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Article ; Online: Exploiting meta-analysis of genome-wide interaction with serum 25-hydroxyvitamin D to identify novel genetic loci associated with pulmonary function.

Seo, Jungkyun / Gaddis, Nathan C / Patchen, Bonnie K / Xu, Jiayi / Barr, R Graham / O'Connor, George / Manichaikul, Ani W / Gharib, Sina A / Dupuis, Josée / North, Kari E / Cassano, Patricia A / Hancock, Dana B

The American journal of clinical nutrition

2024 Volume 119, Issue 5, Page(s) 1227–1237

Abstract: Background: Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new biological insights into pulmonary function.: Objectives: ... ...

Abstract	Background: Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new biological insights into pulmonary function. Objectives: We aimed to identify novel genetic variants associated with pulmonary function by accounting for 25(OH)D interactions. Methods: We included 211,264 participants from the observational United Kingdom Biobank study with pulmonary function tests (PFTs), genome-wide genotypes, and 25(OH)D concentrations from 4 ancestral backgrounds-European, African, East Asian, and South Asian. Among PFTs, we focused on forced expiratory volume in the first second (FEV Results: Our GWAS meta-analyses, accounting for interaction with 25(OH)D, revealed 30 genetic variants significantly associated with FEV Conclusion: Genetic variant associations with lung function can be modified by 25(OH)D, and smoking history can further modify variant×25(OH)D interactions. These results expand the known genetic architecture of pulmonary function and add evidence that gene-environment interactions, including with 25(OH)D and smoking, influence lung function.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Lung/physiology ; Female ; Respiratory Function Tests ; Male ; Genetic Loci ; Middle Aged ; United Kingdom ; Polymorphism, Single Nucleotide ; Aged ; Forced Expiratory Volume ; Vital Capacity/genetics
Chemical Substances	25-hydroxyvitamin D (A288AR3C9H) ; Vitamin D (1406-16-2)
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1016/j.ajcnut.2024.03.007
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Article: Proteomic Networks and Related Genetic Variants Associated with Smoking and Chronic Obstructive Pulmonary Disease.

Konigsberg, Iain R / Vu, Thao / Liu, Weixuan / Litkowski, Elizabeth M / Pratte, Katherine A / Vargas, Luciana B / Gilmore, Niles / Abdel-Hafiz, Mohamed / Manichaikul, Ani W / Cho, Michael H / Hersh, Craig P / DeMeo, Dawn L / Banaei-Kashani, Farnoush / Bowler, Russell P / Lange, Leslie A / Kechris, Katerina J

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with ... ...

Abstract	Background: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features. Methods: Leveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS. Results: We identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts. Conclusions: In this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.26.24303069
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Article ; Online: Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes.

Brænne, Ingrid / Onengut-Gumuscu, Suna / Chen, Ruoxi / Manichaikul, Ani W / Rich, Stephen S / Chen, Wei-Min / Farber, Charles R

Scientific reports

2021 Volume 11, Issue 1, Page(s) 22651

Abstract: Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain ...

Abstract	Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain largely unknown. We hypothesized that genetic and environmental risk factors can both contribute to T1D through dynamic alterations of molecular interactions in physiologic networks. To test this hypothesis, we utilized longitudinal blood transcriptomic profiles in The Environmental Determinants of Diabetes in the Young (TEDDY) study to generate gene co-expression networks. In network modules that contain immune response genes associated with T1D, we observed highly dynamic differences in module connectivity in the 600 days (~ 2 years) preceding clinical diagnosis of T1D. Our results suggest that gene co-expression is highly plastic and that connectivity differences in T1D-associated immune system genes influence the timing and development of clinical disease.
MeSH term(s)	Case-Control Studies ; Child ; Child, Preschool ; Computational Biology ; Diabetes Mellitus, Type 1/genetics ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genome-Wide Association Study ; Humans ; Male ; Models, Statistical ; Prospective Studies ; Systems Biology ; Transcriptome
Language	English
Publishing date	2021-11-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-01840-z
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Article ; Online: The association between aging-related monocyte transcriptional networks and comorbidity burden: the Multi-Ethnic Study of Atherosclerosis (MESA).

