Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

Lutz, Dennis; Gazdhar, Amiq Ur Rahman; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günthert, Andreas Reinhold; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars (2015). Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis. American journal of respiratory cell and molecular biology, 52(2), pp. 232-243. American Lung Association 10.1165/rcmb.2014-0078OC

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Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)

UniBE Contributor:

Gazdhar, Amiq Ur Rahman; Günthert, Andreas Reinhold; Geiser, Thomas and Knudsen, Lars

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1044-1549

Publisher:

American Lung Association

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

10 Mar 2015 08:47

Last Modified:

10 Mar 2015 08:47

Publisher DOI:

10.1165/rcmb.2014-0078OC

PubMed ID:

25033427

Uncontrolled Keywords:

alveolar epithelial type II cells, collapse induration, pulmonary fibrosis, stereology, surfactant

URI:

https://boris.unibe.ch/id/eprint/64372

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