Intrabreath oscillometry is a sensitive test for assessing disease control in adults with severe asthma.

BACKGROUND: Asthma control is not well reflected by spirometry, yet this is the most frequently used measure of lung function in asthma clinics. Oscillometry is an alternative technique suitable for those with severe asthma. OBJECTIVE: To investigate usefulness of oscillometry in subjects with severe asthma to determine which outcome variables best reflected asthma control. METHODS: Adults with severe asthma were recruited from a severe asthma clinic in Brazil. Oscillometry (conventional multifrequency measurements between 6 and 32 Hz; intrabreath tracking at 8 Hz) and spirometry were performed. Asthma control was determined by the asthma control test. RESULTS: A total of 60 adults were evaluated; mean age was 56.7 years. There was predominance of women (82%), and most patients (63%) reported onset of asthma symptoms in childhood or adolescence. There were no differences between controlled and uncontrolled asthma in spirometry. Uncontrolled asthma was associated with higher resistance (at 8 and 10 Hz) and more negative reactance (for 6, 8, and 10 Hz) (P < .05) on conventional oscillometry. Intrabreath oscillometry revealed significant differences between controlled and uncontrolled patients with asthma (P < .01 for changes in resistance and reactance between end expiration and end inspiration). The accuracy of the lung function tests in discriminating between controlled and uncontrolled asthma was higher for intrabreath variables (area under the curve = 0.65-0.72). CONCLUSION: Oscillometry, particularly the intrabreath technique, better reflected asthma control than spirometry measures. Our findings suggest that oscillometry may be a useful technique to aid management of severe asthma, with a potential to reflect loss of disease control.

Omalizumab in Chronic Spontaneous Urticaria: A Brazilian Real-Life Experience.

BACKGROUND: Current guidelines on chronic spontaneous urticaria (CSU) suggest a treatment based on a 3-step approach that aims at total symptom control, starting with H1-antihistamines. However, a significant number of patients present an antihistamine-resistant urticaria that must be treated with an alternative third-line therapy such as omalizumab. METHODS: Patients with a history of CSU who did not respond to treatment with high doses of modern antihistamines were treated with 150 or 300 mg of omalizumab every 4 weeks. The response to treatment was recorded as complete (CR), partial (PR) or no response. A dose adjustment was proposed according to response. RESULTS: We treated 47 CSU patients with omalizumab (40 females), of whom 39.5% had evidence of autoimmunity. The average number of treatments was 11.4 (range 2-87). All patients had been refractory to high-dose modern antihistamines. A CR was seen in 84.6% of patients who started with 300 mg and in 60% of those who started with 150 mg. Only 1 patient had no response to both the 150- and 300-mg doses. In 6 of the PR patients with 150 mg, a higher dose of 300 mg was proposed and 4 had a CR. Four patients discontinued the treatment. No severe adverse events were reported in the patients who finished the study. DISCUSSION: Although good results were seen in both groups, CR rates were higher in those under a high-dose initial treatment. Our data strongly suggest that the therapy should be individualized.

Epidemiological characterization of rare diseases in Brazil: A retrospective study of the Brazilian Rare Diseases Network.

BACKGROUND: The Brazilian Policy for Comprehensive Care for People with Rare Diseases was implemented in 2014; however, national epidemiological data on rare diseases (RDs) are scarce and mainly focused on specific disorders. To address this gap, University Hospitals, Reference Services for Neonatal Screening, and Reference Services for Rare Diseases, all of which are public health institutions, established the Brazilian Rare Diseases Network (RARAS) in 2020. The objective of this study was to perform a comprehensive nationwide epidemiological investigation of individuals with RDs in Brazil. This retrospective survey collected data from patients receiving care in 34 healthcare facilities affiliated with RARAS in 2018 and 2019. RESULTS: The survey included 12,530 participants with a median age of 15.0 years, with women representing 50.5% of the cohort. Classification according to skin color demonstrated that 5044 (47.4%) participants were admixed. Most had a confirmed diagnosis (63.2%), with a predominance of phenylketonuria (PKU), cystic fibrosis (CF), and acromegaly. Common clinical manifestations included global developmental delay and seizures. The average duration of the diagnostic odyssey was 5.4 years (± 7.9 years). Among the confirmed diagnoses, 52.2% were etiological (biochemical: 42.5%; molecular: 30.9%), while 47.8% were clinical. Prenatal diagnoses accounted for 1.2%. Familial recurrence and consanguinity rates were 21.6% and 6.4%, respectively. Mainstay treatments included drug therapy (55.0%) and rehabilitation (15.6%). The Public Health System funded most diagnoses (84.2%) and treatments (86.7%). Hospitalizations were reported in 44.5% of cases, and the mortality rate was 1.5%, primarily due to motor neuron disease and CF. CONCLUSION: This study marks a pioneering national-level data collection effort for rare diseases in Brazil, offering novel insights to advance the understanding, management, and resource allocation for RDs. It unveils an average diagnostic odyssey of 5.4 years and a higher prevalence of PKU and CF, possibly associated with the specialized services network, which included newborn screening services.

