Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis.

Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism-recA, recA sequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI-TOF and recA sequencing to identify Bcc species. The recA sequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes.

Systematic review on fecal calprotectin in cystic fibrosis.

OBJECTIVES: Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies. SOURCES: The articles were selected from PubMed, Web of Science, Scielo and Lilacs. SUMMARY OF THE FINDINGS: Nine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis. CONCLUSION: Further studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association).

Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

Emergence of Thymidine-Dependent Staphylococcus aureus Small-Colony Variants in Cystic Fibrosis Patients in Southern Brazil.

We characterized Staphylococcus aureus small-colony variant (SCV) strains isolated from cystic fibrosis (CF) patients in southern Brazil. Smaller colonies of S. aureus were isolated from respiratory samples collected consecutively from 225 CF patients from July 2013 to November 2016. Two phenotypic methods-the auxotrophic classification and a modified method of antimicrobial susceptibility testing-were employed. PCR was conducted to detect the mecA, ermA, ermB, ermC, msrA, and msrB resistance genes. Furthermore, DNA sequencing was performed to determine the mutations in the thyA gene, and multilocus sequence typing was used to identify the genetic relatedness. S. aureus strains were isolated from 186 patients (82%); suggestive colonies of SCVs were obtained in 16 patients (8.6%). The clones CC1 (ST1, ST188, and ST2383), CC5 (ST5 and ST221), and ST398 were identified. Among SCVs, antimicrobial susceptibility testing showed that 77.7% of the isolates were resistant to multiple drugs, and all of them were susceptible to vancomycin. mecA (2), ermA (1), ermB (1), ermC (3), and msrB (18) were distributed among the isolates. Phenotypically thymidine-dependent isolates had different mutations in the thyA gene, and frameshift mutations were frequently observed. Of note, revertants showed nonconservative or conservative missense mutations. SCVs are rarely identified in routine laboratory tests. IMPORTANCE Similar findings have not yet been reported in Brazil, emphasizing the importance of monitoring small-colony variants (SCVs). Altogether, our results highlight the need to improve detection methods and review antimicrobial therapy protocols in cystic fibrosis (CF) patients.

Systematic review on fecal calprotectin in cystic fibrosis

Abstract Objectives: Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies. Sources: The articles were selected from PubMed, Web of Science, Scielo and Lilacs. Summary of the findings: Nine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis. Conclusion: Further studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.

VITAMIN D RECEPTOR GENE MUTATIONS AND VITAMIN D SERUM LEVELS IN ASTHMATIC CHILDREN. / MUTAÇÕES DO GENE DO RECEPTOR DE VITAMINA D E NÍVEIS SÉRICOS DE VITAMINA D EM CRIANÇAS COM ASMA.

OBJECTIVE: To verify the relationship between polymorphisms of the vitamin D receptor gene (VDR), clinical findings, and serum vitamin D (VD) levels in asthmatics. METHODS: A cross sectional study of 77 children aged 7 to 14 years old, who were attended at a specialized clinic. The children were divided into 3 groups: asthmatics who had been using inhaled corticosteroids (ICS) for more than one year; asthmatics who had not been using ICS; non-asthmatics, and children without allergies (according to the International Study of Asthma and Allergies in Childhood -- ISAAC). Spirometry, skin prick tests, the presence of a VDR promoter CDX2 polymorphism from an allele-specific polimerase chain reaction (PCR), exons 2 and 3 polymorphisms genotyping by PCR-SSCA (single-strand conformational analysis), total immunoglobulin E (IgE) and specific IgE to mites and grass were evaluated in these three groups. Levels of 25-hydroxyvitamin D were determined in asthmatics only. RESULTS: The mean age of the children was 10.8±2.0 years old, 57% were male, 38 were asthmatic and using ICS, 22 were asthmatic and not using ICS, and 17 were non-asthmatic. Allergic rhinitis was present in 90% of asthmatics. Homozygous CDX2 was detected in 23% of the patients and absent in the control group (p=0.03). Lower forced expiratory volume in 1 second (FEV1%) values were observed in CDX2 homozygous asthmatics (p=0.001). Variations in the exon 2 and 3 sequences were not related to asthma or the other tests. VD deficiency or insufficiency was detected in 98% of asthmatics. There was no association between VD levels and genetic polymorphisms from exons 2 and 3. CONCLUSIONS: There was a positive association between homozygous CDX2 polymorphism, asthma and lower FEV1% values. CDX2 is capable of modifying cell interaction between VDR and VD, and it could be associated with the prevalence of asthma, and the difficulty in controlling the disease.

