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Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-017-0179-7

Abstract:
The 2010 Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) guidelines are the only Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for cow’s milk allergy (CMA). They indicate oral food challenge (OFC) as the reference test for diagnosis, and suggest the choice of specific alternative formula in different clinical conditions. Their recommendations are flexible, both in diagnosis and in treatment. Using the Scopus citation records, we evaluated the influence of the DRACMA guidelines on milk allergy literature. We also reviewed their impact on successive food allergy and CMA guidelines at national and international level. We describe some economic consequences of their application. DRACMA are the most cited CMA guidelines, and the second cited guidelines on food allergy. Many subsequent guidelines took stock of DRACMA’s metanalyses adapting recommendations to the local context. Some of these chose not to consider OFC as an absolute requirement for the diagnosis of CMA. Studies on their implementation show that in this case, the treatment costs may increase and there is a risk of overdiagnosis. Interestingly, we observed a reduction in the cost of alternative formulas following the publication of the DRACMA guidelines. DRACMA reconciled international differences in the diagnosis and management of CMA. They promoted a cultural debate, improved clinician’s knowledge of CMA, improved the quality of diagnosis and care, reduced inappropriate practices, fostered the efficient use of resources, empowered patients, and influenced some public policies. The accruing evidence on diagnosis and treatment of CMA necessitates their update in the near future.
Tsung-Chieh Yao, Ann Chen Wu, Ya-Wen Huang, Jiu-Yao Wang,
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0202-7

Abstract:
Anaphylaxis is a severe, potentially fatal, and systemic allergic reaction. Previous studies document increasing trends in incidence rates of anaphylaxis-related events in Western countries, yet little is known about the incidence and trend of anaphylaxis in Asia. In this study, we aimed to determine time trends in incidence rates of anaphylaxis-related events in Taiwan from 2001 through 2013. We utilized medical claims data from the National Health Insurance Research Databases in Taiwan. We identified anaphylaxis-related events (ICD-9-CM-codes: 995.0, 995.60–995.69, 999.41–999.42, and 999.49) and calculated incidence rates. Poisson regression models were applied to examine trends and incidence rates. A total of 2496 patients (mean age, 45.11 years; 56% male) with first-time anaphylaxis were identified during 34,430,000 person-years of observation time. The overall incidence of anaphylaxis was 7.25 (95% confidence interval (CI) = 6.97–7.53) per 100,000 person-years, increasing from 4.79 in 2001 to 8.20 in 2013, with an incidence rate ratio (IRR) of 1.05 (95%CI = 1.04–1.06). Over the 13-year period, the increasing trends were found in incident diagnosis of anaphylaxis-related outpatient or emergency department visits (IRR = 1.06, 95%CI = 1.05–1.08) and admissions to intensive care units (IRR = 1.06, 95%CI = 1.03–1.10), whereas the trends in incidence of anaphylaxis-related hospitalizations remained steady. The proportion of patients requiring hospitalizations among all patients with anaphylaxis (p_trend = 0.01), as well as the proportion requiring intensive care treatment among patients who were hospitalized (p_trend = 0.01), both increased with age. The incidence rate of anaphylaxis in Taiwan has increased at an average rate of 5% annually since 2001, paralleling the rising trends in several Western countries. The online version of this article (10.1186/s40413-018-0202-7) contains supplementary material, which is available to authorized users.
D. Samreth, S. Arnavielhe, F. Ingenrieth, A. Bedbrook, G.L. Onorato, R. Murray, R. Almeida, , , , et al.
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0194-3

Abstract:
Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel networK: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission’s Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58.5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users’ life privacy. k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0191-6

Abstract:
The development of oral tolerance or food allergy is an active process, related to dynamic interactions between host immune cells, microbiome, dietary factors, and food allergens. Oral tolerance is the default immune response in the gut. A food allergy occurs when this process fails and a pathologic Th2 response is activated. Oral food immunotherapy (OIT) aims to restore immune tolerance in food-allergic individuals. The stimulation of Tregs production seems to represent a crucial step in inducing long-term tolerance, but other mechanisms (e.g., the suppression of mast cell and basophil reactivity, changes in allergen-specific cells with regulatory markers) are involved. Several studies reported the efficacy of OIT in terms of "sustained unresponsiveness" (SU), an operational definition of immune tolerance. In successfully treated subjects, the ability to pass an oral food challenge 2 to 8 weeks after stopping the food allergen exposure seems to be conditioned by the treatment starting age, frequency, amount or type of food consumed, and by the duration of the maintenance phase. Based on the available data, the percentage of milk- and egg-allergic subjects achieving sustained unresponsiveness after an OIT ranges from 21% to 58,3%. A comprehensive understanding of mechanisms underlying the induction of oral tolerance with OIT, or natural tolerance to food allergens in healthy individuals, could potentially lead to advances in development of better treatment options for food allergic patients.
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0208-1

Abstract:
In recent years there has been increasing recognition of varying asthma phenotypes that impact treatment response. This has led to the development of biological therapies targeting specific immune cells and cytokines in the inflammatory cascade. Currently, there are two primary asthma phenotypes, Type 2 hi and Type 2 lo, which are defined by eosinophilic and neutrophilic/pauci- granulocytic pattern of inflammation respectively. Most biologics focus on Type 2 hi asthma, including all four biologics approved for treatment of uncontrolled asthma in the United States — omalizumab, mepolizumab, reslizumab, and benralizumab. Potential new targets for drug development are being investigated, such as IL-13, IL-4α receptor, CRTH2, TSLP, IL-25, IL-13, IL-17A receptor, and CXCR2/IL-8. This review will discuss the role of these molecules on the inflammatory response in uncontrolled asthma and the emerging biologics that address them. Through the delineation of distinct immunological mechanisms in severe asthma, targeted biologics are promising new therapies that have the potential to improve asthma control and quality of life.
, Paola Rottoli, Caterina Bucca, Maria Cristina Zappa, Giovanni Michetti, Bruno Macciocchi, , Pierachille Santus, Marta Bartezaghi, Laura Rigoni
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0214-3

Abstract:
This study demonstrated that in severe allergic asthma, omalizumab improves patient-reported outcomes such as patients' illness perception and QoL, while confirming improvement of asthma control and exacerbation rate reduction in Italian patients.
Published: 1 January 2018
World Allergy Organization Journal, Volume 11; https://doi.org/10.1186/s40413-018-0196-1

Abstract:
Although asthma cannot be cured, appropriate management can ensure adequate control of the disease, prevent disease progression and even reverse the illness, enabling people to enjoy good quality of life. Predisposing factors for inappropriate asthma management, including limited diagnostic options and inadequate supply of medications, are features of health institutions in developing countries like Ethiopia. This study was launched to determine the appropriateness of asthma management in patients visiting ambulatory clinic of the Gondar University Hospital. Cross-sectional study was conducted on asthmatic patients who were on chronic follow-up at Gondar University Hospital. Data were collected by review of patients’ medical records and through a semi-structured questionnaire. The Global Initiative for Asthma guideline was used as a reference for determining the appropriateness of asthma management whereas the eight-item Morisky medication adherence scale (MMAS-8) was used to collect data on patients’ adherence to asthma medications. The study participants’ ages ranged from 20 to 80 years with a mean age of 49.3 ± 13.6 years. Mild asthma showed a slight predominance in frequency accounting for 38.7% of cases. Asthma management was found to be inappropriate in 52.0% of the patients. Inappropriateness of therapy is attributed to incorrect dosing of medications, addition of unnecessary medications and omission of necessary medications. Patients who had moderate asthma were more likely to receive appropriate treatment [AOR = 728: 63.2, 8386.06], whereas having a treatment regimen of beclomethasone with salbutamol was found to be predictor of inappropriate treatment [AOR = 0.004: 0.001, 0.07]. More than half (56.7%) of the study subjects reported to have high adherence to their medications. Having no formal education was a predictor of low adherence to asthma medications [AOR = 0.051: 0.003, 0.978] whereas, increased monthly income was found to have a positive association with adherence [AOR = 1.923: 1.037, 3.566]. High prevalence of inappropriate therapy in this study may be attributed primarily to limited accessibility of asthma medications, as 86% of the patients received medium dose beclomethasone with salbutamol for exacerbations despite being at different severity of asthma and level of control. The findings of the study showed more than half of asthmatic patients received inappropriate treatment. Nevertheless, a larger proportion of the patients claimed to be highly adherent to their medications.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-017-0142-7

