Dataset Information

LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

ABSTRACT: The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect these to standardized pulmonary function test results such as FEV1%. Among other things, the problem is complicated by the fact that a particular airway feature may be an important (relevant) predictor only when it pertains to segments of certain generations. Thus, the key is an efficient, consistent method for simultaneously conducting group selection (lung airway feature types) and within-group variable selection (airway generations), i.e., bi-level selection. Here we streamline a comprehensive procedure to process the lung airway data via imputation, normalization, transformation and groupwise principal component analysis, and then adopt a new composite penalized regression approach for conducting bi-level feature selection. As a prototype of composite penalization, the proposed composite bridge regression method is shown to admit an efficient algorithm, enjoy bi-level oracle properties, and outperform several existing methods. We analyze the MDCT lung image data from a cohort of 132 subjects with normal lung function. Our results show that, lung function in terms of FEV1% is promoted by having a less dense and more homogeneous lung comprising an airway whose segments enjoy more heterogeneity in wall thicknesses, larger mean diameters, lumen areas and branch angles. These data hold the potential of defining more accurately the "normal" subject population with borderline atypical lung functions that are clearly influenced by many genetic and environmental factors.

SUBMITTER: Chen K

PROVIDER: S-EPMC5340208 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

Chen Kun K Hoffman Eric A EA Seetharaman Indu I Jiao Feiran F Lin Ching-Long CL Chan Kung-Sik KS

The annals of applied statistics 20161201 4

The human lung airway is a complex inverted tree-like structure. Detailed airway measurements can be extracted from MDCT-scanned lung images, such as segmental wall thickness, airway diameter, parent-child branch angles, etc. The wealth of lung airway data provides a unique opportunity for advancing our understanding of the fundamental structure-function relationships within the lung. An important problem is to construct and identify important lung airway features in normal subjects and connect ...[more]

PMID: 28280520

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Project description:Progressive decline in lung function is a hallmark of chronic obstructive pulmonary disease (COPD). Although airway dysbiosis occurs in COPD, whether it contributes to disease progression remains unknown. Here, through a longitudinal analysis on 181 COPD individuals from two large cohorts involving four UK clinical centers, we showed that baseline airway dysbiosis, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. Co-presence of Moraxella, Staphylococcus and Stenotrophomonas was associated with an accelerated FEV1 decline by 139.7 mL/year. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at clinical stability, two critical events contributing to long-term FEV1 decline. The microbiota association with FEV1 decline was validated in a third, independent cohort in China. Human multi-omics, murine and cellular mechanistic studies showed that chronic airway colonization of Staphylococcus aureus promoted lung function decline through producing homocysteine, which elicited an apoptosis-to-NETosis shift in neutrophils toward persistent inflammation via AKT1-S100A8/A9 axis. Prophylactic and therapeutic depletion of S. aureus via bacteriophage restored lung function in emphysema mice. These results provide a fresh approach to slow COPD progression by targeting the airway microbiome. Linked studies:UPLC-MS/MS assays of human samples are reported in this study.UPLC-MS/MS assays of murine samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6894' rel='noopener noreferrer' target='_blank'>MTBLS6894</a>.UPLC-MS/MS assays of original cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4017' rel='noopener noreferrer' target='_blank'>MTBLS4017</a>.

Dataset Information

LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

Publications

LINKING LUNG AIRWAY STRUCTURE TO PULMONARY FUNCTION VIA COMPOSITE BRIDGE REGRESSION.

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