A document by Marguerite Lawler. Click on the document to view its contents.

Dietary diversity during infancy and the association with childhood food allergen sensitization Authors: Kate Maslin PhD1,2, Kaci Pickett MSc3, Suzanne Ngo3,4 MD, William Anderson3,4 MD, Taraneh Dean PhD2,5, Carina Venter PhD2,3,4School of Nursing and Midwifery, University of Plymouth, Plymouth, UK.The David Hide Asthma and Allergy Centre, St. Mary’s Hospital, Isle of Wight, UKUniversity of Colorado School of Medicine, Colorado, USAAllergy and Immunology Section, Children’s Hospital Colorado, Colorado, USAUniversity of Brighton, Brighton, UKRunning title: Dietary diversity and food sensitization

Graded home introduction of egg is safe, well received and cost effective when managing childhood egg allergyTo the Editor,In Australia, an IgE mediated allergy to egg is a common food allergy in children.1-2 The 2011 HealthNuts study determined that 8.9% of children in Australia have an egg allergy.1-2IgE mediated allergy to egg can be mild and most children may outgrow this by 4-5 years of age.3-4 Almost 80% of children with IgE mediated egg allergy are tolerant of egg in a baked form with wheat being used as a matrix.1,3 Turner et al. suggests that the outcome of baked egg challenges can be unpredictable and can lead to anaphylaxis even in children with prior mild symptoms.5 Tolerance to baked egg is generally confirmed by a baked egg food challenge in hospital after which patients are encouraged to introduce baked egg products at home.6 Patients are reassessed and subsequently undergo a lightly cooked egg challenge in hospital where resolution is confirmed if successful.6Whereas there is evidence that majority of children with an egg allergy are tolerant to baked egg, there is debate as to whether it can reduce the duration of egg allergy.7-9 Recently, Gotesdyner et al found that a structured graded exposure using baked egg followed by lightly cooked egg compared to complete avoidance helped achieve tolerance to egg.3 Their findings suggest that an egg ladder may promote a faster resolution of egg allergy. However, due to the case control study design and small sample size definite conclusions could not be drawn.3Our Paediatric Allergy Service is a busy tertiary level clinic with more than 2000 outpatient interactions annually. To reduce the burden on tertiary resources, an egg tolerance ladder was developed (Appendix 1). It has been offered to patients considered low risk which includes (but is not limited to) patients with a single food allergy; mild or no eczema; mild, well controlled or no coexisting asthma; and/or a history of IgE mediated egg allergy without anaphylaxis. It has been designed to allow slow introduction of baked egg followed by foods containing small amounts of cooked egg and finally lightly cooked egg at home. Support throughout the home introduction process is provided by the treating team via email and phone contact.The aim of this study was to evaluate the use of this structured “egg ladder” with regards to its safety as well as user satisfaction and barriers that arose in negotiating it. We also attempted to determine potential risk factors which increased likelihood of clinical reaction to foods containing egg and rates of eventual tolerance to lightly cooked and raw egg achieved in the home environment. This study was approved by the Ethics Committee at John Hunter Children’s Hospital (2020/ETH01192).Patients with mild to moderate IgE mediated egg allergy aged 0-18 years seen in the Paediatric Allergy Clinic and commenced on an egg tolerance ladder by the Paediatric Immunologist were recruited retrospectively. Verbal and written education on the use of the ladder had been provided at the time of clinic review. Patients were excluded from home introduction if they had a history of anaphylaxis to any food containing egg or a non-IgE mediated egg allergy.A file audit identified a total of 98 patients for inclusion in this study who had been commenced on the egg ladder between September 2018 and June 2020. Patients were contacted by email and phone, and offered participation in a telephone survey to evaluate the use of the egg tolerance ladder. Almost half (47 patients) consented to the study. At the time of commencing the egg ladder, patients had a mean age of 40 months (IQR: 12-60 months). Six children did not have a skin prick test (SPT). The majority were sensitised with a mean SPT of 3.1mm. Most (66%) had at least one atopic comorbidity and almost half had more than one food allergy. The vast majority (87.2%) of patients commenced the egg ladder at home. This includes 23 patients already tolerant to baked egg prior to clinic presentation, based on clinical history. Only 3 (6%) used the resources of an inpatient challenge.Patients had spent an average of 15.5 months (IQR: 9-21.5 months) on the ladder. At the time of review, 43% of patients