OBJETIVO: Verificar a relação dos polimorfismos do gene do receptor de vitamina D (RVD) com sinais clínicos e níveis de vitamina D (VD) em asmáticos. MÉTODOS: Estudo transversal com 77 crianças de 7 a 14 anos de um ambulatório especializado, divididas em 3 grupos: asmáticos, em uso de corticoide inalatório (ICS) por mais de um ano; asmáticos sem necessidade de ICS; não asmáticos e não alérgicos (de acordo com o International Study of Asthma and Allergies in Childhood - ISAAC. Foram avaliados: espirometria, testes alérgicos, presença do polimorfismo CDX2 do promotor do RVD por reação em cadeia da polimerase (PCR) e genotipagem de polimorfismos dos éxons 2 e 3 por PCR-SSCA (single-strand conformational analysis), imunoglobulina E (IgE) total e IgE específica para ácaros e gramíneas nos três grupos estudados. Níveis de 25-hidroxivitamina D foram dosados nos asmáticos. RESULTADOS: A média de idade foi 10,8±2,2 anos, 57% masculinos, 38 asmáticos com ICS, 22 sem ICS e 17 não asmáticos. Rinite alérgica esteve presente em 90% dos asmáticos, polimorfismo CDX2 em 23% dos asmáticos e ausente nos controles (p=0,03). Menores níveis de volume expiratório forçado no primeiro segundo (VEF1%) foram observados nos asmáticos homozigotos para CDX2 (p=0,001). Variações nas sequências dos éxons 2 e 3 não foram relacionadas com a asma ou demais testes. Deficiência ou insuficiência de VD foi diagnosticada em 98% dos asmáticos. Não houve associação entre níveis de VD e polimorfismos genéticos dos éxons 2 e 3. CONCLUSÕES: Observou-se associação positiva entre polimorfismo CDX2 em homozigoze com asma e menores valores de VEF1%. O CDX2 pode modificar a interação celular do RVD com a vitamina, bem como pode estar associado com a asma e com a dificuldade de controle da doença.

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association) / Diretrizes brasileiras para o tratamento farmacológico pulmonar na fibrose cística. Documento oficial da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

RESUMO A fibrose cística (FC) é uma doença genética que resulta em disfunção da proteína reguladora de condutância transmembrana da FC (CFTR), que é um canal de cloro e bicarbonato expresso na porção apical de células epiteliais de diversos órgãos. A disfunção dessa proteína resulta em manifestações clínicas diversas, envolvendo primariamente os sistemas respiratório e gastrointestinal com redução da qualidade e expectativa de vida. A FC ainda é uma patologia incurável, porém o horizonte terapêutico e prognóstico é hoje totalmente distinto e muito mais favorável. O objetivo destas diretrizes foi definir recomendações brasileiras baseadas em evidências em relação ao emprego de agentes farmacológicos no tratamento pulmonar da FC. As perguntas PICO (acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome [desfecho] de interesse) abordaram aspectos relativos ao uso de moduladores de CFTR (ivacaftor, lumacaftor + ivacaftor e tezacaftor + ivacaftor), uso de dornase alfa, terapia de erradicação e supressão crônica de Pseudomonas aeruginosa, e erradicação de Staphylococcus aureus resistente a meticilina e do complexo Burkholderia cepacia. Para a formulação das perguntas, um grupo de especialistas brasileiros foi reunido e realizou-se uma revisão sistemática sobre os temas, com meta-análise quando aplicável. Os resultados encontrados foram analisados quanto à força das evidências compiladas, sendo concebidas recomendações seguindo a metodologia GRADE. Os autores acreditam que o presente documento represente um importante avanço a ser incorporado na abordagem de pacientes com FC, objetivando principalmente favorecer seu manejo, podendo se tornar uma ferramenta auxiliar na definição de políticas públicas relacionadas à FC.

