{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:55:20Z","timestamp":1789379720740,"version":"build-2803163510"},"reference-count":76,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T00:00:00Z","timestamp":1616198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2021,4]]},"DOI":"10.1016\/j.celrep.2021.108974","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T10:23:11Z","timestamp":1618482191000},"page":"108974","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":61,"title":["High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status"],"prefix":"10.1016","volume":"35","author":[{"given":"Matthew J.","family":"Camiolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Oriss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5236-9673","authenticated-orcid":false,"given":"Qi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-7754","authenticated-orcid":false,"given":"Michael","family":"Gorry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Horne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0473-2730","authenticated-orcid":false,"given":"John B.","family":"Trudeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Scholl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7196-8703","authenticated-orcid":false,"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K.","family":"Kolls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabir","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian J.","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine M.","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nima","family":"Aghaeepour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-2955","authenticated-orcid":false,"given":"Kari","family":"Nadeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4242-0164","authenticated-orcid":false,"given":"Sally E.","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuradha","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2021.108974_bib1","doi-asserted-by":"crossref","first-page":"eaan2946","DOI":"10.1126\/sciimmunol.aan2946","article-title":"An immune clock of human pregnancy","volume":"2","author":"Aghaeepour","year":"2017","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib2","series-title":"topGO: Enrichment analysis for gene ontology","author":"Alexa","year":"2020"},{"key":"10.1016\/j.celrep.2021.108974_bib3","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.immuni.2009.05.006","article-title":"Genome-wide analysis of histone methylation reveals chromatin state-based regulation of gene transcription and function of memory CD8+ T\u00a0cells","volume":"30","author":"Araki","year":"2009","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2021.108974_bib4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1126\/science.1254803","article-title":"T cell memory. Skin-resident memory CD8+ T\u00a0cells trigger a state of tissue-wide pathogen alert","volume":"346","author":"Ariotti","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.celrep.2021.108974_bib5","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.4049\/jimmunol.158.9.4036","article-title":"Engagement of the signaling lymphocytic activation molecule (SLAM) on activated T\u00a0cells results in IL-2-independent, cyclosporin A-sensitive T\u00a0cell proliferation and IFN-gamma production","volume":"158","author":"Aversa","year":"1997","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib6","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.jaci.2013.12.1091","article-title":"Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes","volume":"133","author":"Baines","year":"2014","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib7","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jaci.2010.10.020","article-title":"Costs of asthma in the United States: 2002-2007","volume":"127","author":"Barnett","year":"2011","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib8","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.4049\/jimmunol.1600737","article-title":"Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells","volume":"198","author":"Basdeo","year":"2017","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib9","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1038\/s41467-019-13055-y","article-title":"Automated optimized parameters for T-distributed stochastic neighbor embedding improve visualization and analysis of large datasets","volume":"10","author":"Belkina","year":"2019","journal-title":"Nat. Commun."},{"issue":"9","key":"10.1016\/j.celrep.2021.108974_bib10","article-title":"blocbuster: an R package for model based co-clustering","volume":"76","author":"Bhatia","year":"2017","journal-title":"J.\u00a0Stat. Soft."},{"key":"10.1016\/j.celrep.2021.108974_bib11","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1109\/34.865189","article-title":"Assessing a mixture model for clustering with teh integrated completed likelihood","volume":"22","author":"Biernacki","year":"2000","journal-title":"IEEE Trnas. Pattren Anal. Mach. Intell."},{"key":"10.1016\/j.celrep.2021.108974_bib12","doi-asserted-by":"crossref","first-page":"1800936","DOI":"10.1183\/13993003.00936-2018","article-title":"Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma","volume":"52","author":"Bleecker","year":"2018","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.celrep.2021.108974_bib13","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S2213-2600(15)00197-6","article-title":"Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial","volume":"3","author":"Brightling","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib14","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/377441a0","article-title":"Control of p70 s6 kinase by kinase activity of FRAP in\u00a0vivo","volume":"377","author":"Brown","year":"1995","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2021.108974_bib15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.pupt.2017.01.011","article-title":"Reslizumab in patients with inadequately controlled late-onset asthma and elevated blood eosinophils","volume":"43","author":"Brusselle","year":"2017","journal-title":"Pulm. Pharmacol. Ther."