had completed the egg ladder but interestingly, four parents believed their child was still allergic to egg. The mean age of commencement on the egg ladder was higher than expected (40 months), and around the age a child is expected to outgrow an allergy to egg.3-4 Despite this, many patients reported reactions while using the egg ladder. A mild reaction was reported by 18 (38%) parents, 16 required treatment and of those one was given adrenaline. This child was 6 years of age, had an isolated egg allergy and small skin test (3.5mm). They reacted to Step 5 and have continued Step 4 at home successfully. Both families reporting a severe reaction recommenced the ladder and were able to subsequently progress successfully to Step 5 or 6. The majority had a mild skin response (rash or hives). Skin testing was a poor differentiator for clinical reaction with 38% of those with negative skin testing reporting a mild reaction with baked egg.Parental satisfaction was high with 78.7% satisfied or very satisfied with the egg ladder. Most of the remaining families were neutral with no families dissatisfied with the ladder use. Many stated that they valued the structured approach of introducing egg which helped identify their child’s level of tolerance, and allowed them to progress at their own pace. A number of parents identified the main barrier to progressing the ladder was the taste and/or texture of egg after successfully completing the ladder and subsequent difficulty maintaining regular lightly cooked egg in the diet. These families continued egg as an ingredient in cooked or baked food.There were some limitations to this study. Firstly, this was a retrospective small sized survey and some patients were unable to accurately recall timelines. As a voluntary survey there is also a risk of ascertainment bias. Baseline patient demographics (age, sex, SPT size, comorbid allergy diagnoses) of non-responders were compared to the study cohort with no significant differences identified. The initial education on commencing on the egg ladder was provided by multiple clinicians and information therefore was unable to be standardised. As expected, a number of patients at the time of the survey were still navigating the egg ladder and therefore had not had enough time to reach their individual threshold to determine if their child had outgrown their allergy. This may lead to under-reporting of egg tolerance on the ladder. Finally, follow up or assistance with the egg ladder was not provided unless the parent contacted the team. This may have resulted in less children completing the ladder due to parental anxiety over mild reactions.We have shown that the use of a structured egg ladder for egg allergic children without a history of anaphylaxis can be safe, is well tolerated and is a positive experience for families. It can prevent time consuming and costly inpatient supervised challenges unnecessarily consuming valuable and scarce resources in busy allergy clinics. Future prospective studies will help establish the role of home egg introduction in childhood egg allergy management in both tertiary and secondary health care settings.Conflicts of InterestNo conflicts to be declared.Leah Thomas1Jan Belcher1Rachael Phillips1Kahn Preece, MBBS, FRACP1Rani Bhatia, MBBS, FRACP11Department of Paediatric Allergy and Immunology, John Hunter Children’s Hospital, Newcastle, AustraliaReferences1. Osborne NJ, Koplin JJ, Martin PE, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. Journal of Allergy and Clinical Immunology. 2011;127:668-76.2. Dang TD, Peters RL, Koplin JJ, et al. Egg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts. Allergy. 2019; 74: 2.3. Gotesdyner L, Zeldin Y et al. A structured graduated protocol with heat denatured eggs in the treatment of egg allergy. Pediatric Allergy and Immunology. 2019;30:824-832.4. Leonard SA, Sampson HA, Sicerer SH, et al. Dietary baked egg accelerates resolution of egg allergy in children. Journal of Allergy and Clinical Immunology. 2012;13:2.5. Turner PJ, Mehr S, Joshi P et al. Safety to food challenges to extensively heated egg in egg-allergic children: a prospective cohort study. Pediatric Allergy and Immunology. 2013;24:450-455.6. Clark A, Islam S, King Y. A longitudinal study of resolution of allergy to well-cooked and uncooked egg. Clinical & Experimental Allergy. 2011;41:706-712.7 Lambert R, Grimshaw K, Elis B et al. Evidence that eating baked egg or milk influences egg or milk allergy resolution: A Systematic Review. Clin Exp Allergy. 2017;47(6):829-837.8. Upton J, Nowak-Wegrzyn A. The impact of baked egg and baked milk diets on IgE and Non-IgE mediated allergy. Clinical Reviews in Allergy & Immunology. 2018;55(2):118-138.9. Leonard SA, Caubet JC, Kim, JS, Groetch M, Wegrzyn AN. Baked Milk- and Egg-Containing Diet in the Management of Milk and Egg Allergy. Journal of Allergy and Clinical Immunology. 2015;1:13 – 23.

