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Expression of epithelial injury biomarkers in lung tissue from necropsy of patients with sepsis and acute respiratory distress syndrome

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Author(s):
Natalia de Souza Xavier Costa
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Luiz Fernando Ferraz da Silva; Marisa Dolhnikoff; Elnara Márcia Negri; Heraldo Possolo de Souza
Advisor: Luiz Fernando Ferraz da Silva
Abstract

Acute respiratory distress syndrome (ARDS) is characterized by edema, severe hypoxemia, and decreased pulmonary compliance. Histologically, diffuse alveolar damage is considered the hallmark of the exudative phase of ARDS. ARDS accounts for 10.4% of intensive care unit admissions. Mortality rate can range from 34.9% to 46.1% depending on its severity, and it is estimated that about 40% of cases are undiagnosed. As it remains a challenge to identify ARDS patients and differentiate them from other causes of acute respiratory failure, many studies have focused on identifying biomarkers. Despite advances in this area, there is no single reliable biomarker being used in clinical practice currently. The aim of this study is to evaluate and compare the tissue expression of RAGE, elafin and SP-D in the lung epithelium of ARDS patients, septic patients and control subjects. To this end, we selected patients diagnosed with ARDS (n = 47), later subclassified as mild, moderate and severe; patients diagnosed with sepsis without criteria for ARDS (n = 30); and control patients who died of non-pulmonary causes (n = 27) with autopsies performed at the São Paulo Autopsy Service (SVOC). We collected information from the autopsy reports and laboratory tests. We observed an increased protein expression of elafin in the sepsis and ARDS groups. The severe ARDS showed higher elafin expression in the lung tissue compared to the mild ARDS and sepsis group. In addition, we observed increased protein expression of RAGE in severe ARDS compared to mild ARDS and decreased protein expression of SP-D in septic and ARDS patients compared to controls. In ARDS patients, elafin and RAGE expressions on the lung tissue correlate with several blood gas parameters, a correlation between the severity of the hypoxemia and the expression of these markers. In addition, they correlate with the percentage of bronchopneumonia and hyaline membrane score. SP-D expression does not show any correlation with blood gas parameters or histological scores. RAGE expression was negatively correlated with Mechanical Ventilation (MV) duration in both ARDS and septic patients. In septic patients, the markers almost did not correlate with blood gas parameters, except for the RAGE that correlates with O2 saturation. Moreover, elafin was positively correlated with ICU stay, SP-D was positively correlated with serum lactate and RAGE was also correlated with C-reactive protein. Thus, looking solely at the tissue expression of elafin, RAGE and SP-D does not discriminate sepsis patients from ARDS patients, however the expression of elafin and RAGE, but not SP-D, does correlate with ARDS severity (AU)

FAPESP's process: 17/22903-3 - EXPRESSION OF EPITHELIAL LESION BIOMARKERS IN PULMONARY TISSUE FROM NECROPSIA OF PATIENTS DIAGNOSED WITH SEPSIS AND ACUTE RESPIRATORY DISTRESS SYNDROME.
Grantee:Natália de Souza Xavier Costa
Support Opportunities: Scholarships in Brazil - Doctorate