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Background The Brazilian population has a tri-hybrid composition with a high degree of ethnic admixture. We hypothesized that Brazilian individuals with CF from different Brazilian regions have a specific distribution of CFTR variants. Methods Individuals with CF with data available in the Patient Registry and without an established genotype were submitted to CFTR sequencing by Next Generation Sequencing (NGS) methodology, and results were anonymously incorporated to the Registry Database. Genotyping results were expressed as ‘positive’, ‘inconclusive’ or ‘negative’. Logistic regression models were performed to investigate the association between demographic/clinical variables and genotyping results. Mediation analysis was conducted to estimate direct and indirect effects of Brazilian region on a binary positive genotyping response. Results In October 2017, data from 4,654 individuals with CF were available, and 3,104(66.7%) of them had a genotyping result. A total of 236 variants (114 new variants) were identified, with F508del identified in 46% of the alleles tested. Genotyping revealed 2,002(64.5%) individuals positive, 757(24.4%) inconclusive and 345(11.1%) negative. Distribution of genotype categories was markedly different across Brazilian Regions, with greater proportions of negative individuals in the North (45%) and Northeast (26%) regions. Newborn screening (CF-NBS) and age at diagnosis were identified as mediators of the effect of Brazilian region on a positive genotyping result. Conclusions This large initiative of CFTR genotyping showed significant regional discrepancies in Brazil, probably related to socio-economic conditions, lack of adequate CF-NBS and poor access to reliable sweat testing. These results may be useful to indicate Regions where CF care demands more attention.

Differences in the clinical presentation of cystic fibrosis (CF) may be due to microbiota components and their relationship with the host’s immune system. In this pilot study, we aimed to investigate the composition of the respiratory and gut microbiota of a cohort of clinically stable children with CF, homozygous for the p.Phe508del mutation. Oropharyngeal swabs and stool samples were obtained from these children attending the CF referral clinics at the Hospital of Clinics, Federal University Paraná (CHC – UFPR). Oropharyngeal and gut microbiota were assessed by V3-V4 sequencing of the 16S ribosomal RNA, and bioinformatics analyses were performed using a proprietary pipeline. We identified a total of 456 bacterial taxa belonging to 164 genera, of which 65 (39.6 %) were common to both the respiratory and gastrointestinal tracts. Taxa from eight genera dominated more than 75 % of the microbial composition of both the niches. Among these dominant taxa, only Prevotella spp. were common to both the sites. Overall, the respiratory and gut microbiota were homogeneous among all the patients. Longitudinal studies targeting a larger cohort are important for an improved understanding of how the composition of bacterial communities is related to changes in the clinical status of CF

Objective: To evaluate the viability of sputum cytology in asthmatic children, recognizing inflammatory patterns and correlating them with clinical, epidemiological and functional variables of the disease. Methods: This was a cross-sectional and observational study of children with asthma who underwent sputum induction through increasing concentrations of nebulized hypertonic saline solution from 3% to 7%. The samples were processed according to the technique developed by Pizzichini et al. and the cytological pattern classified as pauci-granulocytic, neutrophilic, eosinophilic and mixed. Samples with cell viability> 50% were considered adequate. Asthma control was assessed using the asthma control test (ACT). Results: Seventy-nine children performed sputum induction. Thirty-three samples were excluded because they were not viable for analysis, resulting in 46 samples. The children’s average age was 9.4 (± 3) years. There was a predominance of eosinophilic (25/46, 54.3%), followed by mixed (13/46, 28.3%), pauci-granulocytic (7/46, 15.2%) and neutrophilic (1/46, 2.2%) pattern. Sixty-three percent of the children had severe asthma and 84.7% were treated with inhaled corticosteroids. The ACT showed that 25 (56.8%) patients had the disease under control. Forty-five children (97.8%) underwent pulmonary function tests (spirometry) and in 13 cases (28.9%) an obstructive ventilatory defect was found. Conclusions: The eosinophilic profile was predominant in the assessed asthmatic children. Non-eosinophilic phenotypes were found, but less frequently. There was no difference between the clinical variables and the sputum profile in this study group. Sputum induction in children with asthma is feasible and safe and can contribute to a specific and personalized approach to the disease.

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.

RESUMO 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. ABSTRACT 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.

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.

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.