Are pediatricians familiar with hereditary angioedema?

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. Methods: An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Results: Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). Conclusion: Knowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.

The specialty of allergy and clinical immunology in Brazil.

Objective: To assess the profile of allergist/immunologist (A/I) physicians in Brazil, the workplace, the access to diagnostic and therapeutic procedures, and the impact of the COVID-19 pandemic on professional practice. Methods: This cross-sectional study was conducted as an online survey. All adhering members of the Brazilian Association of Allergy and Immunology (ASBAI) received a Google Forms tool by email. The questionnaire addressed sociodemographic and professional aspects of the Brazilian allergists/immunologists (A/I) daily routine. The information was analyzed by SPSS version 20.0. Results: Four hundred and sixty members answered the questionnaire. Women were predominant among the responders (336; 73%), and the median age was 47 years (range, 27-82 years). Most participants worked in the private sector (437, 95%), whereas 256 (47%) worked in the public sector. Among the public sector employees, 210 (82%) reported having access to some diagnostic test for allergic diseases and inborn errors of immunity. Only 91 (35%) A/I physicians in the public system had access to allergen-specific immunotherapy, compared to 416 (95, 9%) of those in the private sector. Regarding biological drugs, 135 (52.7%) and 314 (71.9%) of the A/I physicians working in the public and private sector, respectively, reported access. Two hundred and eighty-three (61.6%) had at least a 50% reduction in the number of consultations, and 245 (56%) provided telemedicine care during the COVID-19 pandemic. Conclusion: Brazilian A/I have incorporated the most recent advances in managing immunoallergic diseases into their clinical practice, but they still have little access to various diagnostic methods. Strategies to enable the presence of A/I in public health services should be discussed and implemented. The coronavirus pandemic has accelerated the incorporation of telemedicine as a viable and promising method of medical care and can expand access to the specialty.

Prevalence of the eosinophilic phenotype among severe asthma patients in Brazil: the BRAEOS study.

OBJECTIVE: To assess the prevalence of the eosinophilic and allergic phenotypes of severe asthma in Brazil, as well as to investigate the clinical characteristics of severe asthma patients in the country. METHODS: This was a cross-sectional study of adult patients diagnosed with severe asthma and managed at specialized centers in Brazil. The study was conducted in 2019. RESULTS: A total of 385 patients were included in the study. Of those, 154 had a blood eosinophil count > 300 cells/mm3 and 231 had a blood eosinophil count of ≤ 300 cells/mm3. The median age was 54.0 years, and most of the patients were female, with a BMI of 29.0 kg/m2 and a history of allergy (81.6%). The prevalence of patients with a blood eosinophil count > 300 cells/mm3 was 40.0% (95% CI: 35.1-44.9), and that of those with a blood eosinophil count > 300 cells/mm3 and a history of allergy was 31.9% (95% CI: 27.3-36.6). Age and BMI showed positive associations with a blood eosinophil count > 300 cells/mm3 (OR = 0.97, p < 0.0001; and OR = 0.96, p = 0.0233, respectively), whereas the time elapsed since the onset of asthma symptoms showed an increased association with a blood eosinophil count > 300 cells/mm3 (OR = 1.02, p = 0.0011). CONCLUSIONS: This study allowed us to characterize the population of severe asthma patients in Brazil, showing the prevalence of the eosinophilic phenotype (in 40% of the sample). Our results reveal the relevance of the eosinophilic phenotype of severe asthma at a national level, contributing to increased effectiveness in managing the disease and implementing public health strategies.

Hereditary angioedema: how to approach it at the emergency department?

