Abstract
Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP.Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization.Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]).Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.
Highlights
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children
One hundred and eighty-eight previously healthy children hospitalized with CAP were enrolled between February 1, 2011, and May 15, 2012
Of the remaining 183 patients, 152 (83%) whole blood samples were available and successfully underwent transcriptional profile analysis. These patients were matched with 39 healthy controls for age, sex and race, that were enrolled as part of the study
Summary
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. The clinical features of CAP are variable and may overlap with other respiratory diseases, such as asthma or bronchiolitis (Margolis and Gadomski, 1998; Lynch et al, 2004) This makes appropriate triage of children with CAP problematic in many cases, and there are currently no reliable tools to objectively classify patients according to disease severity, or to predict which patients will develop complications or need a higher level of care. Guidelines for the diagnosis and management of CAP in children propose a number of areas for future research, including definition of risk factors for respiratory failure and hospitalization, and development of new diagnostic tests, to determine the etiology of CAP but to assess disease severity and response to therapy (Bradley et al, 2011)
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