Long-term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-ß-enriched formula after weaning.

BACKGROUND: Oral tolerance induction in early life is a promising approach for food allergy prevention. Its success requires the identification of factors necessary for its persistence. OBJECTIVES: We aimed to assess in mice duration of allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF-ß supplementation after weaning would prolong it. METHODS: We quantified ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed whether OVA-immunized mice exposed to OVA during lactation could prevent allergic diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-ß-enriched formula was given after weaning. RESULTS: At 6 weeks, only 13% and 34% of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven OVA challenges vs. 44% and 72% in mice breastfed by naïve mothers (P = 0.02 and 0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific IgE (P < 0.0001). At 13 weeks, although OVA-specific IgE remained low (P = 0.001), diarrhoea occurrence increased to 32% and 46% after six and seven OVA challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not significantly inhibited. Supplementation with TGF-ß after weaning induced a strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth, sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017). MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged protection was only observed in mice rendered tolerant by breastfeeding and was associated with an improved gut barrier. CONCLUSIONS: In mice, prevention of food allergy by breastfeeding-induced tolerance is of limited duration. Nutritional intervention by TGF-ß supplementation after weaning could prolong beneficial effects of breast milk on food allergy prevention.

Validation of the MASK-rhinitis visual analogue scale on smartphone screens to assess allergic rhinitis control.

BACKGROUND: Visual Analogue Scale (VAS) is a validated tool to assess control in allergic rhinitis patients. OBJECTIVE: The aim of this study was to validate the use of VAS in the MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) app (Allergy Diary) on smartphones screens to evaluate allergic rhinitis symptoms and disease control. METHODS: Each user filled 4 different VAS measuring overall, nasal, ocular, and asthma symptoms at least once. Following COSMIN guidelines, we evaluated internal consistency, (Cronbach's alpha coefficient and test-retest), reliability (intraclass correlation coefficients), sensitivity, and acceptability of the MASK-Rhinitis VAS. RESULTS: Between 1 August 2015 and 31 July 2016, the app was used 14 612 times in 15 countries. A total of 1225 users used it more than once, during the evaluated period. The tool resulted to be statistically satisfactory, showing excellent internal consistency (Cronbach's test > 0.84, test-retest > 0.7), reliability (>0.9), and acceptability. In addition, the tool had a good sensitivity when users (n = 521) answered the VAS twice in less than 3 hours. CONCLUSIONS AND CLINICAL RELEVANCE: The MASK-rhinitis VAS is a reliable and valid tool to assess allergic control on smartphone screens, at the population level.

Exercise-induced bronchospasm related to different phenotypes of rhinitis without asthma in primary schoolchildren: the French Six Cities Study.

BACKGROUND: Exercise-induced bronchospasm (EIB) is frequent among asthmatic children. However, opinions differ on the relation between EIB and rhinitis in the absence of asthma. OBJECTIVES: We assessed the relationship between EIB and various phenotypes of rhinitis according to asthmatic status at the general population level in the Six Cities Study. METHODS: Of 7781 schoolchildren with a mean age of 10 years underwent an EIB test and skin prick test to assess allergic sensitization. Their parents completed a standardized questionnaire recording asthma-like symptoms and past-year rhinoconjunctivitis, ever hay fever (EHF), and a score for allergic rhinitis (SFAR) ≥7 as a marker of 'past-year allergic rhinitis'. Exercise-induced bronchospasm was defined as a fall in peak expiratory flow rate ≥15% after exercise. RESULTS: Of the 6813 schoolchildren retained for analysis, 227 (3.33%) experienced EIB after exercise. Odds ratios [95% confidence intervals] between EIB and allergic rhinitis phenotypes in the absence of asthma were 1.56 [0.92-2.63] for EHF, 1.97 [1.16-3.35] for past-year rhinoconjunctivitis, and 1.84 [1.16-2.91] for a SFAR ≥7. Results were unchanged after adjustment for confounders. Multiple correspondence analysis showed that EIB, although related to asthma, constitutes a separate entity. Exercise-induced bronchospasm was not significantly related to familial history of asthma. CONCLUSION: In our large population-based sample of children, different phenotypes of atopic rhinitis were associated with EIB, independently of asthma. Exercise-induced bronchospasm, although related to asthma, seems to constitute a separate entity. CLINICAL RELEVANCE: In this large (6813) sample of 10-year children drawn from the general population, EIB is associated with rhinitis phenotypes in the absence of asthma. Furthermore, it constitutes an entity independent from asthma and is not related to a familial history of asthma. Thus, investigating these symptoms could be important in this disease, as a specific nasal treatment might improve EIB in these children.