Angioedema attacks are common causes of emergency care, and due to the potential for severity, it is important that professionals who work in these services know their causes and management. The mechanisms involved in angioedema without urticaria may be histamine- or bradykinin-mediated. The most common causes of histamine-mediated angioedema are foods, medications, insect sting and idiopathic. When the mediator is bradykinin, the triggers are angiotensin-converting enzyme inhibitors and factors related to acquired angioedema with deficiency of C1-inhibitor or hereditary angioedema, which are less common, but very important because of the possibility of fatal outcome. Hereditary angioedema is a rare disease characterized by attacks of edema that affect the subcutaneous tissue and mucous membranes of various organs, manifesting mainly by angioedema and abdominal pain. This type of angioedema does not respond to the usual treatment with epinephrine, antihistamines and corticosteroids. Thus, if not identified and treated appropriately, these patients have an estimated risk of mortality from laryngeal edema of 25% to 40%. Hereditary angioedema treatment has changed dramatically in recent years with the development of new and efficient drugs for attack management: plasma-derived C1 inhibitor, recombinant human C1-inhibitor, bradykinin B2 receptor antagonist (icatibant), and the kallikrein inhibitor (ecallantide). In Brazil, plasma-derived C1 inhibitor and icatibant have already been approved for use. Proper management of these patients in the emergency department avoids unnecessary surgery and, especially, fatal outcomes.

Space-time analysis of the effect of air pollution on children's health. / Análise espaço-temporal do efeito da poluição do ar na saúde de crianças.

The study aimed to investigate the short-term association between air pollution and emergency treatments for respiratory diseases in children 0 to 6 years of age. This was an ecological space-time study in Greater Metropolitan Vitória, Espírito Santo State, Brazil. A Poisson regression general additive model (GAM) used the number of daily treatments for respiratory diseases as the dependent variable, and the independent variables were daily concentrations of air pollutants (PM10, SO2, NO2, O3, and CO), temperature, humidity, and precipitation. Average daily concentrations were used to make estimates for the entire metropolitan area and in loco analyses considering children residing in a 2km radius around 8 air quality monitoring stations. An increase of 10µg/m3 in the concentration of air pollutants increased the risk of emergency treatment for respiratory disease. In the overall area, for PM10, the increase was 2.43%, 2.73%, and 3.29% in the cumulative values at 5, 6, and 7 days, respectively. For SO2, the increase was 4.47% on the day of exposure, 5.26% two days later, and 6.47%, 8.8%, 8.76%, and 7.09% for the cumulative values at days 2, 3, 4, and 5 days, respectively. CO showed a significant association for residents around two stations, and O3 for only one. Even within the limits set by the World Health Organization, the pollutants PM10, SO2, NO2, and O3 are associated with increased risk of treatment for respiratory diseases in children 0 to 6 years of age, and some effects were only identified when disaggregating by neighborhood, i.e., in loco, which allows capturing greater variation in the data.

O objetivo foi investigar a associação de curto prazo entre a poluição do ar e atendimentos em emergências por doenças respiratórias, em crianças de 0 a 6 anos. Estudo ecológico, espacial e temporal realizado na Região Metropolitana da Grande Vitoria, Espírito Santo, Brasil. Utilizou-se o modelo aditivo generalizado (MAG) de regressão de Poisson, com a variável dependente o número diário de atendimentos por doenças respiratórias, e as variáveis independentes, concentrações diárias dos poluentes atmosféricos (MP10, SO2, NO2, O3 e CO), temperatura, umidade e precipitação pluviométrica. Por meio das médias diárias das concentrações, foram feitas estimativas para toda a região e análises in loco com a consideração de crianças residentes no entorno de 2km de oito estações de monitoramento da qualidade do ar. O incremento de 10µg/m3 nos níveis de concentração dos poluentes atmosféricos aumentou o risco de atendimento em emergência por doença respiratória. Na região geral, para o MP10, o aumento foi de 2,43%, 2,73% e 3,29% nos acumulados de 5, 6 e 7 dias, respectivamente. Para o SO2, o acréscimo foi de 4,47% no dia da exposição, 5,26% dois dias após, 6,47%, 8,8%, 8,76% e 7,09% nos acumulados de 2, 3, 4 e 5 dias, respectivamente. O CO apresentou associação significativa para residentes no entorno de duas estações, e o O3 somente em uma. Mesmo dentro dos limites estabelecidos pela Organização Mundial da Saúde, os poluentes MP10, SO2, NO2 e O3 estão associados ao maior risco para atendimento por doenças respiratórias em crianças de 0 a 6 anos, e alguns efeitos só foram identificados nas localidades desagregadas por região, isto é, in loco, o que possibilita captar maior variabilidade dos dados.

