[Idiopathic pulmonary fibrosis: Desperately seeking a model]. / Fibrose pulmonaire idiopathique : recherche modèle désespérément.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease of which the origin and development mechanisms remain unknown. The few available pharmacological treatments can only slow the progression of the disease. The development of curative treatments is hampered by the absence of experimental models that can mimic the specific pathophysiological mechanisms of IPF. The aim of this mini-review is to provide an overview of the most commonly used experimental animal models in the study of IPF and to underline the urgent need to seek out new, more satisfactory models.

Gender influences physical activity changes during adolescence: The HELENA study.

BACKGROUND: We compared differences in physical activity (PA) between pre/mid-pubertal and post-pubertal participants according to gender. METHODS: The study included a total of 1842 healthy participants aged 12.5-17.4 years, who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. Participants wore a uniaxial accelerometer (ActiGraph© GT1M, Pensacola, FL, USA) attached to their lower back for seven consecutive days to measure PA. Pubertal status was assessed by physical examination and the population was classified as pre/mid-pubertal (Tanner stages 1-3) or post-pubertal (Tanner stages 4-5). PA was compared between these groups according to gender during the whole week, on school-free days and on school days, before and after school, and during lessons and recesses. RESULTS: When comparing the pre/mid-pubertal group with the post-pubertal group, girls' total PA did not differ between groups. However, a slight difference was observed in boys, among whom PA on school-free days showed a difference of 17.6% between the pre/mid-pubertal group and the post-pubertal group (679 kcounts vs 564 kcounts, respectively; P = 0.0007) and 20% (162 kcount vs 135 kcounts; P = 0.006) for school recess. There was no difference among girls. CONCLUSIONS: A reduced level of PA in the post-pubertal groups was only observed in boys during non-organized times such as on school-free days and during school recesses, with a moderate impact on total PA.

Inflammation in metabolically healthy and metabolically abnormal adolescents: The HELENA study.

BACKGROUND AND AIMS: Inflammation may influence the cardio-metabolic profile which relates with the risk of chronic diseases. This study aimed to assess the inflammatory status by metabolic health (MH)/body mass index (BMI) category and to assess how inflammatory markers can predict the cardio-metabolic profile in European adolescents, considering BMI. METHODS AND RESULTS: A total of 659 adolescents (295 boys) from a cross-sectional European study were included. Adolescents were classified by metabolic health based on age- and sex-specific cut-off points for glucose, blood pressure, triglycerides, high density cholesterol and BMI. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin (IL-6), complement factors (C3, C4) and cell adhesion molecules were assessed. RESULTS: Metabolically abnormal (MA) adolescents had higher values of C3 (p < 0.001) and C4 (p = 0.032) compared to those metabolically healthy (MHy). C3 concentrations significantly increased with the deterioration of the metabolic health and BMI (p < 0.001). Adolescents with higher values of CRP had higher probability of being in the overweight/obese-MH group than those allocated in other categories. Finally, high C3 and C4 concentrations increased the probability of having an unfavorable metabolic/BMI status. CONCLUSIONS: Metabolic/BMI status and inflammatory biomarkers are associated, being the CRP, C3 and C4 the most related inflammatory markers with this condition. C3 and C4 were associated with the cardio-metabolic health consistently.

Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

[Hepatitis B and pregnancy. Part 1. Thirteen practical issues in antenatal period]. / Hépatite B et grossesse. Partie 1. Treize questions pratiques en période anténatale.

In France, the prevalence of chronic hepatitis B is about 1% in pregnant women (usually asymptomatic carriers of HBsAg). The risk of maternal-fetal transmission of hepatitis B is particularly high when viral load measured by PCR is higher in mothers (above 7 log) or HBeAg is present. In case of maternal-fetal transmission of hepatitis B, the risk to the newborn of developing subsequent chronic hepatitis B is very high (90%), with long-term complications such as cirrhosis and hepatocellular carcinoma. The prevention of maternal-fetal transmission is based on systematic testing for hepatitis B during pregnancy, followed by serovaccination of the newborn at birth. If necessary, amniocentesis can be realised but will avoid the realization of a transplacental gesture. In case of high viral load, the establishment of a maternal antiviral treatment with lamivudine or tenofovir from 28SA can further reduce the risk of transmission. Given the low resistance it induces, tenofovir should be used preferentially.