Avaliação da adesão ao tratamento da asma em crianças: a influência do atendimento especializado / Assessment of asthma treatment adherence in children: the influence of specialized care

Introdução: A asma é a doença crônica mais prevalente na infância. O controle da doença é desafiador, porém fundamental para evitar exacerbações graves e danos em longo prazo. Estudos em adultos já mostraram que a baixa adesão medicamentosa, bem como aos cuidados do ambiente, impactam no controle da doença. Objetivo: Conhecer a adesão ao tratamento da asma na população pediátrica e associá-lo ao controle da doença e outras variáveis clínicas. Métodos: Trata-se de um estudo observacional transversal onde foram incluídos 104 pacientes com asma, acompanhados no Serviço de Alergia, Imunologia e Pneumologia Pediátrica do Complexo Hospital de Clínicas da Universidade Federal do Paraná. Foram realizadas entrevistas com base em questionários sobre adesão ao uso de medicação, controle ambiental e crenças populares sobre a asma. Resultados: Foi possível identificar uma correlação positiva entre pacientes que acreditavam em um ou mais mitos sobre a asma e pior adesão ao uso da medicação (p = 0,025). Também foi possível identificar uma relação significativa, entre uma boa adesão à medicação e o controle total da asma (p = 0,038) medido pelo Asthma Control Test (ACT) de 25 pontos. Cinquenta e um por cento dos participantes entrevistados relatou boa e ótima adesão ao controle de ambiente. Conclusão: A adesão e o controle de ambiente avaliados foram satisfatórios na população de crianças asmáticas de um ambulatório de referência. As crenças populares mostraram influência na adesão e no controle da asma dos pacientes entrevistados. Os achados reforçam a importância da comunicação assertiva entre médico e paciente, bem como do papel da educação da asma também voltada para a população pediátrica.

Background: Asthma is the most common chronic disease in childhood. Disease control is challenging but critical to prevent severe exacerbations and long-term damage. Studies in adults have shown that poor adherence to medication and environmental control practices has an impact on disease control. Objective: To determine pediatric asthma treatment adherence and associate it with disease control and other clinical variables. Methods: This was a cross-sectional observational study of 104 patients with asthma followed up at the Pediatric Allergy, Immunology and Pulmonology Service of the Hospital de Clínicas Complex of the Federal University of Paraná, south of Brazil. Participants were interviewed using questionnaires about medication adherence, environmental control, and popular myths about asthma. Results: There was a positive correlation between patients who believed in 1 or more myths about asthma and poorer medication adherence (p=0.025). There was also a significant association between good medication adherence and total asthma control (p=0.038) measured by the 25-point Asthma Control Test. Good and excellent adherence to environmental control practices was reported by 51% of respondents. Conclusion: Medication adherence and environmental control were satisfactory in the population of asthmatic children from a specialized outpatient clinic. Popular beliefs influenced adherence and asthma control in these patients. The findings highlight the importance of assertive communication between physicians and patients, as well as of pediatric asthma education programs.

Pneumonite de hipersensibilidade na infância / Hypersensitivity pneumonitis in childhood

Neste relato descrevemos as características clínicas, epidemiológicas e radiológicas da pneumonite de hipersensibilidade, uma causa rara de insuficiência respiratória em pediatria. Paciente masculino, com 8 anos de idade, proveniente da zona rural, admitido em serviço terciário por quadro de febre, vômitos, tosse seca, dispneia progressiva, anorexia e perda de peso há 15 dias, associado a taquipneia, esforço respiratório, hipóxia e estertores finos em base direita. Tomografia computadoriza de tórax demonstrou opacidades com atenuações em vidro fosco, com comprometimento difuso e distribuição predominantemente centrolobular e acinar, característicos de pneumonite por hipersensibilidade. Na revisão das condições e hábitos de vida, foi relatado pela responsável do paciente a presença de um aviário e convívio com aves de várias espécies na residência, reforçando a hipótese diagnóstica, após descartadas outras causas de insuficiência respiratória. Iniciado corticoterapia com metilprednisolona 1 mg/ kg/dia por 7 dias, seguido de redução progressiva nas semanas posteriores. Paciente evoluiu com melhora do quadro e alta hospitalar, após orientações sobre controle ambiental e importância do afastamento dos antígenos desencadeantes. A pneumonite por hipersensibilidade é uma síndrome incomum na população pediátrica, que pode levar à insuficiência respiratória e fibrose pulmonar, devendo ser considerada nos pacientes com epidemiologia positiva. Pela sua raridade e semelhança com outras infecções respiratórias, ressalta-se ainda a importância da coleta de dados sobre os hábitos de vida dos pacientes, destacando sua importância para a elucidação diagnóstica.

