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202. Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

Author

Hoda, Uruj, Pavlidis, Stelios, Bansal, Aruna T, Takahashi, Kentaro, Hu, Sile, Ng Kee Kwong, Francois, Rossios, Christos, Sun, Kai, Bhavsar, Pankaj, Loza, Matthew, Baribaud, Frederic, Chanez, Pascal, Fowler, Stephen J, Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Krug, Norbert, Sandstrom, Thomas, Shaw, Dominic E, Lutter, Rene, Fleming, Louise J, Howarth, Peter H, Caruso, Massimo, Sousa, Ana R, Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Dahlen, Sven-Erik, Djukanovic, Ratko, Sterk, Peter J, Guo, Yike, Adcock, Ian M, Chung, Kian Fan, Pulmonology, AII - Inflammatory diseases, and Commission of the European Communities

Subjects
severe asthma, Bronchi/pathology, Medicine (miscellaneous), PHENOTYPES, 1110 Nursing, 610 Medicine & health, Bronchi, Research & Experimental Medicine, Sputum/metabolism, Cohort Studies, Humans, CEACAM5, Asthma/genetics, Science & Technology, STATEMENT, Sputum, Transcriptome/genetics, Asthma, frequent exacerbators, Oncology, Medicine, Research & Experimental, asthma exacerbations, Molecular Medicine, U-BIOPRED study group, 610 Medizin und Gesundheit, Transcriptome, Life Sciences & Biomedicine, persistent frequent exacerbators, LUNG
Abstract

BACKGROUND: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.OBJECTIVES: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.METHODS: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, RESULTS: Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short-acting beta-agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T-helper type-17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.CONCLUSION: The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.

Published
2022

203. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

INTRODUCTION: Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. METHODS: Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. RESULTS: A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10-20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10-4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. CONCLUSIONS: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carn

Published
2022
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204. Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma

Author

Badi, Yusef Eamon, Pavel, Ana B., Pavlidis, Stelios, Riley, John H., Bates, Stewart, Kermani, Nazanin Zounemat, Knowles, Richard, Kolmert, Johan, Wheelock, Craig E., Worsley, Sally, Uddin, Mohib, Alving, Kjell, Bakke, Per S., Behndig, Annelie, Caruso, Massimo, Chanez, Pascal, Fleming, Louise J., Fowler, Stephen J., Frey, Urs, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Maitland-van der Zee, Anke H., Montuschi, Paolo, Roberts, Graham, Sanak, Marek, Shaw, Dominick E., Singer, Florian, Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Eric, Guo, Yi-Ke, Chung, Kian Fan, Guttman-Yassky, Emma, Adcock, Ian M., Badi, Yusef Eamon, Pavel, Ana B., Pavlidis, Stelios, Riley, John H., Bates, Stewart, Kermani, Nazanin Zounemat, Knowles, Richard, Kolmert, Johan, Wheelock, Craig E., Worsley, Sally, Uddin, Mohib, Alving, Kjell, Bakke, Per S., Behndig, Annelie, Caruso, Massimo, Chanez, Pascal, Fleming, Louise J., Fowler, Stephen J., Frey, Urs, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Maitland-van der Zee, Anke H., Montuschi, Paolo, Roberts, Graham, Sanak, Marek, Shaw, Dominick E., Singer, Florian, Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Eric, Guo, Yi-Ke, Chung, Kian Fan, Guttman-Yassky, Emma, and Adcock, Ian M.

Abstract

Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases. Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti-IL-22 (fezakinumab [FZ]) is enriched in severe asthma. Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort. Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, T(H)2, and T(H)17/T(H)22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P < .05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P < .05) and particularly in neutrophilic and mixed granulocytic sputum (P < .05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with T(H)22/IL-22 pathways. Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.

Published
2022
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205. A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes

Author

Abdel-Aziz, Mahmoud I., Vijverberg, Susanne J.H., Neerincx, Anne H., Brinkman, Paul, Wagener, Ariane H., Riley, John H., Sousa, Ana R., Bates, Stewart, Wagers, Scott S., De Meulder, Bertrand, Auffray, Charles, Wheelock, Åsa M., Bansal, Aruna T., Caruso, Massimo, Chanez, Pascal, Uddin, Mohib, Corfield, Julie, Horvath, Ildiko, Krug, Norbert, Musial, Jacek, Sun, Kai, Shaw, Dominick E., Sandström, Thomas, Montuschi, Paolo, Fowler, Stephen J., Lutter, René, Djukanovic, Ratko, Howarth, Peter, Skipp, Paul, Sanak, Marek, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Kraneveld, Aletta D., Maitland-Van der Zee, Anke H., Abdel-Aziz, Mahmoud I., Vijverberg, Susanne J.H., Neerincx, Anne H., Brinkman, Paul, Wagener, Ariane H., Riley, John H., Sousa, Ana R., Bates, Stewart, Wagers, Scott S., De Meulder, Bertrand, Auffray, Charles, Wheelock, Åsa M., Bansal, Aruna T., Caruso, Massimo, Chanez, Pascal, Uddin, Mohib, Corfield, Julie, Horvath, Ildiko, Krug, Norbert, Musial, Jacek, Sun, Kai, Shaw, Dominick E., Sandström, Thomas, Montuschi, Paolo, Fowler, Stephen J., Lutter, René, Djukanovic, Ratko, Howarth, Peter, Skipp, Paul, Sanak, Marek, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Kraneveld, Aletta D., and Maitland-Van der Zee, Anke H.

Abstract

A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.

Published
2022
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206. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6x10(-20)), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5x10(-4)), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carniti

Published
2022

211. A Transcriptome-driven Analysis of Epithelial Brushings and Bronchial Biopsies to Define Asthma Phenotypes in U-BIOPRED

Author

Kuo, Chih-Hsi Scott, Pavlidis, Stelios, Loza, Matthew, Baribaud, Fred, Rowe, Anthony, Pandis, Ioannis, Hoda, Uruj, Rossios, Christos, Sousa, Ana, Wilson, Susan J., Howarth, Peter, Dahlen, Barbro, Dahlen, Sven-Erik, Chanez, Pascal, Shaw, Dominick, Krug, Norbert, Sandström, Thomas, De Meulder, Bertrand, Lefaudeux, Diane, Fowler, Stephen, Fleming, Louise, Corfield, Julie, Auffray, Charles, Sterk, Peter J., Djukanovic, Ratko, Guo, Yike, Adcock, Ian M., and Chung, Kian Fan

Published
2017
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215. A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model

Author

Yeh, Lu-Yang, primary, Fang, Yu-Ting, additional, Lee, Hong-Sheng, additional, Liu, Chia-Hao, additional, Chen, You-Yin, additional, Lo, Yu-Chun, additional, Laiman, Vincent, additional, Liou, Jing-Ping, additional, Chung, Kian Fan, additional, Chuang, Hsiao-Chi, additional, and Lin, Chien-Huang, additional

Published
2022
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216. Oxygen Desaturation Is Associated With Fibrocyte Activation via Epidermal Growth Factor Receptor/Hypoxia-Inducible Factor-1α Axis in Chronic Obstructive Pulmonary Disease

Author

Wang, Chun-Hua, primary, Lo, Chun-Yu, additional, Huang, Hung-Yu, additional, Wang, Tsai-Yu, additional, Weng, Chih-Ming, additional, Chen, Chih-Jung, additional, Huang, Yu-Chen, additional, Chung, Fu-Tsai, additional, Lin, Chang-Wei, additional, Chung, Kian Fan, additional, and Kuo, Han-Pin, additional

Published
2022
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217. Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China

Author

Huang, Kewu, primary, Chung, Kian Fan, additional, Yang, Ting, additional, Xu, Jianying, additional, Yang, Lan, additional, Zhao, Jianping, additional, Zhang, Xiangyan, additional, Bai, Chunxue, additional, Kang, Jian, additional, Ran, Pixin, additional, Shen, Huahao, additional, Wen, Fuqiang, additional, Chen, Yahong, additional, Sun, Tieying, additional, Shan, Guangliang, additional, Lin, Yingxiang, additional, Xu, Guodong, additional, Wu, Sinan, additional, Wang, Ying, additional, Gu, Xiaoying, additional, Wang, Ruiying, additional, Shi, Zhihong, additional, Xu, Yongjian, additional, Ye, Xianwei, additional, Song, Yuanlin, additional, Wang, Qiuyue, additional, Zhou, Yumin, additional, Li, Wen, additional, Ding, Liren, additional, Wan, Chun, additional, Yao, Wanzhen, additional, Guo, Yanfei, additional, Xiao, Fei, additional, Lu, Yong, additional, Peng, Xiaoxia, additional, Xiao, Dan, additional, Bu, Xiaoning, additional, Zhang, Hong, additional, Zhang, Xiaolei, additional, An, Li, additional, Zhang, Shu, additional, Cao, Zhixin, additional, Zhan, Qingyuan, additional, Yang, Yuanhua, additional, Liang, Lirong, additional, Wang, Wenjun, additional, Dai, Huaping, additional, Cao, Bin, additional, He, Jiang, additional, and Wang, Chen, additional