},{"key":"10.1016\/j.celrep.2021.108974_bib16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nm.2628","article-title":"An essential role for TH2-type responses in limiting acute tissue damage during experimental helminth infection","volume":"18","author":"Chen","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1183\/09031936.00202013","article-title":"International ERS\/ATS guidelines on definition, evaluation and treatment of severe asthma","volume":"43","author":"Chung","year":"2014","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.celrep.2021.108974_bib18","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1056\/NEJMoa1704064","article-title":"Tezepelumab in Adults with Uncontrolled Asthma","volume":"377","author":"Corren","year":"2017","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib19","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/S0167-5699(99)01486-3","article-title":"CD26, let it cut or cut it down","volume":"20","author":"De Meester","year":"1999","journal-title":"Immunol. Today"},{"key":"10.1016\/j.celrep.2021.108974_bib20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2021.108974_bib21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nri3786","article-title":"Type 2 inflammation in asthma--present in most, absent in many","volume":"15","author":"Fahy","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib22","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1164\/rccm.200701-085OC","article-title":"A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma","volume":"176","author":"Flood-Page","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib23","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1164\/rccm.201504-0763PP","article-title":"Evolving Concepts of Asthma","volume":"192","author":"Gauthier","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib24","doi-asserted-by":"crossref","first-page":"e94580","DOI":"10.1172\/jci.insight.94580","article-title":"Severe asthma in humans and mouse model suggests a CXCL10 signature underlies corticosteroid-resistant Th1 bias","volume":"2","author":"Gauthier","year":"2017","journal-title":"JCI Insight"},{"key":"10.1016\/j.celrep.2021.108974_bib25","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1164\/rccm.200711-1754OC","article-title":"Cluster analysis and clinical asthma phenotypes","volume":"178","author":"Haldar","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib26","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1164\/rccm.201208-1414OC","article-title":"Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study","volume":"187","author":"Hanania","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jaci.2013.03.044","article-title":"Biomarker surrogates do not accurately predict sputum eosinophil and neutrophil percentages in asthmatic subjects","volume":"132","author":"Hastie","year":"2013","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib28","doi-asserted-by":"crossref","first-page":"1602298","DOI":"10.1183\/13993003.02298-2016","article-title":"Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma","volume":"50","author":"Hekking","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.celrep.2021.108974_bib29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1471-2105-5-17","article-title":"VisANT: an online visualization and analysis tool for biological interaction data","volume":"5","author":"Hu","year":"2004","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.celrep.2021.108974_bib30","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/j.1365-2567.2008.02899.x","article-title":"Differential expression of CD26 on virus-specific CD8(+) T\u00a0cells during active, latent and resolved infection","volume":"126","author":"Ibegbu","year":"2009","journal-title":"Immunology"},{"key":"10.1016\/j.celrep.2021.108974_bib31","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1164\/rccm.201107-1317PP","article-title":"Severe asthma: lessons learned from the National Heart, Lung, and Blood Institute Severe Asthma Research Program","volume":"185","author":"Jarjour","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib32","doi-asserted-by":"crossref","first-page":"23243","DOI":"10.1074\/jbc.M503659200","article-title":"Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment","volume":"280","author":"Jee","year":"2005","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.celrep.2021.108974_bib33","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"10.1016\/j.celrep.2021.108974_bib34","doi-asserted-by":"crossref","first-page":"10224","DOI":"10.1038\/ncomms10224","article-title":"RSV-specific airway resident memory CD8+ T\u00a0cells and differential disease severity after experimental human infection","volume":"6","author":"Jozwik","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2021.108974_bib35","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ajpath.2014.09.005","article-title":"In\u00a0vivo depletion of CD206+ M2 macrophages exaggerates lung injury in endotoxemic mice","volume":"185","author":"Kambara","year":"2015","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.celrep.2021.108974_bib36","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nri914","article-title":"Regulation of mast-cell and basophil function and survival by IgE","volume":"2","author":"Kawakami","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib37","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1084\/jem.20081712","article-title":"Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation","volume":"206","author":"Kleinschek","year":"2009","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib38","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.neunet.2012.09.018","article-title":"Essentials of the self-organizing map","volume":"37","author":"Kohonen","year":"2013","journal-title":"Neural Netw."