Abstract:
Tropical forests cover less than 10 per cent of all land area (1.8 × 107 km2) and over half of the tropical-forest area (1.1 × 107 Km2) is represented by humid tropical forests (also called tropical rainforests). The Amazon basin contains the largest rainforest on Earth, almost 5.8 million km2, and occupies about 40% of South America; more than 60% of the basin is located in Brazil and the rest in Bolivia, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname and Venezuela. Over the past decade the positive role of tropical rainforests in capturing large amounts of atmospheric carbon dioxide (CO2) has been demonstrated. In response to the increase in atmospheric CO2 concentration, tropical forests act as a global carbon sink. Accumulation of carbon in the tropical terrestrial biosphere strongly contributes to slowing the rate of increase of CO2 into the atmosphere, thus resulting in the reduction of greenhouse gas effect. Tropical rainforests have been estimated to account for 32–36% of terrestrial Net Primary Productivity (NPP) that is the difference between total forest photosynthesis and plant respiration. Tropical rainforests have been acting as a strong carbon sink in this way for decades. However, over the past years, increased concentrations of greenhouse gases, and especially CO2, in the atmosphere have significantly affected the net carbon balance of tropical rainforests, and have warmed the planet substantially driving climate changes through more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods. The role of tropical forests in mitigating climate change is therefore critical. Over the past 30 years almost 600,000 km2 have been deforested in Brazil alone due to the rapid development of Amazonia, this is the reason why currently the region is one of the ‘hotspots’ of global environmental change on the planet. Deforestation represents the second largest anthropogenic source of CO2 to the atmosphere, after fossil fuel combustion. There are many causes of deforestation, including socioeconomic and natural factors, such as clear-cutting for agriculture, ranching and development, unsustainable logging for timber, as well as droughts, fires and degradation due to climate change. About natural causes of forest degradation, in the context of the Amazon, the major agent of change in the forest ecosystem would most likely be decreased dry-season precipitation. Of the 23 global climate models employed by the Intergovernmental Panel on Climate Change (IPCC) in their 2007 report, 50–70% predict a substantial (above 20%) reduction of dry-season rainfall in eastern Amazonia under mid-range greenhouse gas emissions scenarios, 40% in central Amazonia and 20% in the west. While annual carbon emissions from fossil-fuel combustion have been continually increasing since 1960s, historical trends of deforestation and associated carbon emissions have remained poorly understood.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-017-0148-1

Abstract:
Allergic and hypersensitivity reactions such as anaphylaxis and asthma exacerbations may occur during air travel. Although the exact incidence of in-flight asthma and allergic emergencies is not known, we have concerns that this subject has not received the attention it warrants. There is a need to provide passengers at risk and airlines with the necessary measures to prevent and manage these emergencies. A review of the epidemiology, management and approaches to prevention of allergic and asthma emergencies during air travel is presented with the goal of increasing awareness about these important, potentially preventable medical events.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-017-0146-3

Abstract:
Subcutaneous allergen immunotherapy (SCIT) is a well-documented treatment for allergic disease which involves injections of native allergen or modified (allergoid) extracts. The use of allergoid vaccines is a growing sector of the allergy immunotherapy market, associated with shorter-course therapy. The aim of this study was the structural and immunological characterisation of group 1 (Lol p 1) IgG-binding epitopes within a complex mix grass allergoid formulation containing rye grass. HP-SEC was used to resolve a mix grass allergoid preparation of high molecular weight into several distinct fractions with defined molecular weight and elution profiles. Allergen verification of the HP-SEC allergoid fractions was confirmed by mass spectrometry analysis. IgE and IgG immunoreactivity of the allergoid preparations was explored and Lol p 1 specific IgG-binding epitopes mapped by SPOT synthesis technology (PepSpot™) with structural analysis based on a Lol p 1 homology model. Grass specific IgE reactivity of the mix grass modified extract (allergoid) was diminished in comparison with the mix grass native extract. A difference in IgG profiles was observed between an intact mix grass allergoid preparation and HP-SEC allergoid fractions, which indicated enhancement of accessible reactive IgG epitopes across size distribution profiles of the mix grass allergoid formulation. Detailed analysis of the epitope specificity showed retention of six Lol p 1 IgG-binding epitopes in the mix grass modified extract. The structural and immunological changes which take place following the grass allergen modification process was further unravelled revealing distinct IgG immunological profiles. All epitopes were mapped on the solvent exposed area of Lol p 1 homology model accessible for IgG binding. One of the epitopes was identified as an ‘immunodominant’ Lol p 1 IgG-binding epitope (62-IFKDGRGCGSCFEIK-76) and classified as a novel epitope. The results from this study support the concept that modification allows shorter-course therapy options as a result of providing an IgG epitope repertoire important for efficacy. Additionally, the work paves the way to help further develop methods for standardising allergoid platforms.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-017-0151-6

Abstract:
Psychoneuroimmunoendocrinology, which was first described in 1936, is the study of the interactions between the psyche, neural and endocrine functions and immune responses. The aim of psychoneuroimmunoendocrinology is to apply medical knowledge to the treatment of different allergic, immune, autoimmune, rheumatic, neoplastic, endocrine, cardiovascular and dental pathologies, among other disorders. Epigenetic factors and major stresses from different types of stimuli acting through distinct pathways and neurotransmitters are highly involved in altering the psychoneuroimmunoendocrine axis, resulting in the emergence of disease. The main purpose of this report is to expand the understanding of psychoneuroimmunoendocrinology and to demonstrate the importance of the above-mentioned interactions in the etiology of multiple pathologies. In this review, a search of the medical literature using PubMed (free access search engine for the Medline database of the National Library of Medicine of the United States) over the years 1936 to 2016 was conducted, and descriptive and experimental studies and reviews of the scientific literature were included.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-017-0163-2

Abstract:
Grasses release the most widespread aeroallergens with considerable sensitization rates, while different species produce several pollen concentration peaks throughout the season. This study analyzed the prevalence of grass species in three different European city areas and compared the flowering period of these species with daily pollen concentrations and the symptom loads of grass pollen allergy sufferers. The most prevalent grass species in Vienna (Austria), Berlin (Germany) and Turku (Finland) were studied and examined by use of three different approaches: phenology, pollen monitoring and symptom load evaluation. A mobile pollen exposure chamber was employed to observe reaction patterns of grass pollen allergy sufferers to three common grass species evaluated in this study versus placebo. Common meadow grass (Poa pratensis) and the fescue grass species (Festuca spp.) are important contributors within the grass pollen season. The pollination period of orchard grass (Dactylis glomerata) and false-oat grass (Arrhenatherum elatius) indicated a greater importance in Berlin and Vienna, whereas a broader spectrum of grass species contributed in Turku to the main pollen season. The standardized provocation induced a nasal symptom load, reduction in nasal flow and increased secretion, in contrary to the placebo control group in grass pollen allergic subjects. The phenological observations, pollen measurements and symptom data evaluation provided unique insights into the contribution of multiple grass species in different European regions. All investigated grass species in the provocation induced rhinitis symptoms of comparable significance, with some degree of variation in symptom patterns.
Published: 1 January 2017
World Allergy Organization Journal, Volume 10; https://doi.org/10.1186/s40413-016-0136-x

Abstract:
Galacto-oligosaccharides (GOS) are prebiotics added to commercial milk formula of infants and mothers. In recent years, cases of allergy related to GOS in atopic children have been reported in the South East Asian region. We describe a series of pregnant (n = 4) and lactating mothers (n = 2) who developed anaphylactic reactions after consumption of maternal milk formula containing GOS. All six subjects had pre-existing atopy and a positive skin prick test to GOS and 5/5 of the subjects who were tested had positive basophil activation tests to GOS. All of the mothers and their babies had normal neonatal outcomes after the reactions. The supplementation of GOS into milk and beverages in the Asian region should take into account the rare chance of allergenicity of GOS in the atopic population.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0093-4