El objetivo fue investigar la asociación de corto plazo entre la contaminación del aire y la atención en urgencias por enfermedades respiratorias, en niños de 0 a 6 años. Estudio ecológico, espacial y temporal realizado en la Región Metropolitana de la Grande Vitória, Espírito Santo, Brasil. Se utilizó el modelo aditivo generalizado (MAG) de regresión de Poisson, con la variable dependiente que es el número diario de consultas por enfermedades respiratorias, y las variables independientes: concentraciones diarias de los contaminantes atmosféricos (MP10, SO2, NO2, O3 y CO), temperatura, humedad y precipitación pluviométrica. Mediante las medias diarias de las concentraciones, se realizaron estimativas para toda la región y análisis in loco, considerando a niños residentes en un entorno de 2km con 8 estaciones de monitoreo de la calidad del aire. El incremento de 10µg/m3 en los niveles de concentración de los contaminantes atmosféricos aumentó el riesgo de atención en urgencias por enfermedad respiratoria. En la región como un todo, en el caso del MP10, el aumento fue de 2,43%, 2,73% y 3,29% en los acumulados de 5, 6 y 7 días, respectivamente. En el SO2, el incremento fue de 4,47% durante el día de la exposición, 5,26% dos días después, 6,47%, 8,8%, 8,76% y 7,09% en los acumulados de 2, 3, 4 y 5 días, respectivamente. El CO presentó asociación significativa para residentes alrededor de dos estaciones, y el O3 solamente en una. Incluso dentro de los límites establecidos por la Organización Mundial de la Salud, los contaminantes MP10, SO2, NO2 y O3 están asociados a un mayor riesgo en relación con la atención por enfermedades respiratorias en niños de 0 a 6 años, y algunos efectos sólo se identificaron en las localidades desagregadas por región, esto es, in loco, lo que posibilita captar una mayor variabilidad de los datos.

Desafios e propostas para a assistência aos pacientes com doenças imunoalérgicas no Sistema Único de Saúde brasileiro ­ Carta de Maceió / Challenges and proposals for the care of patients with immune and allergic diseases within the Brazilian Unified Health System: The Maceió Charter

A Carta de Maceió foi elaborada com base nas discussões do 3º Fórum SUS da Associação Brasileira de Alergia e Imunologia (ASBAI). O documento destaca os desafios e propostas para aprimorar a assistência a pacientes com doenças imunoalérgicas no Sistema Único de Saúde (SUS) do Brasil. Tais condições, frequentemente crônicas e debilitantes, afetam milhões de brasileiros e exigem uma abordagem integrada, desde a atenção primária à saúde até a atenção especializada. Foram discutidos a necessidade de aprimorar a gestão de referência e contrarreferência, a urgência na superação da carência de especialistas e o desafio representado pelo limitado acesso tanto a diagnóstico quanto a tratamento adequados. As doenças raras, incluindo os erros inatos da imunidade (EII), apresentam um desafio adicional, exigindo acesso a tecnologias de alto custo para diagnóstico e tratamento e cuidado multidisciplinar. Do fórum emergiram propostas como o financiamento adequado da saúde, o fortalecimento do diagnóstico precoce, a gestão integrada de cuidados, a educação continuada dos profissionais de saúde e a implementação de telemedicina. Essas ações visam um sistema de saúde mais inclusivo, eficiente e humanizado, atendendo às necessidades dos pacientes com doenças imunoalérgicas.

The Maceió Charter was based on discussions held at the 3rd Unified Health System Forum (Fórum SUS) of the Brazilian Association of Allergy and Immunology (ASBAI). This document highlights challenges and proposals to improve care for patients with immune and allergic diseases within the Brazilian Unified Health System (SUS). Such conditions, often chronic and debilitating, affect millions of Brazilians and require an integrated approach from primary health through to specialty care. The need for improved management of referrals and counter-referrals, the urgency of overcoming the shortage of specialists, and the challenge represented by limited access to proper diagnosis and treatment alike were discussed. Rare diseases, including inborn errors of immunity (IEI), pose an additional challenge, requiring access to high-cost technologies for diagnosis and treatment as well as multidisciplinary care. Several proposals emerged from the Forum, such as securing sufficient funding for health, strengthening early diagnosis, integrating management, continuing education for health professionals, and implementation of telemedicine. These proposed interventions seek a more inclusive, efficient, and humanized healthcare system which meets the needs of patients with immune and allergic diseases.

