ACCURACY OF THE EOSINOPHILIC ESOPHAGITIS ENDOSCOPIC REFERENCE SCORE IN CHILDREN.

BACKGROUND: To assess the efficacy of applying the endoscopic reference score for EoE (EREFS) in children with symptoms of esophageal dysfunction naïve to proton pump inhibitor (PPI) therapy. METHODS: An observational cross-sectional study was conducted by reviewing reports and photographs of upper gastrointestinal endoscopies (UGE) and esophageal biopsies of patients with symptoms of esophageal dysfunction. Patients who were treated with PPI or had other conditions that may cause esophageal eosinophilia were excluded. RESULTS: Of the 2,036 patients evaluated, endoscopic findings of EoE were identified in 248 (12.2%) and more than one abnormality was observed in 167 (8.2%). Among all patients, 154 (7.6%) presented esophageal eosinophilia (≥15 eosinophils per high power field) (P<0.01). In this group, 30 patients (19.5%) had normal endoscopy. In patients with EoE, edema (74% vs 6.5%, P<0.01) and furrows (66.2% vs 2.4%, P<0.01) were more prevalent than in the control group. Association of edema and furrows was more frequent in patients with EoE than in the control group (29.2% vs 1.6%, P<0.01, OR=24.7, CI=15.0-40.5). The presence of more than one endoscopic finding had sensitivity of 80.5%, specificity of 93.4%, positive predictive value (PPV) of 50%, negative predictive value (NPV) of 98.3%, and accuracy of 92.4%. CONCLUSION: In conclusion, this study showed that endoscopic features suggestive of EoE had high specificity and NPV for diagnosing EoE in children naïve to PPI therapy. These findings highlight the importance of the EREFS in contributing to early identification of inflammatory and fibrostenosing characteristics of EoE, making it possible to identify and to avoid progression of the disease. BACKGROUND: • The EoE endoscopic reference score (EREFS) was developed and validated in adults and has been demonstrated to be an adequate tool for diagnosing and assessing treatment response in children. BACKGROUND: • The presence of more than one endoscopic finding stronglysuggests EoE. BACKGROUND: • The EoE endoscopic reference score presents high specificity and negative predictive value for diagnosing EoE in children naïve to proton pump inhibitor (PPI) therapy. BACKGROUND: • Endoscopic findings suggestive of EoE in patients naïve to treatment may be useful to characterize disease phenotype and individualize treatment according to the initial clinical presentation.

Acurácia do escore de referência endoscópico para esofagite eosinofílica em crianças / Accuracy of the eosinophilic esophagitis endoscopic reference score in children

ABSTRACT Background: To assess the efficacy of applying the endoscopic reference score for EoE (EREFS) in children with symptoms of esophageal dysfunction naïve to proton pump inhibitor (PPI) therapy. Methods: An observational cross-sectional study was conducted by reviewing reports and photographs of upper gastrointestinal endoscopies (UGE) and esophageal biopsies of patients with symptoms of esophageal dysfunction. Patients who were treated with PPI or had other conditions that may cause esophageal eosinophilia were excluded. Results: Of the 2,036 patients evaluated, endoscopic findings of EoE were identified in 248 (12.2%) and more than one abnormality was observed in 167 (8.2%). Among all patients, 154 (7.6%) presented esophageal eosinophilia (≥15 eosinophils per high power field) (P<0.01). In this group, 30 patients (19.5%) had normal endoscopy. In patients with EoE, edema (74% vs 6.5%, P<0.01) and furrows (66.2% vs 2.4%, P<0.01) were more prevalent than in the control group. Association of edema and furrows was more frequent in patients with EoE than in the control group (29.2% vs 1.6%, P<0.01, OR=24.7, CI=15.0-40.5). The presence of more than one endoscopic finding had sensitivity of 80.5%, specificity of 93.4%, positive predictive value (PPV) of 50%, negative predictive value (NPV) of 98.3%, and accuracy of 92.4%. Conclusion: In conclusion, this study showed that endoscopic features suggestive of EoE had high specificity and NPV for diagnosing EoE in children naïve to PPI therapy. These findings highlight the importance of the EREFS in contributing to early identification of inflammatory and fibrostenosing characteristics of EoE, making it possible to identify and to avoid progression of the disease.