Background: The ‘old friends’ hypothesis posits that reduced exposure to previously ubiquitous microorganisms is one factor involved in the increased rates of allergic diseases. Cytomegalovirus (CMV) may be one of the “old friends” hypothesized to help prevent allergic diseases. We sought to elucidate whether early-life CMV infection is associated with childhood atopy via perturbations of the gut microbiota. Methods: Participants were recruited from a population-based birth cohort (CHILD study) and followed prospectively until age five years in four Canadian cities. A total of 928 participants provided stool microbiome data, urine for CMV testing, skin-prick tests, and questionnaires-based detailed environmental exposures. CMV infection was assessed in the first year of life while the main outcome was defined by persistent sensitization to any allergen at ages 1, 3, and 5 years. Results: Early CMV infection was associated with increased beta and decreased alpha diversity of the gut microbiota. Both changes in diversity measures and early CMV infection were associated with persistent allergic sensitization at age 5 years (aOR= 2.08; 95%CI: 1, 4.33). Mediation analysis demonstrated that perturbation of gut microbial composition explains 30% of the association. Conclusions: Early-life CMV infection is associated with an alteration in the intestinal microbiota, which mediates the effect of the infection on childhood atopy. This work indicates that preventing CMV infection would not put children at increased risk of developing atopy. Rather, a CMV vaccine, in addition to preventing CMV-associated morbidity and mortality, might reduce the risk of childhood allergic diseases.

Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled LTB4, characterizes childhood asthma. While FeNO has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15-HETE, but not TXB2, showed significant difference between asthmatics (N=318) and healthy controls (N=97), particularly the severe group showed the lowest levels of exhaled 15-HETE. Receiver Operating Characteristic (ROC) analyses revealed similar distinguishing power for the levels of 15-HETE, FEV1 and FeNO, whilethe 15-HETE/LTB4 ratio was significantly lower in subjects with severe asthma (p<0.01). Analysis of asthmatics (N=75) during exacerbation and convalescence showed significant improvement in lung function (FEV1; p<0.001), but not FeNO, concomitant with significantly increased levels of 15-HETE (p<0.001) and reduced levels of TXB2 (p<0.05) after therapy, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and LXA4 at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15-HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15-HETE were prominent after treatment.

Background: Quantifying age trends in healthcare costs of pediatric asthma leads to better understanding of the natural history of the disease and informed decision-making on the allocation of healthcare resources. Methods: We identified children with incident asthma from the health administrative data of British Columbia, Canada (Jan 1998 to Dec 2015), and followed them from their first diagnosis of asthma or wheezing until age 18. We estimated direct medical costs (in 2016 Canadian dollars [$]), including inpatient and outpatient encounters and pharmacy costs, attributed to asthma (primary outcome) and other respiratory diseases (secondary outcome). We assessed the impact of sex and socioeconomic status on age trends, adjusting for calendar effect. Results: The final analysis included 44,552 children with asthma (62% boys). From age 0 to 18, costs of asthma/wheezing and other respiratory conditions decreased from $1,036 to $29/child-year, and from $1,145 to $31/child-year, respectively. Children under 3 years of age incurred 4–fold higher costs for asthma/wheezing and other respiratory conditions. In particular, costs of asthma hospitalizations were 10 times higher in this age group compared to older children. Age trends were generally similar between sex groups and across socioeconomic status. However, medication costs for asthma/wheezing decreased in boys, whereas those in girls declined during childhood but increased during adolescence. Conclusions: The highest costs of pediatric asthma are concentrated in children younger than 3. Age trends were generally consistent between sex and across socioeconomic status.