Guia prático para o uso de imunobiológicos em doenças alérgicas - ASBAI / Practical guide for the use of immunobiologic agents in allergic diseases - ASBAI

Os anticorpos monoclonais são uma nova classe de medicamentos que representa um marco na evolução da terapia de doenças alérgicas graves. Além de possibilitar uma terapia imunológica alvo específico, proporciona maior controle de sintomas, redução de exacerbações, melhoria da qualidade de vida e da segurança. A eficácia e a segurança dos anticorpos monoclonais no tratamento de doenças alérgicas estão bem documentadas nos estudos clínicos pivotais, de extensão e de vida real. No Brasil, estão licenciados atualmente pela Agência Nacional de Vigilância Sanitária (ANVISA) imunobiológicos para asma, dermatite atópica (DA), esofagite eosinofílica (EoE), granulomatose eosinofílica com poliangeíte (GEPA), rinossinusite crônica com pólipo nasal (RSCcPN), síndromes hipereosinofílicas (SHE) e urticária crônica espontânea (UCE). Com a incorporação do uso dessas novas terapias no dia a dia do médico alergologista e imunologista, naturalmente emergem aspectos práticos que exigem orientações práticas perante as evidências científicas mais atuais, a fim de se manter a boa prática médica, com uso criterioso e consciente pelo especialista capacitado. Assim, nesse guia prático, abordaremos os imunobiológicos aprovados até o momento para doenças alérgicas graves, com objetivo de auxiliar o especialista em Alergia e Imunologia na prescrição e manejo dessas medicações, incluindo indicações, contraindicações, monitoramento da eficácia e segurança, notificação de eventos adversos, bem como aspectos associados aos cuidados com vacinas, populações especiais, acesso, transporte, armazenamento e aplicação domiciliar.

Monoclonal antibodies are a new class of drugs that represent a milestone in the evolution of therapy for severe allergic diseases. In addition to allowing targeted immunologic therapy, they can improve symptom control, reduce exacerbations, and increase quality of life and safety. The efficacy and safety of monoclonal antibodies in the treatment of allergic diseases are well documented in pivotal, extension, and real-life clinical studies. In Brazil, immunobiologic agents are currently licensed by the National Health Surveillance Agency (ANVISA) for use in asthma, atopic dermatitis (AD), eosinophilic esophagitis (EoE), eosinophilic granulomatosis with polyangiitis (EGPA), chronic rhinosinusitis with nasal polyps (CRSwNP), hypereosinophilic syndrome (HES), and chronic spontaneous urticaria (CSU). With the incorporation of these new therapies into the daily practice of the allergist and immunologist, practical aspects will naturally emerge and require practical guidelines in light of the most current scientific evidence in order to maintain good medical practice, with judicious and conscious use by a qualified specialist. Therefore, in this practical guide, we will address the immunobiologic agents currently approved for severe allergic diseases, aiming to assist allergy and immunology specialists in the prescription and practical management of these medications, including indications, contraindications, efficacy and safety monitoring, adverse event reporting, as well as health care factors associated with vaccination, special populations, access, transport, storage, and home use.

O omalizumabe no tratamento da urticária no contexto da pandemia de COVID-19 / Omalizumab as urticaria treatment in the context of the COVID-19 pandemic

O início da pandemia de COVID-19 foi marcado por incertezas diante do desconhecimento sobre a doença. Uma série de dúvidas relacionadas ao uso de imunobiológicos no contexto da pandemia foi levantada, inclusive em relação ao tratamento com omalizumabe em pacientes com urticária crônica (UC). Este estudo teve como objetivo analisar os dados relacionados à gravidade da COVID-19 e a evolução da urticária em pacientes em terapia com omalizumabe acompanhados por especialistas no Brasil. Foi realizada análise retrospectiva de dados de pacientes com UC tratados com omalizumabe entre julho/2020 e junho/2021 que apresentaram COVID-19. Foram avaliados dados relacionados às características clínicas dos pacientes e evolução da urticária durante a infecção pelo SARS-CoV2. Foram incluídos 28 pacientes em tratamento com omalizumabe, sendo 27 com urticária crônica espontânea (UCE), dos quais 25% tinham alguma urticária induzida associada. A maior parte dos pacientes (71%) estavam utilizando doses quadruplicadas de anti-histamínicos modernos de 2ª geração associados ao omalizumabe. Todos os pacientes estavam com os sintomas controlados. Entre os sintomas apresentados durante a COVID-19, os mais frequentes foram: febre (43%), cefaleia (36%), mal-estar (32%), hipo/anosmia (29%) e tosse (21%). Quatro pacientes foram hospitalizados, um deles em unidade de terapia intensiva. Um paciente relatou piora dos sintomas da UC durante a COVID-19. Cinco (18%) pacientes apresentaram piora dos sintomas da UC após a resolução da COVID-19. Todos os pacientes se recuperaram da COVID-19 sem sequelas graves. O OMA não pareceu aumentar o risco de COVID-19 grave e poderia ser usado com segurança em pacientes com UC.