Published
2022
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218. Chronic cough in asthma is associated with increased airway inflammation, more comorbidities, and worse clinical outcomes

Author

Deng, Su Jun, primary, Wang, Ji, additional, Liu, Lei, additional, Zhang, Xin, additional, Gibson, Peter G., additional, Chen, Zhi Hong, additional, Birring, Surinder S., additional, Xie, Min, additional, Lai, Ke Fang, additional, Qin, Ling, additional, Liu, Dan, additional, Vertigan, Anne E., additional, Song, Woo-Jung, additional, McGarvey, Lorcan, additional, Luo, Feng Ming, additional, Chung, Kian Fan, additional, Li, Wei Min, additional, and Wang, Gang, additional

Published
2022
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219. Prevalence and burden of chronic cough in China: a national cross-sectional study

Author

Huang, Kewu, primary, Gu, Xiaoying, additional, Yang, Ting, additional, Xu, Jianying, additional, Yang, Lan, additional, Zhao, Jianping, additional, Zhang, Xiangyan, additional, Bai, Chunxue, additional, Kang, Jian, additional, Ran, Pixin, additional, Shen, Huahao, additional, Wen, Fuqiang, additional, Chen, Yahong, additional, Sun, Tieying, additional, Shan, Guangliang, additional, Lin, Yingxiang, additional, Wu, Sinan, additional, Wang, Ruiying, additional, Shi, Zhihong, additional, Xu, Yongjian, additional, Ye, Xianwei, additional, Song, Yuanlin, additional, Wang, Qiuyue, additional, Zhou, Yumin, additional, Li, Wen, additional, Ding, Liren, additional, Wan, Chun, additional, Yao, Wanzhen, additional, Guo, Yanfei, additional, Xiao, Fei, additional, Lu, Yong, additional, Peng, Xiaoxia, additional, Xiao, Dan, additional, Bu, Xiaoning, additional, Zhang, Hong, additional, Zhang, Xiaolei, additional, An, Li, additional, Zhang, Shu, additional, Cao, Zhixin, additional, Zhan, Qingyuan, additional, Yang, Yuanhua, additional, Liang, Lirong, additional, Dai, Huaping, additional, Cao, Bin, additional, He, Jiang, additional, Chung, Kian Fan, additional, and Wang, Chen, additional

Published
2022
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220. SARS-CoV2 and Air Pollution Interactions: Airborne Transmission and COVID-19

Author

Chung, Kian Fan, primary, Abubakar-Waziri, Hisham, additional, Kalaiarasan, Gopinath, additional, Adcock, Ian M, additional, Dilliway, Claire, additional, Fang, Fangxin, additional, Pain, Christopher, additional, Kumar, Prashant, additional, Ransome, Emma, additional, Savolainen, Vincent, additional, Bhavsar, Pankaj, additional, and Porter, Alexandra, additional

Published
2022
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224. Contributors

