Allergic sensitisation did not affect bronchial hyper-responsiveness in children without respiratory tract symptoms.

AIM: The potential for immunotherapy to prevent asthma development has become a hot topic. This prompted us to revisit data from an early study that examined allergic sensitisation on bronchial hyperresponsiveness (BHR) in children with and without respiratory symptoms. Unlike previous studies, it used both indirect and direct test methods. METHODS: The study was conducted in Kuopio, Finland, in 1994 and 247 children (55.1% boys) with a mean age 10.5 ± 1.7 years were recruited using a school survey: 165 with lower respiratory symptoms and 82 healthy controls. Each child underwent a 6-min free-running test and a methacholine test with a cumulative dose of 4900 µg. All participants underwent skin-prick tests: 127were sensitised and 120 were non-sensitised. RESULTS: There were no significant differences in lung function between the sensitised and non-sensitised children. However, sensitisation was associated with BHR which was measured by both the methacholine test (2400 µg versus >4900 µg, p < 0.001) and the free-running test (-3.5% versus -2.6%, p = 0.042). No such differences were observed among the healthy controls. Sensitisation was a predictor of allergic diseases, and only multisensitisation to a minimum of four allergens increased the incidence of asthma. CONCLUSION: Allergic sensitisation did not affect BHR in children without respiratory symptoms.

Impulse oscillometry and free-running tests for diagnosing asthma and monitoring lung function in young children.

BACKGROUND: Separating individuals with viral-induced wheezing from those with asthma is challenging, and there are no guidelines for children under 6 years of age. Impulse oscillometry, however, is feasible in 4-year-old children. OBJECTIVE: To explore the use of impulse oscillometry in diagnosing and monitoring asthma in young children and evaluating treatment response to inhaled corticosteroid (ICS). METHODS: A total of 42 children (median age 5.3 years, range 4.0-7.9 years) with physician-diagnosed asthma and lability in oscillometry were followed for 6 months after initiation of ICS treatment. All children performed the 6-minute free-running test and impulse oscillometry at 3 time points. After the baseline, they attended a second visit when they had achieved good asthma control and a third visit approximately 60 days after the second visit. A positive ICS response was defined as having greater than 19 points in asthma control test and no hyperreactivity on the third visit. RESULTS: In total, 38 of 42 children responded to ICS treatment. Exercise-induced increases of resistance at 5 Hz decreased after ICS treatment (61% vs 18% vs 13.5%, P < .001), and running distance during the 6-minute test was lengthened (800 m vs 850 m vs 850 m, P = .001). Significant improvements in childhood asthma control scores occurred between the baseline and subsequent visits (21 vs 24 vs 24, P < .001) and acute physicians' visits for respiratory symptoms (1, (0-6) vs 0, (0-2), P = .001). Similar profiles were observed in children without aeroallergen sensitization and among those under 5 years of age. CONCLUSION: Impulse oscillometry is a useful tool in diagnosing asthma and monitoring lung function in young children.

Indoor bacterial microbiota and development of asthma by 10.5 years of age.

BACKGROUND: Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood. OBJECTIVE: We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma. METHODS: Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years. RESULTS: Richness was inversely associated with asthma after adjustments (P = .03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P = .02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > |0.4|) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P < .10), although not independently of each other. The sum relative abundance of these 12 intercorrelated genera was significantly protective and explained the majority of the association of richness with less asthma. CONCLUSION: Our data confirm that phylogenetic differences in the microbiota of infants' homes are associated with subsequent asthma risk and suggest that communities of selected bacteria are more strongly linked to asthma protection than individual bacterial taxa or mere richness.

The interplay between risk and preventive factors explains why some children develop allergies to certain foods and others show tolerance.

