Complementary feeding practices are related to the risk of food allergy in the ELFE cohort.

BACKGROUND: Conflicting results have been obtained when analyzing the relationship between complementary feeding (CF) practices and allergic diseases in childhood. This study aims to further explore the association between allergic diseases in early childhood (10.1016/j.jaci.2012.02.036) and the age at CF introduction (10.1016/S0140-6736(15)00149-X), food diversity in the first year of life (10.1016/j.ijporl.2019.109759) and the delayed introduction of major allergenic foods. METHODS: This analysis focused on 6662 children from the French nationwide ELFE cohort. Data on feeding practices were collected monthly from 3 to 10 months old. Their age at CF introduction was calculated alongside a diversity score, and the number of major allergenic foods (out of eggs, fish, wheat, and dairy products) not introduced at 8 and 10 months. Their associations with parent-reported allergy-related health events between 1 and 5.5 years were assessed using logistic regressions adjusted for confounding factors. A sensitivity analysis excluding early allergic cases (occurring between 2 months and 1 or 2 years) was conducted. RESULTS: Late CF (>6 months) was related to a higher risk of food allergy (OR [95% CI] = 1.35 [1.02; 1.78]), a low diversity score at 8 months to a higher risk of asthma (OR [95% CI] = 1.22 [1.01; 1.48]), and two allergenic foods or more not being introduced at 10 months to a higher risk of rhinoconjunctivitis (OR [95% CI] = 1.20 [1.00; 1.44]) and food allergy (OR [95% CI] = 2.46 [1.77; 3.42]). Only this last association remained significant after the exclusion of early cases. CONCLUSION: The delayed introduction of major allergenic foods is related to a higher risk of food allergy, which supports the updated guidelines for allergy prevention.

Skin prick tests and specific IgE in 10-year-old children: Agreement and association with allergic diseases.

BACKGROUND: Accurate assessment of atopic sensitization is pivotal to clinical practice and research. Skin prick test (SPT) and specific IgE (sIgE) are often used interchangeably. Some studies have suggested a disagreement between these two methods, and little is known about their association with allergic diseases. The aims of our study were to evaluate agreement between SPT and sIgE, and to compare their association with allergic diseases in 10-year-old children. METHODS: Skin prick test, sIgE measurements, and assessment of allergic diseases were performed in children aged 10 years in the Protection against Allergy: STUdy in Rural Environments (PASTURE) cohort. The agreement between SPT and sIgE was assessed by Cohen's kappa coefficient with different cutoff values. RESULTS: Skin prick tests and sIgE were performed in 529 children. The highest agreement (κ=.44) was found with a cutoff value of 3 and 5 mm for SPT, and 3.5 IU/mL for sIgE. The area under the curve (AUC) obtained with SPT was not significantly different from that obtained with sIgE. For asthma and hay fever, SPT (cutoff value at 3 mm) had a significantly higher specificity (P<.0001) than sIgE (cutoff value at 0.35 IU/mL) and the specificity was not different between both tests (P=.1088). CONCLUSION: Skin prick test and sIgE display moderate agreement, but have a similar AUC for allergic diseases. At the cutoff value of 3 mm for SPT and 0.35 IU/mL for sIgE, SPT has a higher specificity for asthma and hay fever than sIgE without difference for sensitivity.

A switch in regulatory T cells through farm exposure during immune maturation in childhood.

BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the 'asthma-protective' farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4+ CD25high FOXP3upper20% ). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. RESULTS: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96-132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-γ (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). CONCLUSIONS: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical 'time window' for Treg-mediated asthma protection via environmental exposure before age 6 years.

High level of fecal calprotectin at age 2 months as a marker of intestinal inflammation predicts atopic dermatitis and asthma by age 6.

