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The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT; (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized; (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease. [ABSTRACT FROM AUTHOR]

Background Early introduction of dietary peanut in high-risk infants with severe eczema, egg allergy, or both prevented peanut allergy at 5 years of age in the Learning Early About Peanut Allergy (LEAP) study. The protective effect persisted after 12 months of avoiding peanuts in the 12-month extension of the LEAP study (LEAP-On). It is unclear whether this benefit is allergen and allergic disease specific. Objective We sought to assess the effect of early introduction of peanut on the development of allergic disease, food sensitization, and aeroallergen sensitization. Methods Asthma, eczema, and rhinoconjunctivitis were diagnosed based on clinical assessment. Reported allergic reactions and consumption of tree nuts and sesame were recorded by questionnaire. Sensitization to food allergens and aeroallergens was determined by means of skin prick testing and specific IgE measurement. Results A high and increasing burden of food allergen and aeroallergen sensitization and allergic disease was noted across study time points; 76% of LEAP participants had at least 1 allergic disease at 60 months of age. There were no differences in allergic disease between LEAP groups. There were small differences in sensitization and reported allergic reactions for select tree nuts, with levels being higher in the LEAP consumption group. Significant resolution of eczema and sensitization to egg and milk occurred in LEAP participants and was not affected by peanut consumption. Conclusion Early consumption of peanut in infants at high risk of peanut allergy is allergen specific and does not prevent the development of other allergic disease, sensitization to other food allergens and aeroallergens, or reported allergic reactions to tree nuts and sesame. Furthermore, peanut consumption does not hasten the resolution of eczema or egg allergy. [ABSTRACT FROM AUTHOR]

Background An emerging paradigm holds that resistance to the development of allergic diseases, including allergic rhinoconjunctivitis, relates to an intact epithelial/epidermal barrier during early childhood. Conceivably, the immunologic and genomic footprint of this resistance is preserved in nonatopic, nonallergic adults and is unmasked during exposure to an aeroallergen. Objective The aim of this study was to obtain direct support of the epithelial/epidermal barrier model for allergic rhinoconjunctivitis. Methods Twenty-three adults allergic to house dust mites (HDMs) (M+) and 15 nonsensitive, nonallergic (M−) participants completed 3-hour exposures to aerosolized HDM ( Dermatophagoides pteronyssinus ) powder on 4 consecutive days in an allergen challenge chamber. We analyzed: (1) peripheral blood leukocyte levels and immune responses; and (2) RNA sequencing–derived expression profiles of nasal cells, before and after HDM exposure. Results On HDM challenge: (1) only M+ persons developed allergic rhinoconjunctivitis symptoms; and (2) peripheral blood leukocyte levels/responses and gene expression patterns in nasal cells were largely concordant between M+ and M− participants; gross differences in these parameters were not observed at baseline (pre-exposure). Two key differences were observed. First, peripheral blood CD4 + and CD8 + T-cell activation levels initially decreased in M− participants versus increased in M+ participants. Second, in M− compared with M+ participants, genes that promoted epidermal/epithelial barrier function (eg, filament-aggregating protein [filaggrin]) versus inflammation (eg, chemokines) and innate immunity (interferon) were upregulated versus muted, respectively. Conclusion An imprint of resistance to HDM challenge in nonatopic, nonallergic adults was muted T-cell activation in the peripheral blood and inflammatory response in the nasal compartment, coupled with upregulation of genes that promote epidermal/epithelial cell barrier function. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested that atopic dermatitis (AD) is associated with aberrant immune responses, which might predispose toward both cutaneous and extracutaneous infections. The goal of this study was to determine whether childhood AD is associated with increased risk of warts, extracutaneous infections, and other atopic diseases and how these disorders cosegregate. Methods: The 2007 National Health Interview Survey from a nationally representative sample of 9417 children age 0 to 17 years was used. Results: Children with AD and other atopic disease had higher odds of warts. In contrast, children with AD with or without other atopic disease had higher odds of extracutaneous infections, including strep throat, other sore throat, head or chest cold, influenza/pneumonia, sinus infections, recurrent ear infections, chickenpox, and urinary tract infections (P < .0001). Children with AD and other atopic disease had a higher number of infections than those with either disorder by itself (P < .0001). Warts were also associated with increased odds of all extracutaneous infections (P < .0001), except recurrent ear infections. Children with warts and AD had a higher number of infections than those with either disorder alone (P < .0001). Finally, children with AD and warts had higher odds of ever receiving a diagnosis of asthma, current asthma, asthma exacerbation in the past year, hay fever, and food allergy. Children with AD with warts had even higher odds of asthma, hay fever, and food allergies than those with AD and no warts. Conclusions: The associations between childhood AD, atopic disease, warts, and extracutaneous infections suggest that barrier disruption, immune disruption, or both contribute to susceptibility to warts and extracutaneous infections in children. [Copyright &y& Elsevier]