},{"key":"10.1016\/j.celrep.2021.108974_bib39","doi-asserted-by":"crossref","first-page":"1602135","DOI":"10.1183\/13993003.02135-2016","article-title":"T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED","volume":"49","author":"Kuo","year":"2017","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.celrep.2021.108974_bib40","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.celrep.2021.108974_bib76","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-12-253","article-title":"Sparse PLS discriminant analysis: biologically relevant feature selection and graphical displays for multiclass problems","volume":"12","author":"Le Cao","year":"2011","journal-title":"BMC Bionformatics"},{"key":"10.1016\/j.celrep.2021.108974_bib41","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1016\/S0140-6736(00)03496-6","article-title":"Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response","volume":"356","author":"Leckie","year":"2000","journal-title":"Lancet"},{"key":"10.1016\/j.celrep.2021.108974_bib42","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.4049\/jimmunol.1701455","article-title":"Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In\u00a0Vivo: A Potential Biomarker of Severe Refractory Disease","volume":"200","author":"Li","year":"2018","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib43","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"10.1016\/j.celrep.2021.108974_bib44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1074-7613(02)00338-2","article-title":"Autoreactive CD8 T\u00a0cells in organ-specific autoimmunity: emerging targets for therapeutic intervention","volume":"17","author":"Liblau","year":"2002","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2021.108974_bib45","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"10.1016\/j.celrep.2021.108974_bib46","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib47","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s12931-020-01526-6","article-title":"NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma","volume":"21","author":"Menzies-Gow","year":"2020","journal-title":"Respir. Res."},{"key":"10.1016\/j.celrep.2021.108974_bib48","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1164\/rccm.201406-1099OC","article-title":"Gene expression in relation to exhaled nitric oxide identifies novel asthma phenotypes with unique biomolecular pathways","volume":"190","author":"Modena","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib49","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1164\/rccm.201607-1407OC","article-title":"Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease","volume":"195","author":"Modena","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib50","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.jaci.2006.11.639","article-title":"Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute\u2019s Severe Asthma Research Program","volume":"119","author":"Moore","year":"2007","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib51","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jaci.2020.03.037","article-title":"Human TH1 and TH2 cells targeting rhinovirus and allergen coordinately promote allergic asthma","volume":"146","author":"Muehling","year":"2020","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib52","doi-asserted-by":"crossref","first-page":"1801809","DOI":"10.1183\/13993003.01809-2018","article-title":"Pulmonary type-2 innate lymphoid cells in paediatric severe asthma: phenotype and response to steroids","volume":"54","author":"Nagakumar","year":"2019","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.celrep.2021.108974_bib53","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.immuni.2017.04.013","article-title":"Biochemical Underpinnings of Immune Cell Metabolic Phenotypes","volume":"46","author":"Olenchock","year":"2017","journal-title":"Immunity"},{"key":"10.1016\/j.celrep.2021.108974_bib54","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S2213-2600(18)30184-X","article-title":"Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials","volume":"6","author":"Panettieri","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib55","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S0140-6736(17)30879-6","article-title":"After asthma: redefining airways diseases","volume":"391","author":"Pavord","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.celrep.2021.108974_bib56","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11882-016-0651-4","article-title":"Biomarkers of Airway Type-2 Inflammation and Integrating Complex Phenotypes to Endotypes in Asthma","volume":"16","author":"Peters","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"10.1016\/j.celrep.2021.108974_bib57","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.it.2017.08.006","article-title":"Mitochondrial Dynamics at the Interface of Immune Cell Metabolism and