Capturing the multifactorial nature of ARDS - “Two-hit” approach to model murine acute lung injury

Hoegl, Sandra; Burns, Nana; Angulo, Martín; Francis, Daniel; Osborne, Christopher M.; Mills, Tingting; Blackburn, Michael R.; Eltzschig, Holger K.; Vohwinkel, Christine U.

doi:10.14814/phy2.13648

Cited by 27 publications

(33 citation statements)

References 53 publications

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“…Additionally, indirect pulmonary injuries can be explained by the “2-hit hypothesis” which states that an inflammatory response related to extra-pulmonary area stimulus (first hit) is followed by systemic inflammatory response (second hit) that can induce lung injury. Common triggers of indirect lung injury induced by systemic inflammatory response include sepsis, shock, acute pancreatitis, bone fracture, and massive blood transfusion [ 19 , 20 ]. It has been shown that severe systemic inflammatory response resulting from sepsis produces numerous circulating inflammatory mediators.…”

Section: Overview Of Lung Inflammatory Injurymentioning

confidence: 99%

Understanding the role of neutrophils in acute respiratory distress syndrome

et al. 2021

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Acute respiratory distress syndrome (ARDS) is difficult to treat and is associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads to life-threatening ARDS. Neutrophil counts are positively correlated with disease severity in ARDS. Neutrophil activation not only plays a significant role in immune defense against infections, but also causes tissue damage and leads to inflammatory diseases. Activated neutrophils rapidly migrate to inflamed lung tissue, releasing toxic granular contents and generating neutrophil extracellular traps. In the last few decades, it has become apparent that neutrophils occupy a central role in ARDS pathology. In this review, we summarize the neutrophil inflammatory responses and their relationships to ARDS. According to the current literature, understanding the function of neutrophils may be helpful in the treatment of ARDS.

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Section: Overview Of Lung Inflammatory Injurymentioning

confidence: 99%

Understanding the role of neutrophils in acute respiratory distress syndrome

et al. 2021

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“…Since patients suffering from ARDS often require ventilatory support, VILI is a complication that eventually aggravates ARDS [ 136 , 214 ]. An early study reported the involvement of P2Y receptors in the pathogenesis of VILI [ 204 ].…”

Section: The Role Of P2 Receptors In Lung Diseasementioning

confidence: 99%

P2 Purinergic Signaling in the Distal Lung in Health and Disease

Wirsching

Fauler

Fois

et al. 2020

IJMS

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The distal lung provides an intricate structure for gas exchange in mammalian lungs. Efficient gas exchange depends on the functional integrity of lung alveoli. The cells in the alveolar tissue serve various functions to maintain alveolar structure, integrity and homeostasis. Alveolar epithelial cells secrete pulmonary surfactant, regulate the alveolar surface liquid (ASL) volume and, together with resident and infiltrating immune cells, provide a powerful host-defense system against a multitude of particles, microbes and toxicants. It is well established that all of these cells express purinergic P2 receptors and that purinergic signaling plays important roles in maintaining alveolar homeostasis. Therefore, it is not surprising that purinergic signaling also contributes to development and progression of severe pathological conditions like pulmonary inflammation, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and pulmonary fibrosis. Within this review we focus on the role of P2 purinergic signaling in the distal lung in health and disease. We recapitulate the expression of P2 receptors within the cells in the alveoli, the possible sources of ATP (adenosine triphosphate) within alveoli and the contribution of purinergic signaling to regulation of surfactant secretion, ASL volume and composition, as well as immune homeostasis. Finally, we summarize current knowledge of the role for P2 signaling in infectious pneumonia, ALI/ARDS and idiopathic pulmonary fibrosis (IPF).

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“…However, no significant differences in the oxygenation index, APACHE II and SOFA scores were found between the 2 groups ( P > .05). This indicated that higher mechanical power is more likely to cause ventilator-associated lung injury in patients with ARDS, further induce aggravation of biological injury, [13] lead to increased secretion of TGF-β1 and CTGF, and accelerate the progression of lung tissue fibrosis in patients with ARDS. In the present study, a significant difference was also found in the 28-day mortality in patients between the LMP group and the HMP group, which indicated that the level of mechanical power is related to the prognosis of patients and may be related to the severity of ARDS.…”

Section: Discussionmentioning

confidence: 99%

Correlation analysis between mechanical power, transforming growth factor-β1, and connective tissue growth factor levels in acute respiratory distress syndrome patients and their clinical significance in pulmonary structural remodeling

Xie¹,

Wang

Liu³

et al. 2019

Medicine

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Background: To identify the clinical correlations between mechanical power and transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in acute respiratory distress syndrome (ARDS) patients, their clinical significance in pulmonary structural remodeling in ARDS patients was investigated. Methods: Ninety-five patients with moderate or severe ARDS, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from January 2017 to February 2019. Their mechanical power was monitored and recorded, the TGF-β1 and CTGF levels were detected by enzyme-linked immunosorbent assay (ELISA), their relevance was analyzed, and the relationship between mechanical power and 28-day survival rate was investigated. According to the high-resolution computed tomography (HRCT) examination, the patients were divided into an ARDS group and an ARDS pulmonary fibrosis (ARDS-PF) group. The differences in mechanical power, TGF-β1, and CTGF between the 2 groups were compared, and the significance of TGF-β1 and CTGF in the diagnosis of ARDS pulmonary interstitial fibrosis were evaluated. Results: A significant positive correlation between mechanical power and serum TGF-β1 and CTGF in patients with ARDS was found and the correlation coefficients were 0.424 and 0.581, respectively. The difference between mechanical power and 28-day survival rate was statistically significant ( P < .05), while the area under the receiver operating characteristic curves of TGF-β1 and CTGF for the diagnosis of ARDS pulmonary fibrosis was 0.838 and 0.884, respectively ( P < .05). Conclusion: A significant correlation between mechanical power and serum fibrosis biomarkers TGF-β1 and CTGF in ARDS patients was found, and its level was related to the survival prognosis of patients. Mechanical power, TGF-β1, and CTGF were clinically evaluated for the assessment of lung structural remodeling, such as ARDS pulmonary fibrosis. This study has particular significance to the early prevention of ventilator-induced lung injury and pulmonary fibrosis in patients with ARDS receiving mechanical ventilation.

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Capturing the multifactorial nature of ARDS - “Two-hit” approach to model murine acute lung injury

Cited by 27 publications

References 53 publications

Understanding the role of neutrophils in acute respiratory distress syndrome

Understanding the role of neutrophils in acute respiratory distress syndrome

P2 Purinergic Signaling in the Distal Lung in Health and Disease

Correlation analysis between mechanical power, transforming growth factor-β1, and connective tissue growth factor levels in acute respiratory distress syndrome patients and their clinical significance in pulmonary structural remodeling

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