FGF10 Signaling differences between type I pleuropulmonary blastoma and congenital cystic adenomatoid malformation.

BACKGROUND: Type I pleuropulmonary blastoma (PPB) and congenital cystic adenomatoid malformation of the lung (CCAM) are cystic lung diseases of childhood. Their clinical and radiological presentations are often similar, and pathologic discrimination remains difficult in many cases. As a consequence, type I PPB and CCAM are frequently confused, leading to delayed adequate management for type I PPB. Recent studies have suggested a role for fibroblast growth factor (FGF) 10 signal pathway in CCAM pathogenesis. The objective of our study was to determine whether FGF10 signaling differs between CCAM and type I PPB. METHODS: Immunohistochemical studies were performed for expression of FGF10, its receptor FGFR2b, and its inhibitor sonic hedgehog (SHH) in focal type I PPB (n=6), CCAM type I (n=7), CCAM type II (n=7), and control lungs (n=5). RESULTS: FGF10, FGFR2b, and SHH expressions differed markedly between type I PPB and both types of CCAM. Type I and type II CCAM cystic walls expressed FGF10, FGFR2b, and SHH, whereas staining was absent or poor in type I PBB cystic walls. Expression of FGF10, FGFR2b, and SHH did not differ between CCAM cystic walls and control airway walls. CONCLUSIONS: These findings show that immunohistochemistry with FGF10, FGFR2b, or SHH could be useful in differentiating CCAM from type I PPB, when a child presents with a focal cystic lung lesion. The absence of strong expression of FGF10, FGFR2b, and/or SHH makes the diagnosis of CCAM very doubtful.

Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey.

Omalizumab has been shown to reduce exacerbation rates in moderate to severe allergic asthma. Our aim was to evaluate omalizumab efficacy and safety in a real-life setting in severe asthmatic children. 104 children (aged 6-18 years), followed up in paediatric pulmonary tertiary care centres, were included at the beginning of omalizumab treatment. Asthma control levels, exacerbations, inhaled corticosteroid dose, lung function and adverse events were evaluated over 1 year. Children were characterised by allergic sensitisation to three or more allergens (66%), high IgE levels (mean 1125 kU · L(-1)), high rate of exacerbations (4.4 per year) and healthcare use during the previous year, and high inhaled corticosteroid dose (mean 703 µg equivalent fluticasone per day). Asthma control levels defined as good, partial or poor, improved from 0%, 18% and 82% at entry to 53%, 30% and 17% at week 20, and to 67%, 25% and 8% at week 52, respectively (p<0.0001). Exacerbation and hospitalisation rates dropped by 72% and 88.5%, respectively. At 12 months, forced expiratory volume in 1 s improved by 4.9% (p=0.023), and inhaled corticosteroid dose decreased by 30% (p<0.001). Six patients stopped omalizumab for related significant adverse events. Omalizumab improved asthma control in children with severe allergic asthma and was generally well tolerated. The observed benefit was greater than that reported in clinical trials.

Antioxidant potential is correlated to ω6 / ω3 ratio and Brasfield score in cystic fibrosis children.

OBJECTIVES: Oxidative stress is associated with the condition of cystic fibrosis (CF), but no guidelines exist for its assessment or treatment. Our aim was to evaluate a test that measures the blood antioxidant capability in CF children. METHODS: This antioxidant capability was assessed by the Kit Radicaux Libres (KRL) test in 44 CF children (24 boys). We recorded also anthropometric measures, pulmonary function, CF severity scores, and plasma nutritional and inflammatory parameters (proteins, vitamins, erythrocyte fatty acids, and micronutrients). We performed univariate and multivariate analyses with linear regression models. RESULTS: The mean age at the first KRL assessment was 12.2 ± 3.8 years. Factors that correlated with decreased antioxidant capacity were mostly related to the severity of pulmonary disease [ forced expiratory volume at 1 second (FEV1), acute exacerbation, and congestion. In multivariate analysis, the correlation between Brasfield score and erythrocyte antioxidant potential remained significant (ß = - 0.611, p < 0.001). Among nutritional factors, the ω6/ω3 ratio was significantly correlated to erythrocyte antioxidant potential (ß = - 1.213, p = 0.01). CONCLUSION: The blood antioxidant capability, measured by the KRL test, appears to be an interesting biomarker to evaluate oxidative stress in CF. This study suggests that the ω6/ω3 ratio should be regarded as a nutritional marker in antioxidant management in CF children.