Abstract:
There exist several reports of atopy and allergen-specific IgE-mediated hypersensitivity transferred by bone marrow transplantation, and it has been concluded that the transfer of allergic reactivity results from adoptive transfer of IgE-producing donor-derived B- and/or plasma cells. To the best of our knowledge we report the first case of peanut allergy after PBSCT. A 55-year-old anciently non allergic man with secondary acute myeloid leukemia (AML) received an allogeneic peripheral blood stem cell transplantation from a matched unrelated donor following reduced-intensity conditioning. On day 32 after PBSCT, while still on prophylactic systemic immunosuppression, the patient noticed a first episode of angioedema with swelling of the nasal and oral mucosa 30 min after consuming peanut puffs. In a second episode, eight months after PBSCT, he again developed angioedema, generalized pruritus and nausea within minutes after eating biscuits containing hazelnut and peanut. Moreover, after topical application of a peanut oil-containing ointment, the patient experienced facial erythema and angioedema. Nine months after PBSCT an evaluation for peanut allergy revealed a highly increased specific IgE to peanut of 75.9 kU/l. Accordingly, skin prick tests for peanut extract were also positive. In consequence, the patient was counseled to strictly avoid peanut-related products, and provided with an emergency set. No adverse allergic events have occurred since for an observation time of 15 months after PBSCT. The stem cell donor was contacted and confirmed intolerance to peanuts. His specific serum IgE pattern nine month after PBSCT harvest was analysed and showed similar sensitization profiles compared to those of the transplant recipient. Because of the close temporal association between the onset of allergic symptoms in the PBSC recipient it is reasonable to assume that the acquired peanut allergy had been transferred from the donor to the recipient by the PBSC graft.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9, pp 11-11; https://doi.org/10.1186/s40413-016-0103-6

Abstract:
In an attempt to circumvent low response rates and high cost of classical epidemiological trials, we carried out a real-life survey among practicing physicians consulting patients for nasal symptoms. In this fragment of our work we analyze similarities and differences between children and adults and within the different strata of pediatric age. A survey was carried out by 69 physicians across Bulgaria (general practitioners, allergists and otorhinolaryngologists) and made possible calculation of the proportion of subjects with nasal symptoms from all other patients seen. Its structure allowed classification of rhinitis according the ARIA guidelines. Out of the 1685 completed survey forms, 506 pertained to the age group below 18 years. The gender predominance differed in children and adults: 57.3 % vs. 42.8 % of males respectively, P < 0.001. The prevalence of persistent rhinitis in children was 55.7 %, lower than in adults, 63.3 %, P = 0.004. In both pediatric and adult patients moderately severe and severe forms of rhinitis prevailed, 93.7 % vs. 94.6 %, with nasal obstruction as leading symptom: 59.9 % vs. 58.8 %. Cough was significantly more prevalent among children, 72.5 %, gradually decreasing until reaching adulthood, 58.7 %, P < 0.001. Prevalence of doctor diagnosed asthma was also higher among children, 25.1 %, than in adults, 19.5 %, P = 0.011. A gradient for characteristics, which were different in children, emerged across the pediatric age strata. Our study uses an unorthodox design targeting the patient population visiting physicians’ offices because of nasal symptoms, achieving a much higher level of credibility of the results at minimal expense. As we base our survey on international guidelines, we believe this approach demonstrates the applicability of such consensus documents for practical purposes when in the hands of qualified physicians. Moderate and severe rhinitis symptoms motivate patients and their guardians to seek medical advice. While nasal congestion is a leading bothersome symptom in both adults and children, specific other features characterize the pediatric age and differ across its strata.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9, pp 12-12; https://doi.org/10.1186/s40413-016-0104-5

Abstract:
Oral food challenge test doses are recommended to be performed at least 20 min apart; however, the times of symptom provocation from the start of the oral food challenge have never been compared between different foods. In this study, the durations from the start of the oral food challenge to symptom development in children with egg or milk allergy were compared. Thirty-eight and 74 children who had previously passed oral food challenges to 96 g of yogurt and pumpkin cake containing ¼ whole egg underwent oral food challenges with 200 mL raw cow’s milk and 1 whole scrambled egg, respectively; of these, 15/38 and 33/74 children had a reaction. The median ages of patients with a positive challenge were 5.8 and 5.1 years for milk and eggs, respectively. The median times for the first symptom occurrence were 20 min (range, 5–55 min) and 50 min (5–480 min), respectively (p = 0.009). The first symptoms developed within 30, 60, and 90 min in 12/15 (80 %), 15/15 (100 %), and 15/15 (100 %) children with milk allergies, and in 10/33 (30.3 %), 20/33 (60.6 %), and 26/33 (78.8 %) children with egg allergies, respectively. The median times of peak symptoms were 50 min (10–210 min) and 120 min (30–560 min) (p = 0.001), and those of symptom disappearance were 90 min (30–240 min) and 180 min (80–700 min) for milk and eggs (p = 0.002), respectively. Based on the results of our study, symptoms developed within 30 min for only a subset of patients for eggs, and may even take upwards of 60 min to develop. The times of symptom disappearance were 90 min and 180 min for milk and eggs, respectively, indicating that egg-allergic patients should be observed for a longer period time than milk-allergic patients. Allergic reactions induced by milk appeared and disappeared sooner than those induced by eggs.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9, pp 15-15; https://doi.org/10.1186/s40413-016-0106-3

Abstract:
Allergen specific immunotherapy (AIT) has been the only pathogenetically relevant treatment of IgE-mediated allergic diseases (ADs) for many years. The use of AIT for atopic dermatitis (AD) treatment is dubious and has both followers and opponents. The improvement of subcutaneous AIT (SCIT) and introduction of Sublingual immunotherapy (SLIT) gives prospects of their application both for adults and children suffering from AD. This review presents results of scientific research, system and meta-analyses that confirm the clinical efficacy of AIT for children with AD who has the sensitization to allergens of house dust mite, grass and plant pollen suffering from co-occurring respiratory ADs and with moderate and severe course of allergic AD. There have been analyzed the most advanced achievements in AIT studies as well as there have been specified the unmet needs in AD. The preliminary diagnostics of IgE-mediated AD and pathophysiological disorders, including immune ones, will allow a doctor to develop appropriate comprehensive treatment algorithm for children’s AD aimed at its correction. The including of AIT to the children’s comprehensive therapy program is reasonable only if AD has the allergic form. It is necessary better to design the randomized research studies and to acquire extended clinical practice in children with AD. Use of the successes of molecular-based allergy diagnostics will help to optimize and personalize the process of selecting the necessary allergens to determine the most appropriate vaccines for children considering the results of the allergen component diagnostics. The strategy of treatment of children with AD in future will be based on individual target therapy.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0127-y

Abstract:
Chronic urticaria (CU) is defined as the spontaneous appearance of wheals, with or without angioedema, persisting for ≥6 weeks. Chronic Spontaneous Urticaria (CSU) is a type of CU which affects 0.5–1 % of the global population, but it represents a high burden to patients. In recent years, omalizumab is available as treatment of disease. Our aim is to extend previous findings, analyzing effects of omalizumab on symptoms in Latin American patients with CSU. Retrospective analysis of patients treated with omalizumab in Cuenca-Ecuador. 150 mg omalizumab was administered every 4 weeks, and its effects were measured by Urticaria Activity Score (UAS) at baseline and each month in follow up. Complete response was defined as a UAS of 0 or 1, and partial response was classified as a UAS of 2 or more. Also, demographic and clinical variables were collected. Descriptive analyses were employed. Response rates were summarized as counts and percentages after 3 and 5 months. Related Samples Wilcoxon signed rank tests were used to compare UAS at baseline and after 3 months. P values <0.05 indicated statistical significance. 26 subjects were enrolled, almost half were female individuals (57.7 %), with mean age 47.8 years (range, 18–81 years). Mean duration of CU after diagnosis was 23.3 months (range, 2–180 months). Mean UAS at baseline was 5.7 points (range, 4–6 points). Nine patients (34.6 %) completed 3 months of treatment (33 % reported a complete response), with a mean difference in UAS of 3.33 (p = 0.01). Four patients completed 5 months of treatment (75.0 % showed a complete response). All patients previously treated with first-generation antihistamines plus corticosteroids showed no responses at neither 3 nor 5 months of treatment. Omalizumab is an effective treatment for patients with CU. It is necessary to conduct some future investigations where we can establish if 150 mg could be an option in developing countries. The online version of this article (doi:10.1186/s40413-016-0127-y) contains supplementary material, which is available to authorized users.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0124-1

