Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection

Cortjens, Bart; Jong, Rineke de; Bonsing, Judith; Woensel, Job B. M. van; Antonis, A.F.G.; Reinout, A.

doi:10.1136/thoraxjnl-2017-210289

Cited by 40 publications

(45 citation statements)

References 12 publications

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“…As a countermeasure, deoxyribonuclease I (DNase I) can work to promote the clearance of overproduced NETs and, thus, minimize unwarranted neutrophil-mediated collateral damage (25). This concept is supported by the report that DNase I treatment reduced NET-induced airway obstruction during respiratory syncytial virus infection (10). Furthermore, DNase I has been proven to reduce the human hepatitis B virus (HBV) genome copy number through catabolism of the DNA genome (20).…”

Section: Lung Epitheliummentioning

confidence: 99%

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease

Golonka

Saha

Yeoh

et al. 2020

Physiological Genomics

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Section: Lung Epitheliummentioning

confidence: 99%

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease

Golonka

Saha

Yeoh

et al. 2020

Physiological Genomics

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“…A currently available therapeutic that degrades DNA and dissolves NETs is recombinant DNase (Pulmozyme, Genentech), which may allow better penetration of coadministered compounds into affected lungs (Cortjens et al, 2018). However, circulating DNase-1-generated NET degradation products still possess pro-inflammatory capabilities as well as protease activity (Schauer et al, 2014).…”

Section: Recombinant Dnase-1mentioning

confidence: 99%

Neutrophilia and NETopathy as Key Pathologic Drivers of Progressive Lung Impairment in Patients With COVID-19

et al. 2020

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There is an urgent need for new therapeutic strategies to contain the spread of the novel coronavirus disease 2019 (COVID-19) and to curtail its most severe complications. Severely ill patients experience pathologic manifestations of acute respiratory distress syndrome (ARDS), and clinical reports demonstrate striking neutrophilia, elevated levels of multiple cytokines, and an exaggerated inflammatory response in fatal COVID-19. Mechanical respirator devices are the most widely applied therapy for ARDS in COVID-19, yet mechanical ventilation achieves strikingly poor survival. Many patients, who recover, experience impaired cognition or physical disability. In this review, we argue the need to develop therapies aimed at inhibiting neutrophil recruitment, activation, degranulation, and neutrophil extracellular trap (NET) release. Moreover, we suggest that currently available pharmacologic approaches should be tested as treatments for ARDS in COVID-19. In our view, targeting host-mediated immunopathology holds promise to alleviate progressive pathologic complications of ARDS and reduce morbidities and mortalities in severely ill patients with COVID-19.

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“…A 15% absolute reduction seems ambitious for a single intervention. However, previous studies using dornase alfa in animal lung injury models and in ventilated patients suffering atelectasis demonstrated striking results [35,[38][39][40][41]55].…”

Section: Study Limitationsmentioning

confidence: 95%

Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients

Pottecher

Noll

Borel

et al. 2020

Trials

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Background: Acute respiratory distress syndrome continues to drive significant morbidity and mortality after severe trauma. The incidence of trauma-induced, moderate-to-severe hypoxaemia, according to the Berlin definition, could be as high as 45%. Its pathophysiology includes the release of damage-associated molecular patterns (DAMPs), which propagate tissue injuries by triggering neutrophil extracellular traps (NETs). NETs include a DNA backbone coated with cytoplasmic proteins, which drive pulmonary cytotoxic effects. The structure of NETs and many DAMPs includes double-stranded DNA, which prevents their neutralization by plasma. Dornase alfa is a US Food and Drug Administration-approved recombinant DNase, which cleaves extracellular DNA and may therefore break up the backbone of NETs and DAMPs. Aerosolized dornase alfa was shown to reduce trauma-induced lung injury in experimental models and to improve arterial oxygenation in ventilated patients.

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Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection

Cited by 40 publications

References 12 publications

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease

Harnessing innate immunity to eliminate SARS-CoV-2 and ameliorate COVID-19 disease

Neutrophilia and NETopathy as Key Pathologic Drivers of Progressive Lung Impairment in Patients With COVID-19

Protocol for TRAUMADORNASE: a prospective, randomized, multicentre, double-blinded, placebo-controlled clinical trial of aerosolized dornase alfa to reduce the incidence of moderate-to-severe hypoxaemia in ventilated trauma patients

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