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1. 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, Kwong, Francois Ng Kee, 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, Meulder, Bertrand De, Lefaudeux, Diane, Dahlen, Sven-Erik, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Chung, Kian Fan, and Publica

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

Published
2022

4. List of Contributors

Author

Ahlstrom, Jon D., primary, Ahsan, Taby, additional, Allickson, Julie, additional, Almarza, Alejandro J., additional, Anderson, James M., additional, Andrews, Peter, additional, Aslan, Hadi, additional, Atala, Anthony, additional, Badylak, Stephen F., additional, Batra, Ashok, additional, Baumann, M. Douglas, additional, Bellamkonda, Ravi V., additional, Bergman, Nicole M., additional, Beyhan, Z., additional, Bhatia, Mickie, additional, Bhatia, Sangeeta N., additional, Black, Peter M., additional, Blau, Helen, additional, Boden, Scott D., additional, Brey, Eric M., additional, Brivanlou, Ali H., additional, Brown, Chris R., additional, Bruder, Scott P., additional, Chambers, S.M., additional, Chen, Christopher S., additional, Chen, LiHow, additional, Chen, Mike, additional, Chen, Sulin, additional, Cheng, N., additional, Christ, George J., additional, Chung, Seyung, additional, Cibelli, J.B., additional, Cimini, Massimo, additional, De Coppi, Paolo, additional, Dodla, Mahesh C., additional, Dominguez-Bendala, Juan, additional, Doyle, AM, additional, Durfor, Charles N., additional, Echelard, Yann, additional, Effros, Rita B., additional, Elisseeff, Jennifer, additional, Ellis, Ewa C.S., additional, Emamaullee, Juliet A., additional, Erickson, Carol A., additional, De Filippo, Roger, additional, Fink, Donald, additional, Fissell, William H., additional, Friedlaender, Gary E., additional, Furth, Mark E., additional, Gafni, Yossi, additional, Gage, Keneth, additional, Garcia, Andres, additional, Gavin, William, additional, Gazit, Daniel, additional, Gazit, Zulma, additional, Gemmiti, Christopher S., additional, Gerlach, Jörg C., additional, Gokhale, Paul J., additional, Goodell, M.A., additional, Griffith, May, additional, Guenin, Louis M., additional, Giuliani, Stefano, additional, Guldberg, Robert E., additional, Hacker, M.C., additional, Harrison, Benjamin S., additional, Hartmann, Bernd, additional, Hilbert, Stephen H., additional, Hillel, Alexander, additional, Hipp, Jason, additional, Holcomb, Col. J.B., additional, Hollinger, Jeffrey O., additional, Holy, Chantal E., additional, Hout, Mariah, additional, Hu, Jiang, additional, Huang, George T.-J., additional, Huard, Johnny, additional, Hui, Elliot E., additional, Humes, H. David, additional, Intaglietta, Marcos, additional, Ji, Junfeng, additional, Jiang, Yueha, additional, Johnen, Christa, additional, Johnston, Josephine, additional, Joraku, Akira, additional, Kaplan, David L., additional, Kaplan, David S., additional, Khang, Gilson, additional, Khanzada, Rehan N., additional, Kim, Soon Hee, additional, Kim, Moon Suk, additional, Kimelman, Nadav, additional, Klimanskaya, Irina, additional, Kluge, Jonathan A., additional, Kolambkar, Yash, additional, Koh, Chester J., additional, Komura, Makoto, additional, Kondziolka, Douglas, additional, Konya, Deniz, additional, Kues, Wilfried A., additional, Kwong, Francois Ng kee, additional, Lamba, Deepak, additional, Lee, Hai Bang, additional, Lee, Hyukjin, additional, Leisk, Gary G., additional, Leong, Kam W., additional, Levine, Ariel J., additional, Li, Ren Ke, additional, Li, Wan-Ju, additional, Lim, Grace J., additional, Lin, Yan, additional, Lindblad, William J., additional, Liu, Wendy F., additional, Liu, Xiaohua, additional, Lucas-Hahn, Andrea, additional, Luttun, Aernout, additional, Lynch, Samuel, additional, Ma, Peter X., additional, Maher, Ellen, additional, Martins-Green, Manuela, additional, McClelland, Randall E., additional, McFarland, Richard, additional, McIntire, Larry V., additional, Meade, Harry, additional, Melican, David L., additional, Mikos, A.G., additional, Montoya, Fernando Ulloa, additional, Nerem, Robert M., additional, Niemann, Heiner, additional, Nori, Aparna, additional, Pabst, Patrea L., additional, Park, Kook In, additional, Park, Tae Gwan, additional, Patterson, David P., additional, Pauwelyn, Karen, additional, Pelled, Gadi, additional, Perin, Laura, additional, Petreaca, M., additional, Pileggi, Antonello, additional, Pomerantz, Jason H., additional, Porter, Blaise, additional, Radisic, Milica, additional, Ratner, Buddy D., additional, Reddi, A. Hari, additional, Reh, Thomas A., additional, Reid, Lola M., additional, Ricordi, Camillo, additional, Ross, Jeff, additional, Russell, Alan J., additional, Santos, Filipe N.C., additional, Schmitz, John P., additional, Schuch, Gunter, additional, Sedrakyan, Sargis, additional, Sefton, Michael V., additional, Serafini, Marta, additional, Shah, Paulesh, additional, Shapiro, A.M. James, additional, Sheardown, Heather, additional, Shoichet, Molly S., additional, Siddiqui, M. Minhaj, additional, Sidman, Richard L., additional, Silverman, Ronald, additional, Skuk, Daniel, additional, Snyder, Evan, additional, Soker, Shay, additional, Spector, Myron, additional, Stocum, David L., additional, Strom, Stephen C., additional, Taylor, Doris A., additional, Teng, Yang D., additional, Thomson, James, additional, Tranquillo, Robert T., additional, Tremblay, Jacques P., additional, Tsai, Amy, additional, Tuan, Rocky S., additional, Tubo, Ross S., additional, Van Dyke, Mark, additional, Vavoie, Deborah, additional, Verfaillie, Catherine, additional, Volenec, F. Jerry, additional, Wargo, Sara, additional, Warnwath, Joseph W., additional, Wechsler, Lawrence, additional, Wei, Shen, additional, Weisel, Richard D., additional, West, Jennifer L., additional, Williams, Chrysanthi, additional, Williams, J. Koudy, additional, Witten, Celia, additional, Wolf, Steven E., additional, Woo, Savio L.-Y., additional, Wosnick, Jordan H., additional, Wrenzycki, Christine, additional, Xaymardan, Munira, additional, Yao, Hsin-Lei, additional, Yazdani, Saami K., additional, Yelick, Pamela C., additional, Yoo, James J., additional, Yu, Junying, additional, Zeilinger, Katrin, additional, Zeng, Lepeng, additional, Zenovich, Andrey G., additional, Zhong, Bonan, additional, Ziomek, Carol A., additional, and Zoloth, Laurie, additional