RESUMO Contexto: Avaliar a eficácia da aplicação do escore de referência endoscópico para EoE (EREFS) em crianças com sintomas de disfunção esofágica sem tratamento prévio com inibidores da bomba de prótons (IBP). Métodos: Foi realizado um estudo transversal observacional por meio de revisão de laudos e fotos de endoscopia digestiva alta (EDA) e biópsias de esôfago de pacientes com sintomas de disfunção esofágica. Pacientes tratados com IBP ou com outras condições que podem causar eosinofilia esofágica foram excluídos. Resultados: Dos 2.036 pacientes avaliados, os achados endoscópicos de EoE foram identificados em 248 (12,2%) e mais de uma anormalidade foi observada em 167 (8,2%). Entre todos os pacientes, 154 (7,6%) apresentaram eosinofilia esofágica (≥15 eosinófilos por campo de grande aumento) (P<0,01). Nesse grupo, 30 pacientes (19,5%) apresentaram endoscopia normal. Em pacientes com EoE, edema (74% vs 6,5%, P<0,01) e linhas verticais (66,2% vs 2,4%, P<0,01) foram mais prevalentes quando comparados ao grupo controle. A associação de edema e linhas verticais foi mais frequente em pacientes com EoE do que no grupo controle (29,2% vs 1,6%, P<0,01, OR=24,7, IC=15,0-40,5). A presença de mais de um achado endoscópico teve sensibilidade de 80,5%, especificidade de 93,4%, valor preditivo positivo de 50%, valor preditivo negativo de 98,3% e acurácia de 92,4%. Conclusão: Em conclusão, esse estudo mostrou que as características endoscópicas sugestivas de EoE apresentam especificidade e VPN elevados para o diagnóstico da enfermidade em crianças sem tratamento prévio com IBP. Estes achados reforçam a importância do EREFS em contribuir para a identificação precoce de características inflamatórias e fibroestenosantes, possibilitando identificar e evitar a progressão da doença.

Latin American anaphylaxis registry.

Background: Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective: To provide updated and extended data on anaphylaxis in this region. Method: An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results: Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions: Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.

Environmental contributions to the interactions of COVID-19 and asthma: A secondary publication and update.

An outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19, especially for those with severe disease or non-allergic phenotypes, deserves further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations, and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, an earlier start and extension of the pollinating season, and the increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable of persisting in the environment and can be transported by bioaerosols which can further influence its transmission rate and seasonality. The COVID-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns and loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.

Allergic manifestations of inborn errors of immunity and their impact on the diagnosis: A worldwide study.

Background: Allergies have long been observed in Inborn Errors of Immunity (IEI) and might even be the first presentation resulting in delayed diagnosis or misdiagnosis in some cases. However, data on the prevalence of allergic diseases among IEI patients are limited and contradictory. Objective: To provide a worldwide view of allergic diseases, across a broad spectrum of IEI, and their impact on the timely diagnosis of IEI. Methods: This is a worldwide study, conceived by the World Allergy Organization (WAO) Inborn Errors of Immunity Committee. A questionnaire was developed and pilot-tested and was sent via email to collect data from 61 immunology centers known to treat pediatric and/or adult IEI patients in 41 countries. In addition, a query was submitted to The United States Immunodeficiency Network (USIDNET) at its website. Results: Thirty centers in 23 countries caring for a total 8450 IEI patients responded. The USIDNET dataset included 2332 patients. Data from responders showed that a median (IQR) of 16.3% (10-28.8%) of patients experienced allergic diseases during the course of their IEI as follows: 3.6% (1.3-11.3%) had bronchial asthma, 3.6% (1.9-9.1%) atopic dermatitis, 3.0% (1.0-7.8%) allergic rhinitis, and 1.3% (0.5-3.3%) food allergy. As per the USIDNET data, the frequency of allergy among IEI patients was 68.8% (bronchial asthma in 46.9%). The percentage of IEI patients who presented initially with allergic disorders was 8% (5-25%) and diagnosis delay was reported in 7.5% (0.9-20.6%). Predominantly antibody deficiencies had the highest frequency of allergic disease followed by combined immunodeficiency with a frequency of 40.3% (19.2-62.5%) and 20.0% (10-32%) respectively. As per the data of centers, anaphylaxis occurred in 25/8450 patients (0.3%) whereas per USIDNET dataset, it occurred in 249/2332 (10.6%); drugs and food allergy were the main causes in both datasets. Conclusions: This multinational study brings to focus the relation between allergic diseases and IEI. Major allergies do occur in IEI patients but were less frequent than the general population. Initial presentation with allergy could adversely affect the timely diagnosis of IEI. There is a need for policies to raise awareness and educate primary care and other referring specialties on the association of allergic diseases with IEI. This study provides a network among centers for future prospective studies in the field.