Function","volume":"39","author":"Rambold","year":"2018","journal-title":"Trends Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib58","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1172\/JCI80911","article-title":"High IFN-\u03b3 and low SLPI mark severe asthma in mice and humans","volume":"125","author":"Raundhal","year":"2015","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.celrep.2021.108974_bib59","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1172\/JCI84144","article-title":"Current concepts of severe asthma","volume":"126","author":"Ray","year":"2016","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.celrep.2021.108974_bib60","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1152\/physrev.00023.2019","article-title":"Are we meeting the promise of endotypes and precision medicine in asthma?","volume":"100","author":"Ray","year":"2020","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.celrep.2021.108974_bib61","series-title":"R: A Language and Environment for Statistical Computing","year":"2014"},{"key":"10.1016\/j.celrep.2021.108974_bib62","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1365-2222.2004.02038.x","article-title":"Increased number of CD34+ cells in nasal mucosa of allergic rhinitis patients: inhibition by a local corticosteroid","volume":"35","author":"Sergejeva","year":"2005","journal-title":"Clin. Exp. Allergy"},{"key":"10.1016\/j.celrep.2021.108974_bib63","doi-asserted-by":"crossref","first-page":"eaav5581","DOI":"10.1126\/sciimmunol.aav5581","article-title":"Generation and persistence of human tissue-resident memory T\u00a0cells in lung transplantation","volume":"4","author":"Snyder","year":"2019","journal-title":"Sci. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib64","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.jaci.2016.09.002","article-title":"Current application of exhaled nitric oxide in clinical practice","volume":"138","author":"Spahn","year":"2016","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib65","doi-asserted-by":"crossref","first-page":"108079","DOI":"10.1016\/j.celrep.2020.108079","article-title":"Mitofusin 2 in Macrophages Links Mitochondrial ROS Production, Cytokine Release, Phagocytosis, Autophagy, and Bactericidal Activity","volume":"32","author":"Tur","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2021.108974_bib66","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/cyto.a.22625","article-title":"FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data","volume":"87","author":"Van Gassen","year":"2015","journal-title":"Cytometry A"},{"key":"10.1016\/j.celrep.2021.108974_bib67","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1164\/rccm.201811-2221OC","article-title":"BAL Cell Gene Expression in Severe Asthma Reveals Mechanisms of Severe Disease and Influences of Medications","volume":"200","author":"Weathington","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib68","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12931-020-01503-z","article-title":"SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma","volume":"21","author":"Wechsler","year":"2020","journal-title":"Respir. Res."},{"key":"10.1016\/j.celrep.2021.108974_bib69","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nm.2678","article-title":"Asthma phenotypes: the evolution from clinical to molecular approaches","volume":"18","author":"Wenzel","year":"2012","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib70","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1056\/NEJMoa1304048","article-title":"Dupilumab in persistent asthma with elevated eosinophil levels","volume":"368","author":"Wenzel","year":"2013","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.celrep.2021.108974_bib71","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1164\/ajrccm.162.supplement_2.ras-5","article-title":"Regulation of interleukin 4 gene transcription: alterations in atopic disease?","volume":"162","author":"Wierenga","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib72","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1016\/j.jaci.2017.08.020","article-title":"TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status","volume":"141","author":"Wisniewski","year":"2018","journal-title":"J.\u00a0Allergy Clin. Immunol."},{"key":"10.1016\/j.celrep.2021.108974_bib73","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1164\/rccm.200903-0392OC","article-title":"T-helper type 2-driven inflammation defines major subphenotypes of asthma","volume":"180","author":"Woodruff","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib74","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1164\/rccm.201808-1543OC","article-title":"Multiview Cluster Analysis Identifies Variable Corticosteroid Response Phenotypes in Severe Asthma","volume":"199","author":"Wu","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.celrep.2021.108974_bib75","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in Tissue Repair, Regeneration, and Fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124721002886?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124721002886?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T11:15:44Z","timestamp":1761909344000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124721002886"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":76,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["S2211124721002886"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2021.108974","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2021,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2021.108974","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s).","name":"copyright","label":"Copyright"}],"article-number":"108974"}}