Background: Little is known about the epidemiology of eczema in adults. The goal of this study was to determine the prevalence of and associations with adult eczema in the United States. Methods: We used the 2010 National Health Interview Survey from a nationally representative sample of 27,157 adults age 18 to 85 years. Results: Overall, the 1-year prevalence of eczema was 10.2% (95% CI, 9.7% to 10.6%). The 1-year prevalence of eczema with asthma and/or hay fever was 3.2% (95% CI, 2.8% to 3.3%). Adult eczema was associated with higher prevalence of asthma (P < .001, Rao-Scott ?2 test), more asthma attacks in the past year (P < .001), and more persistent asthma (P = .02). In multivariate models eczema prevalence was significantly higher in older participants; female subjects; those with Hispanic ethnicity, US birthplace, and higher level of household education; and those currently working (all P ? .02, logistic regression). Conclusions: This study provides US population–based estimates of eczema prevalence and asthma associations in adults. The results suggest multiple demographic and socioeconomic influences on the US prevalence of adult eczema. [Copyright &y& Elsevier]

Background: Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. Objectives: We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen–induced rhinoconjunctivitis. Methods: Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. Results: The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P < .0001 for both). Reductions were observed in total symptom scores and ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. Conclusions: Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons. [ABSTRACT FROM AUTHOR]

Background: Wild-type varicella zoster virus infection (WTVZV) early in childhood has been shown to protect against the development of asthma and atopy. Objective: To determine whether WTVZV in childhood protects against atopic dermatitis (AD). Methods: This retrospective, practice-based, case-control study randomly sampled 256 children and adolescents (age 1-18 years) with AD and 422 age-matched healthy controls from 2005 to 2007. Observations were made before the a priori hypothesis. Results: (1) A single episode of WTVZV in childhood is associated with decreased odds ratio (OR) of developing AD (conditional logistic regression; OR, 0.55; 95% CI, 0.34-0.89; P = .01). (2) When using intervals for age corresponding to bimodal distribution of age of WTVZV infection, the effects of WTVZV infection are significant when occurring at age 0 to 8 years (OR, 0.56; 95% CI, 0.35-0.90; P = .02), but not at 8 to 18 years (OR, 0.50; 95% CI, 0.19-1.31; P = .16). Considering 5-year intervals has similar findings. (3) WTVZV is associated with decreased odds of moderate AD (multinomial logistic regression; OR, 0.08, 95% CI, 0.04-0.15; P < .0001) or severe AD (OR, 0.04; 95% CI, 0.01-0.13; P < .0001). (4) WTVZV in children is associated with prolonged AD-free survival (Kaplan-Meier; median, 15.3 years; 95% CI, 10.9-18.0) compared with controls (median, 7.5 years; 95% CI, 4.8-11.9; log-rank test, P < .0001). (5) Children with WTVZV, compared with vaccine, who eventually develop AD require fewer pediatrician sick visits for management of AD (logistic regression; OR, 0.17; 95% CI, 0.06-0.51; P = .001). Conclusion: WTVZV in childhood protects up to 10 years of age against AD, delays onset of AD symptoms, and decreases AD severity and office visits. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous allergen-specific immunotherapy is an effective treatment of IgE-mediated allergies, but it requires repeated allergen injections with a risk of systemic allergic reactions. Transcutaneous immunotherapy may improve patient compliance and safety. Objective: To assess the safety and efficacy of epicutaneous allergen immunotherapy. Methods: This monocentric, placebo-controlled, double-blind trial was conducted from March 2006 to December 2007 at the University Hospital Zurich. Thirty-seven adult patients with positive skin prick and nasal provocation tests to grass pollen were randomized to receive patches containing either allergen (n = 21) or placebo (n = 16). Treatment took place before and during the pollen season 2006, and follow-up visits took place before (n = 26) and after the pollen season 2007 (n = 30). The primary outcome measures were nasal provocation tests. Results: Allergen-treated patients showed significantly decreased scores in nasal provocation tests in the first (P < .001) and second year (P = .003) after treatment. In contrast, placebo-treated patients had decreased scores in the first treatment year, 2006 (P = .03), but the effect diminished in the second year (P = .53). Although improvement of nasal provocation test scores was not significantly better in the verum versus placebo group, the overall treatment success was rated significantly higher by the allergen-treated group than by the placebo group (2006, P = .02; 2007, P = .005). No severe adverse events were observed. Occurrence of eczema after allergen patch applications proved stimulation of specific T-cell responses, but was noted as an adverse effect of the treatment. Conclusion: Epicutaneous allergen immunotherapy is a promising strategy to treat allergies and merits further investigation. [Copyright &y& Elsevier]