Author

Adams, Lewis, primary, Adler, Dan Elie, additional, Agusti, Alvar, additional, Akoumianaki, Evangelia, additional, Alberg, Anthony J., additional, Albertine, Kurt H., additional, Alexander, Barbara D., additional, Alfille, Paul H., additional, Anantham, Devanand, additional, Arenberg, Douglas A., additional, Ayas, Najib T., additional, Bagchi, Aranya, additional, Balmes, John Randolph, additional, Banaei, Niaz, additional, Barnett, Christopher F., additional, Baughman, Robert P., additional, Becklake, Margaret R., additional, Benditt, Joshua O., additional, Benowitz, Neal L., additional, Bhakta, Nirav R., additional, Bhave, Anant D., additional, Blanc, Paul D., additional, Bleecker, Eugene R., additional, Bove, Alfred A., additional, Bradley, T. Douglas, additional, Brambilla, Elisabeth, additional, Broaddus, V. Courtney, additional, Brochard, Laurent, additional, Brock, Malcolm V., additional, Brown, Kevin K., additional, Brunetta, Paul G., additional, Cadranel, Jacques, additional, Celli, Bartolome, additional, Chan, Edward D., additional, Channick, Richard N., additional, Chastre, Jean, additional, Cheng, Guang-Shing, additional, Chin, Kelly, additional, Chung, Kian Fan, additional, Clerici, Christine, additional, Colby, Thomas V., additional, Collard, Harold R., additional, Cool, Carlyne D., additional, Cordier, Jean-François, additional, Cordioli, Ricardo Luiz, additional, Corte, Tamera J., additional, Cottin, Vincent, additional, Courey, Mark S., additional, Cowie, Robert L., additional, Crothers, Kristina, additional, Curley, Gerard F., additional, Daley, Charles L., additional, Davis, J. Lucian, additional, De Marco, Teresa, additional, Deresinski, Stanley C., additional, Deroose, Christophe, additional, Dobbs, Leland G., additional, Dooms, Christophe, additional, Downey, Gregory P., additional, du Bois, Roland M., additional, Dulohery, Megan M., additional, Effros, Richard M., additional, Eisner, Mark D., additional, Elicker, Brett M., additional, Ernst, Armin, additional, Ernst, Joel D., additional, Fahy, John V., additional, Fedullo, Peter F., additional, Feller-Kopman, David, additional, Fenster, Brett E., additional, Fingerlin, Tasha E., additional, Fontenot, Andrew P., additional, Frankel, Stephen K., additional, Garcia, Joe G.N., additional, Gebhart, G.F., additional, Gilstrap, Daniel Lee, additional, Girard, Nicolas, additional, Gladwin, Mark T., additional, Glenny, Robb W., additional, Gold, Warren M., additional, Gotway, Michael B., additional, Grasselli, Giacomo, additional, Greenberg, James M., additional, Griffith, David E., additional, Gruden, James F., additional, Han, MeiLan King, additional, Henderson, William, additional, Hill, Nicholas S., additional, Hoover, Wynton, additional, Hopewell, Philip C., additional, Horan-Saullo, Jennifer L., additional, Horner, Richard L., additional, Huang, Laurence, additional, Huchon, Gérard, additional, Inoue, Yoshikazu, additional, Iseman, Michael D., additional, Jackson, James E., additional, Jakubzick, Claudia V., additional, Janssen, Julius P., additional, Jett, James R., additional, Jones, Kirk, additional, Judson, Marc A., additional, Kato-Maeda, Midori, additional, Kavanagh, Brian P., additional, Keshavjee, Shaf, additional, Kim, Kami, additional, Kimoff, R. John, additional, King, Talmadge E., additional, Klein, Jeffrey S., additional, Koth, Laura L., additional, Kotloff, Robert M., additional, Kraft, Monica, additional, Küpeli, Elif, additional, Laffey, John G., additional, Lapinsky, Stephen E., additional, Lazarus, Stephen C., additional, Lee, Frances Eun-Hyung, additional, Lee, Jarone, additional, Lee, Y.C. Gary, additional, Lee, Warren L., additional, Lee-Chiong, Teofilo L., additional, Lemière, Catherine, additional, Light, Richard W., additional, Limper, Andrew H., additional, Loddenkemper, Robert, additional, Lugogo, Njira, additional, Luisetti, Maurizio, additional, Luks, Andrew M., additional, Luyt, Charles-Edouard, additional, Machado, Roberto F., additional, MacIntyre, Neil R., additional, MacNee, William, additional, Madtes, David K., additional, Maier, Lisa A., additional, Maldonado, Fabien, additional, Malhotra, Atul, additional, Martin, Thomas R., additional, Maskell, Nick A., additional, Mason, Robert J., additional, Massion, Pierre P., additional, Matthay, Michael A., additional, Matthay, Richard A., additional, Mayer, Annyce S., additional, Mazzone, Stuart B., additional, McCool, F. Dennis, additional, McCormack, Francis Xavier, additional, Mehta, Atul C., additional, Menéndez, Rosario, additional, Morgenthau, Adam S., additional, Morris, Alison, additional, Morris, Timothy A., additional, Muncey, Aaron R., additional, Murray, John F., additional, Myers, Jeffrey L., additional, Nadel, Jay A., additional, Nelson-Piercy, Catherine, additional, Neuman, Tom S., additional, Nosanchuk, Joshua D., additional, O'Riordan, Thomas G., additional, Ortega, Victor Enrique, additional, Panse, Prasad M., additional, Pao, William, additional, Paré, Peter A., additional, Park, David R., additional, Pastis, Nicholas J., additional, Patroniti, Nicolò, additional, Patterson, Karen C., additional, Pesenti, Antonio, additional, Pickens, Allan, additional, Pinsky, Benjamin A., additional, Pletcher, Steven D., additional, Powell, Frank L., additional, Que, Loretta G., additional, Redente, Elizabeth F., additional, Riches, David W.H., additional, Robinson, Bruce W.S., additional, Rodriguez-Roisin, Roberto, additional, Rose, Cecile S., additional, Routes, John M., additional, Rowe, Steven M., additional, Ryan, Clodagh M., additional, Ryu, Jay H., additional, Samet, Jonathan M., additional, Sandrock, Christian E., additional, Schoene, Robert B., additional, Schwartz, David A., additional, Schwartzstein, Richard M., additional, Schwarz, Marvin I., additional, Selman, Moisés, additional, Sequist, Lecia V., additional, Shannon, John M., additional, Shovlin, Claire L., additional, Silvestri, Gerard A., additional, Simonian, Philip L., additional, Singer, Jonathan P., additional, Slutsky, Arthur S., additional, Smaldone, Gerald C., additional, Solomon, George M., additional, Sorscher, Eric J., additional, Swenson, Erik R., additional, Tanner, Nichole T., additional, Tanowitz, Herbert B., additional, Torres, Antoni, additional, Trapnell, Bruce C., additional, Travis, William David, additional, Treanor, John J., additional, Tzelepis, George E., additional, Vandenplas, Olivier, additional, Vansteenkiste, Johan F., additional, Varghese, Thomas K., additional, Vestbo, Jørgen, additional, Wagner, Peter D., additional, Wahidi, Momen M., additional, Wallace, W. Dean, additional, Weiss, Louis M., additional, Weiss, Scott T., additional, Wells, Athol U., additional, West, John B., additional, White, Douglas B., additional, Wiener-Kronish, Jeanine P., additional, Wikenheiser-Brokamp, Kathryn A., additional, Woodruff, Prescott G., additional, Wunderink, Richard G., additional, Yeh, D. Dante, additional, Zemans, Rachel L., additional, Zimmerman, Leslie, additional, and Zuwallack, Richard L., additional