We report the clinical, epidemiological, and radiological features of hypersensitivity pneumonitis, a rare cause of respiratory failure in pediatrics. An 8-year-old male patient, from a rural area, was admitted to a tertiary care facility for fever, vomiting, dry cough, progressive dyspnea, anorexia, and weight loss for 15 days, associated with tachypnea, respiratory effort, hypoxia, and fine rales at the right base. Chest computed tomography showed ground-glass opacities, diffuse involvement, and predominantly centrilobular and acinar distribution, characteristic of hypersensitivity pneumonitis. In the review of living conditions and habits, the patient's guardian reported the presence of an aviary and interaction with birds of various species in the residence, supporting the presumptive diagnosis of hypersensitivity pneumonitis, after ruling out other causes of respiratory failure. Corticosteroid therapy was started with methylprednisolone 1 mg/kg/day for 7 days, followed by tapering over subsequent weeks. The patient's condition improved, and he was discharged home after receiving guidance on environmental control and the importance of removing the triggering antigens. Hypersensitivity pneumonitis is an uncommon syndrome in the pediatric population. It can lead to respiratory failure and pulmonary fibrosis and should therefore be considered in patients with a positive epidemiological history. Due to its rarity and similarity to other respiratory diseases, collecting data on patients' lifestyle habits is highlighted as an important diagnostic tool.

Brazilian guidelines for the diagnosis and treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by dysfunction of the CFTR gene. It is a multisystem disease that most often affects White individuals. In recent decades, various advances in the diagnosis and treatment of CF have drastically changed the scenario, resulting in a significant increase in survival and quality of life. In Brazil, the current neonatal screening program for CF has broad coverage, and most of the Brazilian states have referral centers for the follow-up of individuals with the disease. Previously, CF was limited to the pediatric age group. However, an increase in the number of adult CF patients has been observed, because of the greater number of individuals being diagnosed with atypical forms (with milder phenotypic expression) and because of the increase in life expectancy provided by the new treatments. However, there is still great heterogeneity among the different regions of Brazil in terms of the access of CF patients to diagnostic and therapeutic methods. The objective of these guidelines was to aggregate the main scientific evidence to guide the management of these patients. A group of 18 CF specialists devised 82 relevant clinical questions, divided into five categories: characteristics of a referral center; diagnosis; treatment of respiratory disease; gastrointestinal and nutritional treatment; and other aspects. Various professionals working in the area of CF in Brazil were invited to answer the questions devised by the coordinators. We used the PubMed database to search the available literature based on keywords, in order to find the best answers to these questions. RESUMO A fibrose cística (FC) é uma doença genética autossômica recessiva caracterizada pela disfunção do gene CFTR. Trata-se de uma doença multissistêmica que ocorre mais frequentemente em populações descendentes de caucasianos. Nas últimas décadas, diversos avanços no diagnóstico e tratamento da FC mudaram drasticamente o cenário dessa doença, com aumento expressivo da sobrevida e qualidade de vida. Atualmente, o Brasil dispõe de um programa de ampla cobertura para a triagem neonatal de FC e centros de referência distribuídos na maior parte desses estados para seguimento dos indivíduos. Antigamente confinada à faixa etária pediátrica, tem-se observado um aumento de pacientes adultos com FC tanto pelo maior número de diagnósticos de formas atípicas, de expressão fenotípica mais leve, assim como pelo aumento da expectativa de vida com os novos tratamentos. Entretanto, ainda se observa uma grande heterogeneidade no acesso aos métodos diagnósticos e terapêuticos para FC entre as diferentes regiões brasileiras. O objetivo dessas diretrizes foi reunir as principais evidências científicas que norteiam o manejo desses pacientes. Um grupo de 18 especialistas em FC elaborou 82 perguntas clínicas relevantes que foram divididas em cinco categorias: características de um centro de referência; diagnóstico; tratamento da doença respiratória; tratamento gastrointestinal e nutricional; e outros aspectos. Diversos profissionais brasileiros atuantes na área da FC foram convidados a responder as perguntas formuladas pelos coordenadores. A literatura disponível foi pesquisada na base de dados PubMed com palavras-chave, buscando-se as melhores respostas às perguntas dos autores.

