{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T20:01:40Z","timestamp":1793217700106,"version":"4.5.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>To improve disease outcomes in idiopathic pulmonary fibrosis (IPF), it is essential to understand its early pathophysiology so that it can be targeted therapeutically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Perform three-dimensional assessment of the IPF lung microstructure using stereology and multiresolution computed tomography (CT) imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Explanted lungs from patients with IPF (n\u2009=\u20098) and donor control subjects (n\u2009=\u20098) were inflated with air and frozen. CT scans were used to assess large airways. Unbiased, systematic uniform random samples (n\u2009=\u20098\/lung) were scanned with microCT for stereological assessment of small airways (count number, and measure airway wall and lumen area) and parenchymal fibrosis (volume fraction of tissue, alveolar surface area, and septal wall thickness).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>The total number of airways on clinical CT was greater in IPF lungs than control lungs (P\u2009&amp;lt;\u20090.01), owing to an increase in the wall (P\u2009&amp;lt;\u20090.05) and lumen area (P\u2009&amp;lt;\u20090.05) resulting in more visible airways with a lumen larger than 2 mm. In IPF tissue samples without microscopic fibrosis, assessed by the volume fraction of tissue using microCT, there was a reduction in the number of the terminal (P\u2009&amp;lt;\u20090.01) and transitional (P\u2009&amp;lt;\u20090.001) bronchioles, and an increase in terminal bronchiole wall area (P\u2009&amp;lt;\u20090.001) compared with control lungs. In IPF tissue samples with microscopic parenchymal fibrosis, terminal bronchioles had increased airway wall thickness (P\u2009&amp;lt;\u20090.05) and dilated airway lumens (P\u2009&amp;lt;\u20090.001) leading to honeycomb cyst formations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study has important implications for the current thinking on how the lung tissue is remodeled in IPF and highlights small airways as a potential target to modify IPF outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202103-0585oc","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T15:06:15Z","timestamp":1628003175000},"page":"1048-1059","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":75,"title":["Small Airway Reduction and Fibrosis Is an Early Pathologic Feature of 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