acute lung injury

Acute lung injury, and the more severe acute respiratory distress syndrome (ARDS), represent a spectrum of lung disease characterized by the sudden onset of pulmonary edema, inflammatory cell infiltration, and impaired oxygenation.1

The estimated incidence of acute lung injury in the United States is approximately 200,000 patients annually, with a corresponding mortality rate of up to 40%.2

Acute Lung Injury Associated with COVID-19 Pneumonia

Over the past 15 years, three respiratory viruses have attracted special attention because of the high proportion of affected patients who develop acute lung injuries: influenza, particularly influenza A H1N1 2009, and two novel coronaviruses, Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and SARS coronavirus (SARS-CoV).3 Coronavirus Disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, SARS-CoV-2. According to World Health Organization (WHO) Interim Guidance, the most common diagnosis in severe COVID-19 patients is severe pneumonia. Approximately 14% develop severe disease requiring hospitalization and oxygen support and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by ARDS, sepsis and septic shock, and multiorgan failure, including acute kidney injury and cardiac injury.4

There are no approved pharmacologic therapies for acute lung injury or acute respiratory distress syndrome, which represent a worldwide treatment challenge for patients who are currently suffering from COVID-19.5 The only approved treatment for COVID-19 is remdesivir, which is an anti-viral whose proposed mechanism of action does not address the underlying acute organ injury seen in serious COVID-19 cases.

The Role of HGF and c-Met in Acute Lung Injury

Recent published literature indicates HGF-based therapeutic strategies for acute lung injury and the more severe ARDS are promising, showing HGF helps the lung heal and promotes alveolar regeneration. In addition, studies indicate the importance of the HGF/c-Met pathway in attenuating lung injury during influenza infection.6,7,8

For instance, an animal model of influenza pneumonia investigating exogenous HGF and oseltamivir (an antiviral drug) demonstrated the administration of HGF in combination with oseltamivir improved outcomes over oseltamivir alone.9

REFERENCES

  1. Walkey AJ, et al. 2012, Clinical Epidemiology
  2. Liebert et al 2010, Journal of Aerosol, Medicine and Pulmonary Drug Delivery
  3. Shah et al 2017, Clin Chest Med
  4. WHO Interim Guidance COVID-19 Mar 2020
  5. Medscape ARDS Mar 2020
  6. Panganiban & Day, 2011 Acta Pharmacologia Sinica
  7. Ito, et al 2014, Am J Physiology, Lung Cellular and Molecular Physiology
  8. Brauer, et al 2016 Am J Respiratory Critical Care Medicine
  9. Narasaraju et al 2014 CurrMolMed