Maternal diet in pregnancy and child's respiratory outcomes: an individual participant data meta-analysis of 18 000 children.

RATIONALE: Severe fetal malnutrition has been related to an increased risk of respiratory diseases later in life, but evidence for the association of a suboptimal diet during pregnancy with respiratory outcomes in childhood is conflicting. We aimed to examine whether a pro-inflammatory or low-quality maternal diet during pregnancy was associated with child's respiratory health. METHODS: We performed an individual participant meta-analysis among 18 326 mother-child pairs from seven European birth cohorts. Maternal pro-inflammatory and low-quality diets were estimated by energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) scores. Preschool wheezing and school-age asthma were measured using questionnaires and lung function by spirometry. RESULTS: After adjustment for lifestyle and sociodemographic factors, we observed that a higher maternal E-DII score (a more pro-inflammatory diet) during pregnancy was associated only with a lower forced vital capacity (FVC) in children (z-score difference -0.05, 95% CI -0.08- -0.02, per interquartile range increase). No linear associations of the maternal E-DII or DASH score with child's wheezing or asthma were observed. In an exploratory examination of the extremes, a very low DASH score (<10th percentile) (a very low dietary quality) was associated with an increased risk of preschool wheezing and a low forced expiratory volume in 1 s/FVC (z-score <-1.64) (OR 1.20, 95% CI 1.06-1.36 and z-score difference 1.40, 95% CI 1.06-1.85, compared to ≥10th percentile), with corresponding population attributable risk fractions of 1.7% and 3.3%, respectively. CONCLUSION: The main results from this individual participant data meta-analysis do not support the hypothesis that maternal pro-inflammatory or low-quality diet in pregnancy are related to respiratory diseases in childhood.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Prenatal exposure to neurotoxic metals and micronutrients and neurodevelopmental outcomes in early school age children from Poland.

Exposure to environmental factors, such as neurotoxic metals and micronutrients, during critical periods of development can contribute to long-term consequences in offspring's health, including neurodevelopmental outcomes. The aim of this study was to evaluate the association between simultaneous prenatal exposure to metals [lead (Pb), cadmium (Cd), mercury (Hg)] and micronutrients [selenium (Se), zinc (Zn), copper (Cu)] and neurodevelopmental outcomes in school-age children from the Polish Mother and Child Cohort (REPRO_PL). Metals and micronutrients concentrations were measured in cord blood (Pb, Cd, Se, Zn, Cu) and in maternal hair (Hg) collected during the 3rd trimester of pregnancy. Behavioral and emotional problems, as well as children's cognitive and psychomotor development, were assessed in 436 school-age children using the Strengths and Difficulties Questionnaire (SDQ, filled in by the mothers) and the Polish adaptation of the Intelligence and Development Scales (IDS, administered by trained psychologists). Multivariate regression models were applied after imputation of missing values, using two approaches: (i) a joint analysis taking into account all metals and micronutrients simultaneously, and (ii) an ExWAS study (single-exposure model). In the SDQ, Hyperactivity/Inattention problems and Total difficulties were associated with higher Hg concentrations in maternal hair (0.18, 95% CI: 0.05; 0.3; and 0.14, 95% CI: 0.01; 0.3, respectively), whereas Emotional symptoms were inversely associated with Se and Zn levels in cord blood (-0.13, 95% CI: -0.3; 0.004; and -0.10, 95% CI: -0.2; 0.02, respectively). In the IDS, cord blood Pb levels were found to be negatively associated with Fluid and Crystallized IQ (-0.12, 95% CI: -0.3; 0.02; and -0.14, 95% CI: -0.3; 0.007, respectively) as well as Mathematical skills (-0.15, 95% CI: -0.3; 0.01). The current research has been able to simultaneously assess the exposure to various interacting chemicals during the prenatal period. We demonstrate that prenatal co-exposures to Pb, Hg, Zn and Se have long-term influences on the neuropsychological outcome of school-age children.