Guia Prático de Atualização no tratamento da exacerbação de asma na criança e no adolescente ­ Posicionamento conjunto da Associação Brasileira de Alergia e Imunologia e Sociedade Brasileira de Pediatria / Practical Update Guide on the treatment of asthma exacerbation in children and adolescents ­ Joint position of the Brazilian Association of Allergy and Immunology and the Brazilian Society of Pediatrics

Exacerbação aguda de asma é uma condição frequente na criança e no adolescente e uma das causas mais comuns de procura aos pronto atendimentos e de internações. Pode ocorrer em pacientes que ainda não foram diagnosticados como asmáticos, e mesmo naqueles cujo controle da doença não se encontre adequado. Reconhecer a exacerbação e iniciar seu tratamento desde o domicílio até o adequado manejo inicial em ambiente hospitalar é fundamental para evitar sua evolução para complicações que coloquem o paciente em risco de vida. O tratamento compreende o reconhecimento e tratamento da hipoxemia, da obstrução e do processo inflamatório, além de fornecer orientações na alta hospitalar e encaminhamentos para continuidade do tratamento.

Acute exacerbation of asthma is a frequent condition in children and adolescents and one of the most common causes of seeking emergency care and hospitalization. It can occur in patients who have not yet been diagnosed with asthma, and even in those whose disease control is not adequate. Recognizing the exacerbation and starting its treatment from home until proper initial management in a hospital environment is essential to avoid its evolution to complications that put the patient at risk of life. Treatment comprises the recognition and treatment of hypoxemia, obstruction, and the inflammatory process, in addition to providing guidance at hospital discharge and referrals for continued treatment.

Entendendo a alergia ocular / Understanding eye allergy

A associação entre sintomas de asma, rinoconjuntivite (RCA) e conjuntivite alérgica (CA) é frequente, e sintomas oculares podem afetar 75% dos pacientes com rinite, e 20% dos asmáticos. Embora asma e RCA sejam comumente associadas, a prevalência desta em crianças e os fatores de risco para seu desenvolvimento têm sido estudados com menor frequência. A CA é um espectro de condições clínicas que varia de formas agudas a formas crônicas e graves. A CA é frequentemente subdiagnosticada em pacientes com RA e asma, pois os sintomas são pouco valorizados. O desenvolvimento de RCA depende de fatores genéticos e ambientais, e estudos indicam que sexo, história familiar de atopia, sensibilização precoce, alergia alimentar e dermatite atópica são fatores de risco. Existem seis formas clínicas de alergia ocular: conjuntivite alérgica sazonal, conjuntivite alérgica perene, ceratoconjuntivite vernal, conjuntivite papilar gigante, ceratoconjuntivite atópica e blefaroconjuntivite de contato. As diferentes formas clínicas envolvem diferentes mecanismos imunológicos, principalmente reações de hipersensibilidade Tipo 1 e Tipo 4. Os principais sintomas são prurido ocular, hiperemia conjuntival, secreção ocular e lacrimejamento, sendo o prurido o sintoma cardinal. A avaliação do especialista em alergia é importante para a identificação de possíveis agentes desencadeantes, e do oftalmologista para avaliar possíveis complicações. A maioria dos pacientes com alergia ocular inicia o tratamento com automedicação, geralmente com colírios não específicos. Anti-histamínicos são os principais medicamentos utilizados. Corticoides tópicos são reservados para casos graves. Imunomoduladores podem beneficiar esses pacientes, bem como imunoterapia. Imunobiológicos têm sido estudados para casos refratários.

Association between asthma, allergic rhinoconjunctivitis (ARC) and allergic conjunctivitis (AC) is frequent, and ocular symptoms may affect 75% of patients with rhinitis and 20% of those with asthma. Although asthma and ARC are commonly associated, the prevalence of eye allergy in children and the risk factors for its development are not well established. AC is a spectrum of clinical conditions ranging from acute to severe chronic cases. It is frequently underdiagnosed in patients with asthma and rhinitis because symptoms are underestimated. ARC development depends on genetic and environmental factors, and studies indicate that sex, family history of atopy, early sensitization, food allergy and atopic dermatitis are risk factors. There are six clinical forms of eye allergy: seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis and contact blepharoconjunctivitis. Different clinical aspects involve different immunologic mechanisms, especially type 1 and type 4 hypersensitivity reactions. The most common symptoms are itchy eyes, conjunctival hyperemia, ocular discharge and watering. The evaluation of an allergy specialist is important to identify possible triggering factors, and an ophthalmologist is able to evaluate possible complications. Most patients with eye allergy start treatment with self-medication, generally non-specific eye drops. Anti-histamines are the most commonly used medications. Topical corticosteroids are reserved for severe cases. Immunomodulators may benefit such patients, as well as immunotherapy. Biologics are being studied for refractory cases.