Allergic rhinitis aggravated by air pollutants in Latin America: A systematic review.

The aim of this systematic review (SR) was to evaluate the most frequent pollutants and their effect on allergic rhinitis in Latin American countries. Observational studies up to December 2020 and comparing different indoor and outdoor pollutants that had allergic rhinitis (AR) as an outcome were included in the systematic review. Random-effect meta-analyses were conducted for the presence of allergic rhinitis. Estimates were presented as pooled odds ratios (ORs) and their respective 95% confidence intervals (CIs). Twenty-two publications comprised this review according to the inclusion and exclusion criteria and 12 had data that could be analyzed statistically. The most frequent pollutant was PM10, followed by NO2 /O3 and PM2.5 in studies conducted in Argentina, Brazil, Bolivia, Chile, Colombia, Costa Rica, and Peru. The OR of an exposed subject experiencing allergic rhinitis was 1.43 (95% CI 1.026; 1.980). The OR of children and adolescents experiencing of allergic rhinitis was 1.359 (95% CI 1.051; 1.759). Asymmetry and great variability in the effect estimated from the selected studies were observed. The publication bias was quantified by Kendall's correlation and Egger's test resulted in 0.152 (p-value = 0.493). Egger's test provided an intercept equal to 2.511 and a p-value = 0.398. The I2 statistic was 89.3% and reinforces the hypothesis of heterogeneity. This first systematic review conducted in Latin America confirmed the chance of a person exposed to pollutants and experiencing allergic rhinitis is 43% greater than that of a non-exposed person, reinforcing the importance of policies to reduce pollutant exposure and the use of protection systems for workforces exposed to occupational pollutants in work environments.

Erratum to "IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper" [World Allergy Organ J 13/2 (2020) 100080].

[This corrects the article DOI: 10.1016/j.waojou.2019.100080.].

Thunderstorm allergy and asthma: state of the art.

Thunderstorm-triggered asthma (TA) can be defined as the occurrence of acute asthma attacks immediately following a thunderstorm during pollen seasons. Outbreaks have occurred across the world during pollen season with the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for allergic patients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed atopic patients with IgE-mediated sentitization to pollen allergens. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen but also other pollens such as Parietaria and moulds in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which can be followed by a late inflammatory phase. There is evidence that, during pollen season, thunderstorms can induce allergic asthma outbreaks, sometimes also severe asthma crisis and sometimes deaths in patients suffering from pollen allergy. It has been observed that changes in the weather such as rain or humidity may induce hydratation of pollen grains during pollen seasons and sometimes also their fragmentation which generates atmospheric biological aerosols carrying allergens. Asthma attacks are induced for the high concentration at ground level of pollen grains which may release allergenic particles of respirable size after rupture by osmotic shock. In other words, it is a global health problem observed in several cities and areas of the world that can strike without sufficient warning, inducing sometimes severe clinical consequences also with deaths of asthma patients. Due to constant climate change, future TA events are likely to become more common, more disastrous and more unpredictable, as a consequence it is important to have deep knowledge on this topic to prevent asthma attacks. Other environmental factors, such as rapid changes in temperature and agricultural practices, also contribute to causing TA.