Maternal diet during pregnancy and risk of allergic diseases in children up to 7-9 years old from Polish Mother and Child Cohort study.

BACKGROUND: The impact of maternal diet during pregnancy on the risk of allergic diseases in childhood is an increasing scientific and public health concern. We evaluated the associations of maternal type of diet and essential elements and vitamins intake during pregnancy with offspring allergic and respiratory outcomes. METHODS: The study population included 557 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire filled in between the 20th-24th week of pregnancy, overall maternal diet was evaluated as the difference between the Prudent Dietary Pattern (PDP) score and Western Dietary Pattern (WDP) score ((PDP-WDP) score) and maternal achievement of dietary recommendations (estimated average requirement, EAR) for essential elements and vitamins was assessed. Children's health examination at age of 1, 2, and 7-9 years covered the following symptoms: infections, wheezing/asthma, food allergy, allergic rhinitis, and atopic dermatitis. At age of 7-9 years, children underwent spirometry and skin-prick tests. RESULTS: Children of the mothers who were not achieving adequate intake of vitamin C during pregnancy had a higher risk of wheezing and having more than two infections within the first two years of life comparing to those who met EAR (OR = 2.6, p = 0.05, and OR = 2.3, p = 0.04, respectively). Inadequate intake of vitamin E during pregnancy was related to a higher risk of atopic dermatitis (OR = 2.7, p = 0.04), whereas inadequate intake of magnesium during pregnancy was associated with the risk of wheezing in the offspring at age of two years (OR = 3.7, p = 0.03). A lower (PDP-WDP) score during pregnancy (indicating unhealthier diet) was associated with a higher risk of infections (OR = 1.5, p = 0.007) but a lower risk of atopic dermatitis (OR = 0.7, p = 0.02) at age of 7-9 years. CONCLUSIONS: These results may contribute to the body of evidence for the impact of maternal diet during pregnancy for children's optimal health, however further studies are needed before drawing conclusions and recommendations for clinical practice.

A severity grading system of food-induced acute allergic reactions to avoid the delay of epinephrine administration.

BACKGROUND: Substantial discrepancies among anaphylaxis severity scores may delay epinephrine administration. OBJECTIVE: The study aims to develop a transparent severity grading system of food-induced acute allergic reactions with a decision model for epinephrine use. METHODS: The natural course of 315 acute food-induced allergic reactions in children hospitalized at the Allergology department between May 2016 and July 2019 owing to follow-up treatment and allergy diagnostics was evaluated. The severity of episodes was classified according to the 5 most accepted grading systems. The interrater reliability of classification between anaphylaxis severity scores was assessed. All symptoms were grouped into a heat map according to their real-life incidence and clinical relevance. Based on the heat map analysis, a severity grading system of food-induced acute allergic reactions in children with the epinephrine administration decision model was created. RESULTS: Data from 259 food-induced anaphylaxis episodes in 157 children were included in the analysis. Comparing the grading systems, we observed a 24.7% to 70.2% disagreement between severity scores. The heat map illustrated a strong association between 29 symptoms and their categorization. A new severity grading system was developed and a 2-stage decision model was proposed: "epinephrine yes" (any rapidly progressing symptoms, even mild ones or from 1 organ system; any symptoms from more than 1 organ system; or every grade of anaphylaxis), and "epinephrine available and prepared to use" (nonprogressing mild systemic allergic reaction from 1 system area only; no anaphylaxis). CONCLUSION: A new severity grading system of food-induced acute allergic reactions in children could serve as a clinical tool for health care professionals to avoid epinephrine administration delay.

Sensitization to cat and dog components and prediction of symptoms in cat-sensitized children.