Erros inatos de imunidade: tempo de diagnóstico e episódios infecciosos em pacientes ambulatoriais / Inborn errors of immunity: time to diagnosis and infections in outpatients

Introdução: Os erros inatos de imunidade (EII) são distúrbios que ocasionam danos no desenvolvimento e/ou função do sistema imunológico. O diagnóstico muitas vezes não é realizado de imediato devido ao pouco conhecimento sobre as doenças, que leva a complicações graves e diminui a sobrevida e qualidade de vida desses pacientes. O objetivo desse estudo foi avaliar o tempo para o diagnóstico e as ocorrências infecciosas que acometeram pacientes com EII no decorrer de sua vida até o momento do diagnóstico. Método: Foi realizado um estudo transversal, retrospectivo, em pacientes atendidos pelo serviço de Alergia, Imunologia e Pneumologia do Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), no período de junho de 1993 a março de 2019. Foram excluídos pacientes sem história prévia ao diagnóstico e com diagnóstico não confirmado de EII ou indefinido. Resultados: Dos 57 pacientes incluídos no estudo, a maioria (n = 34) era do sexo masculino. A idade ao diagnóstico variou de 2 até 38 anos, sendo a média 9 anos. Dentre as imunodeficiências, 43 (75,4%) tinham deficiência de anticorpos, 10 (17,5%) deficiência combinada, 3 (5,3%) deficiência de fagócitos e 1 (1,8%) deficiência de complemento. Em relação às infecções, os pacientes apresentaram mais de um episódio infeccioso, e também sofreram acometimento em mais de um sítio anatômico. As infecções mais frequentes foram as do trato respiratório inferior (80,7%), seguido das infecções do trato respiratório superior (50,9%). Foi encontrado um atraso médio de diagnóstico de 66,1 meses, sendo que 10,5% dos pacientes foram a óbito. Conclusão: Apesar de já serem bem caracterizados, os EII ainda possuem diagnóstico tardio, levando os pacientes a complicações graves, e até à morte.

Introduction: Inborn errors of immunity (IEIs) cause damage in the development and/or function of the immune system. The diagnosis is often not done immediately because of lack of knowledge about the disorders, leading to serious complications and decreasing the survival and quality of life of these patients. The aim of this study was to evaluate time to diagnosis and occurrence of infections that affected patients with IEI throughout their life-span until the diagnosis. Methods: A retrospective crosssectional study was performed in patients treated at the Division of Allergy, Immunology and Pulmonology of the Complexo Hospital de Clínicas at Universidade Federal do Paraná, from June 1993 to March 2019. Patients with no history prior to diagnosis and those with unconfirmed diagnosis of IIE or undefined diagnosis were excluded from the study. Results: Of the 57 patients included in the study, most were male (n = 34). The mean age at the time of diagnosis was 9 years, ranging from 2 to 38 years. Among the immunodeficiencies, 43 (75.4%) patients had antibody deficiency disorder, 10 (17.5%) had combined immunodeficiency, 3 (5.3%) had phagocyte deficiency and 1 (1.8%) had complement disorder. Regarding infections, patients had more than one infectious episode and were affected in more than one anatomical site. The most frequent infections were those of the lower respiratory tract (80.7%), followed by upper respiratory tract infections (50.9%). A mean diagnosis delay of 66.1 months was found, and 10% of the patients died. Conclusion: Despite being well characterized, IEIs still have late diagnosis, leading patients to serious complications and even death.

Impacto do tabagismo passivo nos sintomas da asma na infância / Impact of passive smoking on childhood asthma symptoms

