Pulmonary Manifestations of Acute Lung Injury: More Than Just Diffuse Alveolar Damage

Hughes, Kenneth T.; Beasley, Mary Beth

doi:10.5858/arpa.2016-0342-ra

Cited by 125 publications

(76 citation statements)

References 53 publications

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“…Pulmonary histopathologic changes related to ARDS are usually similar regardless of its etiology [4][5][6][7]. This observation can be extended to cases caused by SARS-CoV-2 infection [7].…”

Section: Discussionmentioning

confidence: 97%

“…Several studies have shown that platelets participate in lung damage, particularly in acute lung injury [2,3]. MKs are usually not mentioned as a characteristic histopathologic nding associated to acute pulmonary injury [4][5][6][7]. However, a few studies and textbooks point out that their number is increased in the lungs of patients with diffuse alveolar damage (DAD), burns, shock or sepsis [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

Valdivia-Mazeyra

Salas

Nieves-Alonso

et al. 2020

Preprint

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Megakaryocytes are normally present in the lung where they play a role in platelet homeostasis. The latter are well known to participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are usually not mentioned as a characteristic histopathologic finding associated to acute pulmonary injury, a few studies point out that their number is increased in the lungs of patients with diffuse alveolar damage. In this autopsy study we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute respiratory distress syndrome. We have studied pulmonary tissue samples of 18 patients most of which died after prolonged disease and use of mechanical ventilation. Most samples showed fibroproliferative or fibrotic diffuse alveolar damage and an increased number of megakaryocytes. In six, thrombi of the pulmonary microcirculation were seen. We compare our findings with previous published autopsy reports, mainly focusing on the description of megakaryocytes. Our patients showed abnormal coagulation parameters with high levels of fibrinogen, D-dimers and variable thrombocytopenia. Since the lung is considered an active site of megakariopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response. An increased number of pulmonary megakaryocytes suggests and supports a relation with the thrombotic events so often seen in COVID-19. Regardless of its etiology, future studies of patients dying with acute pulmonary injury should include pulmonary megakaryocytes as a histologic variable of interest.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

Valdivia-Mazeyra

Salas

Nieves-Alonso

et al. 2020

Preprint

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“…Several patients with systemic vasculitis in our cohort developed pulmonary hemorrhage. Pulmonary hemorrhage (or diffuse alveolar hemorrhage) occurring in patients with systemic vasculitis involves the fundamental process of bleeding into the acinar portion of the lung and was recognized by the acute development of hemoptysis, anemia, and pulmonary infiltrates on chest radiograph 17 . Indeed, these patients may have severe hypoxemia and require high ventilatory support.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and trajectory of patients with pediatric acute respiratory distress syndrome

Wong

Tan

Lee

et al. 2020

Pediatric Pulmonology

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Objective This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes. Methods This prospective study over November 2017‐October 2019 was conducted in a single‐center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed. Results Eighty‐five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre‐existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them. Conclusion A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.

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“…However, the pathogenesis of ALI remains yet clear so far. Diffused alveolar damage is the predominant pathological feature of ALI [5] . Moreover, hyperactive in ammatory reaction and excessive oxidative stress are the major mechanisms by which type II alveolar epithelial cell (T 2 AECs) are extensively injured under ALI [6] .…”

Section: Introductionmentioning

confidence: 99%

Nrf2 Alleviates TNF-α-Induced Oxidative Stress Damage in Type II Alveolar Epithelial Cells by Down-Regulating the Expression of NOX1

Zhang

Lian

Lin

et al. 2020

Preprint

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Objective: To study the roles of Nrf2 in acute lung injury (ALI) pathogenesis by investigating the effects of Nrf2 on regulating oxidative stress damage in TNF-α-induced type II alveolar epithelial cells (T2AECs).Methods: T2AECs were transfected with Nrf2 siRNA and overexpression vectors for six hours before being induced by TNF-α for 24 hours. Subsequently, levels of interleukins (IL-6 and IL-8), reactive oxygen species (ROS), malondialdehyde (MDA), total antioxidation capability (T-AOC), Nrf2, NOX1 and NF-kB were measured. Additionally, potential Nrf2 binding site in NOX1 promoter was predicted by AliBaba2.1 and two recombinant vectors, namely “pGL3-NOX1-1500” and “pGL3-NOX1-1489, were constructed by inserting the sequence of NOX1 promoter in full-length and that in the absence of Nrf2 binding site to pGL3 basic vector. T2AECs were transfected with these vectors prior to TNF-α induction and the luciferase activity was measured.Results: Levels of IL-6, IL-8, ROS and MDA were increased (P＜0.05) while T-AOC was decreased in TNF-α-induced A549 cells after the transfection of Nrf2 siRNA vector (P＜0.05). In contrast, concentrations of IL-6, IL-8, ROS and MDA were decreased (P＜0.05) whereas T-AOC was increased after the transfection of Nrf2 overexpression vector (P＜0.05). NOX1 promoter possesses one Nrf2 binding site. Cells transfected by “pGL3-NOX1-1500” vector had the highest luciferase activity, followed by cells transfected by “pGL3-NOX1-1489” vector and the control cells (P＜0.05).Conclusion: Nrf2 modulates NOX1 expression via binding to its promoter, by which against TNF-α-induced oxidative stress damage in T2AECs. Thus, Nrf2 might be a therapeutic target for ALI.

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Pulmonary Manifestations of Acute Lung Injury: More Than Just Diffuse Alveolar Damage

Cited by 125 publications

References 53 publications

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

Characteristics and trajectory of patients with pediatric acute respiratory distress syndrome

Nrf2 Alleviates TNF-α-Induced Oxidative Stress Damage in Type II Alveolar Epithelial Cells by Down-Regulating the Expression of NOX1

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