Ding, Jingzhong / Lohman, Kurt / Molina, Anthony / Delbono, Osvaldo / Bertoni, Alain / Shea, Steven / Post, Wendy / Guo, Xiuqing / Barr, R Graham / Manichaikul, Ani W / Pankow, James S / Rotter, Jerome I / Hoeschele, Ina / Kritchevsky, Stephen B / Liu, Yongmei

GeroScience

2022 Volume 45, Issue 1, Page(s) 197–207

Abstract: Translating our knowledge of the biological aging from animal models to humans may give rise to novel approaches of targeting multiple aging-related diseases simultaneously and increasing health span. Here, for the first time, we use transcriptomic ... ...

Abstract	Translating our knowledge of the biological aging from animal models to humans may give rise to novel approaches of targeting multiple aging-related diseases simultaneously and increasing health span. Here, for the first time, we use transcriptomic signatures of monocytes to identify biological aging pathways underlying multiple aging-related diseases in humans. The ordinal logistic regression was used to cross-sectionally investigate transcriptomics of the comorbidity index in 1264 community-based Multi-Ethnic Study of Atherosclerosis (MESA) adults, 47% Caucasian, 32% Hispanic, 21% African American, and 51% female, aged 55-94 years. The comorbidity index was defined as the number of prevalent aging-related diseases including cardiovascular disease, type-2 diabetes, hypertension, cancer, dementia, chronic kidney disease, chronic obstructive pulmonary disease, and hip fracture. We identified 708 gene transcripts associated with the comorbidity index (FDR < 0.05) after adjusting for age, sex, ethnicity, and study site. In a weighted gene co-expression network analysis, as postulated, aging-related declines in apoptosis/autophagy (OR = 1.21 per SD increment, p = 0.0006) and ribosome/mitochondrion (OR = 0.90 per SD increment, p = 0.05) were positively associated with the comorbidity index. After adjusting for multiple comparisons, we identified 10 comorbidity-associated modules (FDR < 0.05), including the module of apoptosis/autophagy. There were three inter-correlated modules of these 10 involved in the complement subcomponent C1q, Fc gamma receptor I, and Fc gamma receptor III of the immune system, respectively. Aging-related upregulation of these three modules was positively associated with the comorbidity index. The odds of comorbidity increased with more of these modules acting together in a dose-response fashion. In conclusion, transcriptomic analysis of human immune cells may identify biomarker panels indicative of comprehensive biological mechanisms, especially immune signaling pathways, contributing to health aging.
MeSH term(s)	Humans ; Female ; Male ; Monocytes ; Gene Regulatory Networks ; Receptors, IgG/metabolism ; Aging/genetics ; Comorbidity ; Atherosclerosis/genetics ; Atherosclerosis/metabolism
Chemical Substances	Receptors, IgG
Language	English
Publishing date	2022-06-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-022-00608-1
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Article ; Online: AtheroSpectrum Reveals Novel Macrophage Foam Cell Gene Signatures Associated With Atherosclerotic Cardiovascular Disease Risk.

Li, Chuan / Qu, Lili / Matz, Alyssa J / Murphy, Patrick A / Liu, Yongmei / Manichaikul, Ani W / Aguiar, Derek / Rich, Stephen S / Herrington, David M / Vu, David / Johnson, W Craig / Rotter, Jerome I / Post, Wendy S / Vella, Anthony T / Rodriguez-Oquendo, Annabelle / Zhou, Beiyan

Circulation

2021 Volume 145, Issue 3, Page(s) 206–218

Abstract: Background: Whereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to ... ...