Identification of the major allergenic proteins from silkworm moth (Bombyx mori) involved in respiratory allergic diseases

INTRODUCTION AND OBJECTIVES: Moths are a significant source of indoor and outdoor aeroallergens. High prevalence of IgE-mediated sensitization was demonstrated in a group of patients with allergic respiratory diseases. There are no studies on adult stage of these moth species allergens involved in allergic respiratory reactions - the aim of this study. MATERIAL AND METHODS: 36 participants were included in an experimental study, submitted to skin prick test with Bombyx mori wing extract and six other common allergens, as well as Western blot analysis with incubated nitrocellulose membrane impregnated with silkworm moth extract and human IgE-antibody. The participants were divided into 3 groups: 1) 21 allergic patients whose skin prick test was positive to Bombyx mori wing extract, 2) eight allergic patients whose skin prick test was positive to mite and negative to Bombyx mori extract 3) seven negative non-allergic subjects. RESULTS: Among the 21 participants from group 1, 19 serum samples reacted to Bombyx mori extract by Western blot. All of them reacted to a protein at 80 kDa and five other proteins (66, 50, 45, 37 and 30 kDa) were identified in more than 50% of the individuals tested, considered as major allergenic proteins. Sera from seven out of eight patients sensitized to house dust mite demonstrated IgE-reactivity to Bombyx mori extract by Western blot analysis. Serum samples from healthy participants did not react at all. CONCLUSION: Six major reactive proteins by immunoblot analysis from moth’s wings sensitized patients can be potential allergens. The one at 80 kDa is the major protein, seen in all IgE-reactive patients from group 1 and in none from group 2, yet to be identified. Future studies should be conducted to better characterize these proteins

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Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).

Air pollution causes significant morbidity and mortality in patients with inflammatory airway diseases (IAD) such as allergic rhinitis (AR), chronic rhinosinusitis (CRS), asthma, and chronic obstructive pulmonary disease (COPD). Oxidative stress in patients with IAD can induce eosinophilic inflammation in the airways, augment atopic allergic sensitization, and increase susceptibility to infection. We reviewed emerging data depicting the involvement of oxidative stress in IAD patients. We evaluated biomarkers, outcome measures and immunopathological alterations across the airway mucosal barrier following exposure, particularly when accentuated by an infectious insult.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis / Citologia do lavado nasal e alterações histopatológicas na mucosa nasal de pacientescom rinite

Abstract Introduction The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. Objective To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. Methods Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. Results Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n = 36) and non-allergic rhinitis (n = 20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. Conclusion In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Resumo Introdução A extensão da lesão epitelial na rinite alérgica e não alérgica e sua associação com alterações inflamatórias no lavado nasal ainda não estão esclarecidas. Objetivo Verificar a relação entre o processo inflamatório no lavado nasal, extensão da lesão epitelial e espessamento da membrana basal na mucosa nasal de pacientes com rinite; determinar o ponto de corte do percentual de eosinófilos no lavado nasal associado à presença de atopia. Método Foram selecionados pacientes com rinite e indicação de septoplastia e (ou) turbinectomia por hipertrofia de conchas nasais, os quais foram submetidos aos testes cutâneos alérgicos, lavado nasal com determinação das concentrações de albumina, interleucina-8 (IL-8), contagem total e diferencial de células, análise da extensão da lesão epitelial, e grau de espessamento da membrana basal por meio de histopatologia da mucosa. Resultado Foram estudados 56 pacientes, mediana de 24,5 anos com diagnóstico de rinite alérgica (n = 36) e rinite não alérgica (n = 20). Nos atópicos os testes cutâneos alérgicos foram positivos para D. pteronyssinus em 35 (97,0%) e L. perenne em 18 (50,0%). Atópicos apresentaram maior índice de escore clínico para rinite em comparação a não atópicos. A contagem total de células, neutrófilos e níveis de albumina e IL-8 não foi diferente entre o lavado nasal de atópicos e não atópicos. O ponto de corte da contagem de eosinófilos no fluido nasal para a distinção de rinite alérgica e rinite não alérgica foi de 4%. Algum grau de lesão epitelial foi mais frequente em pacientes com rinite alérgica (94%) do que em pacientes com rinite não alérgica (65%). Na presença de espessamento da membrana basal, como marcador de remodelamento, não houve diferença no lavado nasal entre pacientes com rinite alérgica e não alérgica. Conclusão Nesta casuística, 4% foi o ponto de corte do número de eosinófilos no lavado nasal, para diferenciação de atopia. Remodelamento da via aérea superior pelo espessamento da membrana basal revelou infiltrado semelhante de células inflamatórias no lavado nasal, independentemente da presença de atopia.

