Omalizumab for the treatment of patients with severe allergic asthma with immunoglobulin E levels above >1500 IU/mL.

Immunoglobulin E (IgE) plays a critical role in the allergen-initiated inflammatory pathway and thus serves as a viable therapeutic target in allergic or IgE-mediated diseases such as asthma. Omalizumab, an anti-IgE biologic, has been approved in the United States (US, 2003) and in the European Union (EU, 2005) as an add-on therapy in patients with moderate-to-severe persistent asthma and severe allergic asthma (SAA) aged 6 years and older. The dose and frequency of omalizumab are adjusted based on the patient's body weight and baseline IgE levels, as recommended by its dosing tables. Currently, these dosing recommendations are limited to patients with baseline IgE levels of up to 1500 IU/mL in the European Union and 700 IU/mL in the United States. However, many patients with SAA have IgE levels >1500 IU/mL, highlighting an unmet need. This review presents the current evidence on the treatment benefits of omalizumab in patients with IgE levels >1500 IU/mL. The findings from the reviewed studies which included >3000 patients support the efficacy and effectiveness of omalizumab in reducing exacerbations, and improving asthma control, lung function, and quality of life in patients with severe asthma having IgE levels beyond the current dosing range. Omalizumab was well-tolerated in these patients, with no new safety signals. In addition, high IgE levels (>1500 IU/mL) are also reported in several comorbidities of asthma (allergic rhinitis, atopic dermatitis, allergic bronchopulmonary aspergillosis [ABPA], food allergy, and nasal polyposis) and omalizumab has demonstrated efficacy and safety in these indications. These data suggest that omalizumab may be considered for administration in SAA patients, with high IgE levels outside the current dosing tables. A detailed assessment of patients with high IgE levels is needed before deciding on the optimal treatment approach. A management algorithm for SAA patients with IgE >1500 IU/mL is proposed in this review and a suggestion to follow the Delphi consensus is advised.

Staphylococcal Sensitization: A Correlate of Type 2-High Inflammation in Children With Severe Asthma.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) has been identified to be a risk factor for asthma, but its determinants remain unclear. OBJECTIVE: To determine the significance of SE sensitization in children with moderate to severe asthma. METHODS: This was an observational cross-sectional analysis performed from 2011 to 2015 including children from the prospective Severe Asthma Molecular Phenotype cohort: school-age children with severe and moderate asthma or preschool-age children with severe and moderate recurrent wheeze. We evaluated sensitization to four SEs (Staphylococcus enterotoxin A, Staphylococcus enterotoxin B, Staphylococcus enterotoxin C, and toxic shock staphylococcic toxin). RESULTS: We analyzed data from 377 children: 233 of preschool age and 144 of school age. Among them, 26 (11.2%) and 59 (41.0%) children, respectively, had sensitization to at least one SE. The burden of sensitization was higher in older children in terms of both specific IgE levels and the number of sensitizations. In multivariable analysis, SE sensitization was associated with elevated total IgE in both populations (odds ratio [OR] = 9.35, P = .01; and OR = 8.06, P < .01), and with bronchoalveolar lavage eosinophilia in both preschool and school-age children (OR = 3.95, P = .03; and OR = 4.11, P = .03, respectively). Classification and regression trees showed an association of SE sensitization with age and with total IgE in the entire population, and with total IgE, bronchoalveolar lavage eosinophilia, and blood eosinophilia in school-age children. CONCLUSIONS: Staphylococcal enterotoxin sensitization was correlated with type 2-high inflammation (eosinophilic inflammation and elevated total IgE count) in this population of moderate to severe asthmatic children.

Maintenance of Asthma Control in Adolescents with Severe Asthma After Transitioning to a Specialist Adult Centre: A French Cohort Experience.

