{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:04:27Z","timestamp":1768511067405,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,25]]},"group-title":"Physiology","reference-count":56,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Rationale<\/jats:title>\n                  <jats:p>Cystic fibrosis is a genetic disorder characterized by recurrent airway infections, inflammation, and progressive decline in lung function. Autopsy and spirometry data suggest that cystic fibrosis may start in the small airways which, due to the fractal nature of the airways, account for most of the airway tree surface area. However, they are not easily accessible for testing.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Here, we tested the hypothesis that mucociliary clearance is abnormal in the small airways of newborn cystic fibrosis pigs.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Current mucociliary clearance assays are limited therefore we developed a dynamic positron emission tomography scan assay with high spatial and temporal resolution. Each study was accompanied by a high-resolution computed tomography scan that helped identify the thin outer region of the lung that contained small airways.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Measurements and Main Results<\/jats:title>\n                  <jats:p>\n                    Clearance of aerosolized [\n                    <jats:sup>68<\/jats:sup>\n                    Ga]macro aggregated albumin from distal airways occurred within minutes after delivery and followed a two-phase process. In cystic fibrosis pigs, both early and late clearance rates were slower. Stimulation of the cystic fibrosis airways with the purinergic agonist UTP further impaired late clearance. Only 1 cystic fibrosis pig treated with UTP out of 6 cleared more than 20% of the delivered dose.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data indicate that mucociliary transport in the small airways is fast and can easily be missed if the acquisition is not fast enough. The data also indicate that mucociliary transport is impaired in small airways of cystic fibrosis pigs. This defect is exacerbated by stimulation of mucus secretions with purinergic agonists.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.05.22.595427","type":"posted-content","created":{"date-parts":[[2024,5,25]],"date-time":"2024-05-25T06:10:10Z","timestamp":1716617410000},"source":"Crossref","is-referenced-by-count":0,"title":["Mucociliary Clearance is Impaired in Small Airways of Cystic Fibrosis Pigs"],"prefix":"10.64898","author":[{"given":"Carley G.","family":"Stewart","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brieanna M.","family":"Hilkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas D.","family":"Gansemer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Dick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Sunderland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud H.","family":"Abou Alaiwa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Zabner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024052803351029000_2024.05.22.595427v1.1","doi-asserted-by":"crossref","first-page":"15010","DOI":"10.1038\/nrdp.2015.10","article-title":"Cystic fibrosis","volume":"1","year":"2015","journal-title":"Nature Reviews Disease Primers"},{"key":"2024052803351029000_2024.05.22.595427v1.2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1502191"},{"key":"2024052803351029000_2024.05.22.595427v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3849"},{"key":"2024052803351029000_2024.05.22.595427v1.4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1089\/jamp.2011.0923","article-title":"Cystic fibrosis: the role of the small airways","volume":"25","year":"2012","journal-title":"Journal of aerosol medicine and pulmonary drug delivery"},{"key":"2024052803351029000_2024.05.22.595427v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.21154"},{"key":"2024052803351029000_2024.05.22.595427v1.6","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320280420"},{"key":"2024052803351029000_2024.05.22.595427v1.7","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.077784"},{"key":"2024052803351029000_2024.05.22.595427v1.8","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.22777"},{"key":"2024052803351029000_2024.05.22.595427v1.9","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.4.2327"},{"key":"2024052803351029000_2024.05.22.595427v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000928"},{"key":"2024052803351029000_2024.05.22.595427v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nature11130"},{"key":"2024052803351029000_2024.05.22.595427v1.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.1255825"},{"key":"2024052803351029000_2024.05.22.595427v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121731119"},{"key":"2024052803351029000_2024.05.22.595427v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-016-2541-4"},{"key":"2024052803351029000_2024.05.22.595427v1.15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/jappl.1968.24.3.373","article-title":"Morphology of the bronchial tree in man","volume":"24","year":"1968","journal-title":"J Appl Physiol"},{"key":"2024052803351029000_2024.05.22.595427v1.16","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.157.5.rsaa-2"},{"key":"2024052803351029000_2024.05.22.595427v1.17","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2021-0499OC"},{"key":"2024052803351029000_2024.05.22.595427v1.18","doi-asserted-by":"crossref","first-page":"17311","DOI":"10.1016\/S0021-9258(17)32556-5","article-title":"Molecular structure of pulmonary surfactant protein D (SP-D)","volume":"269","year":"1994","journal-title":"The Journal of biological chemistry"},{"key":"2024052803351029000_2024.05.22.595427v1.19","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00422.2015"},{"key":"2024052803351029000_2024.05.22.595427v1.20","first-page":"375","article-title":"What makes a good lung?","volume":"139","year":"2009","journal-title":"Swiss Med Wkly"},{"key":"2024052803351029000_2024.05.22.595427v1.21","doi-asserted-by":"publisher","DOI":"10.1007\/BF01951755"},{"key":"2024052803351029000_2024.05.22.595427v1.22","doi-asserted-by":"crossref","unstructured":"Stewart CG , Hilkin B , Gansemer ND , Walsh SA , Acevado MR , Akurathi V , Pandya DN , Comellas AF , Wadas TJ , Dick DW , Sunderland JJ , Stoltz DA , Welsh MJ , Abou Alaiwa MH . 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