A document by Jana Eckert. Click on the document to view its contents.

Background. Whether small airway dysfunction (SAD), which is prevalent in asthma, helps to characterize wheezing phenotypes is undetermined. The objective was to assess whether SAD parameters obtained from impedance measurement and asthma probability are linked. Methods. One hundred and thirty-nine preschool children (mean age 4.7 years, 68% boys) suffering from recurrent wheeze underwent impulse oscillometry that allowed calculating peripheral resistance and compliance of the respiratory system (markers of SAD) using the extended RIC model (central and peripheral Resistance, Inertance and peripheral Compliance of the respiratory system). Children were classified using the probability-based approach of GINA guidelines (few, some, most having asthma). A principal component analysis (PCA) that determined the dimensions of wheezing disease evaluated the links between SAD and asthma probability. Results. Forty-seven children belonged to the few, 28 to the some and 64 to the most having asthma groups. Whereas their anthropometrics and measured parameters were similar, the most having asthma group exhibited the lowest mean value of airway inertance after bronchodilator probably due to airway inhomogeneities. PCA characterized nine independent dimensions including a peripheral resistance (constituted by baseline peripheral resistance, AX, R5-20Hz, X5Hz), a central resistance (baseline central resistance, R20Hz) and an airway size dimension (post-bronchodilator inertance and central resistance). PCA showed that the SAD markers were independent from clinical dimensions (control and asthma probability were two other dimensions) and did not help to define wheezing phenotypes. Conclusions. Lung function parameters obtained from impulse oscillometry and asthma probability were belonging to independent dimensions of the wheezing disease.

Background Beta-lactams generate different allergenic determinants that induce selective or cross-reactive drug hypersensitivity reactions (DHRs). We aimed to identify the drugs involved, the selectivity of the response, the mechanism, and the value of the different diagnostic tests for establishing a diagnosis in children evaluated for DHRs to beta-lactams. Methods Prospective study evaluating children aged under 16 years reporting DHRs to beta-lactams. Reactions were classified as immediate and nonimmediate reactions. The work-up included sIgE, skin testing and drug provocation tests (DPTs) for immediate reactions and patch testing and DPTs for nonimmediate ones. Results Of the 510 included children, 133 were evaluated for immediate reactions and confirmed in 8.3%. Skin test/in vitro IgE contributed to diagnosing half of the cases. Selective reactions occurred with amoxicillin (63%), followed by common penicillin determinants (27%) and cephalosporins (0.9%). Among nonimmediate reactions (11,4% of the 377 children evaluated), most required DPTs, 52.7% of which were positive at 6–7 days of drug challenge. Selective reactions were identified with amoxicillin (80%), penicillin G (7.5%), cephalosporins (7.5%), and clavulanic acid (5%). Urticaria and maculopapular exanthema were the most frequent entities. Conclusions There were few confirmed cases of either type of reaction. Skin testing proved less valuable in nonimmediate reactions, over half of which would also have been lost in a short DPT protocol. Selective responders to amoxicillin were more likely to have nonimmediate reactions, while clavulanic acid-selectivity was exclusive to the nonimmediate typology. Over half the cases with DPTs required 6-7 days of treatment for DHR confirmation.