Published
2016
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225. Cough

Author

Chung, Kian Fan, primary and Mazzone, Stuart B., additional

Published
2016
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227. Additional file 3 of Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China

Author

Zhou, Jianmeng, Yi, Fang, Wu, Feng, Xu, Pusheng, Chen, Meihua, Shen, Huahao, Lin, Lin, Zhang, Yunhui, Li, Suyun, Wu, Changgui, Yuan, Yadong, Wang, Gang, Ye, Xianwei, Zhang, Ping, Tang, Huaping, Ma, Qianli, Huang, Lanqing, Qiu, Zhongmin, Deng, Haiyan, Qiu, Chen, Shi, Guochao, Pan, Jiayu, Luo, Wei, Chung, Kian Fan, Zhong, Nanshan, and Lai, Kefang

Abstract

Additional file 3. Questions for indicating diagnosis of CVA, CPA and CA from questionnaire.

Published
2022
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228. Additional file 1 of Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China

Author

Zhou, Jianmeng, Yi, Fang, Wu, Feng, Xu, Pusheng, Chen, Meihua, Shen, Huahao, Lin, Lin, Zhang, Yunhui, Li, Suyun, Wu, Changgui, Yuan, Yadong, Wang, Gang, Ye, Xianwei, Zhang, Ping, Tang, Huaping, Ma, Qianli, Huang, Lanqing, Qiu, Zhongmin, Deng, Haiyan, Qiu, Chen, Shi, Guochao, Pan, Jiayu, Luo, Wei, Chung, Kian Fan, Zhong, Nanshan, and Lai, Kefang

Abstract

Additional file 1. List of all clinical centers participating in the study.

Published
2022
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229. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, Maria Sparreman, Kolmert, Johan, Andersson, Lars I., Östling, Jörgen, Knowles, Richard G., Gómez, Cristina, Ericsson, Magnus, Thörngren, John Olof, Khoonsari, Payam Emami, Dahlén, Barbro, Kupczyk, Maciej, de Meulder, Bertrand, Auffray, Charles, Bakke, Per S., Beghe, Bianca, Bel, Elisabeth H., Caruso, Massimo, Chanez, Pascal, Chawes, Bo, Fowler, Stephen J., Gaga, Mina, Geiser, Thomas, Gjomarkaj, Mark, Horváth, Ildikó, Howarth, Peter H., Johnston, Sebastian L., Joos, Guy, Krug, Norbert, Montuschi, Paolo, Musial, Jacek, Niżankowska-Mogilnicka, Ewa, Olsson, Henric K., Papi, Alberto, Rabe, Klaus F., Sandström, Thomas, Shaw, Dominick E., Siafakas, Nikolaos M., Uhlén, Mathias, Riley, John H., Bates, Stewart, Middelveld, Roelinde J.M., Wheelock, Craig E., Chung, Kian Fan, Adcock, Ian M., Sterk, Peter J., Bisgaard, Hans, Bønnelykke, Klaus, Vestbo, Jørgen, Vissing, Nadja H., and Olsson, Marianne

Abstract

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

Published
2022

230. Additional file 2 of Characteristics of different asthma phenotypes associated with cough: a prospective, multicenter survey in China

Author

Zhou, Jianmeng, Yi, Fang, Wu, Feng, Xu, Pusheng, Chen, Meihua, Shen, Huahao, Lin, Lin, Zhang, Yunhui, Li, Suyun, Wu, Changgui, Yuan, Yadong, Wang, Gang, Ye, Xianwei, Zhang, Ping, Tang, Huaping, Ma, Qianli, Huang, Lanqing, Qiu, Zhongmin, Deng, Haiyan, Qiu, Chen, Shi, Guochao, Pan, Jiayu, Luo, Wei, Chung, Kian Fan, Zhong, Nanshan, and Lai, Kefang

Abstract

Additional file 2. Case Report Form of the study.