BACKGROUND: Gut microbiota and intestinal inflammation regulate the development of immune-mediated diseases, such as allergies. Fecal calprotectin is a biomarker of intestinal inflammation. OBJECTIVE: We evaluated the association of early-age fecal calprotectin levels to the later development of allergic diseases in children from farming and non-farming environments and further studied the effect of gut microbiota on the fecal calprotectin levels. METHODS: Fecal calprotectin was measured from 758 infants participating in the PASTURE study at the age of 2 months using the ELISA method. Serum-specific IgE levels were measured at 6 years of age. Data of environmental factors, doctor-diagnosed atopic dermatitis (AD) and asthma were collected by questionnaire. Multivariate logistic regression models were used for analysis. The composition of fecal microbiota was analysed in a subgroup of 120 infants with 16S rRNA pyrosequencing. The effect of Escherichia coli lipopolysaccharide (LPS) on in vitro monocyte IL-10 secretion was studied by flow cytometry. RESULTS: The infants with high fecal calprotectin levels at 2 months, that is above the 90th percentile, had an increased risk of developing AD and asthma/asthmatic bronchitis by the age of 6 years (aOR 2.02 (1.06-3.85) and 2.41 (1.25-4.64), respectively). High fecal calprotectin levels correlated negatively with fecal Escherichia. LPS from E. coli stimulated production of IL-10 in monocytes. CONCLUSION AND CLINICAL RELEVANCE: High degree intestinal inflammation at 2 months of age, detected as high fecal calprotectin, predicted asthma and AD by the age of 6 years and was linked to low abundance of fecal Escherichia. Impaired IL-10 activation due to the lack of colonization with E. coli could explain the intestinal inflammation associated high fecal calprotectin and later risk of asthma and AD. Our results have implications for the design of probiotic treatments and suggest that early intestinal colonization has long-term health effects.

Soluble immunoglobulin A in breast milk is inversely associated with atopic dermatitis at early age: the PASTURE cohort study.

BACKGROUND: The role of breastfeeding for the development of atopic diseases in childhood is contradictory. This might be due to differences in the composition of breast milk and levels of antimicrobial and anti-inflammatory components. OBJECTIVE: The objective of this study was to examine whether levels of total immunoglobulin A (IgA) or transforming growth factor-ß1 (TGF-ß1) in breast milk were associated with the risk of developing atopic dermatitis (AD), atopic sensitization or asthma at early age taking breastfeeding duration into account. METHODS: The birth cohort study PASTURE conducted in Finland, France, Germany and Switzerland provided 610 breast milk samples collected 2 months after delivery in which soluble IgA (sIgA) and TGF-ß1 levels were measured by ELISA. Duration of breastfeeding was assessed using weekly food frequency diaries from month 3 to month 12. Data on environmental factors, AD and asthma were collected by questionnaires from pregnancy up to age 6. Atopic status was defined by specific IgE levels in blood collected at the ages of 4 and 6 years. Multivariate logistic regression models were used for statistical analysis. RESULTS: Soluble IgA and TGF-ß1 levels in breast milk differed between countries, and sIgA levels were associated with environmental factors related to microbial load, for example, contact to farm animals or cats during pregnancy, but not with raw milk consumption. sIgA levels were inversely associated with AD up to the of age 2 years (P-value for adjusted linear trend: 0.005), independent of breastfeeding duration. The dose of sIgA ingested in the first year of life was associated with reduced risk of AD up to the age of 2 (aOR, 95% CI: 0.74; 0.55-0.99) and 4 years (0.73; 0.55-0.96). No clear associations between sIgA and atopy or asthma up to age 6 were observed. TGF-ß1 showed no consistent association with any investigated health outcome. CONCLUSION AND CLINICAL RELEVANCE: IgA in breast milk might protect against the development of AD.

Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study.

BACKGROUND: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. OBJECTIVE: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. METHODS: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). RESULTS: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). CONCLUSIONS: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.

Stiffness tomography exploration of living and fixed macrophages.