Identification of the major allergenic proteins from silkworm moth (Bombyx mori) involved in respiratory allergic diseases.

INTRODUCTION AND OBJECTIVES: Moths are a significant source of indoor and outdoor aeroallergens. High prevalence of IgE-mediated sensitization was demonstrated in a group of patients with allergic respiratory diseases. There are no studies on adult stage of these moth species allergens involved in allergic respiratory reactions - the aim of this study. MATERIAL AND METHODS: 36 participants were included in an experimental study, submitted to skin prick test with Bombyx mori wing extract and six other common allergens, as well as Western blot analysis with incubated nitrocellulose membrane impregnated with silkworm moth extract and human IgE-antibody. The participants were divided into 3 groups: 1) 21 allergic patients whose skin prick test was positive to Bombyx mori wing extract, 2) eight allergic patients whose skin prick test was positive to mite and negative to Bombyx mori extract 3) seven negative non-allergic subjects. RESULTS: Among the 21 participants from group 1, 19 serum samples reacted to Bombyx mori extract by Western blot. All of them reacted to a protein at 80 kDa and five other proteins (66, 50, 45, 37 and 30 kDa) were identified in more than 50% of the individuals tested, considered as major allergenic proteins. Sera from seven out of eight patients sensitized to house dust mite demonstrated IgE-reactivity to Bombyx mori extract by Western blot analysis. Serum samples from healthy participants did not react at all. CONCLUSION: Six major reactive proteins by immunoblot analysis from moth's wings sensitized patients can be potential allergens. The one at 80 kDa is the major protein, seen in all IgE-reactive patients from group 1 and in none from group 2, yet to be identified. Future studies should be conducted to better characterize these proteins.

Thymidine-auxotrophic Staphylococcus aureus small-colony variant bacteremia in a patient with cystic fibrosis.

BACKGROUND: Small-colony variants (SCVs) are a morphologic subtype of Staphylococcus aureus that may occur through several mechanisms including auxotrophism for thymidine, hemin, or menadione. Auxotrophic SCV for thymidine fail to synthesize DNA specifically because of mutations in the thymidylate synthase gene. We isolated S. aureus thymidine-dependent SCVs (TD-SCV) from blood and respiratory samples of a pediatric patient with cystic fibrosis and pulmonary exacerbation. METHODS: Nutritional dependence of SCVs on hemin, menadione, and thymidine was evaluated. Antimicrobial susceptibility testing was performed through broth microdilution. Polymerase chain reaction was carried out for mecA, ermA, ermB, ermC, msrA, and msrB resistance genes. DNA sequencing was used to determine mutations in thyA and the multilocus sequence typing to identify genetic relatedness. RESULTS: Methicillin-sensitive S. aureus with normal and TD-SCV phenotypes were isolated from respiratory samples and a TD-SCV phenotype was isolated from blood culture. Macrolides resistance was attributed to ermC and msrB genes. All isolates belonged to ST398. The thyA gene in S. aureus is 957 nucleotides in length and encodes a protein of 318 amino acids. The TD-SCV isolates carried a -2 nt frameshift mutation (delta 667GC668) in thyA, creating a stop codon at residue 222 close to the predicted binding site for deoxyuridine monophosphate. CONCLUSIONS: The pathogenesis of SCVs is complex and not fully elucidated. Factors inherent to the patient such as physiological conditions, recurrent infections, or coinfection should be considered. Although SCVs are considered less virulent, they showed the ability to invade and cause bacteremia in the patient.

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.

Nasal lavage cytology and mucosal histopathological alterations in patients with rhinitis.