AIM: A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance. METHODS: We carried out a thorough review of studies on paediatric food allergies published in the last decade. RESULTS: Food allergy symptoms may affect the skin, nasal and oral mucosa, conjunctivae, gastrointestinal tract or, in severe cases, the respiratory tract and cardiovascular organs. Immunoglobulin E (IgE)-mediated symptoms appear rapidly after exposure to the offending allergen, whereas non-IgE-mediated symptoms are typically delayed. The immunological processes involved in non-IgE-mediated allergic reactions are poorly understood, but T-cell activation is probably involved. There are several factors that influence the food sensitisation process: genetic predisposition, disruption of oral tolerance development, impaired skin barriers in atopic eczema and the influence of microbiomes. CONCLUSION: The symptoms and intensity of reactions vary considerably with regard to food allergies, and these depend on the individual's concomitant immunological and regulatory mechanisms. There is strong evidence that dietary diversity is important for children, even when they come from families with high allergy risks.

Wheat oral immunotherapy was moderately successful but was associated with very frequent adverse events in children aged 6-18 years.

AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18 years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000 mg of wheat protein, followed by three- and nine-month maintenance phases. Blood samples were taken before therapy and at follow-up visits. The study was carried out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were using wheat daily 16 months after the initiation of therapy. Allergic symptoms occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24. Specific immunoglobulin E (IgE) for ω-5-gliadin was significantly higher in patients who did not reach the target dose and were related to the intensity of reactions. CONCLUSION: The majority (57%) of children with wheat allergies could use wheat in their daily diet 16 months after the initiation of OIT, but 94/100 had adverse reactions and 60 were moderate or severe. Specific IgE to ω-5-gliadin may provide a biomarker for how much wheat can be tolerated and the intensity of the reactions to immunotherapy.

Enhanced T helper 1 and 2 cytokine responses at birth associate with lower risk of middle ear infections in infancy.

BACKGROUND: Respiratory tract infections and their symptoms are frequent during early childhood, but their risk factors, including the effect of early immune regulation, are less known. The aim of the study was to analyze whether stimulated cord blood cytokine production is associated with the frequency of respiratory tract infection symptoms or infections during the first year of life. METHODS: The study population consisted of children of mothers from farm or non-farm rural environment from Austria, Finland, Germany, and Switzerland who participated in a prospective birth cohort study (PASTURE: Protection against Allergy-Study in Rural Environments) (N = 550). Cord blood samples were stimulated with the combination of phorbol ester and ionomycin (P/I) for 24 h, and the production of IL-5, IL-10, TNF-α, and IFN-γ was determined using ELISA. Information about infectious morbidity was collected using weekly diaries. RESULTS: P/I-stimulated production of IL-5 (adjusted risk ratio (aRR) for ≤median production, 0.37; 95% confidence interval (CI), 0.25-0.55, aRR for >median production, 0.41; 95% CI, 0.27-0.61 vs. production median production, 0.39; 95% CI, 0.25-0.62 vs. production

Marked variability observed in inpatient management of bronchiolitis in three Finnish hospitals.

AIM: Infants hospitalised for bronchiolitis undergo examinations and treatments not supported by current research evidence and we investigated practice variations with regard to Finnish children under the age of two. METHODS: This prospective, multicentre cohort study was conducted in paediatric units in three university hospitals in Finland from 2008 to 2010. Hospital medical records were reviewed to collect data on clinical course, testing and treatment. Data were analysed separately for children meeting our strict definition of bronchiolitis, aged under 12 months without a history of wheezing, and a loose definition, aged 12-23 months or with a history of wheezing. RESULTS: The median age of the 408 children was 8.1 months. Clinical management varied between the three hospitals when stratified by strict and loose bronchiolitis subgroup definitions: complete blood counts ranged from 15-95% vs 16-94%, respectively, and the other measures were chest x-ray (16-91% vs 14-72%), intravenous fluids (2-47% vs 2-41%), use of nebulised epinephrine (10-84% vs 7-50%), use of salbutamol (18-21% vs 13-84%) and use of corticosteroids (6-23% vs 60-76%). CONCLUSION: The clinical management of bronchiolitis varied considerably with regard to the three hospitals and the two definitions of bronchiolitis. A stronger commitment to evidence-based bronchiolitis guidelines is needed in Finland.

[Update on Current Care Guideline: Food allergy (children)]. / Ruoka-allergia (lapset).

