Conference Coverage

Trio of blood biomarkers elevated in children with LRTIs



– While C-reactive protein, procalcitonin, and proadrenomedullin are associated with development of severe clinical outcomes in children with lower respiratory tract infections, proadrenomedullin is most strongly associated with disease severity, preliminary results from a prospective cohort study showed.

“Despite the fact that pneumonia guidelines call the site of care decision the most important decision in the management of pediatric pneumonia, no validated risk stratification tools exist for pediatric lower respiratory tract infections (LRTI),” lead study author Todd A. Florin, MD, said at the annual Pediatric Academic Societies meeting. “Biomarkers offer an objective means of classifying disease severity and clinical outcomes.”

Dr. Todd A. Florin, a pediatric emergency physician at Cincinnati Children's Hospital Doug Brunk/MDedge News

Dr. Todd A. Florin

Three frequently studied blood biomarkers in adults with LRTI by risk stratification are C-reactive protein (CRP), procalcitonin (PCT), and midregional proadrenomedullin (proADM). CRP is secreted by hepatocytes stimulated by interleukin (IL)-6, IL-1 beta, and tumor necrosis factor (TNF) alpha in response to inflammation and infection. “Elevation of CRP and the failure of CRP to fall over the course of treatment has been shown to be associated with adverse outcomes and severity scores, but not mortality in adults with lower respiratory tract infections,” said Dr. Florin, a pediatric emergency physician at Cincinnati Children’s Hospital.

PCT is a precursor of calcitonin secreted by the thyroid, lung, and intestine in response to bacterial infections. It also has been shown to be associated with adverse outcomes and mortality in adults, with results generally suggesting that it is a stronger predictor of severity than CRP. “There is limited data on the association of CRP or PCT with severe outcomes in children with LRTIs,” Dr. Florin noted. “One recent U.S. study of 532 children did demonstrate an association of elevated PCT with ICU admission, chest drainage, and hospital length of stay in children with [community-acquired pneumonia] CAP.”

ProADM, meanwhile, is a vasodilatory peptide with antimicrobial and anti-inflammatory functions synthesized during severe infections. It has a half-life of several hours and has been shown to be associated with disease severity in adults with LRTI. Recent studies have shown that it has improved prognostication over WBC, CRP, and PCT. “In two small studies of children with pneumonia, proADM levels were significantly elevated in children with complicated pneumonia, compared to those with uncomplicated pneumonia,” Dr. Florin said. “Although all three of these markers demonstrate promise in predicting severe outcomes in adults with LRTIs, very few studies have examined their association with disease severity in pediatric disease. Therefore, the aim of the current analysis was to determine the association between blood biomarkers and disease severity in children who present to the ED with lower respiratory tract infections.”

In a study known as Catalyzing Ambulatory Research in Pneumonia Etiology and Diagnostic Innovations in Emergency Medicine (CARPE DIEM), he and his associates performed a prospective cohort analysis of children with suspected CAP who were admitted to the Cincinnati Children’s Hospital ED between July 2012 and December 2017. They limited the analysis to children aged 3 months to 18 years with signs and symptoms of an LRTI, and all eligible patients were required to have a chest radiograph ordered for suspicion of CAP. They excluded children hospitalized within 14 days prior to the index ED visit, immunodeficient or immunosuppressed children, those with a history of aspiration or aspiration pneumonia, and those who weighed less than 5 kg because of blood drawing maximums. Biomarkers were measured only in children with focal findings on chest x-ray in the ED. The primary outcome was disease severity: mild (defined as discharged home), moderate (defined as hospitalized, but not severe) and severe (defined as having an ICU length of stay of greater than 48 hours, chest drainage, severe sepsis, noninvasive positive pressure ventilation, intubation, vasoactive infusions, or death). Biomarkers were obtained at the time of presentation to the ED, prior to the occurrence of clinical outcomes.

Over a period of 4.5 years, the researchers enrolled 1,142 patients. Of these, 478 had focal findings on chest x-ray and blood obtained. The median age of these 478 children was 4.4 years, 52% were male, and 82% had all three biomarkers performed. Specifically, 456 had CRP and PCT performed, while 358 had proADM performed. “Not every child had every marker performed due to challenges in obtaining sufficient blood for all three biomarkers in some children,” Dr. Florin explained.


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