INTRODUCTION: The extent of epithelial lesion in allergic and non-allergic rhinitis and its association with inflammatory changes in nasal lavage has not been clarified. OBJECTIVE: To verify the association between the inflammatory cells in the nasal lavage, epithelial lesion extent and basement membrane thickness, in the nasal mucosa of patients with rhinitis; to determine the cutoff point of the percentage of eosinophils in the nasal lavage associated with the atopic patients. METHODS: Patients with rhinitis and indication for septoplasty and (or) turbinectomy for turbinate hypertrophy were selected, and were submitted to allergy skin tests, nasal lavage with measurement of albumin and interleukin-8 levels, total and differential counting of cells, and mucosal histopathological analysis to determine the extent of epithelial lesion, and degree of basement membrane thickening. RESULTS: Fifty-six patients with a median age of 24.5 years and a diagnosis of allergic rhinitis (n=36) and non-allergic rhinitis (n=20) were studied. In atopic subjects, allergy skin tests were positive for Dermatophagoides pteronyssinus in 35 (97.0%) and Lolium perenne in 18 (50.0%). Atopic subjects showed a higher clinical score index of rhinitis compared to non-atopic ones. The total count of cells, neutrophils, and levels of albumin and IL-8 were not different in the nasal lavage of atopic and non-atopic subjects. The cutoff point for eosinophil count in nasal fluid for the distinction between allergic rhinitis and non-allergic rhinitis was 4%. Some degree of epithelial lesion was more frequent in allergic rhinitis (94%) than in non-allergic rhinitis (65%) patients. In the presence of basement membrane thickness, as a marker of remodeling, there was no difference in the nasal lavage of patients with allergic rhinitis and non-allergic rhinitis. CONCLUSION: In this series, 4% was the cutoff point for the number of eosinophils in the nasal lavage, for atopy differentiation. Upper airway remodeling accessed by basement membrane thickness showed similar inflammatory cell infiltrate in the nasal lavage, regardless of the presence of atopy.

Determinação da potência relativa de extratos alergênicos de Phleum pratense por testes cutâneos / Establishing the relative potency of Phleum pratense allergenic extracts using skin prick tests

Objetivos: Comparar a potência de extratos europeus de Phleum pratense para imunoterapia sublingual (ITSL), em relação ao extrato referência norte-americano. Métodos: Foram selecionados 15 sujeitos, com idade entre 18 e 55 anos, histórico clínico sazonal compatível e teste cutâneo com alta reatividade a gramíneas. O delineamento de estudo foi transversal, triplo cego e randômico, e comparadas as potências dos seguintes extratos alergênicos para ITSL: (A) Soluprick® (30 HEP/mL) e (B) Grazax® 75.000 SQ-T, ambos os extratos da ALK-Abelló; (C) Oralair® e (D) Staloral®, com 300 IR/mL, Stallergènes, França. O extrato de origem norteamericana (E) foi o padrão, contendo 10.000 BAU/mL. Todos os extratos foram usados em forma de concentrados e nas diluições 1:3, 1:10, e 1:30. Os testes foram aplicados em quadruplicata em dois dias não consecutivos. Os diâmetros de pápula e eritema foram registrados após 15 minutos. Resultados: Não houve diferença significativa entre os testes realizados no primeiro e segundo dias (p = 0,37) com extratos concentrados, na diluição 1:3 e também 1:10 (p = 0,20 e p = 0,33, respectivamente). No segundo dia de testes, a média obtida das pápulas do extrato A foi de 16,7 mm na diluição 1:3; de 14,3 mm na diluição 1:10; e de 9,8 mm na diluição 1:30. Houve diferenças significativas entre os extratos A, B, C, D e E na comparação entre as médias das pápulas obtidas em todas as diluições, mostrando diferença de potência entre os extratos. O diâmetro das pápulas obtidas com o material concentrado, em ordem decrescente de potência, foram C > A > E > D > B. As reações observadas com extratos concentrados mostrou que o mais potente foi Staloral, e o menos potente Grazax. Conclusões: Houve variabilidade significativa de potência nos diversos extratos comparados. Isto reforça a necessidade de padronização de extratos alergênicos para ITSL.

