{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:10:33Z","timestamp":1789056633018,"version":"build-2803163510"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"GSK"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lung"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Refractory\/unexplained chronic cough (RCC\/UCC) is a disease associated with substantial clinical and humanistic burden. A variety of endpoints have been used in RCC\/UCC research to measure cough outcomes and impact on patients\u2019 quality of life (QoL), including clinical measures of cough using digital devices, or digital measures, and patient-reported outcomes (PROs). The aim of this review was to determine which endpoints are currently used in studies of RCC\/UCC, and to explore the recent evolution of new digital measures used across research and clinical settings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a scoping literature review (January 1, 2019\u2013October 31, 2024), assessing studies of adults diagnosed with chronic cough (refractory\/unexplained or newly diagnosed). Clinical trials and observational\/real-world studies were included that evaluated objective and PRO measures of cough frequency, severity, symptoms, other cough characterization, and QoL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 70 studies (29 manuscripts, 35 clinicaltrials.gov entries, 6 posters\/abstracts) were included: 36 clinical trials (Phase 2, 3, or 4), 34 observational\/real-world studies. Objective cough frequency was the primary endpoint in 24\/36 clinical trials. In contrast, objective cough frequency was reported in 10\/34 observational\/real-world studies. Observational\/real-world studies had a greater variety of endpoints for cough outcomes and PROs compared with clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Clinical trials and observational\/real-world studies of chronic cough and RCC use a wide range of outcome measures, including objective measures of cough frequency using digital devices (digital endpoints) and subjective PROs. New approaches to digital endpoints and PROs are being developed as the study and treatment of cough evolves.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00408-026-00928-5","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:57:15Z","timestamp":1789055835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Scoping Literature Review of Digital Measures and Patient-Reported Outcomes for Refractory\/Unexplained Chronic Cough: Assessment of Clinical Trials and Real-World Clinical Practice"],"prefix":"10.1007","volume":"204","author":[{"given":"Elizabeth P.","family":"Skinner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Alfonso-Cristancho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atish","family":"De","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Leinwand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"928_CR1","unstructured":"American Lung Association (2025) Chronic cough. https:\/\/www.lung.org\/lung-health-diseases\/lung-disease-lookup\/chronic-cough#:~:text=Chronic%20cough%20is%20a%20persistent,doesn\u2019t%20respond%20to%20treatment. Accessed 25 March 2026."},{"issue":"1","key":"928_CR2","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.chest.2017.10.016","volume":"153","author":"RS Irwin","year":"2018","unstructured":"Irwin RS, French CL, Chang AB, Altman KW , CHEST Expert Cough Panel.