Abstract:
We describe immune phenotypes (innate and adaptive cytokines) according to environmental exposure using latent class analysis. A total of 310 schoolchildren living in Ecuador were assayed for spontaneous cytokine production as well as mitogen (SEB)-stimulated cytokines in whole blood cultures. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Latent class analysis (LCA) was used to group children according to their innate (IL-6, IL-8, IL-10 and TNF-α) and adaptive (IL-5, IL-13, IL-17, IFN-γ and IL-10) cytokine profile. We also conducted multiple-group LCA and LCA with covariates to evaluate the effect of predictors on profile membership. We identified both hyporesponsive and Th2-modified immune phenotypes produced by peripheral blood leukocytes (PBLs) that were associated with intestinal worms and birth order, providing insights into how poor hygiene mediates immunologic effects on immune-mediated diseases.
Wuhong Pei, Sunny C. Huang, Lisha Xu, Kade Pettie, María Laura Ceci, , ,
Published: 1 January 2016
Cell Regeneration, Volume 5, pp 5:3-3; https://doi.org/10.1186/s13619-016-0031-5

Abstract:
We are using genetics to identify genes specifically involved in hearing regeneration. In a large-scale genetic screening, we identified mgat5a, a gene in the N-glycosylation biosynthesis pathway whose activity negatively impacts hair cell regeneration. We used a combination of mutant analysis in zebrafish and a hair cell regeneration assay to phenotype the loss of Mgat5a activity in zebrafish. We used pharmacological inhibition of N-glycosylation by swansonine. We also used over-expression analysis by mRNA injections to demonstrate how changes in N-glycosylation can alter cell signaling. We found that mgat5a was expressed in multiple tissues during zebrafish embryo development, particularly enriched in neural tissues including the brain, retina, and lateral line neuromasts. An mgat5a insertional mutation and a CRISPR/Cas9-generated truncation mutation both caused an enhancement of hair cell regeneration which could be phenocopied by pharmacological inhibition with swansonine. In addition to hair cell regeneration, inhibition of the N-glycosylation pathway also enhanced the regeneration of lateral line axon and caudal fins. Further analysis showed that N-glycosylation altered the responsiveness of TGF-beta signaling. The findings from this study provide experimental evidence for the involvement of N-glycosylation in tissue regeneration and cell signaling. The online version of this article (doi:10.1186/s13619-016-0031-5) contains supplementary material, which is available to authorized users.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0119-y

Abstract:
Despite current therapeutic approaches asthma remains uncontrolled in a significant proportion of patients. Short-acting anticholinergic bronchodilators have a very long history of use in asthma, and recent data confirms the importance of acetylcholine as both a bronchoconstrictor and as a regulator of inflammation and remodeling in the lungs. Data from a comprehensive clinical trial programme, as well as use in primary care, show the efficacy and safety of tiotropium in adults with mild to moderate asthma when it is added to ICS and in severe asthma when it is added to high doses of ICS plus LABA, as well as in adolescents. Tiotropium is cost effective and its benefits are not restricted to particular phenotypes, making it a useful addition to the therapeutic options recommended by the Global Initiative for Asthma (GINA) for people with poorly controlled asthma at steps 4 & 5.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0102-7

Abstract:
The prevalence of allergic diseases in infants, whose parents and siblings do not have allergy, is approximately 10 % and reaches 20–30 % in those with an allergic first-degree relative. Intestinal microbiota may modulate immunologic and inflammatory systemic responses and, thus, influence development of sensitization and allergy. Prebiotics – non-digestible oligosaccharides that stimulate growth of probiotic bacteria – have been reported to modulate immune responses and their supplementation has been proposed as a preventive intervention. The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations about the use of prebiotics in the prevention of allergy. The WAO guideline panel identified the most relevant clinical questions about the use of prebiotics for the prevention of allergy. We performed a systematic review of randomized controlled trials of prebiotics, and reviewed the evidence about patient values and preferences, and resource requirements (up to January 2015, with an update on July 29, 2015). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. Based on GRADE evidence to decision frameworks, the WAO guideline panel suggests using prebiotic supplementation in not-exclusively breastfed infants and not using prebiotic supplementation in exclusively breastfed infants. Both recommendations are conditional and based on very low certainty of the evidence. We found no experimental or observational study of prebiotic supplementation in pregnant women or in breastfeeding mothers. Thus, the WAO guideline panel chose not to provide a recommendation about prebiotic supplementation in pregnancy or during breastfeeding, at this time. WAO recommendations about prebiotic supplementation for the prevention of allergy are intended to support parents, clinicians and other health care professionals in their decisions whether or not to use prebiotics for the purpose of preventing allergies in healthy, term infants. The online version of this article (doi:10.1186/s40413-016-0102-7) contains supplementary material, which is available to authorized users.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0098-z

Abstract:
Skin patch test is the gold standard method in diagnosing contact allergy. Although used for more than 100 years, the patch test procedure is performed with variability around the world. A number of factors can influence the test results, namely the quality of reagents used, the timing of the application, the patch test series (allergens/haptens) that have been used for testing, the appropriate interpretation of the skin reactions or the evaluation of the patient’s benefit. We performed an Internet –based survey with 38 questions covering the educational background of respondents, patch test methods and interpretation. The questionnaire was distributed among all representatives of national member societies of the World Allergy Organization (WAO), and the WAO Junior Members Group. One hundred sixty-nine completed surveys were received from 47 countries. The majority of participants had more than 5 years of clinical practice (61 %) and routinely carried out patch tests (70 %). Both allergists and dermatologists were responsible for carrying out the patch tests. We could observe the use of many different guidelines regardless the geographical distribution. The use of home-made preparations was indicated by 47 % of participants and 73 % of the respondents performed 2 or 3 readings. Most of the responders indicated having patients with adverse reactions, including erythroderma (12 %); however, only 30 % of members completed a consent form before conducting the patch test. The heterogeneity of patch test practices may be influenced by the level of awareness of clinical guidelines, different training backgrounds, accessibility to various types of devices, the patch test series (allergens/haptens) used for testing, type of clinical practice (public or private practice, clinical or research-based institution), infrastructure availability, financial/commercial implications and regulations among others. There is a lack of a worldwide homogeneity of patch test procedures, and this raises concerns about the need for standardization and harmonization of this important diagnostic procedure.
, , Ruby Pawankar, , Yuan Zhang, , Kangmo Ahn, Suleiman Al-Hammadi, Arnav Agarwal, Shreyas Gandhi, et al.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0108-1

Abstract:
The prevalence of allergic diseases is approximately 10 % in infants whose parents and siblings do not have allergic diseases and 20–30 % in those with an allergic first-degree relative. Vitamin D is involved in the regulation of the immune system and it may play a role in the development, severity and course of asthma and other allergic diseases. The World Allergy Organization (WAO) convened a guideline panel to develop evidence-based recommendations addressing the use of vitamin D in primary prevention of allergic diseases. Our WAO guideline panel identified the most relevant clinical questions and performed a systematic review of randomized controlled trials and non-randomized studies (NRS), specifically cohort and case-control studies, of vitamin D supplementation for the prevention of allergic diseases. We also reviewed the evidence about values and preferences, and resource requirements (up to January 2015, with an update on January 30, 2016). We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. Having reviewed the currently available evidence, the WAO guideline panel found no support for the hypothesis that vitamin D supplementation reduces the risk of developing allergic diseases in children. The WAO guideline panel suggest not using vitamin D in pregnant women, breastfeeding mothers, or healthy term infants as a means of preventing the development of allergic diseases. This recommendation does not apply to those mothers and infants who have other indications for prophylactic or therapeutic use of vitamin D. The panel’s recommendations are conditional and supported by very low certainty evidence. WAO recommendations about vitamin D supplementation for the prevention of allergic diseases support parents, clinicians and other health care professionals in their decisions whether or not to use vitamin D in preventing allergic diseases in healthy, term infants.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9, pp 16-16; https://doi.org/10.1186/s40413-016-0107-2