Abstract	Background: Whereas several interventions can effectively lower lipid levels in people at risk for atherosclerotic cardiovascular disease (ASCVD), cardiovascular event risks remain, suggesting an unmet medical need to identify factors contributing to cardiovascular event risk. Monocytes and macrophages play central roles in atherosclerosis, but studies have yet to provide a detailed view of macrophage populations involved in increased ASCVD risk. Methods: A novel macrophage foaming analytics tool, AtheroSpectrum, was developed using 2 quantitative indices depicting lipid metabolism and the inflammatory status of macrophages. A machine learning algorithm was developed to analyze gene expression patterns in the peripheral monocyte transcriptome of MESA participants (Multi-Ethnic Study of Atherosclerosis; set 1; n=911). A list of 30 genes was generated and integrated with traditional risk factors to create an ASCVD risk prediction model (30-gene cardiovascular disease risk score [CR-30]), which was subsequently validated in the remaining MESA participants (set 2; n=228); performance of CR-30 was also tested in 2 independent human atherosclerotic tissue transcriptome data sets (GTEx [Genotype-Tissue Expression] and GSE43292). Results: Using single-cell transcriptomic profiles (GSE97310, GSE116240, GSE97941, and FR-FCM-Z23S), AtheroSpectrum detected 2 distinct programs in plaque macrophages-homeostatic foaming and inflammatory pathogenic foaming-the latter of which was positively associated with severity of atherosclerosis in multiple studies. A pool of 2209 pathogenic foaming genes was extracted and screened to select a subset of 30 genes correlated with cardiovascular event in MESA set 1. A cardiovascular disease risk score model (CR-30) was then developed by incorporating this gene set with traditional variables sensitive to cardiovascular event in MESA set 1 after cross-validation generalizability analysis. The performance of CR-30 was then tested in MESA set 2 ( Conclusions: Our novel computational program (AtheroSpectrum) identified a specific gene expression profile associated with inflammatory macrophage foam cells. A subset of 30 genes expressed in circulating monocytes jointly contributed to prediction of symptomatic atherosclerotic vascular disease. Incorporating a pathogenic foaming gene set with known risk factors can significantly strengthen the power to predict ASCVD risk. Our programs may facilitate both mechanistic investigations and development of therapeutic and prognostic strategies for ASCVD risk.
MeSH term(s)	Aged ; Aged, 80 and over ; Atherosclerosis/etiology ; Atherosclerosis/genetics ; Atherosclerosis/therapy ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/therapy ; Coronary Artery Disease/complications ; Coronary Artery Disease/genetics ; Coronary Artery Disease/therapy ; Female ; Foam Cells/cytology ; Humans ; Macrophages/cytology ; Male ; Middle Aged ; Plaque, Atherosclerotic/complications ; Plaque, Atherosclerotic/genetics ; Plaque, Atherosclerotic/therapy ; ROC Curve ; Risk ; Vascular Calcification/complications ; Vascular Calcification/genetics ; Vascular Calcification/therapy
Language	English
Publishing date	2021-12-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.121.054285
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Article ; Online: Correlations between complex human phenotypes vary by genetic background, gender, and environment.

Cell reports. Medicine

2022 , Page(s) 100844

Abstract: We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between ...

Abstract	We develop a closed-form Haseman-Elston estimator for genetic and environmental correlation coefficients between complex phenotypes, which we term HEc, that is as precise as GCTA yet ∼20× faster. We estimate genetic and environmental correlations between over 7,000 phenotype pairs in subgroups from the Trans-Omics in Precision Medicine (TOPMed) program. We demonstrate substantial differences in both heritabilities and genetic correlations for multiple phenotypes and phenotype pairs between individuals of self-reported Black, Hispanic/Latino, and White backgrounds. We similarly observe differences in many of the genetic and environmental correlations between genders. To estimate the contribution of genetics to the observed phenotypic correlation, we introduce "fractional genetic correlation" as the fraction of phenotypic correlation explained by genetics. Finally, we quantify the enrichment of correlations between phenotypic domains, each of which is comprised of multiple phenotypes. Altogether, we demonstrate that the observed correlations between complex human phenotypes depend on the genetic background of the individuals, their gender, and their environment.
Language	English
Publishing date	2022-12-06
Publishing country	United States
Document type	Journal Article
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100844
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Article ; Online: MUC5B

Thorax

2022 Volume 78, Issue 6, Page(s) 566–573

Abstract: Background: The : Methods: We used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and : Results: The : Conclusions: Longitudinal increases in HAAs were ... ...