Background: Phase III of the International Study of Asthma and Allergies in Childhood measured the global prevalence of symptoms of asthma, rhinoconjunctivitis, and eczema in children. Objective: To investigate the associations between the use of antibiotics in the first year of life and symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Methods: Parents or guardians of children 6 and 7 years old completed written questionnaires on current symptoms and possible risk factors. Prevalence odds ratios (ORs) were estimated by using logistic regression. Results: A total of 193,412 children from 71 centers in 29 countries participated. Reported use of antibiotics in the first year of life was associated with an increased risk of current asthma symptoms (wheezing in the previous 12 months) with an OR (adjusted for sex, region of the world, language, and per capita gross national income) of 1.96 (95% CI, 1.85-2.07); this fell to 1.70 (1.60-1.80) when adjusted for other risk factors for asthma. Similar associations were observed for severe asthma symptoms (OR, 1.82; 95% CI, 1.67-1.98), and asthma ever (OR, 1.94; 95% CI, 1.83-2.06). Use of antibiotics in the first year of life was also associated, but less strongly, with increased risks of current symptoms of rhinoconjunctivitis (OR, 1.56; 95% CI, 1.46-1.66) and eczema (OR, 1.58; 95% CI, 1.33-1.51). Conclusion: There is an association between antibiotic use in the first year of life and current symptoms of asthma, rhinoconjunctivitis, and eczema in children 6 and 7 years old. Further research is required to determine whether the observed associations are causal or are a result of confounding by indication or reverse causation. [Copyright &y& Elsevier]

Background: Immunotherapy with the SQ-standardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis. Allergic asthma and rhinoconjunctivitis are closely linked, and a strategy combining treatment of the upper and lower airways is recommended. Objective: To investigate the efficacy of treatment with the grass tablet on grass pollen–induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children. Methods: A total of 253 children age 5 to 16 years, with grass pollen–induced rhinoconjunctivitis with/without asthma, were randomized 1:1 to active treatment or placebo. Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season. Symptomatic medication was provided as relief medication to both groups in a stepwise fashion. Primary endpoints were rhinoconjunctivitis symptom and medication scores. Results: The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups. The differences in medians relative to placebo were 24%, 34%, and 64% in favor of active treatment. The immunologic response was similar to that observed in adults. The most common adverse reaction was oral pruritus, reported by 40 subjects (32%) in the active and 3 (2%) in the placebo group. Six subjects withdrew because of adverse events. No serious adverse events were assessed as treatment-related. Conclusion: Immunotherapy with the grass tablet reduced grass pollen–induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response, consistent with treatment of the underlying allergic disease. The treatment was well tolerated. [Copyright &y& Elsevier]