Background: The prevalence of severe asthma in adolescents is estimated at 6.7%. Transition to adult health services is a vulnerable period for adolescents where there is a risk of poor treatment adherence and loss to follow-up. Purpose: This retrospective study evaluated the maintenance of asthma control in young severe asthmatics, 6 months and 1 year after transition to a specialist adult centre. Methods: Patients with severe asthma treated in a paediatric pulmonology centre in the Île-de-France and referred at least 6 months previously to an adult service were included. Asthma control was evaluated by measuring the ACT score and respiratory function. Patients were asked to answer an on-line questionnaire about their experiences during transition. Results: Fifty-four adolescents with severe asthma underwent transition to the adult service between 2014 and 2021. Thirteen patients (25%) were lost to follow-up after an average of 22.4 months of follow-up. Three-quarters (73%) of patients had well controlled asthma with an ACT score ≥20 during transition and the majority were able to maintain good control and respiratory function (>60% FEV1 >80%) during follow-up in adult pulmonology. Among the patients that answered the questionnaire, 64.8% were satisfied with the transition process. Conclusion: Asthma control and respiratory function were maintained 6 months and 1 year after transition to the adult centre in the majority of patients. Most patients were satisfied with the transition process, but several improvements can be proposed, including early discussion of the medical plan and the implementation of procedures to reduce loss to follow-up.

Trajectories of IgE sensitization to allergen molecules from childhood to adulthood and respiratory health in the EGEA cohort.

BACKGROUND: Longitudinal studies assessing the association of profiles of allergen-specific IgE (sIgE) sensitization to a large range of allergen molecules and respiratory health are rare. We aimed to assess trajectories of molecular sIgE sensitization profiles from childhood to adulthood and their associations with respiratory health. METHODS: IgE reactivity to microarrayed allergen molecules were measured in childhood (EGEA1) and 12 years later in adult life (EGEA2) among 291 EGEA participants (152 with asthma). At each time point, sIgE sensitization profiles were identified by latent class analysis (LCA) by considering IgE-reactivity to the 38 most prevalent respiratory allergens. The LCA-defined profiles were then studied in association with respiratory health. RESULTS: At baseline, the mean (min-max) age of the population was 11 (4.5-16) years. The LCA identified four sIgE sensitization profiles which were very similar at both time points (% at EGEA1 and EGEA2); A: "no/few allergen(s)" (48%, 39%), B: "pollen/animal allergens" (18%, 21%), C: "most prevalent house dust mite allergens" (22%, 27%) and D: "many allergens" (12%, 13%). Overall, 73% of the participants remained in the same profile from childhood to adulthood. The profiles were associated with asthma and rhinitis phenotypes. Participants of profiles C and D had lower FEV1 % and FEF25-75 % as compared to profile A. Similar patterns of associations were observed for participants with asthma. There was no association with change in lung function. CONCLUSION: Using high-resolution sIgE longitudinal data, the LCA identified four molecular sensitization profiles, mainly stable from childhood to adulthood, that were associated with respiratory health.

Benefits and risks of bronchoalveolar lavage in severe asthma in children.

BACKGROUND: Although bronchoscopy can be part of the exploration of severe asthma in children, the benefit of bronchoalveolar lavage (BAL) is unknown. The present study aimed to decipher whether systematic BAL during a flexible bronchoscopy procedure could better specify the characteristics of severe asthma and improve asthma management. MATERIAL AND METHODS: The study took place in two departments of a university hospital in Paris. Children who underwent flexible bronchoscopy for the exploration of severe asthma between April 2017 and September 2019 were retrospectively included. RESULTS: In total, 203 children were included, among whom 107 had a BAL. BAL cell count was normal in most cases, with an increasing number of eosinophils with age, independently from the atopic status of the patients. Compared with bronchial aspiration only, BAL increased the rate of identified bacterial infection by 1.5. Nonatopic patients had more bacterial infections (p<0.001). BAL induced a therapeutic modification only for azithromycin and omalizumab prescriptions. The practice of a BAL decreased bronchoscopy tolerance (p=0.037), especially in the presence of tracheobronchial malacia (p<0.01) and when performed in a symptomatic patient (p=0.019). DISCUSSION AND CONCLUSION: Although BAL may provide interesting information in characterising severe asthma, in most cases its impact on the patient's management remains limited. Moreover, BAL can be poorly tolerated and should be avoided in the case of tracheobronchial malacia or current asthma symptoms.

Omalizumab Effectiveness in Severe Allergic Asthma with Multiple Allergic Comorbidities: A Post-Hoc Analysis of the STELLAIR Study.