Published
2008
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5. “T2-high” in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin

Author

Pavlidis, Stelios, Takahashi, Kentaro, Kwong, Francois Ng Kee, Xie, Jiaxing, Hoda, Uruj, Sun, Kai, Elyasigomari, Vahid, Agapow, Paul, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Shaw, Dominic E., Fleming, Louise J., Howarth, Peter H., Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Knowles, Richard, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Djukanovic, Ratko, Chung, Kian Fan, Pavlidis, Stelios, Takahashi, Kentaro, Kwong, Francois Ng Kee, Xie, Jiaxing, Hoda, Uruj, Sun, Kai, Elyasigomari, Vahid, Agapow, Paul, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Shaw, Dominic E., Fleming, Louise J., Howarth, Peter H., Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Knowles, Richard, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Djukanovic, Ratko, and Chung, Kian Fan

Abstract

Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild–moderate asthma into a T2-high phenotype. We examined whether currently available clinical biomarkers can predict AEC-defined T2-high phenotype within the U-BIOPRED cohort. The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from interleukin (IL)-13-exposed AECs. 37% of asthmatics (45% nonsmoking severe asthma, n=49; 33% of smoking or ex-smoking severe asthma, n=18; and 28% mild–moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher exhaled nitric oxide fraction (FeNO) and blood and sputum eosinophils, but not serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (30 ppb) and blood eosinophils (300 cells·µL −1 ) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression. T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high. Copyright ©ERS 2019.

Published
2019

6. Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED : an exploratory analysis

Author

Takahashi, Kentaro, Pavlidis, Stelios, Kwong, Francois Ng Kee, Hoda, Uruj, Rossios, Christos, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandström, Thomas, Shaw, Dominic E., Lutter, Rene, Bakke, Per, Fleming, Louise J., Howarth, Peter H., Caruso, Massimo, Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M., Chung, Kian Fan, Takahashi, Kentaro, Pavlidis, Stelios, Kwong, Francois Ng Kee, Hoda, Uruj, Rossios, Christos, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandström, Thomas, Shaw, Dominic E., Lutter, Rene, Bakke, Per, Fleming, Louise J., Howarth, Peter H., Caruso, Massimo, Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M., and Chung, Kian Fan

Abstract

Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Colony-stimulating factor (CSF) 2 protein levels were increased in CSA sputum supernatants, with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene set variation analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.

Published
2018
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