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Allergen immunotherapy, also called desensitisation, is a strategic process by which the immune system is gradually "trained" to tolerate increasing amounts of an allergen, which it previously would have reacted to. In the UK, it is estimated that approximately 20% of the population suffers with at least one allergic disease. The potential to modify the disease process is no longer out of our reach for certain allergies, with the hope of improved quality of life. Immunotherapy can be offered as a treatment for IgE mediated allergic disease such as allergic rhinoconjunctivitis, immediate type food allergies, bee and wasp anaphylaxis, and can have a synergistic effect on asthma and eczema. However, it would be incorrect to consider this treatment as a panacea, as there remain pitfalls, gaps in equity of treatment, and uncertainty with longer-term efficacy of the newer food desensitisation treatments. This review focuses on our current clinical understanding and indications for immunotherapy for children and young people, delivery and monitoring within the UK, and the future scope of immunotherapy. [ABSTRACT FROM AUTHOR]

• All pharmaceutical forms tested in the trial demonstrated peripheral antihistaminic activity compared to placebo at every time point, measured as greater reductions in the wheal and flare area. • Bilastine i.m, i.v. and oral administration showed significantly higher peripheral antihistaminic activity compared to dexchlorpheniramine i.m and placebo. • Oral bilastine achieves a rapid onset of action despite oral administration. • Bilastine i.m, i.v. and oral administration exhibit a favourable safety and tolerability profile devoid of sedative effects. Bilastine is a well-known non-sedating second-generation antihistamine authorised worldwide for the symptomatic treatment of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria with proven efficacy and good safety and tolerability profile. When the oral route is not suitable or a rapid onset of action is preferred, parenteral formulations represent an effective treatment option. However, the parenteral formulations currently available are sedating antihistamines. The objective of this research was to compare the peripheral anti-H 1 activity of different bilastine formulations (i.v., i.m. and oral) and dexchlorpheniramine among them also versus placebo. This was a single-dose, randomized, crossover, double-blind, placebo-controlled, phase I clinical study performed on 25 adult healthy volunteers that compared the peripheral antihistaminic activity of a single dose of bilastine 12 mg i.v., bilastine 12 mg i.m., bilastine 20 mg oral tablets and dexchlorpheniramine 5 mg i.m. among them and versus placebo by inhibiting the histamine-induced wheal and flare (W&F) response. Pharmacokinetics, safety, and tolerability were also evaluated. All bilastine formulations showed a rapid onset of action (15 min for parenteral and 30 min for the oral formulation), and the maximum effect in both wheal (i.v. 74.44 %; i.m.:74.29 %; oral 70,27 %) and flare area reduction (i.v. and i.m. 80.63 %; oral 77.67 %), was significantly larger compared to dexchlorpheniramine i.m. (25.85 % for wheal and 28.65 % for flare) and placebo (1.35 % for wheal and 4.02 % for flare). A more pronounced reduction in itching score was reached for bilastine oral, followed by i.m. and i.v. formulations. No serious adverse events (SAEs) were reported during the study, and 8 treatment-emergent adverse events (TEAEs) were reported by 5 subjects, all resolved without sequelae. For psychomotor assessments, dexchlorpheniramine i.m. showed a fast onset of drowsiness, as well as decreased attention and coordination when compared to all bilastine formulations and placebo. All bilastine formulations showed a peripheral H 1 -blocking effect inducing a significantly greater inhibition of the wheal and flare response as compared to dexchlorpheniramine i.m. or placebo and provided a greater reduction of the itching sensation score. This study reconfirmed that bilastine has no sedative effect, even in a parenteral formulation. These results suggest that new bilastine parenteral formulation (i.v. or i.m.) may represent a suitable alternative for patients requiring immediate treatment of histamine-mediated type I hypersensitivity reactions, such as acute urticaria, or in those cases where oral administration is not possible. [Display omitted] [ABSTRACT FROM AUTHOR]

