A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

American Journal of Respiratory and Critical Care Medicine

Volumn 195, Issue 4, 2017, Pages 443-455

  Kuo, Chih Hsi Scott ^a   Pavlidis, Stelios ^a,b   Loza, Matthew ^b   Baribaud, Fred ^b   Rowe, Anthony ^b   Pandis, Ioannis ^a   Hoda, Uruj ^a,c   Rossios, Christos ^a   Sousa, Ana ^d   Wilson, Susan J ^e   Howarth, Peter ^e   Dahlen, Barbro ^f   Dahlen, Sven Erik ^f   Chanez, Pascal ^g   Shaw, Dominick ^h   Krug, Norbert ⁱ   Sandström, Thomas ^j   De Meulder, Bertrand ^k   Lefaudeux, Diane ^k   Fowler, Stephen ^l   Fleming, Louise ^a,c   Corfield, Julie ^m,n   Auffray, Charles ^k   Sterk, Peter J ^o   Djukanovic, Ratko ^e   Guo, Yike ^a   Adcock, Ian M ^a,c   Chung, Kian Fan ^a,c   more..

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

^c ROYAL BROMPTON AND HAREFIELD NHS FOUNDATION TRUST   (United Kingdom)

^d GLAXOSMITHKLINE   (United Kingdom)

^e UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^f KAROLINSKA INSTITUTE   (Sweden)

^g UMR S901 Aix Marseille 2   (France)

^h UNIVERSITY OF NOTTINGHAM   (United Kingdom)

ⁱ FRAUNHOFER INSTITUTE FOR TOXICOLOGY AND EXPERIMENTAL MEDICINE   (Germany)

^j UMEÅ UNIVERSITY   (Sweden)

^k UNIVERSITÉ DE LYON   (France)

^l UNIVERSITY OF MANCHESTER   (United Kingdom)

^m ASTRAZENECA R AND D   (Sweden)

ⁿ Areteva R and D   (United Kingdom)

^o UNIVERSITY OF AMSTERDAM   (Netherlands)

more..

Author keywords

Corticosteroid insensitivity; Exhaled nitric oxide; Gene set variation analysis; Severe asthma; T helper type 2

Indexed keywords

BIOLOGICAL MARKER; CST2 PROTEIN; EOTAXIN 3; HERMES ANTIGEN; IMMUNOGLOBULIN E; INTERLEUKIN 1 RECEPTOR TYPE II; INTERLEUKIN 25; INTERLEUKIN 33; NELFE PROTEIN; PEPTIDES AND PROTEINS; PREDNISOLONE; THYMIC STROMAL LYMPHOPOIETIN; TRANSCRIPTOME; UNCLASSIFIED DRUG; CORTICOSTEROID;

ADULT; AIRWAY EPITHELIUM CELL; ARTICLE; ASTHMA; BODY MASS; BRONCHUS BIOPSY; CD3+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; CORTICOSTEROID THERAPY; CYTOKINE PRODUCTION; DISEASE EXACERBATION; DISEASE SEVERITY; DRUG TREATMENT FAILURE; EOSINOPHIL; EOSINOPHILIA; EPITHELIAL BRUSHING; FEMALE; FRACTIONAL EXHALED NITRIC OXIDE; GENE EXPRESSION PROFILING; GENE SET VARIATION ANALYSIS; GENETIC ANALYSIS; GENETIC ASSOCIATION; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNE STATUS; IMMUNOGLOBULIN BLOOD LEVEL; INFLAMMATION; INFORMATION PROCESSING; LYMPHOCYTE DIFFERENTIATION; MACHINE LEARNING; MAINTENANCE DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MEMORY T LYMPHOCYTE; MIDDLE AGED; NEUTROPHIL; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; RESPIRATORY TRACT BIOPSY; RESPIRATORY TRACT PARAMETERS; SENSITIVITY AND SPECIFICITY; SPUTUM ANALYSIS; SUBMUCOSA; TH17 CELL; TH2 CELL; TOPOLOGICAL DATA ANALYSIS; TRANSCRIPTOMICS; TREATMENT RESPONSE; UPREGULATION; BIOPSY; BREATH ANALYSIS; BRONCHOSCOPY; BRONCHUS; COHORT ANALYSIS; CYTOLOGY; DEVICES; DRUG RESISTANCE; GENETICS; IMMUNOLOGY; LEUKOCYTE COUNT; PATHOLOGY; PROCEDURES; SEVERITY OF ILLNESS INDEX; SPUTUM;

