scholarly journals Role of DAMPs in respiratory virus-induced acute respiratory distress syndrome—with a preliminary reference to SARS-CoV-2 pneumonia

Author(s):  
Walter Gottlieb Land
Author(s):  
Monika Janagill ◽  
Puneet Aulakh Pooni ◽  
Siddharth Bhargava ◽  
Shibba Takkar Chhabra

AbstractAcute respiratory distress syndrome (ARDS) has high mortality and multiple therapeutic strategies have been used to improve the outcome. Inhaled nitric oxide (INO), a pulmonary vasodilator, is used to improve oxygenation. This study was conducted to determine the role of sildenafil, an oral vasodilator, to improve oxygenation and mortality in pediatric ARDS (PARDS). The prevalence of pulmonary hypertension in PARDS was studied as well. Inclusion criteria included children (1–18 years) with ARDS requiring invasive ventilation admitted to the pediatric intensive care unit of a teaching hospital in Northern India over a 1-year period of time. Thirty-five patients met the inclusion criteria. Cardiologist performed a detailed echocardiogram to determine pulmonary arterial pressure (PAP). Patients with persistent hypoxemia were started on oral sildenafil. The majority (77%) patients had a primary pulmonary etiology of PARDS. Elevated PAP (>25 mm Hg) was detected in 54.3% patients at admission. Sildenafil was given to 20 patients who had severe and persistent hypoxemia. Oxygenation improved in most patients after the first dose with statistically significant improvement in PaO2/FiO2 ratios at both 12 and 24 hours following initiation of therapeutic dosing of sildenafil. Improvement in oxygenation occurred irrespective of initial PAP. Outcomes included a total of 57.1% patients discharged, 28.6% discharged against medical advice (DAMA), and a 14.3% mortality rate. Mortality was related to the severity of PARDS and not the use of sildenafil. This is the first study to determine the effect of sildenafil in PARDS. Sildenafil led to improvement in oxygenation in nearly all the cases without affecting mortality. Due to unavailability of INO in most centers of developing countries, sildenafil may be considered as an inexpensive alternative in cases of persistent hypoxemia in PARDS. We recommend additional randomized controlled trials to confirm the effect of sildenafil in PARDS as determined in this study.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
M. García de Acilu ◽  
S. Leal ◽  
B. Caralt ◽  
O. Roca ◽  
J. Sabater ◽  
...  

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process. Recent report on the prognostic value of eicosanoids in patients with ARDS suggests that modulating the inflammatory response through the use of polyunsaturated fatty acids may be a useful strategy for ARDS treatment. The use of enteral diets enriched with eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) has reported promising results, showing an improvement in respiratory variables and haemodynamics. However, the interpretation of the studies is limited by their heterogeneity and methodology and the effect ofω-3 fatty acid-enriched lipid emulsion or enteral diets on patients with ARDS remains unclear. Therefore, the routine use ofω-3 fatty acid-enriched nutrition cannot be recommended and further large, homogeneous, and high-quality clinical trials need to be conducted to clarify the effectiveness ofω-3 polyunsaturated fatty acids.


2021 ◽  
Vol 134 (5) ◽  
pp. 792-808
Author(s):  
Grace Hogan ◽  
Pierce Geoghegan ◽  
Tomás P. Carroll ◽  
Jennifer Clarke ◽  
Oisín F. McElvaney ◽  
...  

Acute respiratory distress syndrome is characterized by hypoxemia, altered alveolar–capillary permeability, and neutrophil-dominated inflammatory pulmonary edema. Despite decades of research, an effective drug therapy for acute respiratory distress syndrome remains elusive. The ideal pharmacotherapy for acute respiratory distress syndrome should demonstrate antiprotease activity and target injurious inflammatory pathways while maintaining host defense against infection. Furthermore, a drug with a reputable safety profile, low possibility of off-target effects, and well-known pharmacokinetics would be desirable. The endogenous 52-kd serine protease α1-antitrypsin has the potential to be a novel treatment option for acute respiratory distress syndrome. The main function of α1-antitrypsin is as an antiprotease, targeting neutrophil elastase in particular. However, studies have also highlighted the role of α1-antitrypsin in the modulation of inflammation and bacterial clearance. In light of the current SARS-CoV-2 pandemic, the identification of a treatment for acute respiratory distress syndrome is even more pertinent, and α1-antitrypsin has been implicated in the inflammatory response to SARS-CoV-2 infection.


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