biotechnology, and Inmed. G. Washko reports participation in advisory boards and consultancies for Boehringer Ingelheim, CSL Behring, GlaxoSmithKline, Novartis, Phillips, and Vertex Pharmaceuticals. G. Washko is a co-founder and quity shareholder in Quantitative Imaging Solutions, a company that provides consulting services for image and data analytics. G. Washko's spouse works for Biogen. E. Hoffman is a founder and shareholder of VIDA Diagnostics, a company commercializing lung image analysis software developed in part at the University of Iowa. S. E. Wenzel reports grants from Boerhringer-Ingelheim to support SARP3 visits during conduct of the study, as well as grants and personal fees from AstraZeneca, GSK, and Sanofi; grants from Novartis; and personal fees from Pieris outside the submitted work. M. Castro receives university grant funding from the NIH, the American Lung Association, and PCORI and pharmaceutical grant funding from AstraZeneca, GSK, Novartis, Pulmatrix, Sanofi-Aventis, and Shionogi; in addition, he is a consultant for Genentech, Teva, Sanofi-Aventis, and Novartis and a speaker for AstraZeneca, Genentech, GSK, Regeneron, Sanofi, Teva, and he receives royalties from Elsevier. |
Vol 148 - N° 3
P. 752-762 - septembre 2021 Retour au numéro
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