Abstract:
Atopic dermatitis (AD) is a common chronic skin condition in children that has a proven association with other atopic conditions and allergies. These associations, like the general pathophysiology of AD, are complex and not fully understood. While there is evidence for the efficacy of specific immunotherapy (SIT) in pediatric asthma and allergic rhinitis (AR), there is a lack of strong data to support its use in AD. IgE has been shown to be elevated in many patients with AD, but it is an unreliable biomarker due to variability and great fluctuation over time, poor positive predictive value for clinically relevant allergy, and poor correlation with disease state. In spite of this, almost all studies of SIT use either positive skin prick testing (SPT) or serum specific IgE levels to guide therapy. Allergen avoidance, with some exceptions, is generally not effective at controlling AD in children. The few studies that have investigated the efficacy of SIT in children with AD have produced conflicting results, and a lack of reproducibility with a standard treatment protocol. Limited studies have shown clinical improvement in mild to moderate AD cases, but no effect on more severe patients. Uncontrolled studies are difficult to interpret, due to the natural history of remission or “outgrowing” of AD over time in many patients without specific interventions. Drawbacks to SIT include the length of treatment, poor compliance, cost, and potential side effect profile. The potential for misdirection of time and energy away from skin directed therapy could negatively impact on AD outcomes.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0094-3

Abstract:
Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-015-0090-z

Abstract:
There is emerging evidence that children with egg and cow’s milk allergy who can tolerate these allergens cooked in baked goods are more likely to develop tolerance. As a result a hypothesis has arisen that exposure to egg and milk in baked goods may hasten tolerance development; however, it is unclear whether children who develop tolerance do so because they have ingested low levels of egg or milk in baked products. An alternative explanation for the improved prognosis in those who can tolerate food allergens in the baked form is that tolerance to egg and milk in baked goods is simply an indicator of a phenotype that is less likely to be persistent. We discuss the role that the baked egg or milk allergy phenotype plays on predicting tolerance development and suggest that it is the phenotype of the disease rather than exposure to altered allergens that is the strongest predictor of tolerance development.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0114-3

Abstract:
Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus and commonly classified as a Th2-type allergy. Major advances in our understanding of the EoE pathophysiology have recently been made, but clinicians struggle with highly unpredictable therapy responses indicative of phenotypic diversity within the patient population. Here, we summarize evidences for the existence of EoE subpopulations based on diverse inflammatory characteristics of the esophageal tissue in EoE. Additionally, clinical characteristics of EoE patients support the concept of disease subtypes. We conclude that clinical and experimental evidences indicate that EoE is an umbrella term for conditions that are unified by esophageal eosinophilia but that several disease subgroups with various inflammatory esophageal patterns and/or different clinical features exist. We further discuss strategies to study the pathophysiologic differences as observed in EoE patients in murine experimental EoE. Going forward, models of EoE that faithfully mimic EoE subentities as defined in humans will be essential because mechanistic studies on triggers which regulate the onset of diverse EoE subpopulations are not feasible in patients. Understanding how and why different EoE phenotypes develop will be a first and fundamental step to establish strategies that integrate individual variations of the EoE pathology into personalized therapy.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0129-9

Abstract:
Asthma mortality has declined since the 1980s. Nevertheless the World Health Organization (WHO) identified asthma as responsible for 225.000 deaths worldwide in 2005, and 430.000 fatal cases are expected by 2030. Some unexpected and concentrated fatal asthma events all occurred between 2013 and 2015 in Veneto, a North Eastern region of Italy, which prompted a more in-depth investigation of characteristics and risk factors. A web search including key words related to fatal asthma in Italy between 2013 and 2015 has been performed. Concerning the cases that occurred in Veneto, subjects’ clinical records have been evaluated and details about concomitant weather conditions, pollutants and pollen count have been collected. Twenty-three cases of asthma deaths were found in Italy; 16 of them (69%) occurred in the Veneto Region. A prevalence of male and young age was observed. Most of patients were atopic, died in the night-time hours and during the weekends. The possible risk factors identified were the sensitization to alternaria, previous near fatal asthma attacks and the incorrect treatment of the disease. Weather condition did not appear to be related to the fatal exacerbations, whereas among the pollutants only ozone was detected over the accepted limits. Smoking habits, possible drug abuse and concomitant complementary therapies might be regarded as further risk factors. Although not free from potential biases, our web search and further investigations highlight an increasing asthma mortality trend, similarly to what other observatories report. The analysis of available clinical data suggests that the lack of treatment more than a severe asthma phenotype characterizes the fatal events. Asthma mortality still represents a critical issue in the management of the disease, particularly in youngsters. Once more the inadequate treatment and the lack of adherence seem to be not only related to the uncontrolled asthma but also to asthma mortality.
Published: 1 January 2016
World Allergy Organization Journal, Volume 9; https://doi.org/10.1186/s40413-016-0113-4

Abstract:
Eosinophilic cystitis is a rare inflammatory disorder characterized by eosinophilic infiltration of all layers of the urinary bladder wall. Due to lack of consensus and potential for side effect from various therapeutic options, treatment of the disease is often challenging. A 64-year old woman with hypertensive nephropathy resulting in stage III chronic kidney disease, obstructive sleep apnea, and obstructive lung disease presented with a 4 month history of dysuria, urgency, frequency, and persistent hematuria. Based on eosinophilic infiltration on bladder wall biopsy in the absence of any evidence of infection, malignancy, or immune disorder, she was diagnosed with eosinophilic cystitis. Despite multiple medication regimens, her symptoms persisted, requiring high-dose prednisone with steroid-related side effects. After four months, she was started on cyclosporine, which led to symptomatic improvement and reduction in prednisone dosage. At that time, repeat urine cytology and cystoscopy did not reveal friable tissues or eosinophiluria. This case illustrates the utility of using cyclosporine to treat eosinophilic cystitis in adult patient with multiple comorbid conditions.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/s40413-015-0088-6

Abstract:
The term “intolerance” is not mentioned in the World Allergy Organization (WAO) document on allergy nomenclature. “Intolerance” has been used to describe some non-immunological diseases. However, pediatric gastroenterologists mix allergy and intolerance, e.g. by using the term “cow’s milk protein allergy/intolerance (CMPA/I)”, lumping together all types of mechanisms for not tolerating cow’s milk. The basis for this mix is the fact that double-blind oral food challenges are time-consuming and expensive. Therefore, cow’s milk exclusion and reintroduction is proposed to be used in primary care for the diagnosis of CMPA in children with common gastrointestinal (GI) problems such as colic and constipation. This may lead to a widespread use of hypoallergenic formulas in children without proven CMPA. In lay language, intolerance describes “not tolerating”. To discuss the reasons why the term “intolerance” should not be used in the area of allergy. Presently, intolerance is not part of the allergy nomenclature. It is used by lay persons to describe “not tolerating”. Pediatricians use intolerance to describe non-immunological hypersensitivity such as lactose intolerance which is acceptable. However, using the mixed term CMPA/I describing a variety of gastrointestinal symptoms in children, should be avoided. The WAO Nomenclature does not clearly distinguish between non-IgE-mediated allergy and non-allergic hypersensitivity. The term “intolerance” should not be used within the area of allergy. Intolerance should be better defined and the term restricted to some non-immunological/non-allergic diseases and not mixed with allergy, e.g. by using the term CMPA/I. A revision of the WAO nomenclature is proposed.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8, pp 1-5; https://doi.org/10.1186/s40413-014-0052-x

