Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by severe, acute inflammatory processes in the lung following illness or injury.

The pathologic aspects of ARDS include damages to the alveolar-capillary barrier, surfactant depletion, and loss of aerated lung tissue, resulting in increased permeability and subsequent pulmonary edema. Major clinical symptoms of ARDS patients consist of breathing difficulties (dyspnea), rapid breathing (tachypnea), bluish skin coloration (cyanosis), decreased level of oxygen in the circulating blood (hypoxemia), and at a later stage lethargy or even becoming comatose. ARDS can develop at all ages. Every year it is estimated that more than 3 million people are affected around the globe. 

 

Various conditions that cause direct or indirect damages to alveoli and their neighboring capillaries in the lung can lead to ARDS. The common direct causes for ARDS include pneumonia, aspiration of gastric contents, and inhalation of toxic substances, near drowning, fat embolism; while the common indirect causes include sepsis, pancreatitis, trauma, blood transfusion and drug overdose.

 

Newly emerged causes of ARDS are also reported, such as ventilator-associated lung injury (VALI) and e-cigarettes or vaping use-associated lung injuries (EVALI).

 

Among those listed conditions, sepsis and bacterial or viral pneumonia make up 40% to 60% of all ARDS cases. Currently, due to the global pandemic of COVID-19 and the viral pneumonia caused by coronavirus, the ARDS incidence rate has reached a new peak.

 

Management of ARDS remains a challenge to people. In 2016, a multicenter study conducted with over 29,000 patients from 50 countries reported that 10% of ICU admissions and 23% of ventilated patients fulfilled criteria for ARDS, and that a 40%-50% mortality rate was recorded in ARDS patients with majority of the deaths occurring within the first few weeks of disease onset. Furthermore, although most patients who survived ARDS recover normal or near-normal pulmonary function, many still face diminished quality of life with significant physical, psychological, and cognitive sequelae up to 5 years after ARDS.

Current Treatment

To date, pharmacological interventions of ARDS have failed to prove effective. Although inflammation, epithelial and endothelial damage and coagulation disorders are perceived biological pathways attributing to ARDS pathophysiology, none of drugs targeting these pathways have proven to be consistently effective in clinical trials.

 

Conventional ARDS treatment approaches remain largely symptomatic and supportive, which aim to increase blood oxygen levels, provide breathing support and treat the underlying cause of the disease. Standard therapy consists of mechanical ventilation, fluid management, oxygen supplementation (invasive or non-invasive), prone positioning, and ECMO (extracorporeal membrane oxygenation). Antibiotics are often supplemented to fight or prevent infections.

The Latest Research Progress of Stem Cell Therapy for ARDS

Given that many similarities have been observed between coronavirus 2019-induced viral pneumonia and ARDS pathology, many scientists believe that Covid-19 may serve as a model disease from which clinical trial results can be extrapolated into ARDS therapy. 

 

At present, more than thirty-one clinical trials investigating mesenchymal stem cell (MSC) therapy in COVID-19 pneumonia patients are registered with the US National Institutes of Health. (https://clinicaltrials.gov). MSCs used in those trials were derived from multiple tissue origins including umbilical cord, adipose tissues, and placenta. Among those clinical studies, eight studies investigated cell therapy as a treatment for ARDS. So far, findings from those studies indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients, supporting stem cell therapy as a potential adjuvant treatment to improve recovery and to reduce mortality rates of ARDS patients.