Published
2022
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234. Determinants of Exhaled Breath Condensate pH in a Large Population With Asthma

Author

Liu, Lei, Teague, W. Gerald, Erzurum, Serpil, Fitzpatrick, Anne, Mantri, Sneha, Dweik, Raed A., Bleecker, Eugene R., Meyers, Deborah, Busse, William W., Calhoun, William J., Castro, Mario, Chung, Kian Fan, Curran-Everett, Douglas, Israel, Elliot, Jarjour, W. Nizar, Moore, Wendy, Peters, Stephen P., Wenzel, Sally, Hunt, John F., and Gaston, Benjamin

Published
2011
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235. Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma

Author

Tiotiu, Angelica, primary, Badi, Yusef, additional, Kermani, Nazanin Zounemat, additional, Sanak, Marek, additional, Kolmert, Johan, additional, Wheelock, Craig E., additional, Hansbro, Philip M., additional, Dahlén, Sven-Erik, additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Guo, Yike, additional, Mumby, Sharon, additional, Adcock, Ian M., additional, Chung, Kian Fan, additional, Hoda, Uruj, additional, Rossios, Christos, additional, Bel, Elisabeth, additional, Rao, Navin, additional, Myles, David, additional, Compton, Chris, additional, Van Geest, Marleen, additional, Howarth, Peter, additional, Roberts, Graham, additional, Lefaudeux, Diane, additional, De Meulder, Bertrand, additional, Bansal, Aruna T., additional, Knowles, Richard, additional, Erzen, Damijn, additional, Wagers, Scott, additional, Krug, Norbert, additional, Higenbottam, Tim, additional, Matthews, John, additional, Erpenbeek, Veit, additional, Carayannopoulos, Leon, additional, Roberts, Amanda, additional, Supple, David, additional, deBoer, Pim, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Horváth, Ildikó, additional, Musial, Jacek, additional, and Sandström, Thomas, additional

Published
2022
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236. Clinical and Inflammatory Characteristics of the Chinese APAC Cough Variant Asthma Cohort

Author

Lai, Kefang, primary, Zhan, Wenzhi, additional, Wu, Feng, additional, Zhang, Yunhui, additional, Lin, Lin, additional, Li, Wen, additional, Yi, Fang, additional, Jiang, Ziyu, additional, Dai, Yuanrong, additional, Li, Suyun, additional, Lin, Jiangtao, additional, Yuan, Yadong, additional, Jiang, Yong, additional, Qiu, Chen, additional, Zhao, Limin, additional, Chen, Meihua, additional, Qiu, Zhongmin, additional, Li, Hu, additional, Chen, Ruchong, additional, Luo, Wei, additional, Xie, Jiaxing, additional, Guo, Chunxing, additional, Jiang, Mei, additional, Yang, Xiaohong, additional, Shi, Guochao, additional, Sun, Dejun, additional, Chen, Rongchang, additional, Chung, Kian Fan, additional, Shen, Huahao, additional, and Zhong, Nanshan, additional

Published
2022
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237. Influence of Comorbidities and Airway Clearance on Mortality and Outcomes of Patients With Severe Bronchiectasis Exacerbations in Taiwan

Author

Huang, Hung-Yu, primary, Chung, Fu-Tsai, additional, Lin, Chun-Yu, additional, Lo, Chun-Yu, additional, Huang, Yu-Tung, additional, Huang, Yu-Chen, additional, Lai, Yu-Te, additional, Gan, Shu-Ting, additional, Ko, Po-Chuan, additional, Lin, Horng-Chyuan, additional, Chung, Kian Fan, additional, and Wang, Chun-Hua, additional

Published
2022
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238. Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema

Author

Chang, Jer-Hwa, primary, Lee, Yueh-Lun, additional, Laiman, Vincent, additional, Han, Chia-Li, additional, Jheng, Yu-Teng, additional, Lee, Kang-Yun, additional, Yeh, Chi-Tai, additional, Kuo, Han-Pin, additional, Chung, Kian Fan, additional, Heriyanto, Didik Setyo, additional, Hsiao, Ta-Chih, additional, Wu, Sheng-Ming, additional, Ho, Shu-Chuan, additional, Chuang, Kai-Jen, additional, and Chuang, Hsiao-Chi, additional