BACKGROUND: Sensitization to cat and/or dog allergens during childhood represents a risk factor for the development of allergic diseases later in life. OBJECTIVE: The study investigated the association of patterns of sensitization to cat and dog allergen components with clinical symptoms of allergy to these furry animals among cat-sensitized children. METHODS: The children were evaluated for the presence of bronchial asthma, atopic dermatitis and allergic rhinitis. Their mothers completed a questionnaire on pet exposure at home. Levels of serum IgE cat epitopes Fel d (1, 2, 4), as well as dog components Can f (1, 2, 3, 5) were measured in all the studied children. RESULTS: Respiratory symptoms following exposure to the cat allergen were most common in children with Fel d 2 epitope (p = 0.041). After contact with a dog, respiratory symptoms were most common in children with Can f 1 epitope (p = 0.042), atopic dermatitis in children with sensitization to both Can f 1 (p = 0.009) and Can f 2 (p = 0.002), whereas eye symptoms occurred mostly in children with Can f 3 (p = 0.039). CONCLUSIONS: Molecular diagnosis in patients with pet allergy may help clinicians to predict clinical symptoms and their severity.

Longitudinal effect of phthalates exposure on allergic diseases in children.

BACKGROUND: Environmental chemicals, such as phthalates, phenols, and parabens, may affect children's immune development and contribute to the risk of atopic diseases and asthma. OBJECTIVE: To evaluate the associations between prenatal and childhood phthalate exposure and atopic diseases in children at the age of 9 years. METHODS: This analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child Cohort Study. Phthalate metabolite levels were assessed in the urine samples collected from mothers during the third trimester of pregnancy and from children at age of 2 and 9 years. For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical record of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. RESULTS: A higher urine concentration of mono-2-ethyl-5-oxohexyl phthalate increased the risk of food allergy in children at the age of 9 years (odds ratio [OR], 1.75; 95% CI, 1.19-2.57; P = .004) and decreased the risk of atopic dermatitis (OR, 0.49; 95% CI, 0.27-0.87; P = .02). For mono-2-ethyl-5-hydroxyhexyl phthalate, an increased risk of atopic dermatitis was observed (OR, 1.90; 95% CI, 1.18-3.05; P = .008). A higher urine concentration of mono-benzyl phthalate increased the risk of asthma in children (OR, 1.67; 95% CI, 1.08-2.58; P = .02), but the risk of asthma decreased when the concentration of mono-2-ethylhexyl phthalate was higher (OR, 0.64; 95% CI, 10.43-0.97; P = .04). CONCLUSION: Our study has not provided clear evidence of the negative effect of phthalate exposure during pregnancy and within the 9 years after birth on allergic diseases in children.

The role of antioxidants and 25-hydroxyvitamin D during pregnancy in the development of allergic diseases in early school-age children - Polish Mother and Child Cohort Study.

Purpose: Based on the available data, alterations of the antioxidant defense as well as the vitamin status in mothers may affect the prenatal process of lung and immune system development as a pathophysiological background of increased prevalence of allergic diseases. The primary aim of the current study was to assess the associations among cord blood concentrations of zinc (Zn); copper (Cu); selenium (Se); ß-carotene; and vitamin A, E, and D, and the occurrence of atopic dermatitis, food allergy, allergic rhinitis, and asthma in early school-age children. Methods: We evaluated 211 children, 7-9 years old, from the Polish Mother and Child Cohort Study. the women were interviewed during pregnancy to collect demographic and socioeconomic data, and the medical and reproductive history. At delivery, umbilical cord blood plasma was sampled. Seven to nine years after the birth, the child's exposure and health status (including skin-prick test and spirometry for allergy assessment and urine sample for cotinine level) were examined. In the analyses, a multivariable model was applied. Results: Statistically significant relationships were found among Zn; Cu; Se; and vitamin A, E, and D concentrations in cord blood; and the prevalence of food allergy, allergic rhinitis, atopic dermatitis, and asthma in children ages 7-9 years after adjustment for several confounders. Conclusion: We showed an imbalance in the antioxidant defense system in cord blood, which may lead to the occurrence of allergic diseases later in life. The maternal diet may have substantial potential to modify immune tolerance and, consequently, the development of allergic disease in the offspring.Clinical trial NCT01861548, www.clinicaltrials.gov.

