{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:06:29Z","timestamp":1784052389629,"version":"3.55.0"},"reference-count":38,"publisher":"BMJ","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"CSA Medical, USA","award":["No award number"],"award-info":[{"award-number":["No award number"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"accepted":{"date-parts":[[2026,6,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Patients with chronic bronchitis suffer high morbidity and rapid functional decline; thus, novel treatments are needed. Metered cryospray delivers titrated applications of liquid nitrogen to the bronchial tree via bronchoscopy, with between-group efficacy and the mechanism of treatment action unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 1:1 randomised, blinded, sham-controlled, mechanistic trial of metered cryospray in patients with chronic obstructive pulmonary disease and chronic bronchitis, who receive metered cryospray (n=15 treated, n=14 completed follow-up) or sham-bronchoscopy (n=17 completed treatment and follow-up), in addition to standard clinical care. The primary outcome measure was the between group difference in change in mean goblet cell density per mm of epithelial basement membrane in endobronchial cryobiopsy samples at 6\u2009months relative to baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mean age was 69.2 (SD 8.7) years with 16 (50%) females. In the intention-to-treat analysis, metered cryospray did not reduce goblet cell density (60.7\u2009cells CI \u221249.3 to 170.8 per mm basement membrane; p=0.49) at 6\u2009months relative to sham-control. Improvement in St George\u2019s Respiratory Questionnaire total score was observed with metered cryospray at 6\u2009months (\u22129.6 points SD 11.1; p=0.022), compared with sham-control. A reduction in expiratory low attenuation area at \u2212856 Hounsfield units was demonstrated with metered cryospray (\u22128.6% SD 4.6; p&lt;0.0001) at 6 months relative to sham-control. Three serious non-device-related adverse events were reported in two patients in the sham-procedure group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this first randomised sham-controlled study investigating metered cryospray and induced epithelial remodelling as a treatment modality in patients with chronic bronchitis, goblet cell density was not reduced; however, an improvement in symptom burden and radiological air trapping metrics were identified. Metered cryospray demonstrates promise as a safe and efficacious treatment for patients with chronic bronchitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03892694\">NCT03892694<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/thorax-2026-224822","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T17:20:31Z","timestamp":1784049631000},"page":"thorax-2026-224822","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Metered cryospray in patients with chronic bronchitis: a mechanistic randomised controlled 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