Stiffness tomography is a new atomic force microscopy imaging technique that allows highlighting structures located underneath the surface of the sample. In this imaging mode, such structures are identified by investigating their mechanical properties. We present here, for the first time, a description of the use of this technique to acquire detailed stiffness maps of fixed and living macrophages. Indeed, the mechanical properties of several macrophages were studied through stiffness tomography imaging, allowing some insight of the structures lying below the cell's surface. Through these investigations, we were able to evidence the presence and properties of stiff column-like features located underneath the cell membrane. To our knowledge, this is the first evidence of the presence, underneath the cell membrane, of such stiff features, which are in dimension and form compatible with phagosomes. Moreover, by exposing the cells to cytochalasin, we were able to study the induced modifications, obtaining an indication of the location and mechanical properties of the actin cytoskeleton.

Asthma at 8 years of age in children born by caesarean section.

BACKGROUND: Caesarean section might be a risk factor for asthma because of delayed microbial colonisation, but the association remains controversial. A study was undertaken to investigate prospectively whether children born by caesarean section are more at risk of having asthma in childhood and sensitisation at the age of 8 years, taking into account the allergic status of the parents. METHODS: 2917 children who participated in a birth cohort study were followed for 8 years. The definition of asthma included wheeze, dyspnoea and prescription of inhaled steroids. In a subgroup (n = 1454), serum IgE antibodies for inhalant and food allergens were measured at 8 years. RESULTS: In the total study population, 12.4% (n = 362) of the children had asthma at the age of 8 years. Caesarean section, with a total prevalence of 8.5%, was associated with an increased risk of asthma (OR 1.79; 95% CI 1.27 to 2.51). This association was stronger among predisposed children (with two allergic parents: OR 2.91; 95% CI 1.20 to 7.05; with only one: OR 1.86; 95% CI 1.12 to 3.09) than in children with non-allergic parents (OR 1.36; 95% CI 0.77 to 2.42). The association between caesarean section and sensitisation at the age of 8 years was significant only in children of non-allergic parents (OR 2.14; 95% CI 1.16 to 3.98). CONCLUSIONS: Children born by caesarean section have a higher risk of asthma than those born by vaginal delivery, particularly children of allergic parents. Caesarean section increases the risk for sensitisation to common allergens in children with non-allergic parents only.

Polyphosphoinositide hydrolysis by phospholipase C is accelerated by thyrotropin releasing hormone (TRH) in clonal rat pituitary cells (GH3 cells).

Thyrotropin releasing hormone (TRH) accelerates the turnover of phosphatidylinositol in GH3 cells ('phospholipid response'). From the analysis of inositol phosphates in the presence of Li+ which inhibits their dephosphorylation, it can be concluded that the hydrolysis of phosphatidylinositol 4,5-biphosphate, and possibly of phosphatidylinositol 4-phosphate by phospholipase C is markedly accelerated by TRH. It appears that this reaction initiates the acceleration of phosphatidylinositol turnover. The specificity of hormonally regulated phospholipase C reaction for polyphosphoinositides has important implications for the potential role of the phospholipid response as a mechanism of membrane signal transduction.

Acyclovir-induced renal failure: course and risk factors.

Of 19 children treated with high-dose intravenous acyclovir, 7, all of whom had encephalitis, also had a restricted fluid intake. Of these, 3 experienced non-oliguric renal insufficiency (plasma creatinine up to 176, 250 and 351 mumol/l, respectively) which resolved within 1 week of discontinuing acyclovir. Renal function was stable in the remaining 4 patients in this group and in the 12 children treated with acyclovir but without fluid restriction. We suggest the decreased renal function resulted from intratubular acyclovir crystalluria.

[Are infant resistant to carbon monoxide poisoning?]. / Le nourrisson est-il résistant à la toxicité du monoxyde de carbone?

A 20 year old woman and her 13 weeks old infant were found in the same place close together in a house fire. As soon as possible, on-the-spot treatment was initiated simultaneously for both victims, i.e. oxygen (100% FIO2), using endotracheal intubation and mechanical ventilation for the mother, with hyperbaric oxygen when in the hospital, and by facial mask for the baby. On admission (35 minutes after discovery in the fire), the mother remained comatose, whereas the baby showed only moderate neurologic abnormalities. The initial laboratory assessment showed a pH of 7.12 for the mother and 7.06 for the baby.