Background: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abelló A/S, Hørsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. Objective: We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. Methods: The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. Results: The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment. Conclusion: Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment. [Copyright &y& Elsevier]

Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Objective: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. Methods: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen–induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. Results: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. Conclusion: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen–induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. Clinical implications: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use. [Copyright &y& Elsevier]

There have been few studies conducted on the efficacy and safety of specific immunotherapy with allergen extracts of fungi compared with other allergen extracts, and there are no data on the major allergen Alt a 1 of the fungus Alternaria alternata. We sought to evaluate the efficacy and safety of subcutaneous immunotherapy with 2 different doses of Alt a 1 in patients with rhinoconjunctivitis caused by sensitization to A alternata. We performed a multicenter, randomized, double-blind, placebo-controlled trial with Alt a 1 administered subcutaneously in patients with allergic rhinoconjunctivitis with or without controlled asthma aged 12 to 65 years. Three groups were included: the placebo group and active groups receiving 0.2 or 0.37 μg of Alt a 1 per dose. The main end point was the combined symptom and medication score. Secondary end points were cutaneous reactivity and serum IgE and IgG 4 levels to Alt a 1. Recorded adverse reactions were graded according to World Allergy Organization criteria. There were significant reductions in the combined symptom and medication score for the 0.37-μg dose of Alt a 1 compared with placebo at 12 months of treatment. Reduced cutaneous reactivity and IgE levels, together with increased IgG 4 levels, were demonstrated for the 2 active groups versus the placebo group. A similar safety profile was found for both active groups compared with the placebo group. No serious adverse drug reactions were reported. Immunotherapy with Alt a 1 was efficacious and safe, reducing the symptoms and medication consumption associated with rhinoconjunctivitis after only 1 year of treatment. The clinical benefits were associated with reduced skin reactivity and specific IgE levels and increased IgG 4 levels. [ABSTRACT FROM AUTHOR]

Background Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist. Objective We sought to determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma. Methods Seven hundred forty-nine children with asthma participating in the Asthma Phenotypes in the Inner-City study received baseline evaluations and were managed for 1 year with algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by using a questionnaire focusing on individual symptoms, and predefined phenotypes were determined by combining symptom patterns with skin tests and measurement of serum specific IgE levels. Results Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.3%) and least severe. The majority of children remained symptomatic despite use of nasal corticosteroids with or without oral antihistamines. Rhinitis was worse in patients with difficult-to-control versus easy-to-control asthma, and its seasonal patterns partially corresponded to those of difficult–to-control asthma. Conclusion Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. Perennial allergic rhinitis with seasonal exacerbations is the most severe phenotype and most likely to be associated with difficult-to-control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of 1 disease in 2 parts of the airways. [ABSTRACT FROM AUTHOR]

Background Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). Objective We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. Methods Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. Results A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was −0.23 (95% CI, −0.36 to −0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. Conclusions EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA. [ABSTRACT FROM AUTHOR]

Background The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)–induced respiratory allergic disease. Objective This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR). Methods The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1 year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8 weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score. Results Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 ( P = .002) and 1.22 ( P = .001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14 weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated. Conclusion The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14 weeks of treatment onward. [ABSTRACT FROM AUTHOR]