Chronic respiratory diseases are a dealing cause of death and disability worldwide. Their prevalence is steadily increasing and the exposure to environmental contaminants, including Flame Retardants (FRs), is being considered as a possible risk factor. Despite the widespread and continuous exposure to FRs, the role of these contaminants in chronic respiratory diseases is yet not clear. This study aims to systematically review the association between the exposure to FRs and chronic respiratory diseases. Searches were performed using the Cochrane Library, MEDLINE, EMBASE, PUBMED, SCOPUS, ISI Web of Science (Science and Social Science Index), WHO Global Health Library and CINAHL EBSCO. Among the initial 353 articles found, only 9 fulfilled the inclusion criteria and were included. No statistically significant increase in the risk for chronic respiratory diseases with exposure to FRs was found and therefore there is not enough evidence to support that FRs pose a significantly higher risk for the development or worsening of respiratory diseases. However, a non-significant trend for potential hazard was found for asthma and rhinitis/rhinoconjunctivitis, particularly considering urinary organophosphate esters (OPEs) including TNBP, TPHP, TCEP and TCIPP congeners/compounds. Most studies showed a predominance of moderate risk of bias, therefore the global strength of the evidence is low. The limitations of the studies here reviewed, and the potential hazardous effects herein identified highlights the need for good quality large-scale cohort studies in which biomarkers of exposure should be quantified in biological samples. Flame retardants and the risk for chronic respiratory diseases – A Systematic review of observational studies. [Display omitted] • There is a potential risk for asthma with exposure to TNBP and TPHP. • There is a potential risk for wheezing with exposure to EHDPHP (measured as urinary metabolite 5-OH-EHDPHP). • There is a potential risk for rhinoconjunctivitis with exposure to TCEP and TCIPP. [ABSTRACT FROM AUTHOR]

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]

Abstract: Two previous studies have demonstrated a significant relationship between ADAM33 single nucleotide polymorphisms (SNPs) and allergic rhinitis. Here, we investigated this issue in young adult Japanese women. The study included 393 women who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Controls included 767 women without rhinoconjunctivitis according to the ISAAC criteria who had not been diagnosed with allergic rhinitis by a doctor. The GC genotype of rs2787094, the CT genotype of rs628977, and the haplotype containing the rs2787094 C allele, the rs628977 T allele, the rs2853209 T allele, and the rs612709 G allele were significantly inversely associated with rhinoconjunctivitis. The AA genotype of rs2853209, the GA genotype of rs612709, and the haplotype carrying the rs2787094 G allele, the rs628977 C allele, the rs2853209 A allele, and the rs612709 G allele were significantly positively associated with rhinoconjunctivitis. A significant inverse relationship between rs628977 and rhinoconjunctivitis was demonstrated only in women who had never smoked, indicating a significant interaction between rs628977 and smoking. Our results suggest that SNPs and haplotypes in the ADAM33 gene are associated with rhinoconjunctivitis. This study is the first to demonstrate an interaction between rs628977 and smoking that affects rhinoconjunctivitis. [Copyright &y& Elsevier]