BACKGROUND: Immunoglobulin (Ig) E-mediated pathophysiological mechanisms are common in allergic diseases including severe allergic asthma (SAA). The anti-IgE monoclonal antibody omalizumab may be particularly beneficial for patients with SAA and multiple allergic comorbidities (AC) including perennial/seasonal rhinitis, conjunctivitis, atopic dermatitis (AD), and food allergy. METHODS: We conducted a post-hoc analysis of the patients from the STELLAIR study (n=872, 149 minors and 723 adults). The patients were classified based on the presence of multiple AC (≥3 AC or <3 AC) or AD as assessed by questionnaire. Response to omalizumab was assessed after 4-6 months (T4-6) and after 12 months (T12). Asthma response at T4-6 was based on global evaluation of treatment effectiveness, reduction of ≥40% in annual exacerbation rate, and a combination of both. Asthma response at T12 was based on change in yearly exacerbation and hospitalization rates. AC improvement at T12 was based on patient perception. RESULTS: Patients with ≥3 AC demonstrated a higher combined response to omalizumab (74.7% vs 58.3%) at T4-6 and had reduced yearly exacerbation and hospitalization rates (88.9% vs 77.4% and -94.0% vs -70.5%, respectively). Patients with ≥3 AC were more likely to show an improvement in their AC (85.3% vs 51.9%) at T12. Results were similar in minors and adults. The presence of AD was associated with greater omalizumab effectiveness at T4-6 and a greater AC improvement at T12. Improvement of AD and food allergies at T12 were 73.2% and 38.7%, respectively, in the population overall. CONCLUSION: This post-hoc analysis of the STELLAIR study shows that omalizumab is beneficial for all SAA patients and especially for patients with multiple AC or AD. In patients with ≥3 AC, omalizumab also improved AC outcomes.

Mediterranean diet and lung function, sensitization, and asthma at school age: The PARIS cohort.

BACKGROUND: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age. METHODS: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. RESULTS: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV1 and FVC. CONCLUSION: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children.

Determinants of blood eosinophilia in moderate and severe asthmatic patients during childhood: Evidence from the severe asthma molecular phenotype (SAMP) cohort.

BACKGROUND: Asthma is a heterogeneous disease in which the interaction between genetic and environmental factors plays a major role. The significance of blood eosinophil is unclear. The aim of the study was to determine the significance of blood eosinophil count in moderate-to-severe asthmatic children of preschool age and school age. METHODS: This was a prospective cross-sectional study performed from 2011 to 2015 including children from the severe asthma molecular phenotype (SAMP) cohort at Trousseau Hospital (Paris, France). We included children with severe and moderate asthma, or severe and moderate recurrent wheeze, aged from 1 to 15 years at the time of exploration. RESULTS: We analyzed data from 402 children: 248 of preschool age and 154 of school age. Blood eosinophil count third quartile thresholds were 322 and 600 cells/µL for the preschool- and school-age groups, respectively. In multivariate analysis, a blood eosinophil count over this threshold was associated with elevated total IgE (OR = 5.33, P < .01), multiple hospitalizations for asthma attacks (OR = 4.96, P = .03), and a maternal history of asthma (OR = 4.91, P = .01) in preschool children; and with staphylococcal toxin-specific IgE (OR = 2.75, P = .03) in children of school age. Random forest analysis reinforced these results. CONCLUSION: High blood eosinophil count is linked to both atopic features and control of asthma with different parameters associated with these features depending on age.

Association between lung function of school age children and short-term exposure to air pollution and pollen: the PARIS cohort.