Esophageal tissue engineering: Current status and perspectives.

Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials.

Raised immunoglobulin A and circulating T follicular helper cells are linked to the development of food allergy in paediatric liver transplant patients.

BACKGROUND: Post-transplant food allergy (LTFA) is increasingly observed after paediatric liver transplantation (LT). Although the immunopathology of LTFA remains unclear, immunoglobulin (Ig) E seems to be implicated. OBJECTIVE: To study humoral and cellular immunity in paediatric LT patients in search for factors associated with LTFA, and compare with healthy controls (HC) and non-transplant food-allergic children (FA). METHODS: We studied serum Ig levels in 29 LTFA, 43 non-food-allergic LT patients (LTnoFA), 21 FA patients and 36 HC. Serum-specific IgA and IgE against common food allergens in LTFA, IgA1 , IgA2 and joining-chain-containing polymeric IgA (pIgA) were measured. Peripheral blood mononuclear cells were analysed by flow cytometry for B and T cell populations of interest. RESULTS: Serum IgA and specific IgA were higher in LTFA compared to LTnoFA. LTFA patients had the highest proportion of circulating T follicular helper cells (cTfh). The percentage of cTfh correlated positively with serum IgA. Unique in LTFA was also the significant increase in serum markers of mucosal IgA and the decrease in the Th17 subset of CXCR5(-) CD4(+) cells compared to HC. Both LT patients exhibited a rise in IgA(+) memory B cells and plasmablasts compared to HC and FA. CONCLUSIONS: LT has an impact on humoral immunity, remarkably in those patients developing FA. The increase in serum markers of mucosal IgA, food allergen-specific IgA and cTfh cells observed in LTFA, point towards a disturbance in intestinal immune homoeostasis in this patient group.

Congenital esophageal stenosis associated with esophageal atresia.

Congenital esophageal stenosis (CES) is a rare clinical condition but is frequently associated with esophageal atresia (EA). The aim of this study is to report the diagnosis, management, and outcome of CES associated with EA. Medical charts of CES-EA patients from Lille University Hospital, Sainte-Justine Hospital, and Montreal Children's Hospital were retrospectively reviewed. Seventeen patients (13 boys) were included. The incidence of CES in patients with EA was 3.6%. Fifteen patients had a type C EA, one had a type A EA, and one had an isolated tracheoesophageal fistula. Seven patients had associated additional malformations. The mean age at diagnosis was 11.6 months. All but two patients had non-specific symptoms such as regurgitations or dysphagia. One CES was diagnosed at the time of surgical repair of EA. In 12 patients, CES was suspected based on abnormal barium swallow. In the remaining four, the diagnostic was confirmed by esophagoscopy. Eleven patients were treated by dilation only (1-3 dilations/patient). Six patients underwent surgery (resection and anastomosis) because of failure of attempted dilations (1-7 dilations/patient). Esophageal perforation was encountered in three patients (18%). Three patients had histologically proven tracheobronchial remnants. CES associated with EA is frequent. A high index of suspicion for CES must remain in the presence of EA. Dilatation may be effective to treat some of them, but perforation is frequent. Surgery may be required, especially in CES secondary to ectopic tracheobronchial remnants.

Management guidelines of eosinophilic esophagitis in childhood.