Abstract	Background: The Methods: We used data from participants in the Multi-Ethnic Study of Atherosclerosis with high-attenuation areas (HAAs, Examinations 1-6 (2000-2018)) and Results: The Conclusions: Longitudinal increases in HAAs were associated with the
MeSH term(s)	Adult ; Humans ; Lung/diagnostic imaging ; Lung Diseases, Interstitial/diagnostic imaging ; Lung Diseases, Interstitial/genetics ; Lung Diseases, Interstitial/complications ; Genotype ; Telomere/genetics ; Mucin-5B/genetics
Chemical Substances	Mucin-5B ; MUC5B protein, human
Language	English
Publishing date	2022-08-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thorax-2021-218139
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Article ; Online: Incidence of Interstitial Lung Abnormalities: The MESA Lung Study.

McGroder, Claire F / Hansen, Spencer / Hinckley Stukovsky, Karen / Zhang, David / Nath, P Hrudaya / Salvatore, Mary M / Sonavane, Sushilkumar K / Terry, Nina / Stowell, Justin T / D'Souza, Belinda M / Leb, Jay S / Dumeer, Shifali / Aziz, Muhammad U / Batra, Kiran / Hoffman, Eric A / Bernstein, Elana J / Kim, John S / Podolanczuk, Anna J / Rotter, Jerome I /

Manichaikul, Ani W / Rich, Stephen S / Lederer, David J / Barr, R Graham / McClelland, Robyn L / Garcia, Christine Kim

The European respiratory journal

2023

Abstract: The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA have not been previously reported.Trained thoracic radiologists evaluated 13 944 cardiac CT scans for the presence of ILA in 6197 Multi-Ethnic Study of ... ...

Abstract	The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA have not been previously reported.Trained thoracic radiologists evaluated 13 944 cardiac CT scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis longitudinal cohort study participants >45 years of age from 2000 to 2012. 5% of the scans were re-read by the same or a different observer in a blinded fashion. After exclusion of participants with ILA at baseline, incidence rates and incidence rate ratios for ILA and fibrotic ILA were calculated.The intra-reader agreement of ILA was 92.0% (Gwet AC1=0.912, ICC=0.982) and the inter-reader agreement of ILA was 83.5% (Gwet AC1=0.814; ICC=0.969). Incidence of ILA and fibrotic ILA was estimated to be 13.1 cases/1000 person-years and 3.5/1000 person-years, respectively. In multivariable analyses, age (HR 1.06 (1.05, 1.08), p <0.001; HR 1.08 (1.06, 1.11), p <0.001), high attenuation area (HAA) at baseline (HR 1.05 (1.03, 1.07), p <0.001; HR 1.06 (1.02, 1.10), p=0.002), and the
Language	English
Publishing date	2023-05-18
Publishing country	England
Document type	Journal Article
ZDB-ID	639359-7
ISSN	1399-3003 ; 0903-1936
ISSN (online)	1399-3003
ISSN	0903-1936
DOI	10.1183/13993003.01950-2022
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Zs.A 2322: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Large scale proteomic studies create novel privacy considerations.

Hill, Andrew C / Guo, Claire / Litkowski, Elizabeth M / Manichaikul, Ani W / Yu, Bing / Konigsberg, Iain R / Gorbet, Betty A / Lange, Leslie A / Pratte, Katherine A / Kechris, Katerina J / DeCamp, Matthew / Coors, Marilyn / Ortega, Victor E / Rich, Stephen S / Rotter, Jerome I / Gerzsten, Robert E / Clish, Clary B / Curtis, Jeffrey L / Hu, Xiaowei /

Obeidat, Ma-En / Morris, Melody / Loureiro, Joseph / Ngo, Debby / O'Neal, Wanda K / Meyers, Deborah A / Bleecker, Eugene R / Hobbs, Brian D / Cho, Michael H / Banaei-Kashani, Farnoush / Bowler, Russell P

Scientific reports

2023 Volume 13, Issue 1, Page(s) 9254

Abstract: Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level ... ...