BACKGROUND: Daily levels of ambient air pollution and pollen may affect lung function but have rarely been studied together. We investigated short-term exposure to pollen and air pollution in relation to lung function in school-age children from a French population-based birth cohort. METHODS: This study included 1063 children from the PARIS (Pollution and Asthma Risk: an Infant Study) cohort whose lung function and FeNO measurements were performed at age 8 years old. Exposure data were collected up to 4 days before testing. We estimated daily total pollen concentration, daily allergenic risk indices for nine pollen taxa, as well as daily concentrations of three air pollutants (particulate matter less than 10 µm (PM10), nitrogen dioxide (NO2), ozone (O3)). Children with similar pollen and air pollution exposure were grouped using multidimensional longitudinal cluster analysis. Associations between clusters of pollen and air pollution exposure and respiratory indices (FEV1, FVC, FeNO) were studied using multivariable linear and logistic regression models adjusted for potential confounders. RESULTS: Four clusters of exposure were identified: no pollen and low air pollution (Cluster 1), grass pollen (Cluster 2), PM10 (Cluster 3) and birch/plane-tree pollen with high total pollen count (Cluster 4). Compared with children in Cluster 1, children in Cluster 2 had significantly lower FEV1 and FVC levels, and children from Cluster 3 had higher FeNO levels. For FEV1 and FVC, the associations appeared stronger in children with current asthma. Additional analysis suggested a joint effect of grass pollen and air pollution on lung function. CONCLUSION: Daily ambient chemical and biological air quality could adversely influence lung function in children.

Emergence of pollen food allergy syndrome in asthmatic children in Paris.

BACKGROUND: Over the last few decades, the level of pollen from birch and homologous trees has increased in parts of Europe. Sensitization to birch pollen allergens (principally Bet v 1) has been associated with food cross-reactivity called pollen food allergy syndrome (PFAS). OBJECTIVE: To evaluate changes in allergic diseases due to IgE sensitization over 25 years in asthmatic children. METHODS: This was a cross-sectional retrospective study conducted in Paris. We analyzed two cohorts of asthmatic children with similar characteristics explored between 1993-1999 (old cohort = OC) and 2012-2018 (recent cohort = RC). RESULTS: 121 children were in the OC and 120 in the RC. An increase in sensitization to tree pollens was found especially for birch pollen, which was 11.6% in the OC and 31% in the RC (P = .0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, P < .0001). IgE-mediated food allergy increased from 6% to 16% in the OC and RC, respectively, (P = .01) mainly due to PFAS. In the RC, a higher mean Bet v 1-specific IgE level was observed in children with PFAS compared to children without (105.7 KU/L ± 17.8 and 48.9 kU/L ± 15.7, respectively, P < .05). CONCLUSION: Allergic rhinitis and food allergy with tree pollen sensitization have increased in Paris over 25 years mainly due to PFAS. Environmental factors could be responsible for these modifications as described in the literature.

Two Different Composite Markers Predict Severity and Threshold Dose in Peanut Allergy.

BACKGROUND: Safe and cost-effective biological surrogate markers to evaluate the severity and threshold dose of peanut allergy (PA) reactions during an oral food challenge (OFC) are lacking. OBJECTIVE: To evaluate biological markers associated with the severity and threshold dose of an allergic reaction during an OFC in a population of children with PA. METHODS: Demographic and biological parameters of children with peanut OFC and basophil activation test (BAT) results were collected. Patients were stratified into 2 severity groups (mild-to-moderate and severe) and 2 cumulative threshold dose groups: low (LCTG) ≤100 mg crushed peanut and high >100 mg. RESULTS: Among the 68 children included, there was a 96% concordance between the OFC and BAT result for the diagnosis of PA. Of the 56 children with a positive OFC and BAT to peanut (median age: 8.8 years), the severity of an allergic reaction and the cumulative threshold dose were not correlated (P = .24). Higher Ara h 2-specific IgE and FcεRI-positive control values were both associated with severe reactions to peanut. Combining these 2 markers led to a 92% sensitivity (84%-97%) and an 82% specificity (71%-89%) for severe reactions in all subjects. For children in the LCTG, a 4-variable composite marker, including age, normalized basophil sensitivity (EC50), and FcεRI- and fMLP-positive control values, resulted in a 97% sensitivity (89%-99%) and 61% specificity (49%-71%). CONCLUSION: Distinct composite markers including BAT allergen-specific and non-allergen-specific parameters appear to be associated with severity and cumulative threshold dose in children with PA.

Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort.

BACKGROUND: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. METHODS: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. RESULTS: Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8 years. CONCLUSION: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.

Endotypes identified by cluster analysis in asthmatics and non-asthmatics and their clinical characteristics at follow-up: the case-control EGEA study.