Objetivo: Caracterizar a população asmática pediátrica e avaliar as repercussões do tabagismo passivo nos sintomas da asma na infância. Métodos: A amostra é composta de 384 pacientes, entre 2 e 14 anos, com diagnóstico de asma, acompanhados no ambulatório de pneumologia pediátrica do Hospital de Clínicas da Universidade Federal do Paraná. A avaliação ocorreu por meio de uma ficha de dados, aplicada em forma de entrevista aos responsáveis ou à criança participante. Resultados: A exposição ao tabagismo passivo esteve presente em 55% das crianças. Aglomeração domiciliar, menor renda familiar, menor nível de escolaridade materna e paterna foram vistos significativamente no grupo exposto. A população exposta mostrou maior frequência de asma classificada como moderada, maior uso de corticoide inalatório e maior frequência de sintomas diurnos (presentes pelo menos uma vez na semana em 60% dos pacientes). Conclusão: Foi alta a prevalência de crianças asmáticas expostas ao tabagismo passivo. Condição socioeconômica baixa foi confirmada no grupo exposto. Asma de gravidade moderada, maior uso de corticoides inalados e maior frequência de sintomas diurnos foram vistos no grupo de expostos. Este estudo confirma a necessidade imediata de adoção de medidas efetivas no combate ao tabagismo passivo como estratégia imprescindível para o controle da asma na infância.

Objective: To characterize the pediatric asthmatic population and to evaluate the repercussions of passive smoking on childhood asthma symptoms. Methods: The sample consisted of 384 patients, aged 2 to 14 years, diagnosed with asthma, who were followed up at the pediatric pulmonology outpatient clinic of the Hospital de Clínicas of the Federal University of Paraná. The evaluation was carried out by means of a data sheet, administered in the form of an interview to the legal guardians or to the participating child. Results: Exposure to passive smoking was present in 55% of the children. Household agglomeration, lower family income, and lower level of maternal and paternal schooling were seen in the exposed group. The exposed population showed a higher frequency of asthma classified as moderate, greater use of inhaled corticosteroids, and greater frequency of diurnal symptoms (present at least once a week in 60% of patients). Conclusion: The prevalence of asthmatic children exposed to passive smoking was high. Low socioeconomic condition was confirmed in the exposed group. Asthma of moderate severity, greater use of inhaled corticosteroids, and greater frequency of diurnal symptoms were seen in the exposed group. This study confirms the immediate need to adopt effective measures to combat passive smoking as an essential strategy for the control of childhood asthma.

A workshop on asthma management programs and centers in Brazil: reviewing and explaining concepts.

OBJECTIVE: To report the results of a workshop regarding asthma management programs and centers (AMPCs) in Brazil, so that they can be used as a tool for the improvement and advancement of current and future AMPCs. METHODS: The workshop consisted of five presentations and the corresponding group discussions. The working groups discussed the following themes: implementation of asthma management strategies; human resources needed for AMPCs; financial resources needed for AMPCs; and operational maintenance of AMPCs. RESULTS: The workshop involved 39 participants, from all regions of the country, representing associations of asthma patients (n = 3), universities (n = 7), and AMPCs (n = 29). We found a direct relationship between a lack of planning and the failure of AMPCs. Based on the experiences reported during the workshop, the common assumptions about AMPCs in Brazil were the importance of raising awareness of managers; greater community participation; interdependence between primary care and specialized care; awareness of regionalization; and use of medications available in the public health system. CONCLUSIONS: Brazil already has a core of experience in the area of asthma management programs. The implementation of strategies for the management of chronic respiratory disease and their incorporation into health care system protocols would seem to be a natural progression. However, there is minimal experience in this area. Joint efforts by individuals with expertise in AMPCs could promote the implementation of asthma management strategies, thus speeding the creation of treatment networks, which might have a multiplier effect, precluding the need for isolated centers to start from zero.

OBJETIVO: Relatar os resultados de uma oficina de trabalho sobre programas e centros de atenção a asmáticos (PCAAs) no Brasil para que possam servir como instrumento para melhoria e avanço dos PCAAs existentes e criação de novos. MÉTODOS: A oficina de trabalho constituiu-se de cinco apresentações e discussões em grupos. Os grupos de trabalho discutiram os seguintes temas: implementação de uma linha de cuidado em asma; recursos humanos necessários para os PCAA; recursos necessários para financiar os PCAA; e manutenção do funcionamento dos PCAAs. RESULTADOS: A oficina envolveu 39 participantes de todas as regiões do país, representando associações de asmáticos (n = 3), centros universitários (n = 7) e PCAAs (n = 29). Evidenciou-se uma relação direta entre a ausência de planejamento e o insucesso dos PCAAs. Com base nas experiências brasileiras elencadas durante a oficina, as premissas comuns foram a importância da sensibilização do gestor, maior participação da comunidade, interdependência entre a atenção primária e a especializada, observação da regionalização e utilização dos medicamentos disponíveis no sistema público de saúde. CONCLUSÕES: O Brasil já tem um núcleo de experiências na área programática da asma. A implementação de uma linha de cuidado em doenças respiratórias crônicas e sua inclusão nas redes de saúde parecem ser o caminho natural. Porém, a experiência nessa área ainda é pequena. Agregar pessoas com experiência nos PCAAs na elaboração da linha de cuidado em asma encurtaria tempo na criação de redes de atenção com possível efeito multiplicador, evitando que se partisse do zero em cada local isolado.