Background: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. Methods: This study retrospectively analyzed data from the Japan Environment and Children’s Study, a nationwide birth cohort study, conducted between 2011 and 2014. Data of women with singleton births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, a logistic regression model was used to calculate adjusted odds ratios for “wheezing ever,” diagnosis of asthma in the last 12 months, and “asthma ever” in women with MRA, with women who did not receive MRA as the reference. Participants were stratified by term births, and adjusted odds ratios for outcomes were calculated using a logistic regression model. Results: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing ever was 1.17 (95% confidence interval, 1.12–1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. Conclusion: MRA was associated with an increased incidence of childhood wheezing up to three years, irrespective of term births or preterm births. It is important that perinatal physicians consider both the adverse maternal side effects of MRA and its potential effects on the offspring’s childhood.

BACKGROUND: Despite SARS-CoV-2 immunizations have started in most countries, children are not currently included in the vaccination programs, thus it remains crucial to define their anti-SARS-CoV-2 immune response in order to minimize the risk for other epidemic waves. This study seeks to provide a description of the virology ad anti-SARS-CoV-2 immunity in children with distinct symptomatology. METHODS: Between March and July 2020, we recruited 15 SARS-CoV-2 asymptomatic (AS) and 51 symptomatic children (SY), stratified according to WHO clinical classification. We measured SARS-CoV-2 viral load using ddPCR and qPCR in longitudinally collected nasopharyngeal swabs samples. To define anti-SARS-CoV-2 antibodies we measured neutralization activity and total IgG load (Diasorin). We also evaluated antigen-specific B and CD8+T-cells, using a labelled S1+S2 protein and ICAM expression, respectively. Plasma protein profiling was performed with Olink. RESULTS: Virological profiling showed that AS had lower viral load at diagnosis (p=0.004) and faster virus clearance (p=0.0002) compared to SY. Anti-SARS CoV-2 humoral and cellular response did not appear to be associated with the presence of symptoms. AS and SY showed similar titers of SARS-CoV-2 IgG, levels of neutralizing activity, and frequency of Ag-specific B and CD8+T-cells. Whereas pro-inflammatory plasma protein profile was associated to symptomatology. CONCLUSION: We demonstrated the development of anti-SARS-CoV-2 humoral and cellular response with any regards to symptomatology, suggesting the ability of both SY and AS to contribute towards herd immunity. The virological profiling of AS suggested that they have lower virus load associated with faster virus clearance.

1 Conflicts of interestESC has received research support from DBV Technologies; has been a member of advisory boards for Pfizer, Pediapharm, Leo Pharma, Kaleo, DBV, AllerGenis, Sanofi Genzyme, Bausch Health, Avir Pharma; is a member of the healthcare advisory board for Food Allergy Canada; was an expert panel and coordinating committee member of the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Guidelines for Peanut Allergy Prevention; and was co-lead of the CSACI oral immunotherapy guidelines.SJ has been on speaker’s bureaus for Aralez, Novartis, Astra Zeneca, and Sanofi, and on the advisory board for Sanofi.MH has provided speaker services for Pfizer, Pediapharm, and has been part of an advisory board for ALK and provides privately funded OIT.VC has been a participant on advisory boards for Sanofi Genzyme, Bausch Health, and ALK, speaker services for Aralez Pharmaceuticals and CSL Behring.DM has provided consultation and speaker services for Pfizer, Aimmune, Kaleo, Merck, Covis and Pediapharm, and has been part of an advisory board for Pfizer and Bausch Health. He sits on the editorial board for the Journal of Food Allergy.EA Section Head of Anaphylaxis/Food Allergy for the Canadian Society of Allergy and Clinical Immunology; sits on steering committee for Canada’s National Food Allergy Action Plan; moderator/speaker fees from Novartis, GSK, Sanofi, AstraZeneca.LS NoneTW speaking engagements for Pfizer and Stallergenes Greer, Advisory Board member for ALK and Leo PharmaJP is the Section Head of Allied Health for the Canadian Society of Allergy and Clinical Immunology; and sits on the steering committee for Canada’s National Food Allergy Action Plan

