No abstract

Community-acquired pneumonia (CAP) is the leading cause of death in children < 5 years of age worldwide. It is also one of the most frequent infectious diseases in children, leading to large antibiotic use and hospitalization even in the industrialized countries. However, the optimal management of CAP in children is still not well defined. Currently, respiratory viruses are considered the most frequent etiologic agents, but detection of viruses in the upper respiratory tract does not guarantee causation of pneumonia, nor precludes the presence of a bacterial pathogen. In both the upper and lower respiratory tract, respiratory viruses and pathogenic bacteria interact. Emerging evidence indicates that dual viral–bacterial infections function synergistically in many cases and together likely enhance the severity of CAP. Therefore, new and advanced technologies capable of sensitively and specifically discriminating viral, bacterial, and viral–bacterial coinfections are needed. Instead of focusing on the pathogen, analysis of host immune transcriptome profiles from children with CAP can potentially offer diagnostic signatures, help to assess disease severity, and eventually, prognostic indicators. An optimized management strategy by using molecular pathogen testing and transcriptome profiling will facilitate prompt, more appropriate, and targeted therapies, which in turn will lead to improved clinical outcomes in children with CAP.

No abstract

Background: Pneumonia has a major impact on childhood health and health care costs. This study was designed to obtain contemporary information on the clinical characteristics and etiology of community-acquired pneumonia (CAP) in children from both inpatient and outpatient settings in the USA. Methods: We conducted a prospective, multicenter, observational study of CAP among previously healthy children 2 months to 18 years of age in 6 children's hospitals in Ohio from 2015 to 2018. For pathogen detection, nasopharyngeal swabs were collected from all subjects. Blood and pleural fluid cultures were available per standard of care. Results: We enrolled a convenience sample of 441 patients: 380 hospitalized and 61 outpatients. Tachypnea and radiologic findings of consolidation and pleural effusion were more frequent among inpatients than outpatients. A pathogen was detected in 64.6% of patients: viruses in 55.6%, atypical bacteria in 8.8% and pyogenic bacteria in 4.3%. Eighteen (4.1%) patients had both viruses and bacteria detected. Rhinovirus/enterovirus (RV; 18.6%) and respiratory syncytial virus (RSV; 16.8%) were the viruses most frequently detected, and Mycoplasma pneumoniae (8.2%) and Streptococcus pneumoniae (2.3%) were the most common bacteria. Except for S. pneumoniae, which was identified more frequently in inpatients, there were no significant differences between inpatients and outpatients in the proportions of children with specific pathogens detected. Conclusions: Rhinovirus/enterovirus and RSV among viruses and M. pneumoniae and S. pneumoniae among bacteria were the most common pathogens detected in children with CAP. Tachypnea and chest radiographs with consolidation and/or pleural effusion were associated with hospitalization.

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.