The beginning of the COVID-19 pandemic was marked by uncertainty due to lack of knowledge about the disease. Questions were raised about the use of immunobiologicals in the pandemic context, including omalizumab for patients with chronic urticaria (UC). This study assessed COVID-19 severity and the clinical course of urticaria in Brazilian patients on omalizumab therapy who were monitored by specialists. We retrospectively analyzed data from chronic urticaria patients treated with omalizumab between July, 2020 and June, 2021 who presented with COVID- 19. Clinical characteristics and the course of urticaria during SARS-CoV2 infection were analyzed. The sample consisted of 28 patients treated with omalizumab, 27 of whom had chronic spontaneous urticaria (UCE) and 25% of whom had associated chronic inducible urticaria. Most of the patients (71%) were using quadruple doses of second-generation antihistamines associated with omalizumab. The symptoms of all patients were controlled. The most frequent symptoms during COVID-19 were: fever (43%), headache (36%), malaise (32%), hypo/anosmia (29%) and cough (21%). Four patients were hospitalized, including 1 in intensive care. One patient reported worsening chronic urticaria symptoms while infected with COVID-19. Five (18%) patients experienced worsening chronic urticaria symptoms after recovery from COVID-19. All patients recovered from COVID-19 without serious sequelae. Omalizumab did not appear to increase the risk of severe COVID-19 and can be safely used in patients with chronic urticaria.

Hereditary Angioedema with Normal C1 Inhibitor and F12 Mutations in 42 Brazilian Families.

BACKGROUND: Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) is a rare condition with clinical features similar to those of HAE with C1-INH deficiency. Mutations in the F12 gene have been identified in subsets of patients with HAE with normal C1-INH, mostly within families of European descent. OBJECTIVES: Our aim was to describe clinical characteristics observed in Brazilians from 42 families with HAE and F12 gene mutations (FXII-HAE), and to compare these findings with those from other populations. METHODS: We evaluated a group of 195 individuals, which included 102 patients clinically diagnosed with FXII-HAE and their 93 asymptomatic relatives. RESULTS: Genetic analysis revealed that of the 195 subjects, 134 individuals (77.6% females) carried a pathogenic mutation in F12. The T328K substitution was found in 132 individuals, and the c.971_1018+24del72 deletion was found in 2 patients. The mean age at onset of symptoms in patients with FXII-HAE was 21.1 years. The most common symptoms were subcutaneous edema (85.8% of patients), abdominal pain attacks (69.7%), and upper airway edema (32.3%). Of male individuals carrying F12 mutations, 53.3% (16 of 30) were symptomatic. Compared with reports from Europe, fewer female patients (68.6%) reported an influence of estrogen on symptoms. CONCLUSIONS: Our study included a large number of patients with FXII-HAE, and, as the first such study conducted in a South American population, it highlighted significant differences between this and other study populations. The high number of symptomatic males and patients with estrogen-independent FXII-HAE found here suggests that male sex and the absence of a hormonal influence should not discourage clinicians from searching for F12 mutations in cases of HAE with normal C1-INH.

Poluição do ar e saúde respiratória / Air pollution and respiratory health

O aumento da prevalência de doenças respiratórias crônicas coincide com o da exposição aos poluentes atmosféricos pelo crescente processo de industrialização, aumento do tráfego veicular e migração da população para áreas urbanas. A poluição do ar é uma mistura complexa de poluentes e outros compostos químicos tóxicos e não tóxicos, e o efeito na saúde pode derivar dessa mistura e da interação com parâmetros meteorológicos. Apesar disso, busca-se estabelecer o papel de um poluente específico em separado e consideram-se os parâmetros meteorológicos como fatores de confusão. Há evidências de que a exposição aos poluentes contribui para maior morbidade e mortalidade por doenças respiratórias, especialmente nas crianças, mesmo em concentrações dentro dos padrões estabelecidos pela legislação. Identificar os efeitos dos poluentes no sistema respiratório, isoladamente e em associação, é um desafio, e os estudos têm limitações devido à variabilidade de resposta individual, a presença de doenças pré-existentes, aos fatores socioeconômicos, às exposições a poluentes intradomiciliares, ocupacionais e ao tabaco. A maioria das evidências sobre o efeito dos poluentes no sistema respiratório de crianças deriva de estudos que incluem desfechos de função pulmonar. Entretanto, esses estudos têm diferenças quanto ao desenho, ao método de avaliação de exposição aos poluentes, às medidas de função pulmonar, às covariáveis consideradas como capazes de alterar a resposta aos poluentes e aos tipos de modelos utilizados na análise dos dados. Considerar todas essas diferenças é fundamental na interpretação e comparação dos resultados dessas pesquisas com os dados já existentes na literatura.