This guideline, targeted to healthcare workers dealing with food-allergic children, provides a review on the clinical aspects of pediatric food allergy. The main updates include: elimination diets are not recommended for breast-feeding mothers; probiotics are not recommended for allergy prevention or treatment; food challenges are the basis of the diagnosis, but it can be improved by IgE component diagnostics. The treatment for severe symptoms is specific food avoidance, mildly symptomatic children should continue with versatile diet. Specific oral tolerance induction is a safe and effective treatment in most of the pediatric patients.

Prenatal animal contact and gene expression of innate immunity receptors at birth are associated with atopic dermatitis.

BACKGROUND: Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. OBJECTIVE: To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. METHODS: A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. RESULTS: Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. CONCLUSION: Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth.

Bronchial hyperresponsiveness and asthma during oral immunotherapy for egg or peanut allergy in children.

Background: Bronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control. Methods: Methacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT. Results: Methacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 µg, 1104 µg, and 2068 µg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome. Conclusion: BHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.

Observational study of inhaled corticosteroid treatment for improved expiratory variability index in steroid-naïve asthmatic children.

Inhaled corticosteroid treatment improves expiratory variability index in steroid-naïve asthmatic children aged 4-7 years https://bit.ly/3n4vBT3.

Association of serum-soluble CD26 and CD30 levels with asthma, lung function and bronchial hyper-responsiveness at school age.

AIM: There is a need for markers of Th1 and Th2 imbalance in diseases such as asthma. CD30 is an activation marker of Th2 cells, and importance of Th1 marker CD26 was recently found in adult asthma. We studied whether serum-soluble CD30 (sCD30) or serum-soluble CD26 (sCD26) could support early diagnosis of asthma in children at school age. METHODS: sCD26 and sCD30 were measured in 34 children with clinically confirmed asthma, 31 with possible asthma and in 147 controls. In addition, the associations of flow volume spirometry, methacholine inhalation challenge and free running test results with serum sCD26 or sCD30 were analysed. RESULTS: Serum sCD30 was significantly higher in children with confirmed asthma (mean 91.5 IU/mL, SD 23.0) than in the controls (78.8 IU/mL, 25.9; p = 0.042). No significant differences were found in serum sCD26 levels between the groups. There was a negative correlation of mean mid expiratory flow values with serum sCD26 (r = -0.22, p = 0.0018). Neither methacholine inhalation challenge nor free running test results were associated with serum sCD26 or sCD30. CONCLUSION: Serum sCD30 was higher in children with asthma. However, marked overlap in serum sCD30 between asthmatic and healthy children limits the usefulness of sCD30 as a diagnostic marker of asthma.

[Food hyposensitization--new approach and treatment for food allergies]. / Ruokasiedätys--uusi ajattelutapa ja hoito ruoka-aineallergioihin.

Although most infants will recover from food allergy within the early years of life, at least one fifth will carry on with the disease until school age. Recent studies have managed to develop increased tolerance in children with food allergy by food hyposensitization with slowly increasing orally administered doses. In these studies either complete or partial increase of food tolerance for 80% of subjects has been achieved. The clinical results seem promising, and immunologic changes upon food hyposensitization look similar to those observed with other hyposensitization therapies.

[Congenital ciliary dysfunction in children]. / Värekarvojen synnynnäiset toimintahäiriöt lapsilla.

Congenital ciliary dysfunctions are recessively inherited disorders. The disorder is poorly recognized, if the patient has no situs inversus. The diagnosis is delayed, being made on the average at the age of over five years. The review deals with a recent European multinational survey of the occurrence, genetics, diagnostics and treatment of congenital ciliary dysfunctions. Data of Finnish pediatric patients under treatment have also been collected for the survey. The number of congenital ciliary dysfunctions found in Finland is approximately one fifth of that found in other Nordic countries.

Eucapnic voluntary hyperventilation test decreases exhaled nitric oxide level in children.

