Emerging concepts in ventilation-induced lung injury

Madahar, Purnema; Beitler, Jeremy R.

doi:10.12688/f1000research.20576.1

Cited by 22 publications

(14 citation statements)

References 118 publications

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“…Positive pressure ventilation is associated with lung injury (ventilator-associated lung injury or VALI) and is sometimes the underlying cause of such injury (ventilator-induced lung injury or VILI) [ 57 ]. The pathological features of VILI are indistinguishable from other causes of ARDS and are induced by volume and pressure stress within the alveolus [ 58 ]. Ventilation strategies that result in VILI provoke higher levels of inflammatory cytokine release [ 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

et al. 2021

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Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010–2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40–83 years old in the ventilated cohort and 14–80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.

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Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

et al. 2021

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“…Biotrauma, which is the biological response to mechanical injury, may also contribute to the injury process by promoting inflammatory response (reviewed in Ref. 54 ). One example of biotrauma is the transmission of mechanosensory signals.…”

Section: Mechanisms Of Viral Injurymentioning

confidence: 99%

Healing after COVID-19: are survivors at risk for pulmonary fibrosis?

McDonald

2021

American Journal of Physiology-Lung Cellular and Molecular Phys

197

147

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The novel SARS-CoV-2 coronavirus, responsible for Covid-19 disease, was first reported in Wuhan, China in December of 2019. The virus rapidly spread, and the World Health Organization declared a pandemic by March 2020. With millions of confirmed cases world-wide, there is growing concern and considerable debate regarding the potential for coronavirus infection to contribute to an appreciable burden of chronic respiratory symptoms or fibrotic disease among recovered individuals. As the first case of Covid-19 was documented less than one year ago, data regarding long-term clinical outcomes are not yet available and predictions for long-term outcome are speculative at best. However, due to the staggering number of cases and the severity of disease in many individuals, there is a critical need to consider the potential long-term implications of Covid-19. This review examines current basic and clinical data regarding fibrogenic mechanisms of viral injury in the context of SARS-CoV-2. Several intersecting mechanisms between coronavirus infection and fibrotic pathways are discussed to highlight factors and processes that may be targetable to improve patient outcome. Reports of post-infection sequelae from previous coronavirus outbreaks are presented toward the goal of improved recognition of potential contributing risk factors for fibrotic disease.

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“…Positive pressure ventilation is associated with lung injury (ventilator-associated lung injury or VALI) and is sometimes the underlying cause of such injury (ventilator-induced lung injury or VILI) 52 . The pathological features of VILI are indistinguishable from other causes of ARDS and are induced by volume and pressure stress within the alveolus 53 . Ventilation strategies that result in VILI provoke higher levels of inflammatory cytokine release 54,55 .…”

Section: Discussionmentioning

confidence: 87%

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

Baker

Kowk

Berry

et al. 2020

Preprint

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Mortality due to Covid-19 is highly associated with advanced age, owing in large part to severe lower respiratory tract infection. SARS-CoV-2 utilizes the host ACE2 receptor for infection. Whether ACE2 abundance in the lung contributes to age-associated vulnerability is currently unknown. We set out to characterize the RNA and protein expression profiles of ACE2 in aging human lung in the context of phenotypic parameters likely to affect lung physiology. Examining publicly available RNA sequencing data, we discovered that mechanical ventilation is a critical variable affecting lung ACE2 levels. Therefore, we investigated ACE2 protein abundance in patients either requiring mechanical ventilation or spontaneously breathing. ACE2 distribution and expression were determined in archival lung samples by immunohistochemistry (IHC). Tissues were selected from the specimen inventory at a large teaching hospital collected between 2010-2020. Twelve samples were chosen from patients receiving mechanical ventilation for acute hypoxic respiratory failure (AHRF). Twenty samples were selected from patients not requiring ventilation. We compared samples across age, ranging from 40-83 years old in the ventilated cohort and 14-80 years old in the non-ventilated cohort. Within the alveolated parenchyma, ACE2 expression is predominantly observed in type II pneumocytes (or alveolar type II / AT2 cells) and alveolar macrophages. All 12 samples from our ventilated cohort showed histologic features of diffuse alveolar damage including reactive, proliferating AT2 cells. In these cases, ACE2 was strongly upregulated with age when normalized to lung area (p = 0.004) or cellularity (p = 0.003), associated with prominent expression in AT2 cells. In non-ventilated individuals, AT2 cell reactive changes were not observed and ACE2 expression did not change with age when normalized to lung area (p = 0.231) or cellularity (p = 0.349). Additionally, we observed prominent pulmonary endothelial ACE2 expression in 2 patients on either an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). In summary, ACE2 expression increases with age in the setting of alveolar damage observed in patients on mechanical ventilation, providing a potential mechanism for higher Covid-19 mortality in the elderly.

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Emerging concepts in ventilation-induced lung injury

Cited by 22 publications

References 118 publications

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

Healing after COVID-19: are survivors at risk for pulmonary fibrosis?

Angiotensin-converting enzyme 2 (ACE2) expression increases with age in patients requiring mechanical ventilation

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