The aetiology of community-acquired pneumonia (CAP) is not easy to establish. As lung ultrasound (LUS) has already proved to be an excellent diagnostic tool for CAP, we analysed its usefulness for discriminating between the aetiologically different types of CAP in children. We included 147 children hospitalized because of CAP. LUS was performed in all patients at admission, and follow-up LUS was performed in most patients. LUS-detected consolidations in viral CAP were significantly smaller, with a median diameter of 15 mm, compared to 20 mm in atypical bacterial CAP (p = 0.05) and 30 mm in bacterial CAP (p < 0.001). Multiple consolidations were detected in 65.4% of patients with viral CAP and in 17.3% of patients with bacterial CAP (p < 0.001). Bilateral consolidations were also more common in viral CAP than in bacterial CAP (51.9% vs. 8.0%, p < 0.001). At follow-up, a regression of consolidations was observed in 96.6% of patients with bacterial CAP and in 33.3% of patients with viral CAP (p < 0.001). We found LUS to be especially suitable for differentiating bacterial CAP from CAP due to other aetiologies. However, LUS must be interpreted in light of clinical and laboratory findings.

Peripheral lymphadenopathy affects most children at least once in a lifetime and represents a major reason for concern. Therefore, we aimed to identify the most common causes of peripheral lymphadenopathy in hospitalized children and to determine the clinical, laboratory and ultrasound characteristics that enable fast, easy and accurate etiological diagnosis. We performed a cross-sectional study including 139 children who were hospitalized because of peripheral lymphadenopathy. Ultrasound of lymph nodes was performed in 113 (81.3%) patients. Lymphadenopathy was generalized in nine (6.5%) patients. Malignant etiology was established in only three (2.2%) patients. Bacterial lymphadenitis, infectious mononucleosis (IM) and cat scratch disease (CSD) were diagnosed in 66 (47.5%), 31 (22.3%) and 29 (20.9%) patients, respectively. Bacterial lymphadenitis was significantly associated with neutrophilia (p < 0.01), and increased C-reactive protein levels (p < 0.01). IM was associated with pharyngitis (p < 0.01), leukocytosis without neutrophilia (p = 0.03) and increased blood liver enzyme levels (p < 0.01). CSD was associated with recent contact with a cat (p < 0.01), absence of a fever (p < 0.01) and normal white blood cell count (p < 0.01). Thorough history and clinical examination in combination with a few basic laboratory tests enable fast and accurate differentiation between the most common etiologies of lymphadenopathy in children to avoid unnecessary procedures and hospitalizations.

Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10⁻⁸ were used to control for false-positive results. The CpG cg12835256 (PLA2G12A) was genome-wide associated with FeNO in blood samples (coefficient= −0.015, p = 2.53 × 10⁻⁹) and nominally associated in nasal samples (coefficient = −0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was performed in 166 asthma patients from the SLOVENIA study. Patients with an improvement in lung function ≥8% were considered as ICS responders. Suggestively associated variants (p-value ≤ 5 × 10⁻⁶) were evaluated in an independent study (n = 175). Validation of the association with asthma exacerbations despite ICS use was attempted in European (n = 2681) and admixed (n = 1347) populations. Variants previously associated with ICS response were also assessed for replication. As a result, the SNP rs1166980 from the ROBO2 gene was suggestively associated with the change in lung function (OR for G allele: 7.01, 95% CI: 3.29–14.93, p = 4.61 × 10⁻⁷), although this was not validated in CAMP. ROBO2 showed gene-level evidence of replication with asthma exacerbations despite ICS use in Europeans (minimum p-value = 1.44 × 10⁻⁵), but not in admixed individuals. The association of PDE10A-T with ICS response described by a previous study was validated. This study suggests that ROBO2 could be a potential novel locus for ICS response in Europeans.