Stem Cell Therapy for ARDS
Stem Cell Therapy for ARDS

Acute respiratory distress syndrome, or ARDS, is a debilitating condition that leaves sufferers struggling to breathe. It is often seen in those who are already critically ill, as well as those who have suffered significant injuries. In many cases, ARDS is fatal and the risk for death increases dramatically with the age of the patient and the severity of their condition. However, there is evidence that COVID-19-related ARDS, or CARDS as it has been dubbed, may be even more dangerous.

What Is ARDS?

The Mayo Clinic defines ARDS as occurring

"when fluid builds up in the tiny, elastic air sacs (alveoli) in your lungs. The fluid keeps your lungs from filling with enough air, which means less oxygen reaches your bloodstream. This deprives your organs of the oxygen they need to function.

ARDS typically occurs in people who are already critically ill or who have significant injuries. Severe shortness of breath – the main symptom of ARDS – usually develops within a few hours to a few days after the precipitating injury or infection."

What’s the Difference between ARDS and CARDS?

While patients suffering from both ARDS and COVID-19 share many similarities to patients who develop ARDS in other situations, there is mounting evidence that the two conditions are distinct, and that COVID-19-related ARDS may be even more severe and life-threatening.

In a study titled Acute respiratory failure in COVID-19: is it 'typical' ARDS?, published in the journal Critical Care in early May 2020, the authors note several marked differences in CARDS and ARDS symptoms.

"COVID-19 mainly affected the respiratory system with minor damage to other organs. Injury to the alveolar epithelial cells was the main cause of COVID-19-related ARDS, and endothelial cells were less damaged with therefore less exudation. The clinical manifestations were relatively mild in some COVID-19 patients, which was inconsistent with the severity of laboratory and imaging findings.

The onset time of COVID-19-related ARDS was 8–12 days, which was inconsistent with ARDS Berlin criteria, which defined a 1-week onset limit. Some of these patients might have a relatively normal lung compliance. The severity was redefined into three stages according to its specificity: mild, mild-moderate, and moderate-severe. HFNO can be safe in COVID-19-related ARDS patients, even in some moderate-severe patients. The more likely cause of death is severe respiratory failure. Thus, the timing of invasive mechanical ventilation is very important. The effects of corticosteroids in COVID-19-related ARDS patients were uncertain."

What Are the Symptoms of CARDS?

While the symptoms of ARDS and CARDS are similar, there are numerous differences. A study published in JAMA Insights in late April 2020 titled Management of COVID-19 Respiratory Distress highlights some of the key insights and issues in this situation.

"Soon after the onset of respiratory distress from COVID, patients initially retain relatively good compliance despite very poor oxygenation. Minute ventilation is characteristically high. Infiltrates are often limited in extent and, initially, are usually characterized by a ground-glass pattern on CT that signifies interstitial rather than alveolar edema. Many patients do not appear overtly dyspneic.

These patients can be assigned, in a simplified model, to "type L", characterized by low lung elastance (high compliance), lower lung weight as estimated by CT scan, and low response to PEEP. For many patients, the disease may stabilize at this stage without deterioration while others, either because of disease severity and host response or suboptimal management, may transition to a clinical picture more characteristic of typical ARDS. These can be defined as "type H", with extensive CT consolidations, high elastance (low compliance), higher lung weight, and high PEEP response.

Clearly, types L and H are the conceptual extremes of a spectrum that includes intermediate stages, in which their characteristics may overlap. Another feature consistently reported is a highly activated coagulation cascade, with widespread micro- and macro-thromboses in the lung and in other organs; very elevated serum D-dimer levels are a consistent finding associated with adverse outcomes."

The study goes on to note that,

"these observations indicate the fundamental roles played by disproportionate endothelial damage that disrupts pulmonary vasoregulation, promotes ventilation-perfusion mismatch (the primary cause of initial hypoxemia), and fosters thrombogenesis. In addition, remarkably increased respiratory drive may, if unchecked, intensify tidal strains and energy loads from a patient’s respiratory effort applied to highly vulnerable tissue, adding P-SILI to the mix of the lung’s inflammatory assault."

How Might Stem Cell Therapy Help Patients with CARDS?

Mesenchymal stem cells have been investigated heavily for the treatment of ARDS, and they show promise for treating COVID-19-related ARDS, as well. For instance, in a study that concluded in late 2019, patients experienced 25% lower mortality, 40.2% less need for ventilators, 27.2% fewer days in ICU, and dramatically improved quality of life. A report published in the journal Anesthesiology highlighted two earlier trials that showed significant promise in using mesenchymal stem cells to treat ARDS patients.

Stem cells work in multiple ways to combat disease, regenerate tissue, and speed healing. One factor here is that on implantation in the body, stem cells migrate first to the lungs, where they mature and begin to multiply. This means that the lungs are the first organs to benefit from an influx of new stem cells.

Another factor is the anti-inflammatory nature of stem cells. The underlying root cause of ARDS and CARDS, ultimately, is inflammation. Stem cells are powerful anti-inflammatories, which is one reason they’ve been so heavily researched for treating inflammation-related diseases, such as rheumatoid arthritis.

With that being said, it is important to understand that allogeneic stem cells sourced from umbilical cord blood and tissue show the greatest promise. Autologous stem cells, which are sourced from the patient’s own body, are aged, slow to respond, and have accumulated damage that may trigger an autoimmune response in the body. Allogeneic stem cells are youthful, energetic, and damage-free, so they are invisible to the immune system.

It’s also important for patients to understand that because the FDA has not approved any stem cell therapies, all such treatments should be considered experimental.


Indiana Polyclinic

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