The influence of hospital-based intravenous immunoglobulin and home-based self-administrated subcutaneous immunoglobulin therapy in young children with primary immunodeficiency diseases on their parents' / caregivers' satisfaction.

BACKGROUND: Immunoglobulin replacement has been standard therapy for patients with primary immunodeficiency diseases (PIDD). Intravenous immunoglobin (IVIg) is delivered at the hospital, whereas subcutaneous immunoglobin (SCIg) is used for home-based treatment. The aim of the study was to determine the advantages and disadvantages of IVIg and SCIg in Polish children aged 1-5 years, with PIDD, and the satisfaction of their parents / caregivers regarding immunoglobulin replacement. METHODS: The research involved parents of 23 children with PIDD, aged 1-5 years. All children were given IVIg therapy and after at least 6 months they were switched towards home SCIg therapy for at least 6 months. A questionnaire assessing advantages and disadvantages of preferred types of treatment and the quality of life of PIDD patients' families' lives was used. RESULTS: The research showed that IVIg therapy was better accepted by parents than SCIg therapy (P = 0.034) for the following reasons: It made it possible for the children to receive treatment once per month (60%); it reduced the fear of injecting the children (60%), and it provided better control of the disease through regular visits to the hospital (53.33%). Parents noticed, however, that IVIg had a significant impact on absence at school or work (70%). Parents who preferred SCIg for their children were guided mainly by the smaller number of side effects (40%), and the fact that the treatment did not interfere with parents' work or the children's school (40%). CONCLUSION: The results showed that IVIg therapy was better accepted by parents than SCIg therapy Parents of children with SCIg are less satisfied with their life, and feel anxiety about their children disease, which is related to administering the medicine by themselves.

Glycoprotein A (GARP) in children who outgrow food allergy.

BACKGROUND: There is little understanding of the mechanisms by which food allergy (FA) develops into persistent disease, or by which symptoms it regresses. Food allergy is a major health problem in developed countries, where the prevalence reaches up to 6% in children and 3% in the adult population. OBJECTIVE: Children with food allergy remission (FAR) and those without FAR below five years of age, were compared 7-10 years with respect to clinical data and expression of glycoprotein A repetitions predominant (GARP) on peripheral blood mononuclear cells. METHODS: Forty children with FAR and 40 children without FAR at age 7-10, in whom FA was previously diagnosed at age below five years were evaluated. In this prospective study, demographic and clinical data were taken, patients were classified as atopic based on history and serum specific IgE (sIgE) for a specific allergen. Blood samples were obtained from all patients to assess expression of GARP. RESULTS: We observed higher expression of GARP in children with FAR compared to children without FA (p=0.005); optimal cut-off for GARP prediction of the remission was 20.1%. Children with FAR and food-specific IgE in serum had higher expression of GARP compared to children with low food specific IgE (<0.35kU/L). Keeping pets at home decreased, and presence of allergic rhinitis increased ORs for high expression of GARP (hGARP) in our patients. CONCLUSION: hGARP (>20.1%) is related with FAR in school children. Allergic rhinitis, and pets at home modify this effect of GARP. Children with allergic rhinitis have less chance of developing remission despite maintaining immune tolerance (hGARP); quite the opposite case with pets at home.

Usefulness of sRtot and Rint in bronchodilator testing in the diagnosis of asthma in children.

INTRODUCTION: The usefulness of total specific resistance (sRtot) and interrupter resistance (Rint) as a bronchodilator reversibility test (BT) alternative to forced expiratory volume in 1 s (FEV1) in asthma diagnosis in children has not been established. AIM: To compare different applied definitions of airflow obstruction in children measuring response to the bronchodilator by spirometry, plethysmography and the interrupter technique in asthmatic children. MATERIAL AND METHODS: It was a prospective, real-life, non-interventional study. Children, aged 6-18 with newly diagnosed asthma, able to perform lung function tests were included into the study. Subjects underwent a history taking, physical examination, reversibility test in spirometry, plethysmography, and the interrupter technique. A standard cut-off of 12% from the initial value for reversibility in FEV1 was employed. Improvement in the pre-bronchodilator sRtot and Rint ≥ 25% and ≥ 35% was assessed after administration of salbutamol (400 µg) as well as allergen sensitization were measured. RESULTS: We included 135 children diagnosed with asthma into the analysis. All investigated parameters changed statistically significantly due to the bronchodilator administration in the examined patients. The FEV1 was not as useful in diagnostics of asthma as the sRtot and Rint, taking into consideration the fait accompli that all the study participants had aptly been diagnosed as having asthma (p < 0.001). The differences between the sRtot and Rint were not statistically significant (p = 0.215). CONCLUSIONS: Our results suggest that sRtot and Rint may be useful parameters in BT in clinical practice in the asthma diagnostic process in children.