Published
2022
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239. Patterns and Characteristics of Tobacco Withdrawal Symptoms Among Chinese Smokers

Author

cui, ziyang, primary, Li, Yinghua, additional, Liu, Zhao, additional, Li, Li, additional, Nie, Xueqiong, additional, Zhou, Xinmei, additional, Cheng, Anqi, additional, Li, Jinxuan, additional, Qin, Rui, additional, Wei, Xiaowen, additional, Zhao, Liang, additional, Ladmore, Daniella, additional, Pesola, Francesca, additional, Chung, Kian Fan, additional, Chen, Zhengming, additional, Hajek, Peter, additional, Xiao, Dan, additional, Wang, Chen, additional, and Group, China Health Literacy Survey Study, additional

Published
2022
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240. Prevalence and Risk Factors of Alcohol Dependence, and Association with Smoking in China: Findings from a National Cross-Sectional Study

Author

Cui, Ziyang, primary, Li, Yinghua, additional, Liu, Yongzhuang, additional, Liu, Zhao, additional, Li, Li, additional, Nie, Xueqiong, additional, Zhou, Xinmei, additional, Cheng, Anqi, additional, Li, Jinxuan, additional, Qin, Rui, additional, Wei, Xiaowen, additional, Zhao, Liang, additional, Chung, Kian Fan, additional, Chen, Zhengming, additional, Xiao, Dan, additional, Wang, Chen, additional, and Group, China Health Literacy Survey Study, additional

Published
2022
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241. Characteristics of Fine and Ultrafine Aerosols in the London Underground

Author

Kumar, Prashant, primary, Zavala-Reyes, Juan C., additional, Kalaiarasan, Gopinath, additional, Abubakar-Waziri, Hisham, additional, Young, Gloria, additional, Mudway, Ian, additional, Dilliway, Claire, additional, Lakhdar, Ramzi, additional, Kłosowski, Michał M., additional, Pain, Christopher, additional, Adcock, Ian, additional, Watson, Jonathan S., additional, Sephton, Mark A., additional, Chung, Kian Fan, additional, and porter, alex, additional

Published
2022
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242. Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma

Author

Badi, Yusef Eamon, primary, Pavel, Ana B., additional, Pavlidis, Stelios, additional, Riley, John H., additional, Bates, Stewart, additional, Kermani, Nazanin Zounemat, additional, Knowles, Richard, additional, Kolmert, Johan, additional, Wheelock, Craig E., additional, Worsley, Sally, additional, Uddin, Mohib, additional, Alving, Kjell, additional, Bakke, Per S., additional, Behndig, Annelie, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fleming, Louise J., additional, Fowler, Stephen J., additional, Frey, Urs, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Maitland-van der Zee, Anke H., additional, Montuschi, Paolo, additional, Roberts, Graham, additional, Sanak, Marek, additional, Shaw, Dominick E., additional, Singer, Florian, additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlen, Sven-Eric, additional, Guo, Yi-Ke, additional, Chung, Kian Fan, additional, Guttman-Yassky, Emma, additional, and Adcock, Ian M., additional

Published
2022
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247. Modeling for understanding of coronavirus disease-2019 (COVID-19) spread and design of an isolation room in a hospital.

Author

Wu, Xiaofei, Abubakar-Waziri, Hisham, Fang, Fangxin, Dilliway, Claire, Wu, Pin, Li, Jinxi, Yao, Runming, Bhavsar, Pankaj, Kumar, Prashant, Pain, Christopher C., and Chung, Kian Fan

Subjects
SARS-CoV-2, CORONAVIRUSES, COMPUTATIONAL fluid dynamics, COVID-19
Abstract

We have modeled the transmission of coronavirus 2019 in the isolation room of a patient suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Royal Brompton Hospital in London. An adaptive mesh computational fluid dynamics model was used for simulation of three-dimensional spatial distribution of SARS-CoV-2 in the room. The modeling set-up is based on data collected in the room during the patient stay. Many numerical experiments have been carried out to provide an optimal design layout of the overall isolation room. Our focus has been on (1) the location of the air extractor and filtration rates, (2) the bed location of the patient, and (3) consideration of the health and safety of the staff working in the area. [ABSTRACT FROM AUTHOR]

Published
2023
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248. Mouth breathing, dry air, and low water permeation promote inflammation, and activate neural pathways, by osmotic stresses acting on airway lining mucus.

