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Depleted plasma gelsolin linked to severe pneumonia outcomes
Researchers found that a lower concentration of plasma gelsolin, or pGSN, was associated with more severe clinical outcomes in adults hospitalized with community-acquired pneumonia, suggesting that gelsolin therapy may be an effective strategy to reduce morbidity and mortality in these patients.
Wesley H. Self, MD, MPH, vice chair for research in the department of emergency medicine at Vanderbilt University Medical Center, told Infectious Disease News that despite antibiotics and supportive care, pneumonia continues to be a common cause of morbidity and mortality, underscoring a critical need for novel approaches to patient care. To help patients with the most severe forms of pneumonia, pGSN may be the answer.
“We know gelsolin is an abundant protein normally circulating in humans and has several important functions in innate immunity,” Self explained. “With severe infections, circulating gelsolin can be rapidly consumed, potentially making patients more vulnerable to disease progression.”
Self and colleagues conducted an observational study as part of the CDC’s Etiology of Pneumonia in the Community Study, which enrolled adults hospitalized with community-acquired pneumonia (CAP) from January 2010 through June 2012. For the observational study, an enzyme-linked immunosorbent assay measured pGSN concentrations upon admission in 455 adults hospitalized with CAP.
The researchers grouped patients into four categories: general floor care without ICU unit admission, invasive respiratory or vasopressor support (IRVS), or death ICU care without IRVS or death IRVS without death; or death. They compared patients in the lowest quartile of pGSN concentrations with those in the upper three quartiles.
Self and colleagues observed a median pGSN concentration of 38.1 g/mL overall, but lower pGSN concentrations were associated with patients with more severe outcomes (P = .0001). For floor patients, the median pGSN value was 40.3 g/mL and for ICU patients, it was 36.7 g/mL. Among patients receiving IRVS and patients who died, the median pGSN values were 36.5 g/mL and 25.7 g/mL, respectively. According to the study, 21.2% of patients in the lowest pGSN quartile required IRSV compared with 11.7% of patients with higher concentrations (P = .0114). Additionally, patients in the lowest quartile died more often than those with higher pGSN concentrations. Specifically, 8.8% in the lowest quartile died compared with 0.9% in the higher quartiles (P = .0001).
“With the promising results from this study and others, clinical trials of gelsolin therapy are being developed to test its safety and efficacy in severe pneumonia,” Self said.
Procalcitonin-guided therapy has been shown to cut the mortality risk in respiratory patients and safely reduce the duration of antibiotic therapy. Procalcitonin is a biomarker that helps identify the body’s reaction to bacterial infections.
Mark J. DiNubile, MD, an author on the current paper and chief medical officer at BioAegis Therapeutics, said pGSN is not being proposed at a diagnostic biomarker because its “biological variability precludes its use for precisely predicting outcomes in individual patients.”
“The value of measuring gelsolin in this study was to advance our understanding of gelsolin as it pertains to the pathophysiology of severe pneumonia,” DiNubile told Infectious Disease News. “While these data do not directly demonstrate that gelsolin repletion will improve patient outcomes, our findings support investigating supplementation with recombinant human gelsolin as adjunctive therapy in clinical trials of severe community-acquired pneumonia.” – by Marley Ghizzone
Disclosures: DiNubile reports being a paid member of BioAegis Therapeutics. Self reports receiving personal fees from Cempra Pharmaceuticals, Ferring Pharmaceuticals, BioTest AG, Gilead Pharmaceuticals, Pfizer and Merck, all outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.