BACKGROUND: Identifying relevant asthma endotypes may be the first step towards improving asthma management. We aimed identifying respiratory endotypes in adults using a cluster analysis and to compare their clinical characteristics at follow-up. METHODS: The analysis was performed separately among current asthmatics (CA, n=402) and never asthmatics (NA, n=666) from the first follow-up of the French EGEA study (EGEA2). Cluster analysis jointly considered 4 demographic, 22 clinical/functional (respiratory symptoms, asthma treatments, lung function) and four blood biological (allergy-related, inflammation-related and oxidative stress-related biomarkers) characteristics at EGEA2. The clinical characteristics at follow-up (EGEA3) were compared according to the endotype identified at EGEA2. RESULTS: We identified five respiratory endotypes, three among CA and two among NA: CA1 (n=53) with active treated adult-onset asthma, poor lung function, chronic cough and phlegm and dyspnoea, high body mass index, and high blood neutrophil count and fluorescent oxidation products level; CA2 (n=219) with mild asthma and rhinitis; CA3 (n=130) with inactive/mild untreated allergic childhood-onset asthma, high frequency of current smokers and low frequency of attacks of breathlessness at rest, and high IgE level; NA1 (n=489) asymptomatic, and NA2 (n=177) with respiratory symptoms, high blood neutrophil and eosinophil counts. CA1 had poor asthma control and high leptin level, CA2 had hyper-responsiveness and high interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels, and NA2 had high leptin and C reactive protein levels. Ten years later, asthmatics in CA1 had worse clinical characteristics whereas those in CA3 had better respiratory outcomes than CA2; NA in NA2 had more respiratory symptoms and higher rate of incident asthma than those in NA1. CONCLUSION: These results highlight the interest to jointly consider clinical and biological characteristics in cluster analyses to identify endotypes among adults with or without asthma.

Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts.

BACKGROUND: Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults. OBJECTIVE: We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis. METHODS: Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO2, PM10, PM2.5, and PMcoarse (calculated by subtracting PM2.5 from PM10) was estimated using land-use regression models derived from the European Study of Cohorts for Air Pollution Effects project, at the participants' residential address. The score of rhinitis severity (range, 0-12), based on intensity of disturbance due to symptoms reported by questionnaire, was categorized into low (reference), mild, moderate, and high severity. Polytomous logistic regression models with a random intercept for city were used. RESULTS: A total of 1408 adults with rhinitis (mean age, 52 years; 46% men, 81% from the European Community Respiratory Health Survey) were included. The median (1st quartile-3rd quartile) score of rhinitis severity was 4 (2-6). Higher exposure to PM10 was associated with higher rhinitis severity (adjusted odds ratio [95% CI] for a 10 µg/m3 increase in PM10: for mild: 1.20 [0.88-1.64], moderate: 1.53 [1.07-2.19], and high severity: 1.72 [1.23-2.41]). Similar results were found for PM2.5. Higher exposure to NO2 was associated with an increased severity of rhinitis, with similar adjusted odds ratios whatever the level of severity. Adjusted odds ratios were higher among participants without allergic sensitization than among those with, but interaction was found only for NO2. CONCLUSIONS: People with rhinitis who live in areas with higher levels of pollution are more likely to report more severe nasal symptoms. Further work is required to elucidate the mechanisms of this association.

Childhood-onset severe hypereosinophilic asthma: efficacy of benralizumab.

Severe hypereosinophilic asthma in children is extremely rare. This letter adds to the existing literature by providing long-term follow-up, and is the first report of the marked efficacy of benralizumab after failure of other biologic treatments. https://bit.ly/2G7Tc2k.

Asthma and allergic rhinitis risk depends on house dust mite specific IgE levels in PARIS birth cohort children.