The increase in the prevalence of chronic respiratory diseases coincides with that of exposure to air pollutants due to the growing industrialization process, increased vehicular traffic and population migration to urban areas. Air pollution is a complex mixture of pollutants and other toxic and non-toxic chemical compounds and its effect on health can derive from this mixture and the interaction with meteorological parameters. Despite this, it seeks to establish the role of a specific pollutant separately and considers the meteorological parameters as confounding factors. There is evidence that exposure to pollutants contributes to greater morbidity and mortality from respiratory diseases, especially in children, even at concentrations within the standards established by legislation. Identifying the effects of pollutants on the respiratory system, alone and in association, is a challenge and studies have limitations due to the variability of individual response, the presence of pre-existing diseases, socioeconomic factors, exposure to indoor, occupational and environmental pollutants as well tobacco. Most of the evidence on the effect of pollutants on the respiratory system of children comes from studies that include lung function outcomes. However, these studies differ in terms of design, method of assessing exposure to pollutants, measures of lung function, covariates considered capable of altering the response to pollutants, and types of models used in data analysis. Considering all these differences is fundamental in interpreting and comparing the results of these researches with data already existing in the literature.

Prevalence of the eosinophilic phenotype among severe asthma patients in Brazil: the BRAEOS study / Prevalência do fenótipo eosinofílico em pacientes com asma grave no Brasil: o estudo BRAEOS

ABSTRACT Objective: To assess the prevalence of the eosinophilic and allergic phenotypes of severe asthma in Brazil, as well as to investigate the clinical characteristics of severe asthma patients in the country. Methods: This was a cross-sectional study of adult patients diagnosed with severe asthma and managed at specialized centers in Brazil. The study was conducted in 2019. Results: A total of 385 patients were included in the study. Of those, 154 had a blood eosinophil count > 300 cells/mm3 and 231 had a blood eosinophil count of ≤ 300 cells/mm3. The median age was 54.0 years, and most of the patients were female, with a BMI of 29.0 kg/m2 and a history of allergy (81.6%). The prevalence of patients with a blood eosinophil count > 300 cells/mm3 was 40.0% (95% CI: 35.1-44.9), and that of those with a blood eosinophil count > 300 cells/mm3 and a history of allergy was 31.9% (95% CI: 27.3-36.6). Age and BMI showed positive associations with a blood eosinophil count > 300 cells/mm3 (OR = 0.97, p < 0.0001; and OR = 0.96, p = 0.0233, respectively), whereas the time elapsed since the onset of asthma symptoms showed an increased association with a blood eosinophil count > 300 cells/mm3 (OR = 1.02, p = 0.0011). Conclusions: This study allowed us to characterize the population of severe asthma patients in Brazil, showing the prevalence of the eosinophilic phenotype (in 40% of the sample). Our results reveal the relevance of the eosinophilic phenotype of severe asthma at a national level, contributing to increased effectiveness in managing the disease and implementing public health strategies.

RESUMO Objetivo: Avaliar a prevalência dos fenótipos eosinofílico e alérgico da asma grave no Brasil e investigar as características clínicas dos pacientes com asma grave no país. Métodos: Estudo transversal com pacientes adultos com diagnóstico de asma grave atendidos em centros especializados no Brasil. O estudo foi realizado em 2019. Resultados: Foram incluídos no estudo 385 pacientes. Destes, 154 apresentavam contagem de eosinófilos no sangue > 300 células/mm3 e 231 apresentavam contagem de eosinófilos no sangue ≤ 300 células/mm3. A mediana da idade foi de 54,0 anos, e a maioria dos pacientes era do sexo feminino, com IMC de 29,0 kg/m2 e história de alergia (81,6%). A prevalência de pacientes com contagem de eosinófilos no sangue > 300 células/mm3 foi de 40,0% (IC95%: 35,1-44,9), e a daqueles com contagem de eosinófilos no sangue > 300 células/mm3 e história de alergia foi de 31,9% (IC95%: 27,3-36,6). A idade e o IMC apresentaram associações positivas com contagem de eosinófilos no sangue > 300 células/mm3 (OR = 0,97, p < 0,0001 e OR = 0,96, p = 0,0233, respectivamente), ao passo que o tempo decorrido desde o início dos sintomas de asma apresentou associação aumentada com contagem de eosinófilos no sangue > 300 células/mm3 (OR = 1,02, p = 0,0011). Conclusões: Este estudo possibilitou a caracterização da população de pacientes com asma grave no Brasil, mostrando a prevalência do fenótipo eosinofílico (em 40% da amostra). Nossos resultados revelam a relevância do fenótipo eosinofílico da asma grave em nível nacional, contribuindo para aumentar a eficácia no manejo da doença e na implantação de estratégias de saúde pública.