Background Climate factors and pollen counts may play a role in hay fever. Objective We sought to determine the impact of specific climate factors and pollen counts on the US prevalence of hay fever and statewide variation in prevalence. Methods We used a merged analysis of the 2007 National Survey of Children's Health from a representative sample of 91,642 children aged 0 to 17 years and the 2006-2007 National Climate Data Center and Weather Service measurements of relative humidity (%), indoor heating degree days, precipitation, Palmer Hydrological Drought Index, clear sky and issued ultraviolet indices, stratospheric ozone levels, and outdoor air temperature and National Allergy Bureau total pollen counts. Multivariate survey logistic regression models controlled for sex, race/ethnicity, age, household income, and birthplace. Results The US prevalence of hay fever in childhood was 18.0% (95% CI, 17.7% to 18.2%), with the highest prevalence in southeastern and southern states. Hay fever prevalence was significantly lower with second and third quartile mean annual relative humidity (logistic regression, P ≤ .01 for both), fourth quartile mean annual Palmer Hydrological Drought Index ( P = .02), third and fourth quartile mean annual heating degree days ( P < .0001 for both), and third and fourth quartile mean annual stratospheric ozone levels but increased with second, third, and fourth quartile mean annual temperature ( P ≤ .02 for both), fourth quartile mean annual precipitation ( P = .0007), mean total pollen counts ( P = .01), and second, third, and fourth quartile issued ultraviolet index ( P ≤ .0001 for all). Principal-component analysis was also used to determine the combined effects of correlated climate variables and pollen counts. Conclusions This study provides evidence of the influence of climate on the US prevalence of childhood hay fever. [ABSTRACT FROM AUTHOR]

Background: Whether probiotics, which can influence the microbiome, prevent infant eczema or allergic disease remains an open question. Most studies have focused on high-risk infants. Objectives: We sought to assess whether consumption of probiotic milk products protects against atopic eczema, rhinoconjunctivitis, and asthma in early childhood in a large population-based pregnancy cohort (the Norwegian Mother and Child Cohort study). Methods: We examined associations between consumption of probiotic milk products in pregnancy and infancy with questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614 children. Relative risks (RRs) were calculated by using general linear models adjusted for potential confounders. Results: Consumption of probiotic milk in pregnancy was associated with a slightly reduced relative risk (RR) of atopic eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78-0.98) compared with no consumption during pregnancy. Maternal history of allergic disease did not notably influence the associations. When both the mother (during pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no consumption by either. Probiotic milk consumption was not associated with asthma at 36 months. Conclusions: In this population-based cohort consumption of probiotic milk products was related to a reduced incidence of atopic eczema and rhinoconjunctivitis, but no association was seen for incidence of asthma by 36 months of age. [Copyright &y& Elsevier]

Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU, ∗ [∗] SQ-T (standardized quality tablet units) and BAU (biological activity units) are quantitative measures of biological activity; ie, the potency of allergen extracts/vaccines. One grass AIT contains 75,000 SQ-T of timothy (Phleum pratense) grass pollen extract (measure of total biological potency using ALK in-house reference), equivalent to 2,800 BAU (measure of total biological potency, defined by the FDA). ALK, Denmark) or placebo. Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen–induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis. [Copyright &y& Elsevier]

Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. Objective: We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark). Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen–specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. Results: Significant improvements in efficacy were consistently shown during 3 years'' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits. [Copyright &y& Elsevier]

Background: Five published meta-analyses (MAs) seem to prove the efficacy of sublingual immunotherapy in allergic asthma and rhinoconjunctivitis. Objective: We aimed to assess the consistency, magnitude, and robustness of the results of these MAs. Methods: The data reported in the MAs were checked with the data reported in the original studies. Funnel plots were performed to test for potential publication bias, and the trim-and-fill method was used to assess and correct the estimate of the effects if asymmetry was present. Results: The 5 MAs included 43 studies; 17 were used in more than one MA. There were discrepancies among the MAs in the data reported from the same original studies: the MAs reported different estimates for the same outcome or the same estimates for different outcomes in 16 of those 17 studies. The MAs evaluated 15 main outcomes, 10 of which showed benefits that reached statistical significance. Funnel plots showed asymmetry in 7 outcomes, and correction by using the trim-and-fill method led to a decrease in their effect estimates and even to a loss of statistical significance in 4 of the previously significant outcomes. There was inconsistency among the MAs in the benefits when considering age, disease, allergen, or symptoms and medication use. Conclusion: Because of discrepancies, inconsistencies, and lack of robustness, the MAs on sublingual immunotherapy do not provide enough evidence to support its current routine management in patients with allergic asthma or rhinoconjunctivitis. Sensitivity to potential publication bias should be tested and reported in all MAs. [Copyright &y& Elsevier]