Objective: this study aimed to prepare a silkworm moth (Bombyx mori) antigenic extract and to perform skin prick tests with this extract in patients with allergic respiratory diseases; to evaluate serum specific immunoglobulin E (IgE) to Bombyx mori using ImmunoCAP® system and to report the frequency of positivity between the two methods and with clinical data. Methods: this was a cross‐sectional study with 99 children and adolescents diagnosed with asthma and/or allergic rhinitis, who had skin reactivity to at least one of the six aeroallergens tested. Clinical data were evaluated: skin prick tests with Bombyx mori in‐house extract, and total and specific IgE analysis using ImmunoCAP® were performed. Results: the frequency of Bombyx mori specific IgE was found to be 52.5% and 60% using the skin prick test and ImmunoCAP®, respectively. An association between a positive skin test for Bombyx mori and the presence of allergic rhinitis, atopic dermatitis, and urticaria was observed, but the same was not true for asthma or allergic conjunctivitis. There was no relation with the severity of asthma or rhinitis symptoms. Conclusions: a high frequency of sensitization to Bombyx mori was observed in a selected population of patients with respiratory allergic diseases in the city of Curitiba, state of Paraná, Brazil. The extract prepared from the wings of this moth species is effective in demonstrating this sensitivity. Resumo: Objetivo: Preparar extrato antigênico da mariposa do bicho‐da‐seda (Bombyx mori) e realizar testes cutâneos com esse extrato em pacientes com doenças respiratórias alérgicas, avaliar IgE sérica específica para Bombyx mori usando o sistema ImmunoCAP® e relatar a frequência de positividade entre os dois métodos e com dados clínicos. Métodos: Estudo transversal com 99 crianças e adolescentes com diagnóstico de asma e/ou rinite alérgica, que apresentaram reação cutânea a pelo menos um dos seis aeroalérgenos testados. Os dados clínicos foram avaliados; testes cutâneos com extrato de Bombyx mori e análise de IgE total e específica por ImmunoCAP® foram realizados. Resultados: A frequência de IgE específica para Bombyx mori foi de 52,5% e 60%, respectivamente, pelo teste cutâneo e ImmunoCAP®. Foi observada uma associação entre o teste cutâneo positivo para Bombyx mori e a presença de rinite alérgica, dermatite atópica e urticária, mas o mesmo não ocorreu para a asma ou conjuntivite alérgica. Não houve relação com a gravidade dos sintomas de asma ou rinite. Conclusões: Alta frequência de sensibilização à Bombyx mori foi encontrada em uma população selecionada de pacientes com doenças alérgicas respiratórias na cidade de Curitiba, estado do Paraná, Brasil. O extrato preparado a partir das asas dessa espécie de mariposa é eficaz em demonstrar essa sensibilidade. Keywords: Sensitization, Moth, Asthma, Rhinitis, Palavras‐chave: Sensibilização, Mariposa, Asma, Rinite

Objective: The prevalence of allergic conjunctivitis (AC) has not been established. Estimates suggest that ocular allergies affect 15% to 20% of the worldwide population, yet most epidemiological studies encompass nasal and ocular allergy symptoms and have not been specific to AC. The aim of this study was to verify the prevalence of ocular allergy symptoms, co-morbidities, and their impact on adolescents. Methods: Adolescents were selected from a sample of schools, and completed in classrooms a previously validated questionnaire on symptoms of AC. AC diagnosis was considered when more than three episodes of ocular itching were reported in the past 12 months. Related symptoms such as tearing, photophobia, foreign body sensation, impact on daily activities, and diagnosis of AC were analyzed. Results: Questionnaires were obtained from 3,120 adolescents (mean age 13.3 ± 1.1 years). Ocular itching in the past 12 months occurred in 1,592 (51%). The most frequently associated symptom was tearing (74%), followed by photophobia (50.1%) and foreign body sensation (37.1%). The prevalence of AC was 20.7%, affecting more females than males (56.1% versus 45.9%; p = 0.01). The risks of an adolescent with ocular allergy to present asthma, rhinitis, and atopic eczema were (OR = 5.7; 95% CI: 4.5 to 7.1), (OR = 3.6; 95% CI: 3.0 to 4.3), and (OR = 2.6; 95% CI: 2.0 to 3.5), respectively. Severe interference in daily activities was reported by 30.5%. Conclusions: Symptoms of ocular allergy are common, frequently associated to other allergic diseases, and impact the daily activities of adolescents. Resumo: Objetivo: A prevalência de conjuntivite alérgica (CA) não foi estabelecida. Estimativas sugerem que alergias oculares afetam de 15 a 20% da população mundial, ainda que a maioria dos estudos epidemiológicos abranjam sintomas de alergia nasal e ocular e não sejam específicos a respeito da CA. O objetivo deste estudo foi verificar a prevalência de sintomas, comorbidades e o impacto da alergia ocular em adolescentes. Métodos: Os adolescentes foram selecionados de uma amostra de escolas e preencheram, em sala de aula, um questionário previamente validado sobre os sintomas da CA. O seu diagnóstico foi considerado quando mais de três episódios de prurido ocular foram relatados nos últimos 12 meses. Sintomas relacionados, como lacrimejamento, fotofobia, sensação de corpo estranho, impacto sobre as atividades diárias e diagnóstico de conjuntivite alérgica, foram analisados. Resultados: Foram obtidos questionários de 3.120 adolescentes (média de 13,3 ± 1,1 ano). Nos últimos 12 meses, 1.592 (51%) adolescentes tiveram prurido ocular. O sintoma relacionado mais frequente foi lacrimejamento (74%), seguido de fotofobia (50,1%) e sensação de corpo estranho (37,1%). A prevalência de conjuntivite alérgica foi de 20,7%, afetando mais pessoas do sexo feminino do que do masculino (56,1% em comparação a 45,9%; p = 0,01). O risco de um adolescente com alergia ocular apresentar asma, rinite e eczema atópico foi (RC = 5,7; CI de 95%: 4,5 a 7,1); (RC = 3,6; CI de 95%: 3,0 a 4,3) e (RC = 2,6; CI de 95%: 2,0 a 3,5), respectivamente. Uma interferência grave nas atividades diárias foi relatada por 30,5%. Conclusões: Sintomas de alergia ocular são comuns, frequentemente relacionados a outras doenças alérgicas, e causam impacto sobre as atividades diárias de adolescentes. Keywords: Allergic conjunctivitis, Children, Epidemiology, Palavras-chave: Conjuntivite alérgica, Crianças, Epidemiologia