(2018) Classification of cough as a symptom in adults and management algorithms: CHEST guideline and expert panel report. Chest 153(1):196\u2013209. https:\/\/doi.org\/10.1016\/j.chest.2017.10.016","journal-title":"Chest"},{"issue":"6","key":"928_CR3","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00316-2024","volume":"10","author":"KJ Holt","year":"2024","unstructured":"Holt KJ, Dockry RJ, McGuinness K, Barrett E, Smith JA (2024) An exploration of clinically meaningful definitions of cough bouts. ERJ Open Res 10(6):00316-2024. https:\/\/doi.org\/10.1183\/23120541.00316-2024","journal-title":"ERJ Open Res"},{"issue":"5","key":"928_CR4","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00425-2023","volume":"9","author":"L Puente-Maestu","year":"2023","unstructured":"Puente-Maestu L, Davila I, Quirce S et al (2023) Burden of refractory and unexplained chronic cough on patients\u2019 lives: a cohort study. ERJ Open Res 9(5):00425-2023. https:\/\/doi.org\/10.1183\/23120541.00425-2023","journal-title":"ERJ Open Res"},{"issue":"1","key":"928_CR5","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1183\/09031936.00123612","volume":"41","author":"N Yousaf","year":"2013","unstructured":"Yousaf N, Monteiro W, Matos S, Birring S, Pavord I (2013) Cough frequency in health and disease. Eur Respir J 41(1):239\u2013241. https:\/\/doi.org\/10.1183\/09031936.00123612","journal-title":"Eur Respir J"},{"issue":"3","key":"928_CR6","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s00408-015-9701-2","volume":"193","author":"SA Chamberlain","year":"2015","unstructured":"Chamberlain SA, Garrod R, Douiri A et al (2015) The impact of chronic cough: a cross-sectional European survey. Lung 193(3):401\u2013408. https:\/\/doi.org\/10.1007\/s00408-015-9701-2","journal-title":"Lung"},{"issue":"3","key":"928_CR7","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1378\/chest.125.2.482","volume":"152","author":"CL French","year":"2017","unstructured":"French CL, Crawford SL, Bova C, Irwin RS (2017) Change in psychological, physiological, and situational factors in adults after treatment of chronic cough. Chest 152(3):547\u2013562. https:\/\/doi.org\/10.1378\/chest.125.2.482","journal-title":"Chest"},{"issue":"6","key":"928_CR8","doi-asserted-by":"publisher","first-page":"906","DOI":"10.4168\/aair.2020.12.6.906","volume":"12","author":"HJ Jin","year":"2020","unstructured":"Jin HJ, Kim CW (2020) Understanding the impact of chronic cough on the quality of life in the general population. Allergy Asthma Immunol Res 12(6):906\u2013909. https:\/\/doi.org\/10.4168\/aair.2020.12.6.906","journal-title":"Allergy Asthma Immunol Res"},{"key":"928_CR9","doi-asserted-by":"publisher","DOI":"10.1177\/17534666241236025","volume":"18","author":"V Bali","year":"2024","unstructured":"Bali V, Schelfhout J, Sher MR et al (2024) Patient-reported experiences with refractory or unexplained chronic cough: a qualitative analysis. Ther Adv Respir Dis 18:17534666241236025. https:\/\/doi.org\/10.1177\/17534666241236025","journal-title":"Ther Adv Respir Dis"},{"issue":"2","key":"928_CR10","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/S2213-2600(24)00422-3","volume":"13","author":"KF Chung","year":"2025","unstructured":"Chung KF, Mazzone SB, McGarvey L, Song WJ (2025) Chronic cough as a disease: implications for practice, research, and health care. Lancet Respir Med 13(2):110\u2013112. https:\/\/doi.org\/10.1016\/S2213-2600(24)00422-3","journal-title":"Lancet Respir Med"},{"issue":"162","key":"928_CR11","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0127-2021","volume":"30","author":"A Morice","year":"2021","unstructured":"Morice A, Dicpinigaitis P, McGarvey L, Birring SS (2021) Chronic cough: new insights and future prospects. Eur Respir Rev 30(162):210127. https:\/\/doi.org\/10.1183\/16000617.0127-2021","journal-title":"Eur Respir Rev"},{"issue":"10","key":"928_CR12","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1016\/j.mayocp.2013.08.007","volume":"88","author":"VN Iyer","year":"2013","unstructured":"Iyer VN, Lim KG (2013) Chronic cough: an update. Mayo Clin Proc 88(10):1115\u20131126. https:\/\/doi.org\/10.1016\/j.mayocp.2013.08.007","journal-title":"Mayo Clin Proc"},{"issue":"6","key":"928_CR13","doi-asserted-by":"publisher","first-page":"795","DOI":"10.4168\/aair.2023.15.6.795","volume":"15","author":"M Zhang","year":"2023","unstructured":"Zhang M, Morice