Casein-specific IL-4- and IL-13-secreting T cells: a tool to implement diagnosis of cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is a frequent food allergy in young children. The oral food challenge is the gold standard for diagnosis, and there is currently no reliable biological test. Our aim was to evaluate the diagnostic potential of a functional assay quantifying allergen-specific Th2 cells in CMA children. METHODS: A total of 29 children aged 2.8-10.5 years underwent a double-blind, placebo-controlled food challenge (DBPCFC) to cow's milk. Blood was collected before performing the DBPCFC, and peripheral mononuclear cells were cultured in an 18-h ELISpot assay with casein, α-lactalbumin, or ß-lactoglobulin. Numbers of antigen-specific IL-4- and IL-13-secreting lymphocytes and serum-specific IgE, IgG4, and total IgE levels were assessed. Receiver operating characteristic (ROC) curves were generated. RESULTS: A total of 17 (59%) children reacted to cow's milk and were therefore considered as allergic to cow's milk (CMA). The mean number of casein-specific IL-4- and IL-13-secreting T cells was higher in CMA than in non-CMA children (P = 0.009, 0.004, respectively). Moreover, it was inversely correlated with the cumulative dose of cow's milk tolerated (P = 0.003, 0.0009, respectively). ROC curve of combined IL-4 and IL-13 analysis showed an area under the curve of 0.98 (95% CI 0.90-1.06). For a cutoff of 10 IL-4- and 12 IL-13-secreting T cells, sensitivity and negative predictive value were 100%. CONCLUSIONS: Enumeration of casein-specific IL-4- and IL-13-secreting T cells appears a promising tool to improve diagnosis and, if confirmed in larger studies, could permit less frequent use of the oral food challenge.

Externalizing and internalizing behavioural problems related to asthma in school children.

We investigated the relationships of behavioural problems as assessed using the standardized Strengths and Difficulties Questionnaire (SDQ) to asthma in view of improving asthma management. Six thousand eight hundred and eighty children (mean age 10.4 years, male: 49%) were recruited in the French 6 Cities Study. Children with abnormal or borderline emotional symptoms (internalizing problems) or conduct problems (externalizing problems) were more asthmatic than others (P < 0.01). Compared to being normal, abnormal emotional symptoms or conduct problems were found to be related to mild-to-moderate persistent asthma (logistic model adjusted odds ratio = 1.55 (95% CI = 1.26-1.90) and 1.42 (95% CI = 1.17-1.71), respectively) and to early-onset asthma (Cox's model Adjusted Hazard Risk = 1.60 (95% CI = 1.27-2.01) and 1.34 (95% CI = 1.05-1.70). Borderline conduct problems were found to be negatively related to parents' knowledge on how to prevent asthma attacks, compared to normal conduct problems [adjusted OR = 0.51 (95% CI = 0.31-0.85)]. Further data are needed to better understand the involvement of behavioural problems in childhood asthma according to phenotypes.

Urinary S-PMA related to indoor benzene and asthma in children.

INTRODUCTION: Benzene is a ubiquitous pollutant of both indoor and outdoor environments which impacts on respiratory health. Our aim was to relate urinary S-phenylmercapturic acid (S-PMA), a biomarker of benzene exposure, to benzene concentrations and related sources at home and asthma in a population-based sample of children. METHODS: Exposure to benzene was assessed in the dwellings of 63 children (32 asthmatics and 31 controls) through the identification of sources of benzene and in situ assessments with passive samplers. The determination of urinary S-PMA was obtained by liquid chromatography-mass spectrometry. RESULTS: At home, asthmatics were significantly more polluted by benzene levels from ambient sampling than controls (p ≤ 0.05). Benzene exposure significantly aggravated asthma symptoms overall in non-atopic children (OR = 10.10; 95% confidence interval: 10.10). Urinary S-PMA was significantly associated with benzene concentrations in the entire population (regression coefficient = 0.28, 95% CI: 0.07-0.49; p < 0.05) and asthma (OR = 7.69; 95% CI: 1.37-42.52 for an increase of 1 µg/g creatinine of urinary S-PMA). However, after adjustment for environmental tobacco smoking exposure, familial allergy, age and sex, the latter relationship was no more significant (OR = 4.95; 95% CI: 0.91-27.4, p < 0.10). Both benzene concentrations and urinary S-PMA concentrations were higher in dwelling built after 1948 and in flats. CONCLUSIONS: Our study suggests a relationship between childhood asthma and benzene concentrations at home, even at low levels of this pollutant. This was confirmed when considering urinary S-PMA, which was related to both benzene concentrations and asthma. Further epidemiological and toxicological studies are needed to confirm our results.