Objectives: To compare the potency of European Phleum pratense pollen extracts for sublingual immunotherapy (SLIT) compared to the U.S. reference extract. Methods: Fifteen subjects aged between 18 and 55 years, with compatible seasonal clinical history and skin tests highly reactive to grass, were selected. The design was cross-sectional, blind, randomized. The following extracts were compared for SLIT: (A) Soluprick® (30 HEP/mL) and (B) Grazax® 75,000 SQ-T, both from ALK-Abelló; (C) Oralair® and (D) Staloral®, with 300 IR/mL, Stallergènes, France. The American extract (E) was the standard 10,000 BAU/mL. Extracts were used in concentrate form and also diluted in 1:3, 1:10, and 1:30 ratios. Tests were applied in quadruplicate on two nonconsecutive days. Skin test reading were done after 15 minutes. Results: There were no significant differences between the tests conducted on the first and second days with the extracts in concentrate form (p = 0.37) or diluted at 1:3 or 1:10 (p = 0.20, p = 0.33, respectively). On the second day of tests, mean wheal sizes obtained with extract A were 16.7 mm with the 1:3 dilution, 14.3 mm with the 1:10 dilution, and 9.8 mm with the 1:30 dilution. There were significant differences between extracts A, B, C, D and E when comparing mean wheal sizes obtained with all dilutions, demonstrating differences in the extracts' potency. Mean wheal diameters obtained with the concentrates, in decreasing order of potency, were C > A > E > D > B. The reactions showed that the most potent extract was Staloral, and the least potent, Grazax. Conclusions: There were significant potency variations in the different extracts assessed. These results reinforce the need for standardization of allergenic extracts used for SLIT.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis, / IV Consenso Brasileiro sobre Rinite - atualização em rinite alérgica,

Abstract Introduction The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. Objective To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. Methods We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. Results The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. Conclusion A flowchart for allergic rhinitis treatment has been proposed.

Resumo Introdução As diretrizes sobre rinite alergica visam atualizar os conhecimentos sobre a doença e os cuidados para com esses pacientes. A iniciativa designada "Rinite Alergica e seu Impacto na Asma", cujo relatorio inicial foi publicado em 2001 e atualizada em 2008 e 2010, tem sido muito bem sucedida na disseminaçao de informaçoes e evidencias, bem como na formulaçao da classificaçao de gravidade e proposta de sistematizaçao do tratamento. Entretanto, visando a participaçao de outros profissionais medicos no atendimento da rinite alergica, e importante o desenvolvimento de algoritmos que indiquem com precisao o que deve e pode ser feito regionalmente. Objetivo Atualizar o III Consenso Brasileiro sobre Rinites-2012, com elaboraçao de algoritmo para conduta da rinite alergica. Método Foram convidados 24 especialistas indicados pelas Associaçao Brasileira de Alergia e Imunologia, Associaçao Brasileira de Otorrinolaringologia e Cirurgia Cervico-Facial e Sociedade Brasileira de Pediatria para atualizaçao do documento de 2012. Resultados A atualizaçao do ultimo Consenso Brasileiro sobre Rinites, incorporou e adaptou para a realidade brasileira as informaçoes relevantes publicadas em todos os documentos da Iniciativa "Rinite Alergica e seu Impacto na Asma", trazendo novos conceitos como a rinite alergica local, novos medicamentos e metodos de avaliaçao de tratamento. Conclusão Proposto um fluxograma de tratamento para a rinite alergica.

IV Brazilian Consensus on Rhinitis - an update on allergic rhinitis.

INTRODUCTION: The guidelines on allergic rhinitis aim to update knowledge about the disease and care for affected patients. The initiative called "Allergic Rhinitis and its Impact on Asthma", initially published in 2001 and updated in 2008 and 2010, has been very successful in disseminating information and evidence, as well as providing a classification of severity and proposing a systemized treatment protocol. In order to include the participation of other medical professionals in the treatment of allergic rhinitis, it is important to develop algorithms that accurately indicate what should and can be done regionally. OBJECTIVE: To update the III Brazilian Consensus on Rhinitis - 2012, with the creation of an algorithm for allergic rhinitis management. METHODS: We invited 24 experts nominated by the Brazilian Association of Allergy and Immunology, Brazilian Association of Otorhinolaryngology and Head and Neck Surgery and Brazilian Society of Pediatrics to update the 2012 document. RESULTS: The update of the last Brazilian Consensus on Rhinitis incorporated and adapted the relevant information published in all "Allergic Rhinitis and its Impact on Asthma" Initiative documents to the Brazilian scenario, bringing new concepts such as local allergic rhinitis, new drugs and treatment evaluation methods. CONCLUSION: A flowchart for allergic rhinitis treatment has been proposed.