{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T17:01:57Z","timestamp":1778605317667,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>There is uncertainty about the cost\u2010effectiveness of treatment options for children and adolescents with uncontrolled asthma despite inhaled corticosteroid (ICS) treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A Markov state\u2010transition model was developed to simulate costs from the perspective of the National Health Service in the UK and health outcomes associated with low, medium and high dose ICS, ICS in combination with long\u2010acting \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010adrenoceptor agonists (LABAs) or leukotriene receptor antagonists (LTRAs), and LTRA monotherapy. Healthcare resource use and health state utilities were identified from literature searches. Transition probabilities were derived from a systematic review and network meta\u2010analysis. Total costs and quality\u2010adjusted life years were computed, and incremental cost\u2010effectiveness ratios estimated over a 1\u2010year time horizon. Parameter, structural and probabilistic sensitivity analyses were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with low\u2010dose ICS, medium\u2010dose ICS and ICS\u2009+\u2009LABA had incremental cost\u2010effectiveness ratios of \u00a3255,555 and \u00a3304,956 per quality\u2010adjusted life year gained, respectively. High\u2010dose ICS, LTRA alone and in combination with ICS were dominated by alternatives which were less costly and associated with a greater number of quality\u2010adjusted life years. The incremental cost\u2010effectiveness ratio for medium\u2010dose ICS reduced to \u00a314,797 per quality\u2010adjusted life year gained when the transition probabilities were increased to reflect a higher risk of asthma exacerbation. ICS\u2009+\u2009LABA became cost effective with a\u2009&gt;\u200960% reduction in inhaler price.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment escalation beyond low\u2010dose ICS in children and adolescents with uncontrolled asthma may only be cost\u2010effective in the UK if the prices of alternatives reduce or treatment is targeted to those at higher risk of asthma exacerbations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ppul.71414","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:34:49Z","timestamp":1765791289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cost\u2010Effectiveness Analysis of Treatments for Children With Uncontrolled Asthma Symptoms Despite Inhaled Corticosteroids"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-4255","authenticated-orcid":false,"given":"Giovanna","family":"Culeddu","sequence":"first","affiliation":[{"name":"Centre for Health Economics and Medicines Evaluation Bangor University Bangor Wales UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2705-9224","authenticated-orcid":false,"given":"Sofia","family":"Cividini","sequence":"additional","affiliation":[{"name":"Institute of Population Health, Department of Health Data Science University of Liverpool Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7342-5523","authenticated-orcid":false,"given":"Ian","family":"Sinha","sequence":"additional","affiliation":[{"name":"Alder Hey Children's Foundation NHS Trust Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-2290","authenticated-orcid":false,"given":"Sarah","family":"Donegan","sequence":"additional","affiliation":[{"name":"Institute of Population Health, Department of Health Data Science University of Liverpool Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2348-2036","authenticated-orcid":false,"given":"Katie","family":"Rose","sequence":"additional","affiliation":[{"name":"Alder Hey Children's Foundation NHS Trust Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Fulton","sequence":"additional","affiliation":[{"name":"Patient Representative Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8393-5060","authenticated-orcid":false,"given":"Stephen","family":"Turner","sequence":"additional","affiliation":[{"name":"Women and Children Division NHS Grampian Aberdeen Scotland UK"},{"name":"Institute of Applied Health Sciences University of Aberdeen Aberdeen Scotland UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-1445","authenticated-orcid":false,"given":"Catrin Tudur","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Population Health, Department of Health Data Science University of Liverpool Liverpool England UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8247-7459","authenticated-orcid":false,"given":"Dyfrig A.