Primary defects in lung branching morphogenesis, resulting in neonatal lethal pulmonary hypoplasias, are incompletely understood. To elucidate the pathogenetics of human lung development, we studied a unique collection of samples obtained from deceased individuals with clinically and histopathologically diagnosed interstitial neonatal lung disorders: acinar dysplasia (n ¼ 14), congenital alveolar dysplasia (n ¼ 2), and other lethal lung hypoplasias (n ¼ 10). We identified rare heterozygous copy-number variant deletions or single-nucleotide variants (SNVs) involving TBX4 (n ¼ 8 and n ¼ 2, respectively) or FGF10 (n ¼ 2 and n ¼ 2, respectively) in 16/26 (61%) individuals. In addition to TBX4, the overlapping $2 Mb recurrent and nonrecurrent deletions at 17q23.1q23.2 identified in seven individuals with lung hypoplasia also remove a lung-specific enhancer region. Individuals with coding variants involving either TBX4 or FGF10 also harbored at least one non-coding SNV in the predicted lung-specific enhancer region, which was absent in 13 control individuals with the overlapping deletions but without any structural lung anomalies. The occurrence of rare coding variants involving TBX4 or FGF10 with the putative hypomorphic non-coding SNVs implies a complex compound inheritance of these pulmonary hypoplasias. Moreover, they support the importance of TBX4-FGF10-FGFR2 epithelial-mesenchymal signaling in human lung organogenesis and help to explain the histopathological continuum observed in these rare lethal developmental disorders of the lung.

Studies focusing on serum sodium disorders in children with community-acquired-pneumonia (CAP) are nearly entirely lacking, though clinical experience suggests that at least hyponatremia (HN) might be rather common. We evaluated the incidence of hypo- and hypernatremia, in relation to other clinical, laboratory and etiological findings, in pediatric CAP. Serum sodium concentration was measured in 108 ambulatory and hospitalized children with radiologically confirmed CAP of variable severity. The etiology of CAP was revealed by serology in 97 patients. HN (serum sodium < 135 mmol/l) was present in 49 (45.4%) children, and it was mild (> 130 mmol/l) in 92% of the cases. On admission, hyponatremic patients had higher body temperature (38.96 degrees C vs 38.45 degrees C, P = 0.008), white blood cell count (21,074/microl vs 16,592/microl, P = 0.008), neutrophil percentage (78.93% vs 69.33%, P = 0.0001), serum C-reactive protein (168.27 mg/l vs 104.75 mg/l, P = 0.014), and serum procalcitonin (22.35 ng/ml vs 6.87 ng/ml, P = 0.0001), and lower calculated osmolality (263.39 mosmol/l vs 272.84 mosmol/l, P = 0.0001) than normonatremic ones. No association was found with plasma glucose, type of radiological consolidation or etiology of CAP. HN is common but usually mild in children with CAP. HN seems to be associated with the severity of CAP, assessed by fever, need of hospitalization and serum non-specific inflammatory markers.

The present study is an assessment of normal values of nasal nitric oxide (nNO) in healthy children.Healthy children aged between 6-17 yrs were recruited from three schools in Rotterdam (The Netherlands). Breath was held for 10 s, while air was extracted from one nostril at 700 mL?min -1 . The mean nNO value at the response plateau after 7-10 s was recorded and the average of three measurements was used.In total, 340 children participated; the male:female ratio was 156:184. Three reliable measurements were available in 85% of the children. The nNO concentrations were distributed normally (mean 449 ppb, SD 115). They were not associated with sex, passive smoking or body mass index. In children aged ,12 yrs nNO correlated positively with age, history of adenoidectomy and ambient NO. In children aged o12 yrs ambient NO was the only significant modifier. Prediction rules for nNO values in children were formulated.In conclusion, the current study presents normal values for nasal nitric oxide in children, which can be used to assess the value of nasal nitric oxide in respiratory illnesses.

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No clinical or radiological characteristic was helpful in the separation between viral, pneumococcal and atypical bacterial aetiology of community-acquired pneumonia (CAP) in children.