Abstract: Objective: Allergic rhinitis is one of the most frequent chronic diseases among children. The objective of the study was to assess the prevalence of rhinoconjunctivitis and determine clinical, social and environmental associated factors, among school children aged 6–7 years and adolescents aged 13–14 years in Bogotá, Colombia. Methods: We used ISAAC (International Study of Asthma and Allergies in Childhood) phase III study methodology and questionnaire for design and data collection, and we did a secondary analysis of these data. The sample consisted of 3830 registers from adolescents between 13 and 14 years old and 3256 registers from children between 6 and 7 years. Results: The prevalence of rhinoconjunctivitis symptoms in the last year was 17.2% (95% CI, 15.9–18.5) in children vs. 24.9% (95% CI, 23.6–26.3) in adolescents. In both groups there was a female predominance in children (17.8% vs. 16.5%), and in the teenagers group (28.0% vs. 21.4%), though the differences were not statistically significant. The factors associated with rhinoconjunctivitis in the group of 6–7 years where: asthma [OR 3.9; (95% CI, 2.8–5.4)], atopic dermatitis [OR 2.3; (95% CI, 1.7–3.1)], use of acetaminophen in the last year [OR 2.6; (95% CI, 1.4–4.9)], use of antibiotics in the first year of live [OR 1.7; (95% CI, 1.3–2.3)], higher maternal education [OR 1.5; (95% CI, 1.0–2.3)] and cesarean delivery [OR 1.6; (95% CI, 1.2–2.1)]. Among the 13–14 year age-group, factors associated with rhinoconjunctivitis included: asthma [OR 2.6; (95% CI, 2.0–3.4)], atopic dermatitis [OR 1.8; (95% CI, 1.4–2.3)], use of acetaminophen in the last year [OR 1.8; (95% CI, 1.4–2.4)], consumption of fast-food three times or more per week [OR 1.5; (95% CI, 1.2–2.0), ever smoked [OR 1.4; (95% CI, 1.2–1.7)] and meat consumption was protective factor [OR 0.7; (95% CI, 0.5–0.9)]. Conclusion: In both studied groups, the estimated prevalence of rhinoconjunctivitis symptoms was relatively high. Future in-depth research is needed to assess the complex interactions between allergic rhinoconjunctivitis symptoms and social and environmental factors. [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]

Abstract: Background: The summary of product characteristics of the grass allergy immunotherapy tablet (AIT) (Phleum pratense grass pollen allergen extract) states that clinical effect may be observed in the first pollen season of treatment, if treatment is initiated ≥2 months (8 weeks) before the start of the grass pollen season. However, because patients with grass allergy may first present to physicians during the season, immediate treatment initiation (ie, in-season initiation) may increase treatment compliance and reduce the risk for disease progression compared with asking patients to return before the next pollen season to initiate treatment. This “in-season approach” may offer more patients the potentially beneficial treatment option of specific immunotherapy. However, to date, the immunomodulatory effects and tolerability of in-season treatment initiation is unknown. Objective: The aim of this study was to assess the immunologic effects and tolerability of in-season initiation of treatment with the grass AIT. Methods: This multicenter, randomized, double-blind, placebo-controlled trial was carried out in Germany and Austria. Adults with grass pollen allergy (positive skin-prick test and specific grass-pollen immunoglobulin [Ig] E) and grass pollen–induced moderate to severe persistent rhinoconjunctivitis were enrolled. Patients were randomly assigned to receive once-daily grass AIT or placebo, starting during the 2008 grass pollen season and continuing for 8 to 10 weeks. The primary end point was change from baseline in IgE-blocking factor (serum components competing with IgE for allergen binding). Secondary end points included changes from baseline in specific IgE and IgG4 and measures of tolerability (assessed mainly by adverse events [AEs]). Blood samples for immunologic assessment were obtained by the investigators at baseline and after treatment. All AEs observed by the investigator and/or reported by the patient were recorded throughout the trial and follow-up. Results: A total of 276 patients were enrolled and formed the full analysis set (mean age, 35 years; 55% men, 45% women; 99% white; mean weight, 76 kg; history of asthma, 41%; mean duration of grass allergy, 15.1 years). No major differences in medical history were found between the grass AIT group (n = 219) and the placebo group (n = 57). The change from baseline in mean concentration of IgE-blocking factor was significantly greater with grass AIT compared with placebo (+0.14 vs +0.05; P < 0.0001). The changes from baseline in specific IgE and specific IgG4 concentrations were significantly greater with AIT compared with placebo (IgE, +0.59 vs +0.21 log kU/L; IgG4, +0.18 vs +0.04 log relative units; both, P < 0.0001). At least 1 AE was reported in 58% of patients in the AIT group and in 40% of patients in the placebo group. Most AEs considered related to AIT were mild or moderate events in the mouth, throat, and/or ears (eg, oral pruritus). Four serious AEs were reported in the AIT group (sinusitis, road traffic accident, salmonellosis, meniscus lesion), but all were considered unlikely to be related to treatment. Three percent of the grass AIT group and 2% of the placebo group were withdrawn from the trial due to an AE. Conclusions: In-season initiation of grass AIT was associated with an immunomodulatory response in terms of induction of IgE-blocking factor, specific IgE, and specific IgG4. In-season initiation of grass AIT was generally well tolerated in this group of adults with moderate to severe grass pollen–induced rhinoconjunctivitis. These findings are consistent with those related to the preseasonal initiation of AIT therapy. ClinicalTrials.gov identifier: NCT00773240. [Copyright &y& Elsevier]