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Centre for Health Economics and Medicines Evaluation Bangor University Bangor Wales UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"EINSTEIN collaborative group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"issue":"1","key":"e_1_2_16_2_1","first-page":"1","volume":"26","author":"The Global Asthma Report 2022","year":"2022","journal-title":"International Journal of Tuberculosis and Lung Disease"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01450-1"},{"key":"e_1_2_16_4_1","volume-title":"NHS Warning to Parents as Asthma Season Hits","author":"NHS England","year":"2019"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0657-8"},{"key":"e_1_2_16_6_1","unstructured":"Asthma and Lung UK Investing in Breath: Reducing the Economic Cost of Lung Conditions Through Increased Research and Innovation PWC Report (2023) https:\/\/www.asthmaandlung.org.uk\/investinginbreath-reducingeconomiccostoflungconditions-autumn-2023."},{"key":"e_1_2_16_7_1","volume-title":"Global Strategy for Asthma Management and Prevention","author":"GINA Science Committee","year":"2019"},{"key":"e_1_2_16_8_1","unstructured":"National Institute for Health and Care Excellence. Asthma: Diagnosis Monitoring and Chronic Asthma Management (BTS NICE SIGN) NG245. November 2024 https:\/\/www.nice.org.uk\/guidance\/ng245."},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.140681"},{"key":"e_1_2_16_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-040528"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01011-2023"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2013-204114"},{"key":"e_1_2_16_13_1","unstructured":"National Institute for Health and Care Excellence NICE Health Technology Evaluations: The Manual 2022 https:\/\/www.nice.org.uk\/process\/pmg36\/."},{"key":"e_1_2_16_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.23073"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2015.1116087"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2007.116632"},{"key":"e_1_2_16_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02134.x"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62145-9"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104647"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/02770903.2013.767909"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210650"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.3310\/AWOI5587"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00571-2022"},{"key":"e_1_2_16_24_1","volume-title":"2018\/19 National Cost Collection Data Publication","author":"NHS England","year":"2021"},{"key":"e_1_2_16_25_1","unstructured":"L.Curtis Unit Costs of Health and Social Care 2020 Personal Social Services Research Unit University of Kent.https:\/\/www.pssru.ac.uk\/project-pages\/unit-costs\/unit-costs-2020\/."},{"key":"e_1_2_16_26_1","volume-title":"British National Formulary","author":"Joint Formulary Committee","year":"2021"},{"key":"e_1_2_16_27_1","unstructured":"W. S.KuaandS.Davis \u201cSystematic Review of Health State Utilities in Children With Asthma \u201dHealth Economics & Decision Science (HEDS) Discussion Paper Series(School of Health and Related Research University of Sheffield 2016) https:\/\/eprints.whiterose.ac.uk\/102188\/1\/16.12.pdf."},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-7547-5-10"},{"key":"e_1_2_16_29_1","unstructured":"MVH Group Final Report on the Modelling of Valuation Tariffs Centre for Health Economics (University of York 1995) https:\/\/www.york.ac.uk\/media\/che\/documents\/reports\/MVH%20Final%20Report.pdf."},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.3132\/pcrj.2007.00002"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-017367"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.106079"},{"key":"e_1_2_16_33_1","unstructured":"National Institute for Health and Care Excellence Inhaled Corticosteroids for the Treatment of Chronic Asthma in Children Under the Age of 12 years (TA131) (2007) https:\/\/www.nice.org.uk\/guidance\/ta131."},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2008.01724.x"},{"key":"e_1_2_16_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hec.635"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jval.2021.11.1351"},{"key":"e_1_2_16_37_1","volume-title":"Health Trust Reference Costs: 2017\u201318","year":"2018"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-014815"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2016.05.019"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182738"},{"key":"e_1_2_16_41_1","volume-title":"Asthma: Diagnosis, Monitoring and Chronic Asthma Management (Update)","author":"BTS\/NICE\/SIGN collaborative guideline NG245","year":"2024"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71414","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ppul.71414","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.71414","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T15:00:08Z","timestamp":1771426808000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.71414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":40,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/ppul.71414"],"URL":"https:\/\/doi.org\/10.1002\/ppul.71414","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71414"}}