BACKGROUND: Exhaled nitric oxide (FeNO) measurements and eucapnic voluntary hyperventilation (EVH) tests have been used as diagnostic tools for asthma. Data on the impact of hyperventilation on the level of FeNO are limited. AIM: We aimed to evaluate whether EVH tests affect the level of FeNO in children aged 10-16 years. METHODS: A total of 234 children aged 10-16 years had a 6-min EVH test performed. In total, FeNO values for 153 of 234 children were measured before the test and within 15 min after the test. According to a baseline FeNO level of 20 ppb, children were divided into two groups: those with low values (FeNO < 20 ppb) and those with high values (FeNO ≥ 20 ppb). RESULTS: The median age of the children was 13.4 years (interquartile range 12.3-15.3 years); 58% were boys and 42% were girls. Of these children, 51% were sensitized to aeroallergens. In 101 of 153 children (66%), the FeNO values decreased after the EVH test. In children with low and high baseline levels, the median level of FeNO decreased after the EVH test: 10.5 ppb before versus 9.5 ppb after (p < .011), and 31.0 ppb before versus 28.0 ppb after (p < .011), respectively. The decrease in FeNO after EVH test was not associated with induced bronchoconstriction expressed as a change in FEV1 (Rs  = .19). CONCLUSIONS: The EVH test decreases FeNO levels. Therefore, FeNO should be measured before an EVH test is performed.

Intrauterine bacterial growth at birth and risk of asthma and allergic sensitization among offspring at the age of 15 to 17 years.

BACKGROUND: Microbial colonization of the airways and intestine during birth might have an effect on the risk of asthma and allergic diseases later in life. OBJECTIVE: We sought to evaluate the association between intrauterine microbial growth at the time of delivery and the development of asthma and allergic sensitization among offspring. METHODS: Intrauterine bacterial culture results were recorded at the time of cesarean delivery of 460 children who were born at Kuopio University Hospital during 1990-1992. When the children reached the age of 15 to 17 years, self-administered questionnaires were sent to the mothers, and 382 of the children were also examined by using skin prick tests. RESULTS: Intrauterine growth of potential pathogenic anaerobic bacteria and Streptococcus species at birth was associated with an increased risk of doctor-diagnosed asthma ever (odds ratio [OR], 4.51 [95% CI, 1.56-13.0]; OR, 2.53 [95% CI, 1.19-5.38]) and doctor-diagnosed current asthma (OR, 7.34 [95% CI, 2.44-22.03]; OR, 3.37 [95% CI, 1.46-7.76]) at the age of 15 to 17 years compared with the risk seen in subjects with negative microbial cultures. These findings remained significant also after applying the Bonferroni correction. No significant association after the Bonferroni correction was detected between intrauterine microbial growth and allergic sensitization among offspring. CONCLUSION: The results of this study indicated that specific intrauterine microbial growth at the time of birth might increase the risk of asthma among offspring through inflammatory mechanisms. These results indicate new potential targets for future studies on the effects of maternal vaginal microflora and intrauterine infection in the development of asthma among children.

Tracking of Serum DHEAS Concentrations from Age 1 to 6 Years: A Prospective Cohort Study.

CONTEXT: Adrenarche is a gradual process, but its programming is unknown. OBJECTIVE: The objective of this article is to examine the trajectory of dehydroepiandrosterone sulfate (DHEAS) from age 1 to 6 years and the associations of early growth with DHEAS concentration by age 6 years. DESIGN AND PARTICIPANTS: Longitudinal data from a population sample of 78 children (43 girls) with serum samples for DHEAS and insulin-like growth factor 1 (IGF-1) measurements available at ages 1 and 6 years. MAIN OUTCOME MEASURE: Serum DHEAS concentration at age 6 years. RESULTS: DHEAS concentration at age 1 year correlated with DHEAS concentration at age 6 years (r = 0.594, P < .001). DHEAS levels at age 6 years increased with tertiles of DHEAS at age 1 year (medians (µg/dL); 4.2, 14.4, 22.6; P < .001) and with those of greater increase in length by age 1 year (6.0, 11.7, 16.4; P = .047), and decreased with tertiles of birth length (17.7, 13.3, 7.1; P = .042). In a regression model including birth size, biochemical covariates at age 1 year, and growth measures by age 6 years, higher DHEAS concentration at age 1 year was an independent determinant of falling into the highest DHEAS tertile at age 6 years. CONCLUSIONS: Higher serum DHEAS concentrations already at age 1 year are associated with those at age 6 years. Also, shorter birth length and rapid catch-up growth in length by age 1 year are associated with higher DHEAS concentrations at age 6 years. These results corroborate the early origin of adrenarche and strongly suggest that part of adrenarchal programming already takes place by the end of infancy.