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]

Abstract: Objectives: This a priori subgroup analysis was conducted to assess patients'' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis. Methods: The present paper reports the results of a subgroup analysis of a multicenter, randomized, controlled, open-label European study in which adults with grass pollen-induced rhinoconjunctivitis received once-daily treatment with grass allergen tablets with or without a device to aid compliance. Treatment was given ~6 to 12 weeks before the grass pollen season, during the season (~8–10 weeks), and for up to 2 weeks after the end of the season. In the subgroup analysis, patients from Germany and the Netherlands who had been randomized to receive the compliance device were asked to complete a brief questionnaire at the final study visit. The questionnaire included 6 items concerning patients'' use of the device and whether it helped them remember to take their tablets. Results: Of the 91 patients from Germany and the Netherlands who were randomized to use the compliance device along with grass allergen tablets, 71 returned the questionnaire. Among responders, 58 of 71 (82%) reported using the device sometimes or always, 50 of 63 (79%) found the device easy to use, 32 of 69 (46%) found that the device made it easier to remember to take tablets, and 43 of 71 (61%) indicated that they would consider using the device again. Conclusion: Most patients in this subgroup analysis used the compliance device as a medication reminder and rated it easy to use. [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]

Summary: Background: Allergic rhinoconjunctivitis is a global health problem. Around 14 million people in Spain, France, Italy, and Austria suffer from grass pollen induced allergic rhinitis. Standard care only provides symptoms relief, while allergen specific immunotherapy (SIT) treats the underlying cause of the disease. Grazax® from ALK-Abelló is a new, tablet-based, effective route of SIT for home treatment. The objective was to assess the cost-effectiveness of Grazax® in four Southern European countries. Methods: A prospective pharmacoeconomic analyses was carried out alongside a multinational, clinical trial measuring the efficacy of Grazax®. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a nine-year time horizon. The primary outcome measure was quality adjusted life years (QALYs). Results: Grazax® was superior to standard care for all efficacy endpoints, including QALYs gained, and resulted in significantly less use of rescue medication and fewer hours missed from work. Grazax® was cost-effective for all countries for an annual price in the range of €1500–€1900. The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season. Conclusion: The analysis illustrates that allergen SIT with Grazax® for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe. [Copyright &y& Elsevier]

Abstract: Pollinosis of proximity is due to plant species that emit their pollen in a limited perimeter and affect patients who stay in this limited perimeter. The aim of this present work, in addition to reporting five well-documented cases (two cases due to dandelion, one to lupin, one to cyclamen, and one to mimosa pollen), was to review this type of allergy, which is not rare among individuals who are highly exposed to these plants, notably florists and gardeners, concerning which epidemiologic studies have been carried out. Because of the large variety of species that can be involved, these pollinoses can likewise affect the general population, especially atopics, if the conditions of exposure are favourable. Finally, the incidence of these allergies is not well known, while they are regularly the subjects of case reports. Because of the lack of standardized allergen extracts, diagnosis of these allergies depends on the clinical history. [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]