Food allergy endotype with high risk of severe anaphylaxis in children-Monosensitization to cashew 2S albumin Ana o 3.

BACKGROUND: Food allergy in children can be life-threatening. Component-resolved diagnostics approach to food anaphylaxis is rarely assessed in children. The aim of the study was to identify the food allergen components as the triggers responsible for severe anaphylaxis, with regard to characteristics and associated risks, among children in a large, population-based setting. METHODS: Two hundred and seventy-one children who were hospitalized due to systemic allergic reaction (SAR) and food anaphylaxis were recruited. Medical history was assessed, and culprit allergen source and anaphylaxis severity grade were established. Specific IgE to 112 allergen components using multiplex ImmunoCAP ISAC immunoassay and specific IgE to hazelnut, Cor a 14, and cashew, Ana o 3, using singleplex ImmunoCAP immunoassay were determined. RESULTS: We analyzed data from 237 SAR/anaphylaxis in 237 children. Trigger at allergen component level was defined for every episode. The most common triggers of SAR/anaphylaxis were seeds (50.6%), among them, the storage proteins. Anaphylaxis triggered by Ana o 3, 2S albumin from cashews (aOR = 15.0; 95% CI: 3.27 to 73.47); Tri a 19 from wheat (aOR = 9.93; 95% CI: 1.73 to 56.97); and Cor a 9 from hazelnut (aOR = 6.53; 95% CI: 1.16 to 36.72) had the worst clinical presentation including cardiovascular and severe respiratory symptoms (grade IV-V vs I-III in Cox scale). Thirteen out of 237 (5.5%) SAR/anaphylaxis patients were triggered by Ana o 3. Almost 82% of patients with severe Ana o 3 anaphylaxis were sensitized only to this component and had no concomitant food sensitization. CONCLUSION: Monosensitization to Ana o 3 is, irrespective of other parameters, connected with high risk of severe anaphylaxis.

Comparison of the effect of 5-grass pollen sublingual immunotherapy tablets and drops in children with rhinoconjunctivitis.

BACKGROUND: One of the most important aspects of sublingual immunotherapy (SLIT) is the regimen of administration. AIM: To find any differences in symptom-medication scores between the two groups of SLIT tablets and drops, given pre-coseasonally (starting 8 weeks before the pollen season) in children with rhinoconjunctivitis allergy to grass pollen. The secondary outcome were the differences in lung function and induction of T-regulatory forkhead box P3 (FOXP3) positive cells. METHODS: This was a retrospective, secondary analysis of pooled data obtained from our two prospective randomized placebo controlled trials that involved children who underwent SLIT. Forty-one children, ages 6-18 years, with allergic rhinitis (AR), sensitive to grass pollen, participated in the study. RESULTS: Treatment with both tablets and drops significantly reduced all symptoms (nasal, asthma, and ocular) within the groups; there was no significant difference between both groups. When compared with the tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score, but the difference was not statistically significant (p = 0.1036); there was no significant difference in asthma and nasal scores. We showed a significant decrease in the fractional exhaled nitric oxide level comparable in both immunotherapy groups. There were no differences between the groups in the induction of CD4+ CD25+ FOXP3+-positive cells in peripheral blood. CONCLUSIONS: Both protocols showed similar decreases in symptom-medication scores; however, when compared with tablet therapy, there was a trend for drops therapy to be more effective in the reduction of combined symptom-medication score.