OBJECTIVES: Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. With few exceptions, 15 eosinophils per high-power field (peak value) in ≥1 biopsy specimens are considered a minimum threshold for a diagnosis of EoE. The disease is restricted to the esophagus, and other causes of esophageal eosinophilia should be excluded, specifically proton pump inhibitor-responsive esophageal eosinophilia. This position paper aims at providing practical guidelines for the management of children and adolescents with EoE. METHODS: Relevant literature from searches of PubMed, CINAHL, and recent guidelines was reviewed. In the absence of an evidence base, recommendations reflect the expert opinion of the authors. Final consensus was obtained during 3 face-to-face meetings of the Gastroenterology Committee and 1 teleconference. RESULTS: The cornerstone of treatment is an elimination diet (targeted or empiric elimination diet, amino acid-based formula) and/or swallowed, topical corticosteroids. Systemic corticosteroids are reserved for severe symptoms requiring rapid relief or where other treatments have failed. Esophageal dilatation is an option in children with EoE who have esophageal stenosis unresponsive to drug therapy. Maintenance treatment may be required in case of frequent relapse, although an optimal regimen still needs to be determined. CONCLUSIONS: EoE is a chronic, relapsing inflammatory disease with largely unquantified long-term consequences. Investigations and treatment are tailored to the individual and must not create more morbidity for the patient and family than the disease itself. Better maintenance treatment as well as biomarkers for assessing treatment response and predicting long-term complications is urgently needed.

[Esophageal atresia: prevalence, prenatal diagnosis and prognosis]. / Atrésie de l'œsophage : prévalence, diagnostic anténatal et pronostic.

Esophageal atresia (EA) is a rare congenital malformation (1 in 2,500 to 3,500 births). Prenatal diagnosis (PN) is particularly interesting allowing search for associated malformations related to worse prognosis forms (reference ultrasound, MRI and amniocentesis) and planning the birth in an adapted medico-surgical center. Diagnosis of EA is usually suspected because of indirect and non-specific signs: association of polyhydramnios and absent or small stomach bubble. The visualization in ultrasound or MRI of cervical or thoracic fluid image corresponding to the expansion of the bottom of upper esophageal ("pouch sign") increases the specificity of diagnosis. However, prenatal diagnosis remains difficult and less than 50 % of EA are diagnosed prenatally. Biochemical analysis could improve these results. If EA is confirmed at birth, surgical management consists in a primary end-to-end anastomosis in first days of life, or in two-steps surgery if the defect is too large. Although current prognosis of EA is good, frequency of surgical complications and esophageal lesions secondary to gastroesophageal reflux justify a systematic and multidisciplinary extended follow-up.

Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet.

Intake and dietary sources of haem and non-haem iron among European adolescents and their association with iron status and different lifestyle and socio-economic factors.

BACKGROUND/OBJECTIVES: Adolescents are at risk of iron deficiency because of their high iron requirements. The aims of this study were: (1) to assess iron intake, its determinants and its most important food sources and; (2) to evaluate the relation of iron intake and status in European adolescents. SUBJECTS/METHODS: Two non-consecutive 24-h recalls were completed by a computerised tool. The socio-demographic and socio-economic data were collected by a self-reported questionnaire. Weight and height were measured. A distinction was made between haem and non-haem iron. RESULTS: The total iron intake was significantly higher among boys (13.8 mg/day; n=1077) than girls (11.0 mg/day; n=1253). About 97.3% of the boys and 87.8% of the girls met the estimated average requirement, and 72.4% of the boys and 13.7% of the girls met the recommendation for bio-available iron intake. The ratio of haem/non-haem iron intake was lower for girls than boys. Meat (19.2; 76%) and bread and rolls (12.6;3.9%) contributed most to total and haem iron intake. Bread and rolls (13.8%) and meat (10.8%) contributed most to non-haem iron intake. Age, sex and body mass index were associated with iron intake. Only red blood cell concentration was significantly negatively associated with total, haem and non-haem iron intake. CONCLUSION: Girls had lower iron intakes and ratio of haem/non-haem iron intake than boys. The main total iron and haem iron source was meat, while the main non-haem iron source was bread and rolls. Adolescent girls may be a group at risk for iron deficiency. Consequently, special attention and strategies are needed in order to improve iron intakes during adolescence.