Objective: To assess Quality of life (QOL) scores in patients with Japanese cedar (Cryptomeria japonica, CJ) pollinosis. Methods: QOL was measured intraseasonally and extraseasonally in patients (n=69) using the Medical Outcomes Study Short-Form Health Survey, and compared with healthy control subjects (n=50). The differences in intraseasonal QOL scores between short and long disease duration groups were studied. The relation of intraseasonal QOL scores to nose symptoms was evaluated using Spearman’s rank correlation. Results: Significant decrease was observed in two of eight QOL items in intraseasonal measurements of patients. These QOL impairments improved extraseasonally. Scores for emotional problems in patients with long disease duration were less impaired than those with short disease duration. QOL scores in patients correlated poorly with the severity of nasal symptom. Conclusions: This is the first study to report QOL impairment in CJ pollinosis. Based on the findings long disease duration may improve emotional problems, and the correlation between disease severity and QOL is low. [Copyright &y& Elsevier]

Background: It is presumed that exposure to allergens in the environment occurs through both the eyes and the nose. Allergic rhinoconjunctivitis is typically treated with a nasal spray or systemic antihistamine, neither of which may provide adequate relief of the ocular component of the disease.Objective: This study was designed to gain a better understanding of the physiologic interaction between the conjunctival and nasal mucosa and thus help establish a profile for the most effective ocular treatment in patients whose allergies have both an ocular and a nasal component.Methods: This was a single-center, randomized, double-masked clinical study using the conjunctival allergen challenge (CAC) and nasal allergen challenge (NAC) models. It compared the clinical signs and symptoms induced by CAC and NAC, the effects of drugs administered by 3 different routes, and the movement of fluorescein after instillation into the eye and nose (Jones test), and assessed levels of of inflammatory mediators in tears and nasal secretions. At visit l, subjects previously identified as CAC responders underwent NAC to determine the dose of allergen necessary to elicit a sufficient positive reaction. At visit 2, which took place 1 week later, subjects with a positive reaction at visit 1 were randomized to group A (CAC) or group B (NAC), and underwent challenge to confirm the allergen dose necessary to produce a positive reaction. Subjects who qualified were randomized to receive 1 of 3 treatments: olopatadine 0.1% ophthalmic solution, placebo nasal spray, and placebo tablets; mometasone furoate monohydrate 50-μg nasal spray, placebo topical solution, and placebo tablets; or fexofenadine hydrochloride 180-mg tablets, placebo topical solution, and placebo nasal spray. All study medications were administered according to their approved labeling: drops were administered twice daily in the eyes, and the nasal sprays and tablets were administered once daily. At visit 3, which took place 1 week after visit 2, subjects received study medication and 15 minutes later underwent CAC or NAC as before. The primary efficacy variables were ocular itching, ocular redness, and overall nasal symptoms (sneezing, rhino rrhea/postnasal drip, nasal pruritus, palatal pruritus, and nasal congestion) rated on standard scales. Peak nasal inspiratory flow (PNIF) was measured at each visit, and the Jones test was performed at visits 1 and 3. At baseline and after challenge at visits 2 and 3, tear and nasal lavage samples were collected from a subset of randomly selected subjects for analysis of eosinophil cationic protein and tryptase.Results: Seventy-three subjects (42 women, 31 men; mean age, 45.26 years [range, 21–73 years]) were screened, and all were randomized to treatment. Two subjects did not complete the study. CAC induced clinically significant (>1 unit difference) ocular and nasal signs and symptoms, whereas NAC induced clinically significant nasal signs and symptoms only. In group A, there was a greater reduction in ocular itching with olopatadine compared with mometasone and fexofenadine at 3 minutes (P = 0.003 and P = 0.008, respectively) and 5 minutes (P = 0.007 and P = 0.013) after challenge. Although the difference was not statistically significant, overall relief of conjunctival redness (average of 3 vessel beds) was greatest in the olopatadine group, followed by fexofenadine. In group B, prevention of total nasal symptoms was significantly greater with mometasone compared with fexofenadine at 20 minutes (P = 0.006) and 30 minutes (P = 0.014) after challenge. There were no statistically significant differences between treatment groups in nasal symptom scores at any time point after CAC. There were also no significant differences in PNIF between treatment groups. Fluorescein was present in nasal secretions within 5 minutes of being instilled into the eye; no fluorescein was detected in the eye after instillation into the nose.Conclusions: In this study, exposure of the nasal mucosa to allergen resulted in allergic rhinitis, and exposure of the ocular surface to allergen resulted in conjunctivitis with a secondary effect in the nose. These results suggest movement of allergens, their mediators, and antiallergy drugs from the ocular surfaces into the nasal cavity, with no meaningful movement from the nasal cavity to the ocular surface. In this controlled model, both the systemic agent and the nasal spray failed to control ocular symptoms. The topical ophthalmic solution provided the most effective management of allergic ocular signs and symptoms, and the nasal spray was most effective for nasal symptoms. Combined use of a nasal spray and topical ophthalmic solution may provide maximal relief in patients whose allergies have both ocular and nasal components. [Copyright &y& Elsevier]