Indoor pet allergen exposures modify the effects of chemical air pollutants on respiratory symptoms.

SETTING: Indoor volatile organic compound (VOC) levels, which are generally correlated with each other, may have an additive or synergistic effect on health. VOC synergy with allergens is a suspected mechanism affecting respiration.OBJECTIVE: To determine the effect of exposure to interactions between VOCs and allergens on respiratory symptoms in individuals aged ≥15 years.DESIGN: A national cross-sectional survey measured 20 VOCs and dog and cat aeroallergens in 490 main residential dwellings in France. A standardised questionnaire was used to elicit responses on respiratory conditions in 1012 inhabitants. Four VOC factor scores (linear combinations of VOCs) were generated using principal component analysis. In order to take into account the phenomenon of multi-pollution, marginal models were used to model the relationships between exposure to VOC mixture and respiratory conditions. Stratified models were used to examine the interaction between allergens and VOCs.RESULTS: The aromatic hydrocarbon score was associated with rhinitis and wheezing, the aliphatic hydrocarbon score with asthma and cough, the halogenated hydrocarbons with asthma, wheezing and rhinitis. Aldehydes and Can f1 had a significant synergistic effect on wheezing and rhinitis. Aliphatic hydrocarbons had an antagonist effect with Can f1 on wheezing.CONCLUSION: Our data support evidence of adverse effects of exposure to VOC mixture on respiratory conditions; this effect is aggravated in the presence of pet allergens.

Allergy and asthma: Effects of the exposure to particulate matter and biological allergens.

The prevalence of asthma and allergies including atopy has increased during the past decades, particularly in westernized countries. The rapid rise in the prevalence of such diseases cannot be explained by genetic factors alone. Rapid urbanization and industrialization throughout the world have increased air pollution and population exposures, so that most epidemiologic studies are focusing on possible links between air pollution and respiratory diseases. Furthermore, a growing body of evidence shows that chemical air pollution may interact with airborne allergens enhancing the risk of atopic sensitization and exacerbation of symptoms in sensitized subjects. These phenomena are supported by current in vitro and animal studies showing that the combined exposure to air pollutants and allergens may have a synergistic or additive effect on asthma and allergies, although there is an insufficient evidence about this link at the population level. Further research is needed in order to elucidate the mechanisms by which pollutants and biological allergens induce damage in exposed subjects. The abatement of the main risk factors for asthma and allergic diseases may achieve huge health benefits. Thus, it is important to raise awareness of respiratory allergies as serious chronic diseases which place a heavy burden on patients and on society as a whole.

Adverse respiratory effects of outdoor air pollution in the elderly.

Compared to the rest of the population, the elderly are potentially highly susceptible to the effects of outdoor air pollution due to normal and pathological ageing. The purpose of the present review was to gather data on the effects on respiratory health of outdoor air pollution in the elderly, on whom data are scarce. These show statistically significant short-term and chronic adverse effects of various outdoor air pollutants on cardiopulmonary morbidity and mortality in the elderly. When exposed to air pollution, the elderly experience more hospital admissions for asthma and chronic obstructive pulmonary disease (COPD) and higher COPD mortality than others. Previous studies also indicate that research on the health effects of air pollution in the elderly has been affected by methodological problems in terms of exposure and health effect assessments. Few pollutants have been considered, and exposure assessment has been based mostly on background air pollution and more rarely on objective measurements and modelling. Significant progress needs to be made through the development of 'hybrid' models utilising the strengths of information on exposure in various environments to several air pollutants, coupled with daily activity exposure patterns. Investigations of chronic effects of air pollution and of multi-pollutant mixtures are needed to better understand the role of air pollution in the elderly. Lastly, smoking, occupation, comorbidities, treatment and the neighbourhood context should be considered as confounders or modifiers of such a role. In this context, the underlying biological, physiological and toxicological mechanisms need to be explored to better understand the phenomenon through a multidisciplinary approach.