Cut-off values to evaluate exercise-induced asthma in eucapnic voluntary hyperventilation test for children.

BACKGROUND AND AIM: The eucapnic voluntary hyperventilation (EVH) testing is a diagnostic tool for diagnostics of exercise-induced bronchoconstriction; while the testing has become more common among children, data on the test's feasibility among children remain limited. Our aim was to investigate EVH testing feasibility among children, diagnostic testing cut-off values, and which factors affect testing outcomes. METHODS: We recruited 134 patients aged 10-16 years with a history of exercise-induced dyspnoea and 100 healthy control children to undergo 6-min EVH testing. Testing feasibility was assessed by the children's ability to achieve ≥70% of the target minute ventilation of 30 times forced expiratory volume in 1 s (FEV1). Bronchoconstriction was assessed as a minimum of 8%, 10%, 12%, 15% or 20% fall in FEV1. Patient characteristics were correlated with EVH outcomes. RESULTS: Overall, 98% of the children reached ≥70%, 88% reached ≥80%, 79% reached ≥90% and 62% reached ≥100% of target ventilation in EVH testing; of children with a history of exercise-induced dyspnoea, the decline percentages were as follows: 24% (≥8% fall), 17% (≥10% fall), 10% (≥12% fall), 6% (≥15% fall) and 5% (≥20% fall) in FEV1, compared to 11%, 4%, 3%, 1% and 0% among the healthy controls, respectively. Healthy controls and boys performed testing at higher ventilation rates (p < .05). CONCLUSION: Eucapnic voluntary hyperventilation testing is feasible among children aged 10-16 years and has diagnostic value in evaluating exercise-induced dyspnoea among children. A minimum 10% fall in FEV1 is a good diagnostic cut-off value. Disease status appears to be important covariates.

Rhinovirus Type in Severe Bronchiolitis and the Development of Asthma.

BACKGROUND: Respiratory syncytial virus (RSV)- and rhinovirus (RV)-induced bronchiolitis are associated with an increased risk of asthma, but more detailed information is needed on virus types. OBJECTIVE: To study whether RSV or RV types are differentially associated with the future use of asthma control medication. METHODS: Over 2 consecutive winter seasons (2008-2010), we enrolled 408 children hospitalized for bronchiolitis at age less than 24 months into a prospective, 3-center, 4-year follow-up study in Finland. Virus detection was performed by real-time reverse transcription PCR from nasal wash samples. Four years later, we examined current use of asthma control medication. RESULTS: A total of 349 (86%) children completed the 4-year follow-up. At study entry, the median age was 7.5 months, and 42% had RSV, 29% RV, 2% both RSV and RV, and 27% non-RSV/-RV etiology. The children with RV-A (adjusted hazard ratio, 2.3; P = .01), RV-C (adjusted hazard ratio, 3.5; P < .001), and non-RSV/-RV (adjusted hazard ratio, 2.0; P = .004) bronchiolitis started the asthma control medication earlier than did children with RSV bronchiolitis. Four years later, 27% of patients used asthma control medication; both RV-A (adjusted odds ratio, 3.0; P = .03) and RV-C (adjusted odds ratio, 3.7; P < .001) etiology were associated with the current use of asthma medication. The highest risk was found among patients with RV-C, atopic dermatitis, and fever (adjusted odds ratio, 5.0; P = .03). CONCLUSIONS: Severe bronchiolitis caused by RV-A and RV-C was associated with earlier initiation and prolonged use of asthma control medication. The risk was especially high when bronchiolitis was associated with RV-C, atopic dermatitis, and fever.