Abstract:
Cutaneous involvement characterized by urticarial lesions with or without angioedema and itch is commonly observed in routine medical practice. The clinical approach may still remain complex in real life, because several diseases may display similar cutaneous manifestations. Urticaria is a common disease, characterized by the sudden appearance of wheals, with/without angioedema. The term Chronic Urticaria (CU) encompasses a group of conditions with different underlying causes and different mechanisms, but sharing the clinical picture of recurring wheals and/or angioedema for at least 6 weeks. Hereditary Angioedema (HAE) is a rare disorder characterized by recurrent episodes of non-pruritic, non-pitting, subcutaneous or submucosal edema affecting the extremities, face, throat, trunk, genitalia, or bowel, that are referred as “attacks”. HAE is an autosomal dominant disease caused by a deficiency of functional C1 inhibitor, due to a mutation in C1-INH gene (serping 1 gene) characterized by the clonal proliferation of mast cells, leading to their accumulation, and possibly mediator release, in one or more organs. In childhood there are two main forms of mastocytosis, the Systemic and the Cutaneous. The clinical features of skin lesions in urticaria, angioedema and mastocytosis may differ depending on the aetiologic factors, and the underlying pathophysiological mechanisms. The diagnostic process, as stepwise approach in routine clinical practice, is here reviewed for CU, HAE and mastocytosis, resulting in an integrated method for improved management of these cutaneous diseases. Taking into account that usually these conditions have also a relevant impact on the quality of life of children, affecting social activities and behavior, the availability of care pathways could be helpful in disentangle the diagnostic issue achieving the most cost-effective ratio.
Catalina María Gómez Henao, Cristina Isabel Herrera Morales, Ricardo Cardona Villa, Ana Maria Celis Henao
Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/1939-4551-8-s1-a269

Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/s40413-015-0087-7

Abstract:
Health care professionals and patients mix and mingle (hyper)sensitivity, allergy and intolerance. The consequences are discrepancies which result in confusion. The following is a very personal point of view, intended to start a debate to come to consensus. We aimed to clarify the proposed terminology for the primary health care professional from the point of view of the pediatric gastroenterologist. Many patients present with symptoms “related to food ingestion”. We propose to use this wording if no underlying mechanism can be identified. Intolerance should be restricted to carbohydrate malabsorption causing symptoms. Allergy is restricted to IgE mediated allergy and non-IgE manifestations that can only be explained through an immune mediated mechanism, such as food induced atopic dermatitis and allergic colitis with blood in the stools. Unfortunately, primary heath care physicians have no diagnostic tools for non-IgE mediated allergy. A positive challenge test is a proof of a food-induced symptom, but does not proof that the immune system is involved. (Hyper)sensitivity suggests immune mediated mechanisms and should therefore not be used. The pathophysiologic mechanism of many food-related symptoms is unclear. The same symptom can be caused by allergy or be considered functional, such as infantile colic, gastro-esophageal reflux and constipation related to cow’s milk ingestion in infants. In fact, “functional” is used if the pathophysiologic mechanism causing the symptom cannot be explained. Since the long term outcome of “allergy” differs substantially from “functional symptom”, allergy should not be used inappropriate. “Food related symptom” should be used in each patient in which the pathophysiologic mechanism is not clear. Intolerance means a carbohydrate malabsorption that causes symptoms. Allergy should be used when the immune system is involved.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/s40413-015-0064-1

Abstract:
To enhance the dissemination of the ARIA document (Allergic rhinitis (AR) and its impact on asthma) in Mexico, a Working Group composed of 35 specialists of 8 professional medical societies developed a transculturized ARIA México 2014 guideline. The ARIA guidelines use the GRADE system, which builds recommendations and suggestions around clinical questions (CQ). As part of the dissemination strategy and to detect the physicians’ view and knowledge-gaps concerning the treatment of AR an online survey was sent out to members of participating societies containing the CQ of ARIA México. Replies were analyzed per specialty against the ARIA México 2014 experts’ recommendations/suggestions; differences between specialties were analyzed with Pearson’s Chi-squares. 807 surveys were returned, 657 completed (81%). We analyze replies from 158 alergists, 188 ENTs, 64 pulmonologists, 220 pediatricians and 177 GPs/family doctors. More than half of the surveyed physicians of all specialties would give an allergen reduced diet to pregnant/lactating women and avoid pets at home, which is against ARIA experts’ suggestions. ARIA experts suggest intranasal antihistamines can be part of the AR treatment: 46-63% of the ENTs, pulmonologists and pediatricians disagree; and experts prefer oral H1-antihistamines over leukotriene receptor antagonists (LTRA) for the treatment of AR: 52-36% of the pulmonologists, pediatricians and GPs prefer LTRAs. Concerning glucocorticosteroids (GCS): GPs are more reluctant to use intranasal GCS (p < 0.001) and 47% prefers oral H1-antihistamines. As for the treatment of recalcitrant AR ARIA experts suggest the use of oral, but not intramuscular, GCS: a quarter of pulmonologists, pediatricians and GPs considers they should not be used. Contrarily, 40% of ENTs favors intramuscular GCS. In patients with AR and comorbid asthma several physicians of all specialties –except pulmonologists- erroneously considers antihistamines, intranasal GCS and LTRAs useful for the treatment of asthma, while first-line recommended asthma treatment is inhaled GCS. On certain issues in the treatment of AR the physicians’ opinion diverges from the recommendations/suggestions of ARIA experts. Moreover, physicians’ opinions depend on their specialty. As such, an online survey can help to detect knowledge-gaps and guide the development of more focused and specialty-specific postgraduate learning tools. The online version of this article (doi:10.1186/s40413-015-0064-1) contains supplementary material, which is available to authorized users.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/s40413-015-0070-3

Abstract:
Food allergy is a major public health problem affecting nearly 10 % of children in most industrialized countries. Unfortunately, there are no effective therapies for food allergy, relegating patients to simply avoid the offending foods and treat reactions that occur on accidental exposure. Recently however, studies suggest that food immunotherapy may provide a promising new approach to food allergy, particularly using the oral form of immunotherapy (OIT). Enthusiasm for this approach though must be tempered because of the significant allergic reactions that often occur with OIT that tends to limit its use to patients with less severe disease. On the other hand, recent studies suggest that concomitant treatment of patients with omalizumab (anti-IgE monoclonal antibody) during the updosing phase of OIT may greatly reduce the allergic reactions associated with OIT, even in high-risk patients. This combined method may provide a novel approach to successfully and rapidly treat a large fraction of patients with high-risk food allergy.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8; https://doi.org/10.1186/s40413-015-0069-9

Abstract:
Our knowledge of allergen structure and function continues to rise and new scientific data on the homology and cross-reactivity of allergen sources should be considered to extend the work of Lorenz et al., 2009 (Int Arch Allergy Immunol. 148(1):1–1, 2009) and the concept of homologous groups. In addition to this, sophisticated techniques such as mass spectrometry (MS) are increasingly utilised to better characterise the complex mix and nature of allergen extracts. Homology models were used of Fag s 1 (Beech) and Cyn d 1 (Bermuda grass) and compared with template crystal structures of Bet v 1 and Phl p 1 from the ‘exemplar’ species of Birch and Timothy grass, respectively. ELISA experiments were performed to assess cross-reactivity of Beech (tree) and Bermuda (grass) extracts to rabbit sera raised to either “3-Tree” (Birch, Alder and Hazel) extract or “Grass” (12-grass mix extract), respectively. The comparability of biochemical stability of different allergen sources was assessed through statistical methods for a range of tree and grass species. Allergen cross-reactivity and/or structural homology have been described providing justification for inclusion of Beech within the Birch homologous tree group. Data from Bermuda grass (Cyn d 1) provides further justification for the inclusion of this species into the homologous group of the sweet grasses. However, further characterisation of relevant allergens from Bermuda grass and, in particular, comparison of cross-reactive patterns between subjects specifically in areas with high abundance of both Pooideae and Chloridoideae is sought. MS allows the possibility to identify individual proteins or allergens from complex mixes by mass and/or sequence, and this has been extensively applied to the allergen field. New data on the homology, cross-reactivity and biological parameters of allergen sources have been considered to extend the work of Lorenz et al., 2009 in the context of tree and grass species. The concept of homologous groups is certainly dynamic allowing the flexibility and potential in streamlining quality parameters, such as stability profiles, due to extrapolation of exemplar data to a wider range of allergens.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8, pp 14-14; https://doi.org/10.1186/s40413-015-0065-0

