Introduction:
The COVID-19 pandemic has brought to light the ongoing lack of effective therapeutic options for certain acute inflammatory conditions, which are the leading cause of patient morbidity and mortality. Acute respiratory syndrome and sepsis are still the main cause of debilitating state and death. A novel medicinal strategy has recently been researched, including improvement in the creation of pharmacological medicines, recombinant protein medications, and cell and gene therapies. Stratification, tailored therapy, and precision medicines are also being made possible by bioinformatics-based techniques and clinical patient profiling, and this is a good time to highlight cutting-edge developments in the field of critical care medicine, especially those that use novel paradigm-shifting techniques and unconventional thinking to treat this group of conditions. This article will show a state-of-art-update on the latest trials and ongoing pharmacological therapies in acute respiratory distress syndrome (ARDS) and sepsis.
What is Acute Respiratory Distress Syndrome?
Acute respiratory distress syndrome is a lethal condition characterized by acute, diffuse inflammation of the lungs, with poor oxygenation and pulmonary infiltration. Microscopically it is associated with damage to the capillary endothelium and the alveoli. The patient develops vasoconstriction of the pulmonary arteries and develops pulmonary hypertension. Oxygen supplementation is necessary to improve the oxygen levels in the blood. Without sufficient oxygen, the organs can not function properly. The mortality rate for acute respiratory distress syndrome is significantly high, and the treatment modalities to combat this medical condition are very few.
What is Sepsis?
Sepsis is a life-threatening condition caused by a dysregulated host response to an infection.
It is characterized by organ dysfunction. Early recognition and prompt medical intervention are required to prevent the condition's progress from leading to multiple organ failure and death.
It is often seen as a complication post-infection and is the leading cause of neonatal and maternal morbidity and mortality in low and middle-income nations. Though sepsis has an acute onset and mortality burden, it can also lead to long-term morbidity affecting the quality of life.
An early diagnosis and identification of the pathogen are necessary for implementing targeted antimicrobial therapy (identification of the bacteria will narrow down the treatment to a specific antibiotic, decreasing the chances of developing resistant organisms). However, antimicrobial resistance can hinder treatment effectiveness and require empirical antibiotic therapy. Fluid resuscitation is also necessary to maintain the body's fluid volume.
What are the State-of-the-Art-Therapies for Acute Respiratory Distress Syndrome and Sepsis?
Acute respiratory distress syndrome (ARDS) has a high incidence and devastating outcomes. However, specific treatment has not yet been eluded, with the current effective therapy limited to avoiding harmful ventilation and developing positive fluid balance.
State-of-the-art therapies include the use of biomarkers and precision medicine. Biomarkers are biological molecules found in blood and other body fluids indicating a normal or abnormal process or a disease condition. Precision medicine is an intervention that looks into information about an individual's genes or proteins to prevent, diagnose and select a treatment that could work best for an individual.
What are the Biomarkers and Precision Medicine in Acute Respiratory Distress Syndrome?
Numerous efforts have been made to identify physiological, clinical, and laboratory biomarkers that determine the relevant subdivision of acute respiratory distress syndrome. One of the most important among them is the ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PF ratio). They are used in clinical trials for observing better prognosis in clinical trials. Most of the biomarkers could be used for predictive enrichment but couldn't identify the underlying biology of the disease.
The significant biomarkers involved in lung epithelial and endothelial injury, dysregulated immune response, alterations in fibrinolysis (breakdown of a blood clot by enzymes), and coagulation play a key role in the pathophysiology of the disease. They are:
-
Protein C.
-
Von willebrand factor.
-
Plasminogen activator inhibitor-1.
-
Plasma surfactant protein - D.
Several studies provide compelling evidence that there are at least two distinct biomarkers in acute respiratory distress syndrome with distinct physiology and responses to treatment. However, more evidence is required for these findings.
What are the Biomarkers and Precision Medicine in Sepsis?
Several clinical research studies suggest that biomarkers in sepsis will help identify sepsis's molecular phenotypes with distinct clinical features and biology. Three biomarkers of interest in sepsis are:
-
Lactate: Lactic acid in the blood.
-
Procalcitonin: Marker for bacterial infections.
-
Soluble Triggering Receptor Expressed on Myeloid Cells-1: Expressed on phagocytes during bacterial and fungal infections.
Other biomarkers that indicate an increased risk of mortality in sepsis are:
-
Plasma cell-free hemoglobin.
-
Interleukin 6.
-
Interleukin 8.
-
Angiopoietin-1 and 2.
-
Cell-free host DNA.
Several other protein biomarkers show the sepsis prognosis for patients treated with anti-inflammatory therapy.
What are the Uses of Biomarkers and Precision Medicine?
Physicians use biomarkers to diagnose, evaluate a treatment plan and rate the prognosis. They are also used for understanding the pathophysiology of the disease. In precision medicine, biomarkers provide two types of enrichments to make recruiting critical care patients for clinical trials more efficient. They are:
-
Prognostic Enrichment: Certain biomarkers will help identify patients with an increased risk of an outcome of interest, improving the research for particular risk reduction strategies.
-
Predictive enrichment: Identifying patient populations likely to respond to a medical intervention based on their biological phenotypes.
They are used in other specialties too. Biomarkers are of significance in oncology to identify malignancies and targeted therapies. A similar approach is used for patients in intensive care units.
Conclusion:
Recent advances in molecular medicine and computational methods have opened the door to using biomarkers to implement precision medicine in critically ill patients affected by acute respiratory distress syndrome (ARDS) and sepsis. However, the challenges ahead are numerous. The biomarkers in the syndrome keep changing because they are dynamic, and any clinical test should have only a short processing time to manage the patients. Once the biomarkers are available, they are validated in clinical trials. Thus biomarkers are important tools in understanding the biology of acute respiratory distress syndrome and sepsis. Further studies are needed to understand their use in the future to guide clinical care by identifying the molecular phenotypes of critical illness. Advanced clinical research will help identify a biomarker that can help in precision therapy and improve the present criteria and intervention for patient management.
