{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:37:31Z","timestamp":1792701451906,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ARM"],"abstract":"<jats:p>Small-airway disease (SAD) is a key feature of severe asthma and is associated with poor symptom control and frequent exacerbations. Dupilumab has demonstrated efficacy in improving lung function and reducing exacerbations, but real-world evidence on its effects in SAD remains limited. The aim of this study is to evaluate the impact of 12 months of dupilumab treatment on SAD, clinical outcomes, and type 2 inflammation. We included 21 patients. Small-airway function was assessed by impulse oscillometry (R5\u2013R20) and spirometry FEF25\u201375% predicted at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment. Additional assessments included FEV1, the Asthma Control Test (ACT), exacerbation frequency, oral corticosteroid (OCS) use, the blood eosinophil count (BEC), and fractional exhaled nitric oxide (FeNO). At baseline, 62% of patients exhibited SAD (R5\u2013R20 &gt; 0.07 kPa\/L\/s). Dupilumab treatment led to a significant and sustained improvement in small-airway function: mean R5\u2013R20 decreased from 0.18 \u00b1 0.17 kPa\/L\/s to 0.09 \u00b1 0.07 at T12 (p = 0.04), while predicted FEF25\u201375% increased from 29.5 \u00b1 20.8% to 47.0 \u00b1 21.1% (p &lt; 0.001). ACT scores improved from 13.1 \u00b1 4.9 to 19.6 \u00b1 3.8 (p &lt; 0.001). FeNO levels declined from 64.1 \u00b1 50.7 ppb to 24.8 \u00b1 20.9 ppb (p = 0.01). Improvements in R5\u2013R20 correlated with better ACT and FeNO reductions. In this real-world cohort, dupilumab significantly improved SAD, lung function, and asthma control, while reducing exacerbations, OCS dependence, and type 2 inflammation over 12 months.<\/jats:p>","DOI":"10.3390\/arm94020014","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:57:13Z","timestamp":1772125033000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of Dupilumab on Small Airway Disease in Severe Asthma: A 12-Month Retrospective Real-World Study"],"prefix":"10.3390","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2538-1278","authenticated-orcid":false,"given":"Lorenzo","family":"Carriera","sequence":"first","affiliation":[{"name":"Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Pulmonology and Sub-Intensive Respiratory Unit, Ospedale Santa Maria della Misericordia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Coppola","sequence":"additional","affiliation":[{"name":"UOC Pneumologia, Ospedale San Filippo Neri-ASL Roma 1, 00135 Rome, Italy"},{"name":"UniCamillus, Saint Camillus International University of Health Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Lipsi","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Sub-Intensive Respiratory Unit, Ospedale Santa Maria della Misericordia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5250-2868","authenticated-orcid":false,"given":"Stefano","family":"Baglioni","sequence":"additional","affiliation":[{"name":"Department of Pulmonology and Sub-Intensive Respiratory Unit, Ospedale Santa Maria della Misericordia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-217X","authenticated-orcid":false,"given":"Pier-Valerio","family":"Mari","sequence":"additional","affiliation":[{"name":"Ospedale San Carlo di Nancy, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7257-1080","authenticated-orcid":false,"given":"Roberto","family":"Barone","sequence":"additional","affiliation":[{"name":"Facolt\u00e0 di Medicina e Chirurgia, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2838-423X","authenticated-orcid":false,"given":"Simone","family":"Ielo","sequence":"additional","affiliation":[{"name":"UOC Pneumologia e UTIP, Ospedale San Donato, USL Toscana SudEst, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Scala","sequence":"additional","affiliation":[{"name":"UOC Pneumologia e UTIP, Ospedale San Donato, USL Toscana SudEst, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0637-7282","authenticated-orcid":false,"given":"Andrea","family":"Smargiassi","sequence":"additional","affiliation":[{"name":"UOC Pneumologia, Dipartimento Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2843-9966","authenticated-orcid":false,"given":"Riccardo","family":"Inchingolo","sequence":"additional","affiliation":[{"name":"UOC Pneumologia, Dipartimento Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Richeldi","sequence":"additional","affiliation":[{"name":"UOC Pneumologia, Dipartimento Neuroscienze, Organi di Senso e Torace, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Gambacorta","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Otorhinolaryngology, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Di Giovanni","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Otorhinolaryngology, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5761-7018","authenticated-orcid":false,"given":"Eugenio","family":"De Corso","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Otorhinolaryngology, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","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. 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