Abstract:
Owing to their side effects, administration of steroids for bronchial asthma attacks should be minimized. We investigated whether budesonide inhalation suspension (BIS) could replace intravenous steroid administration for the treatment of moderate bronchial asthma attacks. The subjects were children aged 5 years and younger hospitalized for moderate bronchial asthma attacks. Patients were randomly assigned to one of two groups: 20 patients received methylprednisolone (mPSL) and 20 were treated with BIS. The mPSL group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and disodium cromoglycate (2 mL) three times a day and systemic administration of mPSL (1 mg/kg) three times a day. The BIS group began treatment with inhalation of procaterol hydrochloride (0.3 mL) and BIS (0.5 mg) three times a day. The frequency of inhalations and steroid administration was adjusted according to the severity of symptoms. The cortisol level at discharge was measured. There were no significant differences between the two groups in terms of the severity of attacks and duration of management, or in terms of therapeutic efficacy, duration of wheezing, or period of hospitalization. The frequency of inhalations on days 3 to 6 of hospitalization was lower in the BIS group than in the mPSL group, and the cortisol level at discharge was significantly higher in the BIS group (13.9 ± 6.1 μg/dL) than in the mPSL group (8.0 ± 2.1 μg/dL) (p = 0.008). In patients with recurrent wheezing or bronchial asthma of <5 years, the efficacy of BIS is equivalent or better than mPSL for moderate bronchial asthma attacks, and in contrast to steroid treatment, BIS treatment do not suppress adrenocortical function.
Published: 1 January 2015
World Allergy Organization Journal, Volume 8, pp 1-1; https://doi.org/10.1186/1939-4551-8-1

Abstract:
IL-6 is a pro-inflammatory cytokine which has many well-defined effects. Its synthesis and release from mononuclear cells of drug-sensitized patients was related before to in vitro drug-allergy diagnostics but has not yet been studied in detail.The specific release of preformed IL-6 from peripheral blood mononuclear cells (PBMC) after 20 minutes incubation with 0.15-0.5 μM of pure drugs was measured in two groups of drug-allergy suspected donors (159) and respective controls (48). IL-6, TNF-alpha, IL-2, IL-4, IFN-gamma have been measured from cell supernatants by ELISA or by cytometric bead assay. Epicutaneous, intradermal and systemic provocation tests were performed to prove or disprove culprit substances (203 in vivo against 482 in vitro tests). T-test (paired and unpaired); chi2 contingency table; Z statistics and McNemar's test were used to evaluate results.Concanavalin A as positive control released IL-6 from PBMC in linear concentration and exponential time dependent fashion (up to 60 minutes) pointing to the existence of a preformed pool of this cytokine. Preformed IL-6 released at any of 4 standard drug dilutions tested, above 50% over their diluents' levels significantly correlated with the patients' history on drug-induced hypersensitivity symptoms and with in vivo tests. Sensitivity of 85.4% and specificity of 82.4% of the IL-6 release assay were found. The 20' drop in release of TNF-alpha had no diagnostic importance; it has accompanied increased IL-6 release. IL-2, IL-4 and IFN-gamma were undetectable in 20 minutes supernatants. IL-6 release depended on the clinical phenotype but not on the eliciting drug(s) in the molecular mass range of 76-4000 Da. Reactivity of mononuclear cells at the lowest or at multiple drug test concentrations reflected clinical severity per diagnoses and according to area of skin involvement.This rapid test is applicable to detect a wide scale of drug hypersensitivity.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-30; https://doi.org/10.1186/1939-4551-7-30

Abstract:
Synthetic peptide immuno-regulatory epitopes (SPIRE) represent a new class of therapeutics for allergen immunotherapy that offer the potential to suppress the IgE-mediated allergic disease process through induction of T-cell tolerance. These synthetic T-cell-tolerizing peptides have been designed to induce immunologic tolerance via binding to MHC class II molecules on antigen presenting cells, with subsequent upregulation of regulatory T-cells.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7; https://doi.org/10.1186/1939-4551-7-34

Abstract:
Physical exercise has been shown to improve asthma symptoms, QoL, exercise capacity, bronchial hyperresponsiveness and lung function and is recommended as a supplementary treatment to pharmacotherapy for asthma. Clinicians are well placed to promote physically active lifestyles, but their role and practice towards promoting physically active lifestyles among patients has not been fully investigated. This study was designed to investigate the knowledge, propensity, attitude and practices of clinicians towards the promotion of physical activity among patients with asthma and allergies. Two hundred and eighty clinicians (mean age; 46 ± 13 years; with a clinical experience of practice for 15 ± 7 years) participated in a global survey. The survey comprised a 29-item questionnaire, which gathered information on attitudes of the clinicians towards promoting physical activity, their knowledge and their beliefs regarding evidence for benefits of physical activity as a supplementary treatment in patients with asthma and allergies. Almost all respondents were aware of the strong evidence in favor of physical activity for the psychological well-being, weight control, decreased risk of diabetes, ischemic heart disease and arterial hypertension. Evidence for reduction in the risk for developing asthma and for better asthma control were reported by 60.0% and 85.4% of participants, respectively. The majority (85.0%) of clinicians strongly agreed that promoting physical activity is important to health care, although 95.5% considered they required more educational training. Although two thirds of them usually recommended exercise to their asthmatic/allergic patients, only 24.0% reported having previous training on the subject of such counseling. Almost all believed that effective counseling about a healthy diet, exercise and weight management would be easier if the clinician himself/herself was physically fit and healthy. The results of this global survey indicate that clinicians working in the field of allergy and respiratory diseases are well aware of the evidence supporting the benefits of physical activity for asthma and allergic diseases although they need more training in such counseling. Therefore, concerted efforts are needed towards educating clinicians towards promoting physical activity and weight management, as a supplementary treatment for asthma and allergies.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7; https://doi.org/10.1186/1939-4551-7-27

Abstract:
In recent years, the interest of the scientific world towards vitamin D gradually increased, and several studies have been conducted to dissect its possible role in modulating the development/course of allergic diseases. Also, Vitamin D supplementation has been assessed as a beneficial approach for treating allergies in some, but not all studies. We reviewed herein the available and relevant literature concerning the possible links between Vitamin D, its supplementation and allergic diseases. A literature search was made independently by the Authors, identifying articles for a narrative review. As per literature, Vitamin D plays a key role in calcium and phosphate metabolism, and it is essential for bone health in infants, children and adolescents. However, there is presently insufficient evidence to support vitamin D supplementation for prevention or treatment of allergic diseases in infants, children and adolescents, concerning allergic rhinitis, asthma, food allergy and atopic dermatitis.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-29; https://doi.org/10.1186/1939-4551-7-29

Abstract:
Technology and social media have dramatically altered the landscape in which we practice medicine. Clinicians have increasingly turned to technology and the internet to enhance patient care. Allergists have used these modalities to improve utilization and adherence to immunotherapy. Electronic medical records (EMRs) are being widely adopted by allergy practices and some offer allergy/immunology specific modules that aid in daily workflow. The development of specialized devices that reduce pain associated with immunotherapy administration may improve compliance with immunotherapy. Social media and other forms of electronic communication such as e-mail, Facebook, Twitter, short message service (SMS), and YouTube give clinicians multiple avenues to disseminate information and reach their patients, possibly improving patient adherence to therapy. Finally, tablet computers, online networks, and electronic surveys provide additional ways to connect patients and physicians.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-26; https://doi.org/10.1186/1939-4551-7-26