Background: Cystic fibrosis (CF) is reported to be a risk factor for drug hypersensitivity. However, there is conflicting data about true prevalence of drug allergy in children with CF. Methods: The suspicious drug hypersensitivity reactions (DHR) of children with CF were enquired by European Network for Drug Allergy (ENDA) questionnaire and skin tests and/or drug provocation tests were performed according to established guidelines. Results: Two hundred and nineteen children (48.9% boys; median [IQR] age, 8.4 years [4.8-12.4 years]) with cystic fibrosis were included in the study, from whom 22 patients with 24 suspected DHRs were evaluated. Most of the suspected DHRs were non-immediate (n=16, 66.6%) type and the offending drugs were amoxicillin clavulanic acid (n=7), macrolides (n=4), trimethoprim sulfamethoxazole (TMP/SMX) (n=2), piperacillin tazobactam (n=1), pancrelipase (n=1) and ursodeoxycholic acid (n=1). Eight (33.3%) of the DHRs were classified as immediate [ceftriaxone (n=2), ceftazidim (n=2), meropenem (n=1), ambisome (n=2), vancomycin (n=1)]. The main presenting clinical presentations were maculopapular eruption (41.6%) and urticaria (37.5%), accompanied by angioedema (8.3%), flushing (12.5%) and vomiting (8.3%). Nine skin tests (with beta-lactam protocol in 6 patients) and 24 DPTs were performed and none of the skin tests revealed a positive result, however 2 DPTs with TMP/SMX were positive. Conclusion: Actual drug allergy was demonstrated in 2 of 219 patients (0.9%) with nonbeta-lactam antibiotics. These results conflict with previous researches that showed higher drug allergy rates but were consistent with some recent studies. Numerous and long-term use of multiple drugs during management of cystic fibrosis may contribute to tolerance development.

Background: Childhood allergic rhinitis (AR) is clinically highly heterogeneous. We aimed to identify distinct subgroups amongst children with AR, and to ascertain their association with patterns of symptoms, allergic sensitization and concomitant physician-diagnosed asthma. Methods: We recruited 510 children with physician-diagnosed AR, of whom 205 (40%) had asthma. Latent class analysis (LCA) was performed to identify latent structure within the data set using 17 variables (allergic conjunctivitis, eczema, asthma, family history of asthma, family history of allergic rhinitis, skin sensitization to 8 common allergens, tonsillectomy, adenoidectomy). Results: A four−class solution was selected as the optimal model based on statistical fit. We labeled AR latent classes as: (1) AR with grass mono-sensitization and conjunctivitis (n=361, 70.8%); (2) AR with house dust mite sensitization and asthma (n=75, 14.7%); (3) AR with pet and grass polysensitization and conjunctivitis (n=35, 6.9%) and (4) AR among children with tonsils and adenoids removed (n=39, 7.6%). Perennial AR was significantly more common among children in Class 2 (OR 5.83, 95%CI 3.42−9.94, p<0.001) and Class 3 (OR 2.88, 95%CI 1.36−6.13, p=0.006). Mild and intermittent AR symptoms were significantly more common in children in Class 3 compared to those in Class 1. AR was more severe in Class 1, compared to other 3 classes, indicating that upper respiratory symptoms are more severe among children with isolated seasonal rhinitis, than in those with rhinitis and coexisting asthma. Conclusion: We have identified 4 phenotypes in school-age children with AR, which were associated with different patterns of clinical symptoms and comorbidities.

