{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:25Z","timestamp":1790506705652,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1016\/j.jaci.2017.12.982","type":"journal-article","created":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T06:03:20Z","timestamp":1521007400000},"page":"1457-1468","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis"],"prefix":"10.1016","volume":"142","author":[{"given":"Salman","family":"Siddiqui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Shikotra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Doran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Choy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary D.","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Eastham-Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Hargadon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Arron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wardlaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Brightling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam G.","family":"Heaney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bradding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2017.12.982_bib1","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.jaci.2010.07.019","article-title":"Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma","volume":"126","author":"Bousquet","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2466-6-13","article-title":"Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study","volume":"6","author":"Partridge","year":"2006","journal-title":"BMC Pulm Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib3","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/cea.12880","article-title":"Revisiting type 2-high and type 2-low airway inflammation in asthma: current knowledge and therapeutic implications","volume":"47","author":"Robinson","year":"2017","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2017.12.982_bib4","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1164\/rccm.200209-1030OC","article-title":"Airway structural alterations selectively associated with severe asthma","volume":"167","author":"Benayoun","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3109\/01902148.2013.791733","article-title":"Cellular and molecular mechanisms of goblet cell metaplasia in the respiratory airways","volume":"39","author":"Boucherat","year":"2013","journal-title":"Exp Lung Res"},{"key":"10.1016\/j.jaci.2017.12.982_bib6","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.jaci.2007.05.028","article-title":"Vascular remodelling is a feature of asthma and non-asthmatic eosinophilic bronchitis","volume":"120","author":"Siddiqui","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib7","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1183\/09031936.00162506","article-title":"Inflammatory cell microlocalisation and airway dysfunction: cause and effect?","volume":"30","author":"Siddiqui","year":"2007","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2017.12.982_bib8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s40265-014-0250-4","article-title":"Asthma therapy and its effect on airway remodelling","volume":"74","author":"Berair","year":"2014","journal-title":"Drugs"},{"key":"10.1016\/j.jaci.2017.12.982_bib9","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1164\/rccm.201407-1374LE","article-title":"Reduction of airway smooth muscle mass by bronchial thermoplasty in patients with severe asthma","volume":"190","author":"Pretolani","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib10","doi-asserted-by":"crossref","first-page":"301ra129","DOI":"10.1126\/scitranslmed.aab3142","article-title":"TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma","volume":"7","author":"Choy","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib11","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/srep01236","article-title":"Extracting insights from the shape of complex data using topology","volume":"3","author":"Lum","year":"2013","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2017.12.982_bib12","doi-asserted-by":"crossref","first-page":"311ra174","DOI":"10.1126\/scitranslmed.aaa9364","article-title":"Identification of type 2 diabetes subgroups through topological analysis of patient similarity","volume":"7","author":"Li","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib13","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.1038\/ncomms9581","article-title":"Topological data analysis for discovery in preclinical spinal cord injury and traumatic brain injury","volume":"6","author":"Nielson","year":"2015","journal-title":"Nat Commun"},{"key":"10.1016\/j.jaci.2017.12.982_bib14","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1111\/cea.12954","article-title":"Responsiveness to oral prednisolone in severe asthma is related to the degree of eosinophilic airway inflammation","volume":"47","author":"Sousa","year":"2017","journal-title":"Clin Exp Allergy"},{"key":"10.1016\/j.jaci.2017.12.982_bib15","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1056\/NEJMoa012705","article-title":"Mast-cell infiltration of airway smooth muscle in asthma","volume":"346","author":"Brightling","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib16","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jaci.2008.05.020","article-title":"Airway hyperresponsiveness is dissociated from airway wall structural remodeling","volume":"122","author":"Siddiqui","year":"2008","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib17","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jaci.2011.08.031","article-title":"Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma","volume":"129","author":"Shikotra","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib18","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1136\/thoraxjnl-2011-200760","article-title":"Glucocorticoid receptor \u03b2 and histone deacetylase 1 and 2 expression in the airways of severe asthma","volume":"67","author":"Butler","year":"2012","journal-title":"Thorax"},{"key":"10.1016\/j.jaci.2017.12.982_bib19","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jaci.2013.09.016","article-title":"Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma","volume":"133","author":"Butler","year":"2014","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib20","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201208-1470OC","article-title":"Elevated sputum interleukin 5 and submucosal eosinophilia in obese individuals with severe asthma","volume":"188","author":"Desai","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib21","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.jaci.2012.06.025","article-title":"Bronchoscopic exploratory research study of Biomarkers in Corticosteroid-refractory Asthma (BOBCAT) Study Group. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients","volume":"130","author":"Jia","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib22","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1084\/jem.176.5.1381","article-title":"Interleukin 4 is localized to and released by human mast cells","volume":"176","author":"Bradding","year":"1992","journal-title":"J Exp Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1183\/09031936.98.12040811","article-title":"Variation in the measurements of basement membrane thickness and inflammatory cell number in bronchial biopsies","volume":"12","author":"Sullivan","year":"1998","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2017.12.982_bib24","first-page":"862","article-title":"Effects of tissue preparation on glomerular volume and capillary structure in the rat","volume":"63","author":"Miller","year":"1990","journal-title":"Lab Invest"},{"key":"10.1016\/j.jaci.2017.12.982_bib25","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.jaci.2017.12.982_bib26","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.4049\/jimmunol.1002568","article-title":"Gene expression patterns of Th2 inflammation and intercellular communication in asthmatic airways","volume":"186","author":"Choy","year":"2011","journal-title":"J Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00454-002-2885-2","article-title":"Topological persistence and simplification","volume":"28","author":"Edelsbrunner","year":"2002","journal-title":"Discrete Comput Geom"},{"key":"10.1016\/j.jaci.2017.12.982_bib28","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00454-004-1146-y","article-title":"Computing persistent homology","volume":"33","author":"Zomorodian","year":"2005","journal-title":"Discrete Comput Geom"},{"key":"10.1016\/j.jaci.2017.12.982_bib29","first-page":"77","article-title":"Statistical topological data analysis using persistence landscapes","volume":"16","author":"Bubenik","year":"2015","journal-title":"J Machine Learn Res"},{"key":"10.1016\/j.jaci.2017.12.982_bib30","first-page":"2301","article-title":"Confidence sets for persistence diagrams","volume":"42","author":"Terese Fasy","year":"2014","journal-title":"Ann Stat"},{"key":"10.1016\/j.jaci.2017.12.982_bib31","doi-asserted-by":"crossref","unstructured":"JavaPex: a research software package for persistent (co)homology, Proceedings of ICMS 2014, Lecture Notes in Computer Science 8592, 129\u2013136, 2014. Available at: http:\/\/appliedtopology.github.io\/javaplex\/. Accessed November 2016.","DOI":"10.1007\/978-3-662-44199-2_23"},{"key":"10.1016\/j.jaci.2017.12.982_bib32","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1111\/j.1476-5381.2011.01620.x","article-title":"Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide","volume":"165","author":"Kelly","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.jaci.2017.12.982_bib33","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/j.jaci.2015.05.044","article-title":"The airway microbiome in patients with severe asthma: associations with disease features and severity","volume":"136","author":"Huang","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib34","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1183\/13993003.01129-2016","article-title":"Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study","volume":"48","author":"Wilson","year":"2016","journal-title":"Eur Respir J"},{"key":"10.1016\/j.jaci.2017.12.982_bib35","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/bjc.2014.636","article-title":"DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach","volume":"112","author":"Hubers","year":"2015","journal-title":"Br J Cancer"},{"key":"10.1016\/j.jaci.2017.12.982_bib36","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1158\/1078-0432.CCR-06-1633","article-title":"A susceptibility gene set for early onset colorectal cancer that integrates diverse signalling pathways: implication for tumorigenesis","volume":"13","author":"Hong","year":"2007","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.jaci.2017.12.982_bib37","first-page":"3124","article-title":"Transcriptional gene expression profiles of colorectal adenoma, adenocarcinoma, and normal tissue examined by oligonucleotide arrays","volume":"61","author":"Notterman","year":"2001","journal-title":"Cancer Res"},{"key":"10.1016\/j.jaci.2017.12.982_bib38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00441-014-2105-4","article-title":"Keratins and skin disease","volume":"360","author":"Kn\u00f6bel","year":"2015","journal-title":"Cell Tissue Res"},{"key":"10.1016\/j.jaci.2017.12.982_bib39","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/path.4808","article-title":"The extracellular matrix\u2014the under-recognized element in lung disease?","volume":"240","author":"Burgess","year":"2016","journal-title":"J Pathol"},{"key":"10.1016\/j.jaci.2017.12.982_bib40","first-page":"771","article-title":"The epidermal growth factor receptor and its ligand family: their potential role in repair and remodelling in asthma","volume":"54","author":"Davies","year":"1999","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2017.12.982_bib41","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jaci.2014.08.027","article-title":"D prostanoid receptor 2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells","volume":"135","author":"Stinson","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2017.12.982_bib42","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1164\/rccm.201212-2318OC","article-title":"Randomized, double blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma","volume":"188","author":"Busse","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jaci.2017.12.982_bib43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrd4624","article-title":"Targeting key proximal drivers of type 2 inflammation in disease","volume":"15","author":"Gandhi","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.jaci.2017.12.982_bib44","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.pupt.2012.08.005","article-title":"Phenotype modulation of airway smooth muscle in asthma","volume":"26","author":"Wright","year":"2013","journal-title":"Pulm Pharmacol Ther"},{"key":"10.1016\/j.jaci.2017.12.982_bib45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1586\/eci.12.82","article-title":"Role of mast cells in mucosal diseases: current concepts and strategies for treatment","volume":"9","author":"Beunk","year":"2013","journal-title":"Expert Rev Clin Immunol"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918300393?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091674918300393?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:15:15Z","timestamp":1758791715000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091674918300393"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["S0091674918300393"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2017.12.982","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Airway pathological heterogeneity in asthma: Visualization of disease microclusters using topological data analysis","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2017.12.982","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Crown Copyright \u00a9 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. All rights reserved.","name":"copyright","label":"Copyright"}]}}