OBJETIVOS: Avaliar prospectivamente a colonização bacteriana de pacientes com fibrose cística identificados por triagem neonatal. Avaliar a suscetibilidade a antimicrobianos e caracterizar molecularmente as cepas de Staphylococcus aureus isoladas da orofaringe dos pacientes no período do estudo. MÉTODOS: Foram estudados 25 pacientes com fibrose cística, identificados por tripsina imunorreativa e com diagnóstico confirmado por duas ou mais provas de suor, atendidos regularmente no ambulatório de fibrose cística do Hospital de Clínicas da Universidade Federal do Paraná. Foram coletadas amostras de orofaringe com swab e cultivadas por métodos rotineiros; as colônias bacterianas foram identificadas fenotipicamente e testadas quanto à suscetibilidade a antimicrobianos. Os isolados de S. aureus foram submetidos a tipagem molecular por eletroforese em campo pulsado. RESULTADOS: De um total de 234 amostras de orofaringe, S. aureus foi isolado em maior número (76% dos pacientes, 42% das amostras), seguido de Pseudomonas aeruginosa (36% dos pacientes, 16% das amostras) e Haemophilus spp. (76% dos pacientes; 19% das amostras). Dos 19 pacientes colonizados com S. aureus, foram obtidos 73 isolados, 18 oxacilina-resistentes (24,6%), isolados de dois pacientes, com perfis eletroforéticos idênticos ao do clone brasileiro. Os demais isolados oxacilina-sensíveis distribuíram-se entre 18 perfis eletroforéticos distintos. CONCLUSÃO: Observou-se uma maior prevalência de S. aureus, com isolamento mais precoce em relação aos outros patógenos pesquisados. Os isolados multissensíveis distribuíram-se em clones distintos, caracterizando a não transmissibilidade entre as cepas comunitárias. Os S. aureus resistentes a oxacilina isolados apresentaram perfis eletroforéticos idênticos, provavelmente adquiridos no ambiente hospitalar. P. aeruginosa foi pouco freqüente na população estudada. OBJECTIVES: To assess bacterial colonization prospectively in patients with cystic fibrosis identified by neonatal screening. To assess susceptibility to antimicrobials and to perform the molecular typing of Staphylococcus aureus strains isolated from the oropharynx of patients during the study. METHODS: Twenty-five cystic fibrosis patients receiving regular treatment at the Cystic Fibrosis Outpatient Clinic of Hospital de Clínicas of Universidade Federal do Paraná Brazil, were included in the study. All patients were identified by trypsin-like immunoreactivity and their diagnosis was confirmed by two or more sweat tests. Oropharyngeal swabs were collected and cultured according to routine methods; bacterial colonies were phenotypically identified and their susceptibility to antimicrobials was tested. S. aureus isolates were submitted to molecular typing using pulsed-field gel electrophoresis. RESULTS: Out of 234 oropharyngeal swabs, S. aureus was the most frequently isolated strain (76% of patients, 42% of swabs), followed by Pseudomonas aeruginosa (36% of patients, 16% of swabs) and Haemophilus spp. (76% of patients; 19% of swabs). Seventy-three isolates were obtained from 19 patients colonized with S. aureus, of which 18 were oxacillin-resistant (24.6%), isolated from two patients, with the same electrophoretic profiles as that of the Brazilian clone. The remaining oxacillin-sensitive isolates were distributed into 18 electrophoretic profiles. CONCLUSION: There was higher prevalence of S. aureus, with earlier isolation than other pathogens. Multi-sensitive isolates were distributed into different clones, characterizing non-transmissibility among community-acquired strains. The isolated oxacillin-resistant S. aureus showed identical electrophoretic profiles, probably acquired in hospital. P. aeruginosa was not so frequent in the studied population.