AH, Si F et al (2023) New insights into refractory chronic cough and unexplained chronic cough: a 6-year ambispective cohort study. Allergy Asthma Immunol Res 15(6):795\u2013811. https:\/\/doi.org\/10.4168\/aair.2023.15.6.795","journal-title":"Allergy Asthma Immunol Res"},{"issue":"4","key":"928_CR14","doi-asserted-by":"publisher","first-page":"A2487","DOI":"10.1016\/j.chest.2022.08.2039","volume":"162","author":"PV Dicpinigaitis","year":"2022","unstructured":"Dicpinigaitis PV, McGarvey L, Smith AJ et al (2022) Prior specialist consultations and treatments in a refractory chronic cough population enrolled in a phase 2b study of the P2X3 antagonist BLU-5937. Chest 162(4):A2487\u2013A2488. https:\/\/doi.org\/10.1016\/j.chest.2022.08.2039","journal-title":"Chest"},{"key":"928_CR15","unstructured":"Vitalograph (2025) VitaloJAK Model 7100 instructions for use. https:\/\/vitalograph.com\/products\/vitalojak. Accessed 25 March 2026"},{"issue":"9","key":"928_CR16","doi-asserted-by":"publisher","first-page":"5207","DOI":"10.21037\/jtd-2020-icc-003","volume":"12","author":"JI Hall","year":"2020","unstructured":"Hall JI, Lozano M, Estrada-Petrocelli L, Birring S, Turner R (2020) The present and future of cough counting tools. J Thorac Dis 12(9):5207\u20135223. https:\/\/doi.org\/10.21037\/jtd-2020-icc-003","journal-title":"J Thorac Dis"},{"issue":"5","key":"928_CR17","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1183\/09031936.00057407","volume":"31","author":"SS Birring","year":"2008","unstructured":"Birring SS, Fleming T, Matos S, Raj AA, Evans DH, Pavord ID (2008) The Leicester cough monitor: preliminary validation of an automated cough detection system in chronic cough. Eur Respir J 31(5):1013\u20131018. https:\/\/doi.org\/10.1183\/09031936.00057407","journal-title":"Eur Respir J"},{"key":"928_CR18","doi-asserted-by":"publisher","DOI":"10.1177\/17534666221099737","volume":"16","author":"AM Nguyen","year":"2022","unstructured":"Nguyen AM, Schelfhout J, Muccino D et al (2022) Leicester cough questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough. Ther Adv Respir Dis 16:17534666221099737. https:\/\/doi.org\/10.1177\/17534666221099737","journal-title":"Ther Adv Respir Dis"},{"key":"928_CR19","unstructured":"Hyfe (2025) Integrate cough as an endpoint with CoughMonitor Suite. https:\/\/www.hyfe.com\/cough-monitor. Accessed 25 March 2026"},{"issue":"1","key":"928_CR20","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00279-2022","volume":"9","author":"M Kuhn","year":"2023","unstructured":"Kuhn M, Nalbant E, Kohlbrenner D et al (2023) Validation of a small cough detector. ERJ Open Res 9(1):00279-2022. https:\/\/doi.org\/10.1183\/23120541.00279-2022","journal-title":"ERJ Open Res"},{"key":"928_CR21","unstructured":"Hyfe (2024) Overview of regulatory status for current cough counting devices on the market. https:\/\/www.hyfe.com\/insights\/overview-of-regulatory-status-for-current-cough-counting-devices-on-the-market. Accessed 25 March 2026"},{"issue":"10","key":"928_CR22","doi-asserted-by":"publisher","first-page":"7165","DOI":"10.21037\/jtd-24-705","volume":"16","author":"EC Mackay","year":"2024","unstructured":"Mackay EC, Turner RD, Cho PSP, Birring SS (2024) Patient-reported assessments of chronic cough in clinical trials: accessory or primary endpoints? J Thorac Dis 16(10):7165\u20137181. https:\/\/doi.org\/10.21037\/jtd-24-705","journal-title":"J Thorac Dis"},{"issue":"6","key":"928_CR23","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1007\/s00408-023-00647-1","volume":"201","author":"SE Lee","year":"2023","unstructured":"Lee SE, Rudd M, Kim TH et al (2023) Feasibility and utility of a smartphone application-based longitudinal cough monitoring in chronic cough patients in a real-world setting. Lung 201(6):555\u2013564. https:\/\/doi.org\/10.1007\/s00408-023-00647-1","journal-title":"Lung"},{"issue":"4","key":"928_CR24","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.21037\/jtd-23-230","volume":"15","author":"RD