Esophageal atresia: metaplasia, Barrett.

Barrett's esophagus is characterized by the replacement of squamous epithelium by columnar epithelium that is intestinal metaplasia-positive or -negative in the distal esophagus. Gastroesophageal reflux disease, which is frequent and prolonged in esophageal atresia, probably plays a major role in the development of Barrett's esophagus through repeated mucosal damage. Long-term acid exposure contributes to carcinogenesis in Barrett's esophagus of intestinal type, but its effect on gastric metaplasia is less well defined. Recent studies have suggest that metaplasia arises in about 15% of patients with esophageal atresia, with a lag time to developing metaplasia from initial surgical correction of about 10 years. Preliminary data from an ongoing multicenter study including 88 patients with esophageal atresia aged 15-19 years showed gastric metaplasia in 42% of patients (29 fundic and 7 cardial metaplasia), while one patient presented intestinal metaplasia. Esophageal mucosal abnormalities can be observed in esophageal atresia patients at endoscopy despite the absence of symptoms. Whether prolonged, aggressive, acid suppression is beneficial in these situations remains to be determined. Barrett's metaplasia can be removed by endoscopic mucosal resection or destroyed with endoscopic ablative techniques, such as photodynamic therapy, radiofrequency ablation, and cryotherapy. The risk of developing esophageal carcinoma is still a controversial issue as only a few clinical cases have been reported in young adults with esophageal atresia. As late complications of esophageal atresia, particularly esophagitis and Barrett's esophagus, are increasingly being recognized, long-time systematic follow up of the esophageal mucosa including multistage biopsies is therefore required even in asymptomatic patients.

Physical activity attenuates the negative effect of low birth weight on leptin levels in European adolescents; the HELENA study.

We examined whether physical activity (PA) influences the association between birth weight and serum leptin in adolescents. The study comprised a total of 538 adolescents (315 girls), aged 12.5-17.49 years, born at term (≥ 37 weeks of gestation). We measured serum leptin levels and time engaged in moderate-vigorous PA (MVPA) by accelerometry. There was an interaction effect between birth weight and meeting the PA recommendations (60 min/day MVPA) on leptin levels in girls (P = 0.023) but not in boys (P = 0.809). Birth weight was negatively associated with leptin levels in girls not meeting the PA recommendations (i.e. more than 60 min/day of MVPA) (ß = -0.096, P = 0.009), whereas no significant association was observed in those meeting the PA recommendations (ß = -0.061, P = 0.433). In conclusion, meeting the PA recommendations may attenuate the negative effect of low birth weight on serum leptin levels in European female adolescents.

[Esophageal atresia]. / Devenir à moyen et long terme des enfants atteints d'atrésie de l'œsophage.

Most of the children operated for esophageal atresia will survive the neonatal period. However, medium-term and late complications are frequent in this population. Gastroesophageal reflux disease is observed in 26 to 75% of the cases and can be responsible for peptic esophagitis, anastomotic stenosis, and Barrett esophagus, which is a risk factor for adenocarcinoma of the esophagus. Dysphagia is frequently observed, sometimes several years after the surgery, affecting up to 45% of children at the age of 5 years. Growth retardation is present in nearly one-third of children at the age of 5 years. Ear, nose, and throat and respiratory complications are also very frequent but tend to improve with time. Tracheomalacia is found in 75% of these children at birth, sometimes responsible for severe complications (malaise, bradycardia). Respiratory symptoms are dominated by chronic cough, wheezing, and infections reported in 29% of the children by the age of 5 years. Restrictive, obstructive syndromes and bronchial hyperactivity can be observed, but usually remain moderate. All these complications can influence the patient's quality of life, which is moderately impaired compared to healthy controls. The high frequency of late sequelae in esophageal atresia justifies regular and multidisciplinary follow-up through adulthood.