Background: Enterovirus (EV) infections, being among the most prevalent viruses worldwide, have been associated with reduced risk of allergic diseases. We sought to determine the association of EVs with allergic sensitization and disease in early childhood. Methods: The study was carried out in a nested case-control setting within a prospective birth cohort in Finland. We included 138 case children who had specific IgE (s-IgE) sensitization at the age of 5 years and 138 control children without s-IgE sensitization. Allergic disease was recorded at study visits and asked with ISAAC questionary. We screened for the presence of serotype specific antibodies against 41 EVs at 1 to 5 years of age and assessed their association with allergic sensitization and disease. Results: The overall number of EV infections did not differ between s-IgE-sensitized children and non-sensitized control children. However, there was a tendency of case children with an allergic disease having less EV infections than their controls. This observation was statistically significant for species A EVs in case children with atopic dermatitis vs. control children: OR 0.6 (95 % CI 0.36-0.99), P = 0.048. Conclusion: This study supports the evidence that EV exposure and development of allergic disease are inversely associated. Interestingly, the inverse association was not observed for bare atopic IgE sensitization, but for IgE sensitization coupled with clinical atopic disease. This suggests that environmental factors influencing IgE sensitization may differ from those influencing progression to clinical allergic disease.

BACKGROUND: Exercise-induced respiratory symptoms are frequently reported by asthmatics and exercise-induced bronchospasm (EIB) is a frequent cause that requires objective testing for diagnosis. Eucapnic voluntary hyperventilation (EVH) is recommended as an exercise surrogate stimulus for this purpose, but its short-term reproducibility is not yet established in young asthmatics. OBJECTIVE: To evaluate the short-term test-retest agreement and reproducibility of FEV1 changes after EVH in young asthmatics. METHODS: Asthmatics aged between 10 and 20 years underwent EVH for EIB diagnosis on two occasions 2-4 days apart at a specialized university clinic. FEV1 was measured 5, 15 and 30 minutes after EVH with a target ventilation rate 21 times baseline FEV1. EIB was diagnosed as a decrease >10% in FEV1 from baseline. RESULTS: Twenty-six of 62 recruited individuals tested positive for EIB on both visits (positive group) and 17 on one visit only (divergent group); and 19 tested negative on both visits (negative group). The overall agreement was 72.5% (95%CI 61.6%, 83.6%) and positive and negative agreement was 41.9% and 30.6% respectively. Despite overall low bias in FEV1 response between test days (0.87%), the limits of agreement were wide (+20.72%). There were no differences in pre-challenge FEV1 or achieved ventilation rate, between visits either between groups (p=0.097 and p=0.461) or within groups, (p=0.828 and p=0.780). No test was interrupted by symptoms and there were no safety issues. CONCLUSIONS: More than one EVH test should be performed in young asthmatics with a negative test to exclude EIB and minimize misdiagnosis and mistreatment.

Background: Rural communities who consume unpasteurized and traditional fermented milk products on a regular basis, have a low prevalence of allergic diseases. Lactic acid producing bacteria present within these products, is postulated to have an allergy protective role against atopy. Objective: To characterize and compare the bacterial microbiota of fresh unpasteurised cow’s milk and to explore the effect of milk fermentation (commercially and traditionally fermented) on the bovine milk microbiota. Methods: Raw, unpasteurized cow’s milk was collected from urban and rural farms. Another sample, collected from a rural farm, was left to ferment naturally. Three different brands of commercially fermented milk samples were also analysed. The V3 and V4 regions of the 16S rRNA gene were amplified to assess microbiota composition. Results: Urban and rural fresh milk had the highest microbiota alpha diversity, and commercially bought fermented milk products, the least. Commercially fermented milk was consistently dominated by lactic acid producing bacteria, belonging to the phylum Firmicutes, while homemade fermented milk comprised of approximately 50% Firmicutes and 50% Proteobacteria. The relative abundance of several organisms differed between fermented and unfermented milk. Lactococcus lactis dominated all milk products, however its relative abundance was lower in fresh milk compared with fermented milk. Lactobacillus paracasei and Streptococcus infantis were abundant in traditionally fermented milk, but absent in commercially fermented products. Potential pathogens were demonstrated in fresh and home fermented milk. Conclusion: Commercially fermented milk can be promoted as a safe and possible allergy protective complementary feed from 1 year of age.

Treatment-required accidental ingestion and risk factors among nursery children with wheat allergy