ADRENAL CORTEX HORMONES; ADULT; ASTHMA; BIOMARKERS; BIOPSY; BREATH TESTS; BRONCHI; BRONCHOSCOPY; COHORT STUDIES; DRUG RESISTANCE; EOSINOPHILS; FEMALE; GENE EXPRESSION PROFILING; HUMANS; INFLAMMATION; LEUKOCYTE COUNT; MALE; MIDDLE AGED; PHENOTYPE; SEVERITY OF ILLNESS INDEX; SPUTUM; TH2 CELLS;

EID: 85014883674     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201512-2452OC     Document Type: Article

References (45)

1. Trejo Bittar HE, Yousem SA, Wenzel SE. Pathobiology of severe asthma. Annu Rev Pathol 2015; 10:511-545.
2. Bentley AM, Meng Q, Robinson DS, Hamid Q, Kay AB, Durham SR. Increases in activated T lymphocytes, eosinophils, and cytokine mRNA expression for interleukin-5 and granulocyte/macrophage colony-stimulating factor in bronchial biopsies after allergen inhalation challenge in atopic asthmatics. Am J Respir Cell Mol Biol 1993; 8: 35-42.
3. Robinson DS, Ying S, Bentley AM, Meng Q, North J, Durham SR, Kay AB, Hamid Q. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 1993; 92:397-403.
4. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, Arron JR, Fahy JV. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009; 180:388-395.
5. Boniface S, Koscher V, Mamessier E, El Biaze M, Dupuy P, Lorec AM, Guillot C, Badier M, Bongrand P, Vervloet D, et al. Assessment of T lymphocyte cytokine production in induced sputum from asthmatics: a flow cytometry study. Clin Exp Allergy 2003; 33: 1238-1243.
6. + T cells in atopic asthma. Am J Respir Crit Care Med 2005; 171:224-230.
7. Krug N, Madden J, Redington AE, Lackie P, Djukanovic R, Schauer U, Holgate ST, Frew AJ, Howarth PH. T-cell cytokine profile evaluated at the single cell level in BAL and blood in allergic asthma. Am J Respir Cell Mol Biol 1996; 14:319-326.
8. Raundhal M, Morse C, Khare A, Oriss TB, Milosevic J, Trudeau J, Huff R, Pilewski J, Holguin F, Kolls J, et al. High IFN-γ and low SLPI mark severe asthma in mice and humans. J Clin Invest 2015; 125:3037-3050.
9. high immunophenotypes: potential benefits of calcitriol. J Allergy Clin Immunol 2015; 136:628-637.e4.
10. McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, Henry A, Irvin CG, Piganelli JD, Ray A, et al. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 2008; 181:4089-4097.
11. Doe C, Bafadhel M, Siddiqui S, Desai D, Mistry V, Rugman P, McCormick M, Woods J, May R, Sleeman MA, et al. Expression of the T helper 17-associated cytokines IL-17A and IL-17F in asthma and COPD. Chest 2010; 138:1140-1147.
12. Comhair SA, Ricci KS, Arroliga M, Lara AR, Dweik RA, Song W, Hazen SL, Bleecker ER, Busse WW, Chung KF, et al. Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma. Am J Respir Crit Care Med 2005; 172:306-313.
13. Kirkham P, Rahman I. Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacol Ther 2006; 111: 476-494.
14. Comhair SA, Bhathena PR, Farver C, Thunnissen FB, Erzurum SC. Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells. FASEB J 2001; 15:70-78.
15. Dweik RA, Comhair SA, Gaston B, Thunnissen FB, Farver C, Thomassen MJ, Kavuru M, Hammel J, Abu-Soud HM, Erzurum SC. NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response. Proc Natl Acad Sci USA 2001; 98:2622-2627.
16. Ito K, Hanazawa T, Tomita K, Barnes PJ, Adcock IM. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun 2004; 315:240-245.
17. James AL, Bai TR, Mauad T, Abramson MJ, Dolhnikoff M, McKay KO, Maxwell PS, Elliot JG, Green FH. Airway smooth muscle thickness in asthma is related to severity but not duration of asthma. Eur Respir J 2009; 34:1040-1045.
18. Kaminska M, Foley S, Maghni K, Storness-Bliss C, Coxson H, Ghezzo H, Lemière C, Olivenstein R, Ernst P, Hamid Q, et al. Airway remodeling in subjects with severe asthma with or without chronic persistent airflow obstruction. J Allergy Clin Immunol 2009; 124:45-51.e4.
19. Macedo P, Hew M, Torrego A, Jouneau S, Oates T, Durham A, Chung KF. Inflammatory biomarkers in airways of patients with severe asthma compared with non-severe asthma. Clin Exp Allergy 2009; 39: 1668-1676.
20. Chung KF. New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med 2013; 1:639-652.
21. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012; 18:716-725.
22. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, D'Agostino R Jr, Castro M, Curran-Everett D, Fitzpatrick AM, et al.; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010; 181:315-323.
23. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, Wardlaw AJ, Green RH. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008; 178:218-224.
24. Bel EH, Sousa A, Fleming L, Bush A, Chung KF, Versnel J, Wagener AH, Wagers SS, Sterk PJ, Compton CH; Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation. Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax 2011; 66:910-917.
25. Miller MK, Johnson C, Miller DP, Deniz Y, Bleecker ER, Wenzel SE; TENOR Study Group. Severity assessment in asthma: an evolving concept. J Allergy Clin Immunol 2005; 116:990-995.
26. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet 2006; 368:804-813.
27. Chung KF, Adcock IM. Clinical phenotypes of asthma should link up with disease mechanisms. Curr Opin Allergy Clin Immunol 2015; 15: 56-62.
28. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, Ortega H, Chanez P. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380:651-659.
29. Chung KF. Defining phenotypes in asthma: a step towards personalized medicine. Drugs 2014; 74:719-728.
30. Yan X, Chu JH, Gomez J, Koenigs M, Holm C, He X, Perez MF, Zhao H, Mane S, Martinez FD, et al. Noninvasive analysis of the sputum transcriptome discriminates clinical phenotypes of asthma. Am J Respir Crit Care Med 2015; 191:1116-1125.
31. Edelman E, Porrello A, Guinney J, Balakumaran B, Bild A, Febbo PG, Mukherjee S. Analysis of sample set enrichment scores: assaying the enrichment of sets of genes for individual samples in genome-wide expression profiles. Bioinformatics 2006; 22:e108-e116.
32. Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics 2013; 14:7.
33. Bao Z, Zhang C, Yan W, Liu Y, Li M, Zhang W, Jiang T. BMP4, a strong better prognosis predictor, has a subtype preference and cell development association in gliomas. J Transl Med 2013; 11:100.
34. Nicolau M, Levine AJ, Carlsson G. Topology based data analysis identifies a subgroup of breast cancers with a unique mutational profile and excellent survival. Proc Natl Acad Sci USA 2011; 108: 7265-7270.
35. Sarikonda G, Pettus J, Phatak S, Sachithanantham S, Miller JF, Wesley JD, Cadag E, Chae J, Ganesan L, Mallios R, et al. CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes. J Autoimmun 2014; 50:77-82.
36. Thalamuthu A, Mukhopadhyay I, Zheng X, Tseng GC. Evaluation and comparison of gene clustering methods in microarray analysis. Bioinformatics 2006; 22:2405-2412.
37. Auffray C, Adcock IM, Chung KF, Djukanovic R, Pison C, Sterk PJ. An integrative systems biology approach to understanding pulmonary diseases. Chest 2010; 137:1410-1416.
38. Kuo CHS, Pavlidis S, Loza M, Baribaud F, Rowe A, Pandis I, Rossios C, Wilson SJ, Djukanovic R, Sterk PJ, et al. Asthma phenotypes from a semi-supervised machine-learning approach of bronchial biopsy and brush transcriptomics in U-BIOPRED [abstract]. Am J Respir Crit Care Med 2015; 191:A2205.
39. Shaw DE, Sousa AR, Fowler SJ, Fleming LJ, Roberts G, Corfield J, Pandis I, Bansal AT, Bel EH, Auffray C, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J 2015; 46:1308-1321.
40. Athey BD, Braxenthaler M, Haas M, Guo Y. tranSMART: an open source and community-driven informatics and data sharing platform for clinical and translational research. AMIA Jt Summits Transl Sci Proc 2013; 2013:6-8.
41. Abbas AR, Jackman JK, Bullens SL, Davis SM, Choy DF, Fedorowicz G, Tan M, Truong BT, Gloria Meng Y, Diehl L, et al. Lung gene expression in a rhesus allergic asthma model correlates with physiologic parameters of disease and exhibits common and distinct pathways with human asthma and a mouse asthma model. Am J Pathol 2011; 179:1667-1680.
42. Holgate ST. The sentinel role of the airway epithelium in asthma pathogenesis. Immunol Rev 2011; 242:205-219.
43. Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013; 14:536-542.
44. Cohen L, E X, Tarsi J, Ramkumar T, Horiuchi TK, Cochran R, DeMartino S, Schechtman KB, Hussain I, Holtzman MJ, et al.; NHLBI Severe Asthma Research Program (SARP). Epithelial cell proliferation contributes to airway remodeling in severe asthma. Am J Respir Crit Care Med 2007; 176:138-145.
45. Hothorn T, Hornik K, Zeileis A. Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat 2006; 15:651-674.