Haemodynamic and renal effects of dopexamine after cardiac surgery in children.

Dopexamine hydrochloride, a synthetic dopamine analog with predominantly beta and delta agonist properties, has been shown to improve cardiac performance and renal function in adults with heart failure. This study was designed to investigate the haemodynamic and renal effects of dopexamine in children after cardiac surgery. Seven children were selected in whom a need for postoperative vasodilation after cardiac surgery was anticipated. Haemodynamics and renal function were determined under baseline conditions and during a continuous infusion of dopexamine at 2 and 6 micrograms.kg-1.min-1 for 90 minutes, the sequence being randomized for the initial dose. Cardiac output was measured by thermodilution and glomerular filtration rate (GFR) and renal plasma flow (RPF) by the clearances of inulin and para-aminohippurate respectively. Dopexamine induced a dose-related increase in cardiac index (CI) expressed as mean (SD) from 3.5 (0.7) to 3.9 (0.76) and 4.5 (0.8) l.min.-1m-2 (both P < 0.05), and in heart rate (HR) from 107 (17) to 122 (17) and 136 (17) beats.min-1 (P < 0.05). Stroke volume index (SVI) and mean systemic pressure were unchanged, but pulmonary wedge pressure decreased from 14 (3) to 11 (4) and 12 (3) mmHg (both P < 0.05). Systemic vascular resistances (SVR) decreased from 24 (7) to 20 (5) mmHg.l-1.min-1.m-2 (P < 0.05), with dopexamine 6 micrograms.kg-1.min-1. Renal blood flow (RBF) increased from 319 (113) to 441 (230) and 410 (138) ml.min-1.m-2 (both P < 0.05), GFR from 115 (32) to 142 (34) and 146 (29) ml.min-1.1.73m-2 (both P < 0.05), urine output and fractional excretion of sodium respectively from 3.12 (2) to 7.16 (8) and 7.21 (6) ml.kg-1 (both P < 0.05) and from 2.24 (1) to 4.25 (3.4) (P < 0.05) and 3.15 (3.1)% (n.s.). The fraction of CI delivered to the kidneys, the fraction of RBF filtered in the kidneys, plasma renin activity and aldosterone levels remained unchanged. In children after cardiac surgery, dopexamine increases CI at the expense of a concomitant increase in heart rate and demonstrates few selective vascular systemic or intrinsic renal actions.

The application of HPLC methodology for the analysis of receptor mediated changes in phosphoinositide metabolism.

HPLC methodology has found wide application in analytical problems in biochemistry. To study the metabolism of phosphatidylinositol and its regulation by receptor mediated events, HPLC could be a valuable technique. It has been recently demonstrated that a variety of hormones and neurotransmittors act to stimulate hydrolysis of phosphoinositides by a phospholipase C. To monitor this reaction, we have analysed the formation of radiolabelled inositol phosphates from phosphoinositides. The present paper describes a rapid HPLC procedure, to separate inositol phosphates from myo-inositol, which could be used in pharmacological studies of receptors linked to phosphoinositide hydrolysis. The potential of the application of HPLC to the analysis of the phospholipids involved is discussed.

Epoetin alfa in anaemic children or adolescents on regular dialysis.

Eighteen patients aged 5-18 years on regular dialysis had a packed cell volume (PCV) less than 0.27. On treatment with epoetin alfa (EA) PCV increased by 0.05 or more in all patients. Iron supplementation was necessary in 13 patients with a ferritinaemia less than 300 micrograms/l before study. During treatment, plasma potassium increased significantly and more vigorous antihypertensive measures were required in 8 patients, 5 of them being already on antihypertensive drugs before EA. Iliofemoral thrombosis occurred in 1 patient 10 days after renal transplant. The data indicate that EA ameliorates the anaemia of chronic renal disease. The main concerns arising during treatment with EA are hyperkalaemia, arterial hypertension and possibly thrombosis.