Association of the C-terminal 42-peptide fragment of alpha-1 antitrypsin with the severity of ARDS: A pilot study

Background: Acute respiratory distress syndrome is a life-threatening condition with a hospital mortality rate of up to 40%. Biomarkers related to the pathophysiology of ARDS may not only identify patients at risk but may also serve as potential therapeutic targets. This study examined the association between the proteolytic C-ter-minal 42-peptide fragment of alpha-1 antitrypsin and ARDS severity.Methods: The 42-peptide fragment and interleukin-6 levels were measured in 21 patients with mild-to-moderate ARDS and 47 patients with moderate-to-severe ARDS on days 1, 3, and 5 after diagnosis/admission to the intensive care unit. To elucidate the association between both biomarkers and the PaO2/FiO2 ratio, the con-centrations of both biomarkers were compared between the two groups, and a multivariate regression analysis was performed.Results: The concentrations of both biomarkers were higher in patients with moderate-to-severe ARDS. While the PaO2/FiO2 ratio increased from day 1 to day 3, the concentrations of both biomarkers decreased. Multivariate regression analysis revealed negative associations between the PaO2/FiO2 ratio and both the C-terminal 42 -pep-tide of alpha-1 antitrypsin and interleukin-6 on day 1 (beta:-0.138, p = 0.052; beta:-0.096, p = 0.004) and on day 3 (beta:-0.157, p = 0.045; beta:-0.106, p = 0.043).Interpretation: The C-terminal 42-peptide of alpha-1 antitrypsin is a new biomarker associated with ARDS severity. Its predictive value in identifying patients at risk of developing moderate-to-severe ARDS must be investigated in additional, independent prospective studies.