Author

Edwards, David A., Chung, Kian Fan, and Zare, Richard Neil

Subjects
MOUTH breathing, INFLAMMATION, NEURAL pathways, MUCUS, HUMIDITY control, ADENOSINE triphosphate, CHRONIC cough
Abstract

Respiratory disease and breathing abnormalities worsen with dehydration of the upper airways. We find that humidification of inhaled air occurs by evaporation of water over mucus lining the upper airways in such a way as to deliver an osmotic force on mucus, displacing it towards the epithelium. This displacement thins the periciliary layer of water beneath mucus while thickening topical water that is partially condensed from humid air on exhalation. With the rapid mouth breathing of dry air, this condensation layer, not previously reported while common to transpiring hydrogels in nature, can deliver an osmotic compressive force of up to around 100 cm H2O on underlying cilia, promoting adenosine triphosphate secretion and activating neural pathways. We derive expressions for the evolution of the thickness of the condensation layer, and its impact on cough frequency, inflammatory marker secretion, cilia beat frequency and respiratory droplet generation. We compare our predictions with human clinical data from multiple published sources and highlight the damaging impact of mouth breathing, dry, dirty air and high minute volume on upper airway function. We predict the hypertonic (or hypotonic) saline mass required to reduce (or amplify) dysfunction by restoration (or deterioration) of the structure of ciliated and condensation water layers in the upper airways and compare these predictions with published human clinical data. Preserving water balance in the upper airways appears critical in light of contemporary respiratory health challenges posed by the breathing of dirty and dry air. [ABSTRACT FROM AUTHOR]

Published
2023
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249. IL1RAP expression and the enrichment of IL‐33 activation signatures in severe neutrophilic asthma.

Author

Badi, Yusef Eamon, Salcman, Barbora, Taylor, Adam, Rana, Batika, Kermani, Nazanin Zounemat, Riley, John H., Worsley, Sally, Mumby, Sharon, Dahlen, Sven‐Eric, Cousins, David, Bulfone‐Paus, Silvia, Affleck, Karen, Chung, Kian Fan, Bates, Stewart, and Adcock, Ian M.

Subjects
GENE expression, INTERLEUKIN-33, REGULATORY T cells, ASTHMA, INNATE lymphoid cells
Abstract

Background: Interleukin (IL)‐33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes. Objective: To derive gene signatures from in vitro studies of IL‐33‐stimulated cells and use these to determine IL‐33‐associated enrichment patterns in asthma. Methods: Signatures downstream of IL‐33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells. Gene Set Variation Analysis (GSVA) was used to probe U‐BIOPRED and ADEPT sputum transcriptomics to determine enrichment scores (ES) for each signature according to asthma severity, sputum granulocyte status and previously defined molecular phenotypes. Results: IL‐33‐activated gene signatures were cell‐specific with little gene overlap. Individual signatures, however, were associated with similar signalling pathways (TNF, NF‐κB, IL‐17 and JAK/STAT signalling) and immune cell differentiation pathways (Th17, Th1 and Th2 differentiation). ES for IL‐33‐activated gene signatures were significantly enriched in asthmatic sputum, particularly in patients with neutrophilic and mixed granulocytic phenotypes. IL‐33 mRNA expression was not elevated in asthma whereas the expression of mRNA for IL1RL1, the IL‐33 receptor, was up‐regulated in the sputum of severe eosinophilic asthma. The mRNA expression for IL1RAP, the IL1RL1 co‐receptor, was greatest in severe neutrophilic and mixed granulocytic asthma. Conclusions: IL‐33‐activated gene signatures are elevated in neutrophilic and mixed granulocytic asthma corresponding with IL1RAP co‐receptor expression. This suggests incorporating T2‐low asthma in anti‐IL‐33 trials. [ABSTRACT FROM AUTHOR]

Published
2023
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250. A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD.

Author

Do, Ah Ra, An, Jin, Jo, Jinyeon, Kim, Woo Jin, Kang, Hae Yeon, Lee, Sanghun, Yoon, Dankyu, Cho, You Sook, Adcock, Ian M., Chung, Kian Fan, Won, Sungho, and Kim, Tae-Bum

Subjects
GENOME-wide association studies, CHRONIC obstructive pulmonary disease, ASTHMA, GENETIC correlations
Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ( β Asthma - COPD = 0.44, P-valueAsthma-COPD = 3.41 × 10−8), and significant results were replicated with the UK Biobank data ( β Asthma - COPD = 0.04, P-valueAsthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40–45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy. [ABSTRACT FROM AUTHOR]

Published
2022
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