Assistência a pacientes com doenças imunoalérgicas no Sistema Único de Saúde brasileiro ­ Carta de São Paulo / Treating patients with allergic diseases in the Brazilian Unified Health System ­ Letter from São Paulo

O Sistema Único de Saúde (SUS) abrange todos os níveis de atenção à saúde e garante acesso integral, universal e gratuito para toda a população brasileira. As transições demográfica e epidemiológica observadas nas últimas décadas trouxeram um cenário de maior prevalência das doenças imunoalérgicas. Nesse contexto, a implementação de políticas de saúde voltadas à assistência à saúde dessa população tornou-se um desafio. Com o objetivo de discutir a atenção à saúde dos pacientes com doenças alérgicas e imunológicas no Brasil, a Associação Brasileira de Alergia e Imunologia (ASBAI) realizou em 26 de agosto de 2022, na cidade de São Paulo, o Fórum sobre a Assistência a Pacientes com Doenças Imunoalérgicas no SUS. O evento foi estruturado no formato de painéis e contou com a participação de membros da ASBAI e representantes da gestão pública federal, do Ministério Público, de sociedade de pacientes e profissionais de saúde de diversos serviços com experiência em programas e projetos bem sucedidos na assistência a pacientes com doenças imunoalérgicas. Após a discussão, concluiu-se que ainda existem muitas necessidades não atendidas em relação à atenção à saúde da população com doenças alérgicas e imunológicas no Brasil. A ASBAI tem trabalhado no sentido de contribuir para organizar, implantar e manter a assistência a estes pacientes no âmbito do SUS.

The Brazilian Unified Health System covers all levels of health care and guarantees full, universal and free access for the entire population. The demographic and epidemiological transitions observed in recent decades have led to a higher prevalence of allergic diseases. In this context, implementing health policies to benefit these patients has become a challenge. To discuss health care for patients with allergic and immunological diseases in Brazil, the Brazilian Association of Allergy and Immunology (ASBAI) held a forum in São Paulo on August 26, 2022 called "Treating Patients with Allergic Diseases in the Unified Health System". The event's panels included members of ASBAI, representatives of the federal government, the attorney general's office, patients, and health professionals from various services with experience in successful programs for patients with allergic diseases. It was concluded that there are still many unmet health care needs for Brazilians with allergic and immunological diseases. ASBAI is contributing to the organization, implementation, and maintenance of care for these patients within the scope of the Unified Health System.

Reações adversas aos anticorpos monoclonais para doenças alérgicas / Adverse reactions to monoclonal antibodies in allergic diseases

A utilização de agentes imunobiológicos em alergia e imunologia tem sido cada vez mais frequente nos últimos anos, emergindo como potencialmente eficazes para o tratamento de doenças alérgicas e de hipersensibilidade. O uso de imunobiológicos em doenças alérgicas está recomendado nas formas graves onde a eficácia, segurança e custo-efetividade estão comprovados. O objetivo deste artigo é sintetizar os efeitos adversos mais comuns ou significativos, incluindo as reações de hipersensibilidade aos principais anticorpos monoclonais aprovados para o tratamento de doenças alérgicas licenciados e comercializados no Brasil até o momento.

The use of immunobiological agents in allergy and immunology has increased in recent years, emerging as potentially effective strategies to treat allergic and hypersensitivity diseases. The use of immunobiological agents is recommended in the severe forms of allergic diseases, for which their efficacy, safety, and cost-effectiveness have been established. The purpose of this study was to summarize the most common or significant adverse effects, including hypersensitivity reactions to the main monoclonal antibodies approved for the treatment of allergic diseases that are currently licensed and marketed in Brazil.