BACKGROUND: The natural history of allergic sensitization in childhood, and its impact on allergic disease development, needs to be clarified. This study aims to identify allergic sensitization and morbidity patterns during the first 8 years of life. METHODS: The study was conducted in the on-going population-based prospective Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort. Sensitization profiles were identified by k-means clustering based upon allergen-specific IgE levels measured at 18 months and 8/9 years. Allergic morbidity profiles were identified by latent class analysis based on symptoms, symptom severity, treatments, and lifetime doctor-diagnoses of asthma, allergic rhinitis, and atopic dermatitis and on lower respiratory infections before 2 years. RESULTS: Five sensitization and 5 allergic morbidity patterns were established in 714 children. Children not sensitized or with isolated and low allergen-specific sensitization were grouped together (76.8%). A profile of early and transient sensitization to foods that increased the risk of asthma later in childhood was identified (4.9%). Children strongly sensitized (≥3.5 kUA/L) to house dust mite at 8/9 years (9.0%) had the highest risk of asthma and allergic rhinitis. Finally, timothy grass pollen at 8/9 years sensitization profile (5.3%) was related to respiratory allergic diseases, as was early onset and persistent sensitization profile (4.1%), this latter being also strongly associated with atopic dermatitis. CONCLUSIONS & CLINICAL RELEVANCE: We show that accurate assessment of the risk of allergic disease should rely on earliness and multiplicity of sensitization, involved allergens, and allergen-specific IgE levels, and not considering solely allergic sensitization as a dichotomous variable (allergen-specific IgE ≥0.35 kUA/L), as usually done. This is particularly striking for house dust mite. We are hopeful that, pending further confirmation in other populations, our findings will improve clinical practice as part of an approach to allergic disease prevention.

Associations of black carbon with lung function and airway inflammation in schoolchildren.

BACKGROUND: Few studies have investigated the 24-hour respiratory health effects of personal black carbon (BC) and ultrafine particles (UFP) exposure in schoolchildren. The objective of this study was to investigate these associations with the lung function in children 10-years old with and without persistent respiratory symptoms. METHODS: We conducted a cross-sectional study in 305 children (147 and 158 with and without persistent respiratory symptoms, respectively) from three European birth-cohorts: PARIS (France) and INMA Sabadell and Valencia (Spain). Personal 24-hour measurements of exposure concentrations to BC and UFP were performed by portable devices, before lung function testing. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the fraction of exhaled nitric oxide (FeNO) were determined. RESULTS: There was no association of UFP with lung function parameters or FeNO whereas the increase in 24-hour BC exposure concentrations was related to a statistically significant decrease in lung function parameters only among children with persistent respiratory symptoms [-96.8 mL (95% Confidence Interval CI: -184.4 to -9.1 mL) in FVC, and -107.2 mL (95% CI: -177.5 to -36.9 mL) in FEV1 for an inter-quartile range of 1160 ng/m3 exposure increase]. A significant positive association between BC and FeNO was observed only in children with persistent respiratory symptoms with current wheezing and/or medication to improve breathing [FeNO increases with +6.9 ppb (95% CI: 0.7 to 13.1 ppb) with an inter-quartile range BC exposure increase]. CONCLUSION: Children suffering from persistent respiratory symptoms appear to be more vulnerable to BC exposure.

Maternal diet before and during pregnancy and risk of asthma and allergic rhinitis in children.

BACKGROUND: Consumption of certain foods during pregnancy has been shown to have beneficial effects on childhood asthma and allergic disease development and aggravation. However, most studies provide conflicting results and the relationships between maternal preconceptional diet and risks of childhood asthma and allergic disease have not previously been explored. The objective of this study was to assess maternal diet during the year before pregnancy and the last 3 months of pregnancy and investigate their associations with the risks of asthma, wheezing, allergic rhinitis and atopic dermatitis in young children. METHODS: The study sample consisted of 1140 mother-child pairs from the EDEN cohort. Mothers had responded to the food frequency questionnaires used to assess diet before and during pregnancy. Children were followed up using health questionnaires. The health outcomes studied were: asthma, wheezing, allergic rhinitis and atopic dermatitis by the age of 3 years. RESULTS: Using multivariable-adjusted logistic regression models, significant inverse associations were observed between cooked green vegetable consumption before pregnancy and childhood asthma; consumption of eggs and raw vegetables before and during pregnancy, consumption of grains before pregnancy, and consumption of cooked green vegetables during pregnancy and allergic rhinitis. For the first time, a significant positive association was found between meat intake during the preconceptional period and a risk of wheezing, allergic rhinitis and atopic dermatitis. CONCLUSIONS: Based on our findings, preconceptional and prenatal maternal intake of certain type of food groups may be preventive against asthma, wheezing and allergic rhinitis, whereas higher maternal intake of meat before pregnancy may increase the risk of wheezing, allergic rhinitis and atopic dermatitis in young children.