Assessment of Aspergillus sensitization or persistent carriage as a factor in lung function impairment in cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients presenting with persistent carriage of, or sensitization to, Aspergillus fumigatus are often treated with antifungal therapies because the presence of the fungus is commonly thought to impede lung function, even in the absence of allergic bronchopulmonary aspergillosis (ABPA). The aim of this study was to assess Aspergillus-related status modulating the forced expiratory volume in 1 s (FEV1) of CF patients. METHODS: From 1995 to 2007, 251 patients were evaluated. Demographic data, cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations, body mass index, and FEV(1) were recorded. The presence of A. fumigatus and Pseudomonas aeruginosa in sputum and the levels of A. fumigatus precipitin, total IgE (t-IgE), and specific anti-A. fumigatus IgE (Af-IgE) were determined. Patients were divided into 3 groups: (1) ABPA: A. fumigatus precipitin ≥3 lines, Af-IgE > 0.35 IU/ml, and t-IgE ≥500 IU/ml; (2) sensitization: Af-IgE > 0.35 IU/ml but t-IgE < 500 IU/ml; and (3) persistent carriage: Af-IgE ≤ 0.35 IU/ml with either an A. fumigatus persistent positive culture or an A. fumigatus precipitin ≥3 lines, provided this serological finding had been found associated with at least 1 A. fumigatus-positive culture. The remaining patients represented the control group. A multivariate analysis was carried out with FEV(1) as the outcome variable. RESULTS: ABPA, sensitization, and persistent carriage were significantly associated with a larger decline in FEV1 compared with the control group, with odds ratios of 15.9, 14.9, and 10.7, respectively. This association was independent of other associated factors (P. aeruginosa transient detection, age, being underweight, and low FEV1 at baseline). CONCLUSIONS: In addition to ABPA, sensitization and persistent carriage appear to have an impact on pulmonary function in CF patients.

Complex communicating bronchopulmonary foregut malformation with pancreatic heterotopy depicted with fetal magnetic resonance imaging: a case report.

Bronchopulmonary foregut malformation (BPFM) is a group of rare congenital anomalies that affect the respiratory and upper gastrointestinal tracts. We report here the first case of prenatal depiction of communicating BPFM, including extrapulmonary sequestration and foregut cyst, both with pancreatic differentiation. Magnetic resonance imaging on the fetus confirmed a polymalformative syndrome with right-lung and gastric cysts and allowed the detection of respiratory and alimentary tracts communication and aberrant feeding vessels. Diagnosis was confirmed after birth by multidetector computed tomography and postnatal pathologic findings. The patient, a boy, underwent surgery for respiratory distress at 4 weeks of life. This singular case confirms the benefits of early surgery for communicating BPFM.

The surgical management and outcome of congenital mediastinal malformations.

We reviewed our institutional experience with congenital mediastinal masses and compared the postnatal management and outcome of patients with or without prenatal diagnosis. Between January 1997 and August 2011, 24 patients underwent surgical procedures for congenital mediastinal mass. For eight patients, the mass was detected by prenatal ultrasonography at 27 weeks of gestation (range 22-35). Postnatal management consisted in open surgery for seven patients at a mean age of 9 months (range 1 day-20 months) and sclerotherapy for one lymphangioma at 5 months of life. Sixteen patients had postnatal diagnosis at 137 months (±194) of median age. Eight bronchogenic cysts, seven bronchopulmonary foregut malformations, five teratomas, three lymphangiomas and one haemangioma were operated on. The median age at resection was 28 months (1 day-15 years). There were four emergency procedures and no surgical mortality. The median follow-up was 45 months (3-144). The duration of mechanical ventilation and hospital stay was, respectively, 4.6 h and 7.5 days for antenatal patients and 24.3 h and 14.3 days for postnatal diagnosed patients. Prenatal diagnosis allows early management of congenital mediastinal malformations. Early resection can be performed prior to the occurrence of symptoms ∼1 year of life and is associated with an excellent outcome and less morbidity.