Background Traditional metrics of lung disease such as those derived from spirometry and static single-volume CT images are used to explain respiratory morbidity in patients with COPD, but are insufficient. We hypothesised that the mean Jacobian determinant, a measure of local lung expansion and contraction with respiration, would contribute independently to clinically relevant functional outcomes.
Methods We applied image registration techniques to paired inspiratory-expiratory CT scans and derived the Jacobian determinant of the deformation field between the two lung volumes to map local volume change with respiration. We analysed 490 participants with COPD with multivariable regression models to assess strengths of association between traditional CT metrics of disease and the Jacobian determinant with respiratory morbidity including dyspnoea (modified Medical Research Council), St Georges Respiratory Questionnaire (SGRQ) score, 6-min walk distance (6MWD) and the Body Mass Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) index, as well as all-cause mortality.
Results The Jacobian determinant was significantly associated with SGRQ (adjusted regression coefficient β=−11.75,95% CI −21.6 to −1.7; p=0.020), and with 6MWD (β=321.15, 95% CI 134.1 to 508.1; p<0.001), independent of age, sex, race, body mass index, FEV1, smoking pack-years, CT emphysema, CT gas trapping, airway wall thickness and CT scanner type. The mean Jacobian determinant was also independently associated with the BODE index (β=−0.41, 95% CI −0.80 to −0.02; p=0.039) and mortality on follow-up (adjusted HR=4.26, 95% CI 0.93 to 19.23; p=0.064).
Conclusions Biomechanical metrics representing local lung expansion and contraction improve prediction of respiratory morbidity and mortality and offer additional prognostic information beyond traditional measures of lung function and static single-volume CT metrics.
Trial registration number NCT00608764; Post-results.
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SB and SPB contributed equally to the manuscript and are co-first authors.
Collaborators COPDGene Investigators.
Contributors SB and SPB contributed equally to the article. Study concept and design: SPB, SB and JMR. Acquisition, analysis or interpretation of data, critical revision of the manuscript for important intellectual content and study supervision: all authors. Drafting of the manuscript and statistical analysis: SB and SPB.
Funding This study was supported by the COPDGene study (NIH Grant Numbers R01 HL089897 and R01 HL089856), 1K23HL133438-01 (SPB), R01 HL112986 (EAH) and R01 HL079406 (JMR).
Competing interests SPB reports grants from the NIH; MTD reports grants from NHLBI, during the conduct of the study; personal fees and other from Boehringer Ingelheim, personal fees and other from AstraZeneca, personal fees and other from GlaxoSmithKline, personal fees from Genentech, other from Novartis, other from PneumRx, other from Pulmonx, other from Yungjin; EAH is a founder and share holder of VIDA Diagnostics, a company that is commercializing lung image analysis software developed, in part, at the University of Iowa; CHM reports grants from NIH; MKH reports personal fees from BI, personal fees from GSK, personal fees from AstraZeneca, personal fees from Novartis; JMR reports other from VIDA Diagnostics; JDN reports grants from NIH, during the conduct of the study; grants from NIH, grants from Siemens Healthcare, personal fees from VIDA Diagnostics, personal fees from GSK.
Ethics approval Institutional review board at all 21 participating centres.
Provenance and peer review Not commissioned; externally peer reviewed.
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