Is Progression of Pulmonary Fibrosis due to Ventilation-induced Lung Injury?

Abstract

Author Contributions: R.K.A. conceived of the idea of the manuscript; wrote the first draft of all but the section on alveolar micromechanics and the data supplement, which he edited; and wrote the first draft of the revision in response to reviewers' comments. B.S. wrote the first draft of the section on alveolar micromechanics and the data supplement, performed the analyses illustrated in Figure 2 and Figures E1 and E2, and provided suggestions for revising both the original and revised versions of the manuscript. C.E.P. added to and revised the section on alveolar micromechanics and the data supplement and provided suggestions for revising both the original and revised versions of the manuscript. D.A.S. contributed to the idea of the manuscript and provided suggestions for revising the original and revised versions of the manuscript.

Hidden Microatelectases Increase Vulnerability to Ventilation-Induced Lung Injury

“…The presented data suggest a causal relationship between the existence of microatelectases during mechanical ventilation and the progression of VILI, although they do not provide a definite proof. This causality is supported by theoretical considerations using spring models to simulate the distribution of septal stresses and strains within a network of elastic elements (Mead et al, 1970;Makiyama et al, 2014;Albert et al, 2019). As long as the mechanical properties of the spring elements are similar the distribution of stresses and strains, and therefore the tissue deformation, is homogenous.…”

“…The mechanisms of atelectrauma and volutrauma are linked with each other via alveolar interdependence. Derecruited alveoli act as stress concentrators and could increase dynamic strain and therefore micromechanical volutrauma in adjacent, open alveoli (Mead et al, 1970;Makiyama et al, 2014;Albert et al, 2019). In healthy lungs both atelectrauma (e.g., a PEEP of 0 cmH 2 O) and volutrauma (e.g., high tidal volume of 30 ml/kg bodyweight) are required in combination to produce VILI in mice (Seah et al, 2011).…”

“…A more insidious mechanism of volutrauma results from the concept of alveolar interdependence (Mead et al, 1970;Makiyama et al, 2014). In this situation, microatelectases act as stress concentrators that impose tethering forces on surrounding inter-alveolar septal walls so that these areas of lung parenchyma are prone to overdistension and therefore volutrauma (Albert, 2012;Albert et al, 2019).…”

Ginsenoside Rg3 Inhibits Pulmonary Fibrosis by Preventing HIF-1α Nuclear Localisation

“…Idiopathic pulmonary brosis is a severe interstitial lung disease that can cause progressive loss of the lung function and has high lethality [1,2]. Pulmonary brosis is an end-stage change in a large class of lung diseases characterised by abnormal broblast proliferation, extracellular matrix accumulation with in ammatory damage and tissue structure destruction.…”

“…Pulmonary brosis is an end-stage change in a large class of lung diseases characterised by abnormal broblast proliferation, extracellular matrix accumulation with in ammatory damage and tissue structure destruction. The alveolar tissue of patients is damaged and abnormally repaired, causing scarring [1,3,4]. During pulmonary brosis, the abnormal proliferation of broblasts is similar to the biological behaviour of tumour cells [5][6][7].…”