Abstract	Privacy protection is a core principle of genomic but not proteomic research. We identified independent single nucleotide polymorphism (SNP) quantitative trait loci (pQTL) from COPDGene and Jackson Heart Study (JHS), calculated continuous protein level genotype probabilities, and then applied a naïve Bayesian approach to link SomaScan 1.3K proteomes to genomes for 2812 independent subjects from COPDGene, JHS, SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) and Multi-Ethnic Study of Atherosclerosis (MESA). We correctly linked 90-95% of proteomes to their correct genome and for 95-99% we identify the 1% most likely links. The linking accuracy in subjects with African ancestry was lower (~ 60%) unless training included diverse subjects. With larger profiling (SomaScan 5K) in the Atherosclerosis Risk Communities (ARIC) correct identification was > 99% even in mixed ancestry populations. We also linked proteomes-to-proteomes and used the proteome only to determine features such as sex, ancestry, and first-degree relatives. When serial proteomes are available, the linking algorithm can be used to identify and correct mislabeled samples. This work also demonstrates the importance of including diverse populations in omics research and that large proteomic datasets (> 1000 proteins) can be accurately linked to a specific genome through pQTL knowledge and should not be considered unidentifiable.
MeSH term(s)	Humans ; Proteome/genetics ; Bayes Theorem ; Privacy ; Genome-Wide Association Study ; Atherosclerosis/genetics ; Polymorphism, Single Nucleotide
Chemical Substances	Proteome
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-34866-6
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Article ; Online: Characterisation of gas exchange in COPD with dissolved-phase hyperpolarised xenon-129 MRI.

Myc, Lukasz / Qing, Kun / He, Mu / Tustison, Nicholas / Lin, Zixuan / Manichaikul, Ani W / Patrie, James / Cassani, Joanne / Nunoo-Asare, Roselove N / Huang, Yong / Obaida, Zaid / Tafti, Sina / Ropp, Alan M / Miller, Grady Wilson / Mata, Jaime / Altes, Talissa / Mugler, John / Shim, Y Michael

Thorax

2020 Volume 76, Issue 2, Page(s) 178–181

Abstract: To investigate whether hyperpolarised xenon-129 MRI (HXeMRI) enables regional and physiological resolution of diffusing capacity limitations in chronic obstructive pulmonary disease (COPD), we evaluated 34 COPD subjects and 11 healthy volunteers. We ... ...

Abstract	To investigate whether hyperpolarised xenon-129 MRI (HXeMRI) enables regional and physiological resolution of diffusing capacity limitations in chronic obstructive pulmonary disease (COPD), we evaluated 34 COPD subjects and 11 healthy volunteers. We report significant correlations between airflow abnormality quantified by HXeMRI and per cent predicted forced expiratory volume in 1 s; HXeMRI gas transfer capacity to red blood cells and carbon monoxide diffusion capacity (%DLCO); and HXeMRI gas transfer capacity to interstitium and per cent emphysema quantified by multidetector chest CT. We further demonstrate the capability of HXeMRI to distinguish varying pathology underlying COPD in subjects with low %DLCO and minimal emphysema.
MeSH term(s)	Aged ; Case-Control Studies ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/diagnostic imaging ; Pulmonary Disease, Chronic Obstructive/physiopathology ; Pulmonary Gas Exchange ; Tomography, X-Ray Computed ; Xenon Isotopes
Chemical Substances	Xenon Isotopes ; Xenon-129
Language	English
Publishing date	2020-11-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2020-214924
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