Utility of Asthma Control Questionnaire 7 in the assessment of asthma control.

Our objective was to evaluate the reproducibility of Asthma Control Questionnaire 7 (ACQ-7) in asthma patients, comparing our results against those obtained with the Global Initiative for Asthma (GINA) criteria. We evaluated 52 patients. Patients completed the ACQ-7, underwent spirometry, and were clinically assessed to determine the level of asthma control according to the GINA criteria, in two visits, 15 days apart. The ACQ-7 cutoff for uncontrolled asthma was a score of 1.5. The ACQ-7 showed good reproducibility, with a correlation coefficient of 0.73. The ACQ-7 identified a greater number of patients with uncontrolled asthma than did the GINA criteria; according to the GINA criteria, 47 patients (90.4%) presented with partially controlled asthma.

Teste de provocação oral descarta alergia aos fármacos / Oral challenge test rules out drug allergy

O objetivo deste estudo foi avaliar a utilidade do teste de provocação oral (TPO) em pacientes encaminhados para investigação de reações alérgicas a medicamentos. Foi realizado um estudo analítico, transversal, com coleta de dados de pacientes de 0 a 14 anos, com história de reação adversa a medicamentos no período entre junho de 2017 a junho de 2019. Os pacientes foram submetidos aos testes cutâneos alérgicos por puntura (TCA), e na sequência, TPO com os medicamentos suspeitos. Os TPO foram abertos, e se o paciente apresentasse manifestação clínica compatível, o teste era interrompido e considerado positivo. Foram avaliadas 38 reações com fármacos orais. Dentre os 36 pacientes submetidos aos TPO, 23 (63,8%) eram do sexo masculino, média de idade de 5,7 anos; 32 (88,8%) tinham história de atopia, e 13 (36,1%) apresentaram teste cutâneo positivo para aeroalérgenos. Todos (n = 38) relataram sinais e sintomas cutâneos, 9 (25%) com sintomas respiratórios, 2 (5,5%) com sintomas gastrointestinais e 1 (2,7%) com outros sintomas. Todos os TCA para os fármacos avaliados foram negativos. Os TPO foram realizados com: antibióticos em 21 (55,2%), 16 (42,1%) com analgésicos e anti-inflamatórios, e 1 com prednisona (2,6%). Dentre os TPO, somente 1 (2,6%) foi positivo ao ibuprofeno. Concluiu-se que o teste de provocação oral a fármacos teve a finalidade de excluir, mais do que confirmar alergia, o que reforça a importância da confirmação, uma vez que a prevalência de alergia medicamentosa confirmada é baixa, sobretudo em crianças.

The aim of this study was to evaluate the usefulness of the oral challenge test (OCT) in patients referred for investigation of allergic drug reactions. This was a cross-sectional analytical study with data collected from patients aged 0 to 14 years with a history of adverse drug reactions from June 2017 to June 2019. The skin prick test (SPT) and OCT were performed with the suspected drugs. Open OCTs were used and, if the patient had a compatible clinical manifestation, the test was interrupted and considered positive. Thirty-eight reactions to oral drugs were evaluated. Of 36 patients subjected to OCT, 23 (63.8%) were male, with a mean age of 5.7 years, 32 (88.8%) had a history of atopy, and 13 (36.1%) were SPT-positive for aeroallergens. All 38 patients reported cutaneous signs and symptoms, 9 (25%) had respiratory symptoms, 2 (5.5%) had gastrointestinal symptoms, and 1 (2.7%) had other symptoms. All SPTs were negative for the evaluated drugs. OCTs were performed with antibiotics in 21 (55.2%), with analgesics and anti-inflammatory drugs in 16 (42.1%), and with prednisone in 1 (2.6%). Only 1 (2.6%) OCT was positive for ibuprofen. It was concluded that the OCT was intended to rule out rather than to confirm drug allergy, which reinforces the importance of confirmation, since the prevalence of confirmed drug allergy is low, especially in children.