Evaluation of iron status in European adolescents through biochemical iron indicators: the HELENA Study.

BACKGROUND/OBJECTIVES: To assess the iron status among European adolescents through selected biochemical parameters in a cross-sectional study performed in 10 European cities. SUBJECTS/METHODS: Iron status was defined utilising biochemical indicators. Iron depletion was defined as low serum ferritin (SF<15 µg/l). Iron deficiency (ID) was defined as high-soluble transferrin receptor (sTfR>8.5 mg/l) plus iron depletion. Iron deficiency anaemia (IDA) was defined as ID with haemoglobin (Hb) below the WHO cutoff for age and sex: 12.0 g/dl for girls and for boys aged 12.5-14.99 years and 13.0 g/dl for boys aged ≥15 years. Enzyme linked immunosorbent assay was used as analytical method for SF, sTfR and C-reactive protein (CRP). Subjects with indication of inflammation (CRP >5 mg/l) were excluded from the analyses. A total of 940 adolescents aged 12.5-17.49 years (438 boys and 502 girls) were involved. RESULTS: The percentage of iron depletion was 17.6%, significantly higher in girls (21.0%) compared with boys (13.8%). The overall percentage of ID and IDA was 4.7 and 1.3%, respectively, with no significant differences between boys and girls. A correlation was observed between log (SF) and Hb (r = 0.36, P < 0.01), and between log (sTfR) and mean corpuscular haemoglobin (r = -0.30, P < 0.01). Iron body stores were estimated on the basis of log (sTfR/SF). A higher percentage of negative values of body iron was recorded in girls (16.5%) with respect to boys (8.3%), and body iron values tended to increase with age in boys, whereas the values remained stable in girls. CONCLUSIONS: To ensure adequate iron stores, specific attention should be given to girls at European level to ensure that their dietary intake of iron is adequate.

Treatments for pediatric achalasia: Heller myotomy or pneumatic dilatation?

AIM: The treatment of achalasia consists of reducing distal esophageal obstruction by either Heller myotomy surgery or endoscopic pneumatic dilatation. The aim of the present study was to evaluate the short- and middle-term results of these procedures in children. METHODOLOGY: For technical reasons, children under six years old (n=8) were treated by surgery only, whereas patients over six years old (n=14) were treated by either Heller myotomy or pneumatic dilatation. RESULTS: Of the children aged under six years, 75% were symptom-free at six months and 83% at 24 months of follow-up. Of the patients aged over six years, complete remission was achieved by Heller myotomy in 44.5% vs. 55.5% by pneumatic dilatation after six months, and in 40% vs. 65%, respectively, after 24 months. Both pneumatic dilatation and Heller myotomy showed significant rates of failure. CONCLUSION: These results suggest that pneumatic dilatation may be considered a primary treatment in children over six years old. Also, where necessary, Heller myotomy and pneumatic dilatation may be used as complementary treatments.

Is liver transaminases assessment an appropriate tool for the screening of non-alcoholic fatty liver disease in at risk obese children and adolescents?

Pediatric obesity has increased dramatically all over the world and nonalcoholic fatty liver disease (NAFLD) is one of the most frequent complications associated with excess adiposity. NAFLD causes serum transaminase elevation and liver disease, which could end up in fibrosis, cirrhosis and eventually hepatocellular carcinoma. NAFLD seems to be associated with the metabolic complications of obesity, mainly insulin resistance. The aim of the present article is to review the role of serum liver enzyme assessment as a suitable non invasive predictor of NAFLD in children. Although serum liver enzyme elevation does not accurately measure liver damage, it may be a valuable and non invasive test to screen NAFLD in children and adolescents and a marker to control NAFLD evolution. To detect NAFLD in obese children and adolescents, transaminases serum concentrations should be routinely determined in these patients. In this sense, it seems necessary to obtain transaminase reference standards for children and adolescents.