Airway Inspector: a chest imaging biomarker software platform for COPD

The goal of this project is to refactor and develop Airway Inspector as a platform for image-based COPD research. The software platform will be used to create workflows that will be integrated in Slicer 4 for their deployment in the clinical studies.

Raúl San José Estépar

Dr. Raúl San José Estépar

Associate Professor of Radiology in Harvard Medical School
Lead Investigator at Brigham and Women's Hospital
Raúl is Associate Professor of Radiology at Harvard Medical School and a Research Associate at Brigham and Women's Hospital. He is the co-director of the Applied Chest Imaging Laboratory (ACIL).
1249 Boylston St, Room 216
Boston, MA, 02215
p: 617 525-6227
Castaldi PJ, Cho MH, San José Estépar R, McDonald M-LN, Laird N, Beaty TH, Washko G, Crapo JD, Silverman EK, Silverman EK. Genome-wide association identifies regulatory Loci associated with distinct local histogram emphysema patterns. Am J Respir Crit Care Med. 2014;190 (4) :399-409.Abstract

RATIONALE: Emphysema is a heritable trait that occurs in smokers with and without chronic obstructive pulmonary disease. Emphysema occurs in distinct pathologic patterns, but the genetic determinants of these patterns are unknown. OBJECTIVES: To identify genetic loci associated with distinct patterns of emphysema in smokers and investigate the regulatory function of these loci. METHODS: Quantitative measures of distinct emphysema patterns were generated from computed tomography scans from smokers in the COPDGene Study using the local histogram emphysema quantification method. Genome-wide association studies (GWAS) were performed in 9,614 subjects for five emphysema patterns, and the results were referenced against enhancer and DNase I hypersensitive regions from ENCODE and Roadmap Epigenomics cell lines. MEASUREMENTS AND MAIN RESULTS: Genome-wide significant associations were identified for seven loci. Two are novel associations (top single-nucleotide polymorphism rs379123 in MYO1D and rs9590614 in VMA8) located within genes that function in cell-cell signaling and cell migration, and five are in loci previously associated with chronic obstructive pulmonary disease susceptibility (HHIP, IREB2/CHRNA3, CYP2A6/ADCK, TGFB2, and MMP12). Five of these seven loci lay within enhancer or DNase I hypersensitivity regions in lung fibroblasts or small airway epithelial cells, respectively. Enhancer enrichment analysis for top GWAS associations (single-nucleotide polymorphisms associated at P < 5 × 10(-6)) identified multiple cell lines with significant enhancer enrichment among top GWAS loci, including lung fibroblasts. CONCLUSIONS: This study demonstrates for the first time genetic associations with distinct patterns of pulmonary emphysema quantified by computed tomography scan. Enhancer regions are significantly enriched among these GWAS results, with pulmonary fibroblasts among the cell types showing the strongest enrichment.

Castaldi PJ, San José Estépar R, Mendoza CS, Hersh CP, Laird N, Crapo JD, Lynch DA, Silverman EK, Washko GR. Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers. Am J Respir Crit Care Med. 2013;188 (9) :1083-90.Abstract

RATIONALE: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction. OBJECTIVES: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers. METHODS: Using a local histogram-based assessment of lung density, we quantified distinct patterns of low attenuation in 9,313 smokers in the COPDGene Study. To determine if such patterns provide novel insights into chronic obstructive pulmonary disease epidemiology, we tested for their association with measures of physiology, function, and health care use. MEASUREMENTS AND MAIN RESULTS: Compared with percentage of low-attenuation area less than -950 Hounsfield units (%LAA-950), local histogram-based measures of distinct CT low-attenuation patterns are more predictive of measures of lung function, dyspnea, quality of life, and health care use. These patterns are strongly associated with a wide array of measures of respiratory physiology and function, and most of these associations remain highly significant (P < 0.005) after adjusting for %LAA-950. In smokers without evidence of chronic obstructive pulmonary disease, the mild centrilobular disease pattern is associated with lower FEV1 and worse functional status (P < 0.005). CONCLUSIONS: Measures of distinct CT emphysema patterns provide novel information about the relationship between emphysema and key measures of physiology, physical function, and health care use. Measures of mild emphysema in smokers with preserved lung function can be extracted from CT scans and are significantly associated with functional measures.