Quality of life in asthmatic children and their caregivers after two-year treatment with omalizumab, a real-life study.

INTRODUCTION: Omalizumab, a monoclonal anti-immunoglobulin E antibody, has been successfully used as a supplementary therapy to improve asthma control in children aged ≥ 6 years with severe persistent allergic asthma. AIM: To demonstrate the quality of life in children with severe asthma and their caregivers, and changes from baseline in forced expiratory volume in 1 s (FEV1) and daily inhaled corticosteroids (ICS) dose after 2-year treatment with omalizumab. MATERIAL AND METHODS: Participants were seen in the clinic at enrollment (visit 1), after 16 weeks (visit 2), after 52 weeks (visit 3) and after 104 weeks (visit 4) of treatment with omalizumab. We evaluated lung function, ICS use and the quality of life with the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and the Pediatric Asthma Caregiver's Quality of Life Questionnaire (PACQLQ). RESULTS: Nineteen children and caregivers were enrolled. Significant improvement was observed in PAQLQ and PACQLQ scores, both in all domains and in total scores. Significant differences were found between the first and the other visits. A positive correlation between PAQLQ and PACQLQ at the first and at the second visit was found, 63.3% of patients achieved reduction in ICS doses. We did not notice any significant improvement in FEV1. CONCLUSIONS: The improvement in quality of life in asthmatic children and adolescents observed after omalizumab correlates with the improvement of quality of life in caregivers, reduction in ICS use but not with FEV1.

The clinical effect of vitamin D supplementation combined with grass-specific sublingual immunotherapy in children with allergic rhinitis.

BACKGROUND: An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy. OBJECTIVE: To compare the clinical efficacy of SLIT with vitamin D supplementation with placebo in children with allergic rhinitis. Secondary end points included lung function, exhaled nitric oxide concentration, methacholine bronchial provocation test, and serum level of calcifediol (25[OH]D). METHODS: Fifty children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis (eight patients had concomitant asthma) participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received a 5-grass pollen sublingual 300 IR tablet with either vitamin D 1000 IU daily supplementation or placebo. RESULTS: When compared with the placebo group, SLIT plus vitamin D group therapy was more effective in the reduction of nasal symptoms (p = 0.04), asthma symptoms (p = 0.001), and the combined symptom-medication score (p = 0.001); there was no significant difference between the groups in medication and ocular scores. We observed a significant improvement of forced expiratory volume in 1 second (vitamin D group, p = 0.014; placebo group, p = 0.015) and the proportion of a person's vital capacity expired in the first second of forced expiration levels (vitamin D group, p = 0.004; placebo group, p < 0.001), within both groups, between visits. Fractional exhaled nitric oxide and provocative dose producing a 20% fall in forced expiratory volume in 1 second results did not statistically significantly differentiate the study participants in terms of receiving SLIT along with vitamin D or placebo. We showed a significant increase in calcifediol in the SLIT plus vitamin D group as well as in SLIT plus placebo group. CONCLUSIONS: Vitamin D supplementation combined with grass-specific SLIT was more effective in the reduction of nasal and asthma symptoms. Vitamin D supplementation combined with SLIT provides an effective and well-tolerated new immunotherapy modality for treating children with allergic rhinitis. A 5-grass pollen sublingual 300 IR tablet was effective in both studied groups and also in children with comorbid mild asthma.

Serum tryptase level and inflammatory markers in exhaled breath condensate of children with exercise-induced symptoms.