Summary: Aim: To adapt the Asthma Quality of Life Questionnaire (AQLQ(S)), the Asthma Control Questionnaire (ACQ) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) for a personal digital assistant (Palm TX) and to examine the validity of the electronic versions by comparing them with the original paper versions. Methods: 84 adults with asthma and 32 with rhinitis were randomised to complete either the paper or the electronic version first. After 2h, they completed the other version. Results: 68 asthma and 27 rhinitis patients provided analysable data. For the AQLQ(S) and RQLQ(S) differences between paper and electronic were significant. Concordance between paper and electronic, evaluated using an intraclass correlation coefficient were: AQLQ=0.92, ACQ=0.90 and RQLQ=0.85. Concordance for the individual domains of the AQLQ and RQLQ ranged from 0.52 to 0.94. These levels of concordance did not reach the a priori defined requirement for validity. Conclusions: The significant bias between paper and electronic versions and only modest concordance provides evidence that patients may respond differently to questionnaires in different formats and show that different formats must not be used interchangeably. [Copyright &y& Elsevier]

• Uncertainty exists as to the role of air pollution on childhood respiratory health. • Data from five recent European birth cohorts were meta-analyzed. • No evidence found for role of air pollution on asthma and allergies up to 8 years. • Findings consistently null across all cohorts considered. Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries. Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrogen dioxide (NO 2), nitrogen oxides, mass of particulate matter with an aerodynamic diameter <10 μm (PM 10), 10–2.5 μm (PM coarse) and <2.5 μm (PM 2.5), and PM 2.5 absorbance were assigned to the birth, four- and eight-year home addresses using highly defined spatial air pollution exposure models. Cohort-specific cross-sectional associations were assessed using logistic regression models adjusted for demographic and environmental covariates and combined in a random effects meta-analysis. The overall prevalence of pediatric eczema, rhinoconjunctivitis and asthma at four years was 15.4%, 5.9% and 12.4%. We found no increase in the prevalence of these outcomes at four or eight years with increasing air pollution exposure. For example, the meta-analysis adjusted odds ratios (95% confidence intervals) for eczema, rhinoconjunctivitis and asthma at four years were 0.94 (0.81, 1.09), 0.90 (0.75, 1.09), and 0.91 (0.74, 1.11), respectively, per 10 μg/m3 increase in NO 2 at the birth address, and 1.00 (0.81, 1.23), 0.70 (0.49, 1.00) and 0.88 (0.54, 1.45), respectively, per 5 μg/m3 increase in PM 2.5 at the birth address. In this large meta-analysis of five birth cohorts, we found no indication of adverse effects of long-term air pollution exposure on the prevalence of current pediatric eczema, rhinoconjunctivitis or asthma. [ABSTRACT FROM AUTHOR]

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]