Turner","year":"2023","unstructured":"Turner RD, Birring SS (2023) Measuring cough: what really matters? J Thorac Dis 15(4):2288\u20132299. https:\/\/doi.org\/10.21037\/jtd-23-230","journal-title":"J Thorac Dis"},{"issue":"7","key":"928_CR25","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1080\/17476348.2025.2498419","volume":"19","author":"KL Rhatigan","year":"2025","unstructured":"Rhatigan KL, Cho PSP (2025) Value-based outcome measures in cough. Expert Rev Respir Med 19(7):635\u2013637. https:\/\/doi.org\/10.1080\/17476348.2025.2498419","journal-title":"Expert Rev Respir Med"},{"issue":"1","key":"928_CR26","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1183\/09031936.00101307","volume":"32","author":"A Kelsall","year":"2008","unstructured":"Kelsall A, Decalmer S, Webster D et al (2008) How to quantify coughing: correlations with quality of life in chronic cough. Eur Respir J 32(1):175\u2013179. https:\/\/doi.org\/10.1183\/09031936.00101307","journal-title":"Eur Respir J"},{"key":"928_CR27","unstructured":"FDA (2022) Patient-focused drug development: selecting, developing, or modifying fit-for-purpose clinical outcome assessments. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/patient-focused-drug-development-selecting-developing-or-modifying-fit-purpose-clinical-outcome. Accessed 25 March 2026"},{"key":"928_CR28","unstructured":"FDA (2023) Patient-focused drug development: incorporating clinical outcome assessments into endpoints for regulatory decision-making. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/patient-focused-drug-development-incorporating-clinical-outcome-assessments-endpoints-regulatory. Accessed 25 March 2026"},{"key":"928_CR29","unstructured":"FDA (2023) Digital health technologies for remote data acquisition in clinical investigations. Guidance for industry, investigators and other stakeholders. https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/digital-health-technologies-remote-data-acquisition-clinical-investigations. Accessed 25 March 2026"},{"issue":"1","key":"928_CR30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1002\/cpt.3398","volume":"117","author":"JP Bakker","year":"2025","unstructured":"Bakker JP, Izmailova ES, Clement A et al (2025) Regulatory pathways for qualification and acceptance of digital health technology-derived clinical trial endpoints: considerations for sponsors. Clin Pharmacol Ther 117(1):56\u201372. https:\/\/doi.org\/10.1002\/cpt.3398","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"928_CR31","doi-asserted-by":"publisher","first-page":"467","DOI":"10.7326\/m18-0850","volume":"169","author":"AC Tricco","year":"2018","unstructured":"Tricco AC, Lillie E, Zarin W et al (2018) PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation. Ann Intern Med 169(7):467\u2013473. https:\/\/doi.org\/10.7326\/m18-0850","journal-title":"Ann Intern Med"},{"key":"928_CR32","unstructured":"ICIQ The International Consultation on Incontinence Questionnaires. https:\/\/iciq.net\/. Accessed 25 March 2026"},{"issue":"161","key":"928_CR33","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0104-2021","volume":"30","author":"E Kum","year":"2021","unstructured":"Kum E, Guyatt GH, Devji T et al (2021) Cough symptom severity in patients with refractory or unexplained chronic cough: a systematic survey and conceptual framework. Eur Respir Rev 30(161):210104. https:\/\/doi.org\/10.1183\/16000617.0104-2021","journal-title":"Eur Respir Rev"},{"issue":"suppl 63","key":"928_CR34","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2019.PA4342","volume":"54","author":"D Mines","year":"2019","unstructured":"Mines D, Bacci E, Nguyen AM, Shaffer S, Smith J, Vernon M (2019) Assessment of inter- and intra-rater reliability of objective cough frequency in patients with chronic cough. Eur Respir J 54(suppl 