Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis

Joseph Jacob, Brian Jack Bartholmai, Srinivasan Rajagopalan, Coline H.M. Van Moorsel, Hendrik W. Van Es, Frouke T. Van Beek, Marjolijn H.L. Struik, Maria Kokosi, Ryoko Egashira, Anne Laure Brun, Arjun Nair, Simon L.F. Walsh, Gary Cross, Joseph Barnett, Angelo De Lauretis, Eoin P. Judge, Sujal Desai, Ronald Karwoski, Sebastien Ourselin, Elisabetta RenzoniToby M. Maher, Andre Altmann, Athol U. Wells

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume198
Issue number6
DOIs
StatePublished - Sep 15 2018
Externally publishedYes

Fingerprint

Idiopathic Pulmonary Fibrosis
Pharmaceutical Preparations
Lung
Sample Size
Informatics
Survival
Mortality
Population Density
Lung Diseases
Software
Outcome Assessment (Health Care)
Pathology
Costs and Cost Analysis

Keywords

  • Idiopathic pulmonary fibrosis
  • Pulmonary vessels
  • Quantitative computed tomographic imaging

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis. / Jacob, Joseph; Bartholmai, Brian Jack; Rajagopalan, Srinivasan; Van Moorsel, Coline H.M.; Van Es, Hendrik W.; Van Beek, Frouke T.; Struik, Marjolijn H.L.; Kokosi, Maria; Egashira, Ryoko; Brun, Anne Laure; Nair, Arjun; Walsh, Simon L.F.; Cross, Gary; Barnett, Joseph; De Lauretis, Angelo; Judge, Eoin P.; Desai, Sujal; Karwoski, Ronald; Ourselin, Sebastien; Renzoni, Elisabetta; Maher, Toby M.; Altmann, Andre; Wells, Athol U.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 198, No. 6, 15.09.2018, p. 767-776.

Research output: Contribution to journalArticle

Jacob, J, Bartholmai, BJ, Rajagopalan, S, Van Moorsel, CHM, Van Es, HW, Van Beek, FT, Struik, MHL, Kokosi, M, Egashira, R, Brun, AL, Nair, A, Walsh, SLF, Cross, G, Barnett, J, De Lauretis, A, Judge, EP, Desai, S, Karwoski, R, Ourselin, S, Renzoni, E, Maher, TM, Altmann, A & Wells, AU 2018, 'Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis', American Journal of Respiratory and Critical Care Medicine, vol. 198, no. 6, pp. 767-776. https://doi.org/10.1164/rccm.201711-2174OC
Jacob, Joseph ; Bartholmai, Brian Jack ; Rajagopalan, Srinivasan ; Van Moorsel, Coline H.M. ; Van Es, Hendrik W. ; Van Beek, Frouke T. ; Struik, Marjolijn H.L. ; Kokosi, Maria ; Egashira, Ryoko ; Brun, Anne Laure ; Nair, Arjun ; Walsh, Simon L.F. ; Cross, Gary ; Barnett, Joseph ; De Lauretis, Angelo ; Judge, Eoin P. ; Desai, Sujal ; Karwoski, Ronald ; Ourselin, Sebastien ; Renzoni, Elisabetta ; Maher, Toby M. ; Altmann, Andre ; Wells, Athol U. / Predicting outcomes in idiopathic pulmonary fibrosis using automated computed tomographic analysis. In: American Journal of Respiratory and Critical Care Medicine. 2018 ; Vol. 198, No. 6. pp. 767-776.
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AU - Jacob, Joseph

AU - Bartholmai, Brian Jack

AU - Rajagopalan, Srinivasan

AU - Van Moorsel, Coline H.M.

AU - Van Es, Hendrik W.

AU - Van Beek, Frouke T.

AU - Struik, Marjolijn H.L.

AU - Kokosi, Maria

AU - Egashira, Ryoko

AU - Brun, Anne Laure

AU - Nair, Arjun

AU - Walsh, Simon L.F.

AU - Cross, Gary

AU - Barnett, Joseph

AU - De Lauretis, Angelo

AU - Judge, Eoin P.

AU - Desai, Sujal

AU - Karwoski, Ronald

AU - Ourselin, Sebastien

AU - Renzoni, Elisabetta

AU - Maher, Toby M.

AU - Altmann, Andre

AU - Wells, Athol U.

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N2 - Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

AB - Rationale: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

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