Abstract:
We recently identified T cell epitopes associated with human allergic responses. In a majority of cases, responses focused on a few immunodominant epitopes which can be predicted on the basis of MHC binding characteristics. Several observations from our studies challenged the assumption that T cell epitopes are derived from the same allergen proteins that bind IgE. Transcriptomic and proteomics analysis identified pollen proteins, not bound by IgE. These novel Timothy Grass proteins elicited vigorous Th2 responses, suggesting that unlinked T cell help is operational in pollen-specific responses. Thus, the repertoire of antigens recognized by T cells is much broader than IgE-binding allergens. Additionally, we evaluated the use of epitopes from these novel antigens to assess immunological changes associated with Specific Immunotherapy (SIT). We found that a marked decrease in IL5 production is associated with clinically efficacious SIT, suggesting that these novel antigens are potential immunomarkers for SIT efficacy.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-20; https://doi.org/10.1186/1939-4551-7-20

Abstract:
Asthma affects mainly Venezuela’s urban and poor majority. Exacerbations bring about a high demand in health services, thus becoming a significant public health problem. In general, asthma control programs (GINA) with use of inhaled steroid medications have proven effective, although their implementation in real life remains cumbersome. Montelukast could be a useful and practical tool for these deprived socioeconomic sectors. This real-life pilot study was conducted in a prospective, double blinded, placebo-controlled manner with randomized and parallel groups. Asthmatics that had never used leukotriene modifiers were recruited and followed-up every three months. The main outcome was the number of exacerbations meriting use of nebulized bronchodilators administered by the health care system. Eighty-eight asthmatic patients were enrolled, between children and adults. Groups were comparable in: demographic data, previous use of other medications, ACT scores, pulmonary functions (Wright Peak Flow meter), allergy status (Skin Prick Test) as well as adherence to the prescribed Montelukast treatment. By an intention to treat (ITT), a total of 64 patients were included for analysis. For the three and six months time points the difference between placebo and Montelukast was found to be significant (p < 0.03 and p < 0.04, respectively). Such trends continued for the rest of the year, but without statistical significance, due to patient attrition. This real-life pilot study shows that a simplified strategy with oral Montelukast was practical and effective in controlling exacerbations in an asthmatic population of a vulnerable community from Caracas. Such an approach reinforces the role of primary care in asthma treatment.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7; https://doi.org/10.1186/s40413-014-0050-z

Abstract:
To examine the evidence derived from randomized controlled clinical trials on the efficacy and safety of omalizumab compared to placebo in controlling symptoms of chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU). The electronic databases PubMed, Medline, EMBASE, Biomed Central, The Cochrane Central Register of Controlled Trials (CENTRAL), Wiley, OVID, and HighwirePress were reviewed. The date limit was set to May 31th, but it was extended to September 30th of 2014 due to a new publication. No language restriction was used. The articles included were randomized trials controlled with placebo in individuals older than 12 years diagnosed with CIU/CSU refractory to conventional treatment, the intervention being, omalizumab at different doses, and the comparison, placebo. The primary outcome was symptom improvement according to the weekly score of urticaria severity (UAS7), the itch severity score (ISS), the weekly score of number of urticarial lesions, the dermatology life quality index, and the chronic urticaria quality of life questionnaire (CU-QoL). Databases were searched using the following Mesh or EMTREE key words including as intervention “omalizumab” or “humanized monoclonal antibody,” compared to placebo and the disease of interest “urticaria” or “angioedema”. The title, abstract and article were reviewed by two independent investigators, according to the selection criteria in each of the databases. An assessment of the quality of the articles was performed according to the bias tool from the studies of the Cochrane Collaboration. Information such as author data, date of study, number of participants, interventions, dose and frequency of administration, comparison, time of follow-up, measurements of weekly score of urticaria activity, pruritus severity score, weekly urticarial lesions, percentage of angioedema and post-treatment change were extracted. Frequency of adverse events and the ones suspected to be caused by the intervention drug were included. 770 records were identified in all databases described. 720 were eliminated for failing to meet the inclusion criteria in the first review or for duplicate records. 24 articles were reviewed by abstract, 18 additional articles were further removed, leaving 6 records for inclusion. An experimental study was excluded because it wasn’t randomized. Five studies were finally included, with 1117 patients, of these 831 received a dose of omalizumab of 75 mg (183 patients, 16.38%), 150 mg (163 patients, 14.59%), 300 mg (437 patients, 39.12%) or 600 mg (21 patients, 1.8%), as a single dose, or every 4 weeks until 24 weeks maximum. The average age was 42.07 years, predominantly female gender and white ethnicity. It was observed that the use of omalizumab 300 mg lowered the weekly scores of urticarial activity in 19.9 vs. 6.9 on placebo (p <0.01), 19 vs 8.5 and 20.7 vs 8.01 in three studies, the weekly ISS (−9.2 vs. - 3.5, p <0.001, −9.8 vs −5.1 p < 0.01, −8.6 vs −4.0 and −9.4 vs −3.63 p <0.001 in four studies), and the percentage of angioedema-free days (omalizumab 95.5% vs. placebo 89.2% p <0.001, and 91.95% vs. 88.1% p <0.001 in two of the studies respectively). The different doses used throughout the study, time of administration and follow-up periods ranged from single dose to monthly dose for 24 weeks. Therefore no meta-analysis of the review was conducted. Despite the limitations, it is considered that omalizumab 300 mg is effective in treating chronic idiopathic urticaria refractory to H1 antihistamines. Further studies are required to determine the duration of effective treatment. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014010029#.VJDr1vl5PpM (PROSPERO. International Prospective Register of Systematic Reviews).
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-19; https://doi.org/10.1186/1939-4551-7-19

Abstract:
Allergic rhinitis is a morbid condition that is frequently overlooked by patients and physicians. This type of atopy has not been adequately investigated in the United Arab Emirates. This cross-sectional, population-based observational study was conducted in the seven Emirates (Abu Dhabi, Dubai, Sharjah, Ajman, Umm Al-Quwain, Ras Al-Khaimah, and Fujairah). It used the European Community Respiratory Health Survey (ECRHS II) to screen for allergic rhinitis in people living in this region. Symptoms of allergic rhinitis were present in 85 (7%) of the 1,229 study population. Only 33 (39%) patients received treatment. Seventy-six (89%) patients had asthma. Thirty-seven (44%) patients were poly-sensitized. Symptoms were aggravated by dust (59%), grass/pollens (44%) and proximity to animals (21%). Winter was the peak season (37%), followed by spring (30%), autumn (18%) and summer (15%). Grass/pollen allergies were clustered in the winter, spring and summer (p ≤ 0.001). Dust was non-seasonal (p ≥ 0.121) and animal allergy was worse in the winter (p = 0.024) and spring (p = 0.044). Spring symptoms were less common in people living in the inner city (p = 0.003). At least 7% of the studied population had allergic rhinitis. Most (71%) of these patients had environmental triggers and remained untreated. Allergic rhinitis awareness and measures to control allergens and dust are needed. The impact of preventing allergic rhinitis on other common atopies in the region deserves future studies.
Published: 1 January 2014
World Allergy Organization Journal, Volume 7, pp 1-21; https://doi.org/10.1186/1939-4551-7-21

Abstract:
Sublingual immunotherapy is currently considered a viable alternative to the subcutaneous route. The body of evidence of its efficacy is based on the results of 77 clinical trials and 7 meta-analyses, that have been published so far. Nonetheless, the experimental evidence is partially weak due to the large heterogeneity of studies, namely: doses, regimens, patient selection, duration of treatment, outcomes and reporting. In addition, it is virtually impossible to compare the potency of extracts produced by different manufacturers. Also, there is large variability in reporting and in the classification of adverse events, either systemic or local, so that only a rough estimate can be provided. Considering all these aspects, efforts are needed to harmonize the methodology, outcome measures and reporting of SLIT clinical trials, to achieve the ability of comparing the results of various studies. International societies and the World Allergy Organization have recently provided general recommendations on how to design and conduct trials which can provide more interpretable and homogeneous data.
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