BACKGROUND: The pathogenesis of exercise-induced bronchoconstriction (EIB) is poorly understood. OBJECTIVE: To evaluate the biomarkers concentration in exhaled breath condensate (EBC) in schoolchildren with postexercise symptoms. We also evaluated changes in fractional exhaled nitric oxide (FeNO) value and the serum tryptase level after exercise. METHODS: One hundred children with postexercise symptoms were included. Methacholine challenge testing (MCT) was performed at visit 2, and exercise challenge testing (ECT) was performed at visit 3. Before and after ECT serum tryptase levels and FeNO values were measured. EBC was collected after ECT from 10 randomly selected children from each group. The children were assigned to the following groups: ECT(+) MCT(+), ECT(+) MCT(-), ECT(-) MCT(+), ECT(-) MC(-). We measured the following molecules: eotaxin, interleukin (IL) 8, IL-1ra, IL-1 beta, IL-6, IL-1 alpha, IL-12(p40), IL-5, granulocyte-macrophage colony-stimulating factor, IL-7, IL-15, IL-4, IL-2, IL-10, tumor necrosis factor alpha, interferon gamma, IL-13, tumor necrosis factor beta, monocyte chemoattractant protein-1, IL-17A, macrophage inflammatory proteins-1 alpha, macrophage inflammatory proteins-1 beta, IL-12(p70), and regulated on activation, normal T-cell expressed and secreted by using a multiplex immunoassay. Prostaglandin E2 (PGE2), leukotriene B4, and cysteinyl leukotriene were analyzed by using separate enzyme-linked immunosorbent assay kits. RESULTS: In the MCT(+) group, a detectable level of IL4 in EBC and detectible levels of eicosanoids were seen in the ECT(+) group. We observed the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations in patients with detectable compared with patients without detectable levels of cytokines in EBC. We showed ECT-induced reduction in the tryptase level in patients with a nondetectable PGE2 level in EBC and an increase in tryptase levels in patients who had detectable levels of PGE2 in EBC. CONCLUSIONS: EBC was a useful method to estimate inflammation but only in children with symptoms and with EIB shown by a positive ECT. Children with a positive ECT had detectable levels of eicosanoids in EBC; the opposite direction of ECT-induced changes in FeNO and serum tryptase concentrations was observed. The results of above study confirm the role of mast cells and eicosanoids in the pathogenesis of EIB in children.

Effect of Lactobacillus rhamnosus GG and vitamin D supplementation on the immunologic effectiveness of grass-specific sublingual immunotherapy in children with allergy.

BACKGROUND: An important issue in sublingual immunotherapy (SLIT) is how to improve efficacy. OBJECTIVE: To compare the clinical and immunologic efficacy of SLIT given alone and, to enhance clinical efficacy, given with probiotic or vitamin D supplementation. METHODS: One hundred children, ages 5-12 years, sensitive to grass pollen, with allergic rhinitis participated in a 5-month prospective, randomized, double-blind, placebo-controlled trial. Children received 5-grass SLIT 300 IR tablets with either vitamin D 1000 IU daily supplementation, probiotic, or placebo. The control group included children with allergy who did not qualify for immunotherapy. Primary end points included a symptom-medication score, lung function, and exhaled nitric oxide concentration. The secondary end point was the immunologic efficacy measured by the following: CD4(+)CD25(+)Foxp3(+) (forkhead box P3) cells, Toll-like receptor (TLR) 4, interleukin (IL) 1, IL-6, tumor necrosis factor, IL-10, and transforming growth factor ß-1 levels in cell culture supernatants. RESULTS: Reduction in the symptom-medication score and improvement in lung function as well as a significant increase in the percentage of CD4(+)CD25(+)Foxp3(+) in children who received SLIT in all the groups were observed compared with control group. In the SLIT-probiotic group, between-group analysis showed significantly higher CD4(+)CD25(+)Foxp3(+) induction compared with the SLIT group and higher reduction in the percentage of TLR-positive cell group compared with the SLIT-vitamin D group (Fig. 1). An increase in CD4(+)CD25(+)Foxp3(+) induction, reduction in TLR-positive cells recruitment and an increase in transforming growth factor ß-1 production were independently associated with a better clinical effect of SLIT in children. CONCLUSIONS: We demonstrated the clinical and immunologic effect of probiotic and vitamin D supplementation on SLIT. Probiotic supplementation showed better clinical and immunologic response in children with allergic rhinitis.