63):PA4342. https:\/\/doi.org\/10.1183\/13993003.congress-2019.PA4342","journal-title":"Eur Respir J"},{"issue":"7","key":"928_CR35","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.21037\/jtd-22-1492","volume":"15","author":"JS Shim","year":"2023","unstructured":"Shim JS, Kim BK, Kim SH et al (2023) A smartphone-based application for cough counting in patients with acute asthma exacerbation. J Thorac Dis 15(7):4053\u20134065. https:\/\/doi.org\/10.21037\/jtd-22-1492","journal-title":"J Thorac Dis"},{"issue":"1","key":"928_CR36","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/s41598-025-85341-3","volume":"15","author":"C Chaccour","year":"2025","unstructured":"Chaccour C, S\u00e1nchez-Olivieri I, Siegel S et al (2025) Validation and accuracy of the Hyfe cough monitoring system: a multicenter clinical study. Sci Rep 15(1):880. https:\/\/doi.org\/10.1038\/s41598-025-85341-3","journal-title":"Sci Rep"},{"issue":"3","key":"928_CR37","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1159\/000492396","volume":"2","author":"AB Cohen","year":"2018","unstructured":"Cohen AB, Mathews SC (2018) The digital outcome measure. Digit Biomark 2(3):94\u2013105","journal-title":"Digit Biomark"},{"key":"928_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12916-024-03590-x","volume":"22","author":"MS Tackney","year":"2024","unstructured":"Tackney MS, Carpenter JR, Villar SS (2024) Unleashing the full potential of digital outcome measures in clinical trials: eight questions that need attention. BMC Med 22:1\u201320","journal-title":"BMC Med"},{"key":"928_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41746-024-01182-w","volume":"7","author":"SY Tan","year":"2024","unstructured":"Tan SY, Sumner J, Wang Y, Yip AW (2024) A systematic review of the impacts of remote patient monitoring (RPM) interventions on safety, adherence, quality-of-life and cost-related outcomes. npj Digit Med 7:1\u201316","journal-title":"npj Digit Med"},{"key":"928_CR40","doi-asserted-by":"publisher","DOI":"10.2196\/78568","volume":"28","author":"M Liang","year":"2026","unstructured":"Liang M, Rong J, Grosan C, Wang X (2026) Effectiveness of eHealth interventions in alleviating burden on informal caregivers of people with dementia: systematic review and meta-analysis of randomized controlled trials. J Med Internet Res 28:e78568","journal-title":"J Med Internet Res"},{"key":"928_CR41","unstructured":"FDA (2023) Framework for the Use of Digital Health Technologies in Drug and Biological Product Development. https:\/\/www.fda.gov\/science-research\/science-and-research-special-topics\/digital-health-technologies-dhts-drug-development. Accessed 25 March 2026"}],"container-title":["Lung"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00408-026-00928-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00408-026-00928-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00408-026-00928-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:57:21Z","timestamp":1789055841000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00408-026-00928-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["928"],"URL":"https:\/\/doi.org\/10.1007\/s00408-026-00928-5","relation":{},"ISSN":["1432-1750"],"issn-type":[{"value":"1432-1750","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"assertion":[{"value":"29 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"EAD\n                      ,\n                      EPS\n                      and\n                      RA-C\n                      are employees of GSK and hold financial equities in GSK.\n                      EAD\n                      also holds financial equities in AstraZeneca.\n                      AD\n                      and\n                      BL\n                      are employees of Trinity Life Sciences, which received funding from GSK to conduct the study.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"66"}}