OBJETIVOS: Apresentar e analisar os resultados da implantacao do Programa Nacional de Triagem Neonatal em Fibrose Cistica, no Parana, apos 30 meses do seu inicio. METODOS: Foi realizado um estudo descritivo com analise dos dados da triagem feita em aproximadamente 98% dos recem-nascidos entre setembro de 2001 e abril de 2004 no laboratorio do Servico de Triagem Neonatal da Fundacao Ecumenica de Protecao ao Excepcional do Parana. As amostras de sangue para o "teste do pezinho" foram coletadas na alta hospitalar, idealmente entre o segundo e sexto dias de vida, com o envio dos papeis-filtro para a dosagem de tripsina imunorreativa por imunofluorimetria. Criancas com valores da dosagem de tripsina imunorreativa > 70 ng/ml em duas amostras distintas, nos primeiros 30 dias de vida, foram submetidas a determinacao da condutividade do suor pelo metodo de Wescor. Com o resultado maior que 50 mMol/l procedeu-se a dosagem quantitativa de cloro e/ou sodio no suor (iontoforese por pilocarpina). RESULTADOS: De 456.982 exames realizados, 4.028 (0,9%) criancas apresentaram a primeira dosagem de tripsina imunorreativa acima do ponto de corte estabelecido. Dessas, 478 (12,5%) tiveram uma segunda amostra de sangue com dosagem de tripsina imunorreativa acima de 70 ng/ml, das quais, apos a realizacao do teste de suor por condutividade, 56 (11,7%) criancas foram encaminhadas para ambulatorios especializados com resultado acima de 50 mMol/l e 48 (0,01% do total de triagens) tiveram o diagnostico de fibrose cistica confirmado. A incidencia foi de 1:9.520 em nosso estado, embora algumas criancas ainda nao tenham completado a investigacao. CONCLUSOES: A triagem neonatal para fibrose cistica no estado do Parana, de acordo com as normas do Ministerio da Saude, foi uma iniciativa pioneira no Brasil. Realizou-se o diagnostico precocemente em muitos pacientes, mesmo os assintomaticos, fato que representa um desafio a melhora no prognostico dessa doenca fatal.

OBJETIVO: Avaliar a eficácia de budesonida na forma de suspensão, em dose única para inalação, como tratamento adjunto ao b2 inalatório, comparada com dose única de prednisona por via oral, em pacientes com crise aguda de asma. MÉTODO: Estudo prospectivo, randômico, paralelo, duplo-cego, duplo-placebo. Foram selecionadas 49 crianças, com idade entre 2 e 7 anos, em crise aguda de asma, que, após inalação com salbutamol (0,15 mg/kg), foram divididas em três grupos. O grupo I foi tratado com placebo via oral e inalatório; o grupo II, com prednisona via oral (1 mg/kg) e placebo inalatório; e o grupo III, budesonida inalatória (2 mg) e placebo via oral. As avaliações foram realizadas pela aplicação de um escore clínico e medida da saturação transcutânea da hemoglobina, seqüencialmente até 72 horas. Caso o escore clínico fosse igual ou superior ao da avaliação inicial, e a saturação inferior à primeira avaliação, a inalação com b2 adrenérgico era repetida. RESULTADOS: A melhora do escore clínico foi progressiva a partir de 30 minutos, e não houve diferença significativa nos três grupos estudados. Ocorreu aumento significativo da saturação da hemoglobina em relação ao valor inicial, com 2 horas no grupo prednisona, 4 horas no grupo budesonida e 24 horas no grupo placebo. CONCLUSÃO: O número de inalações com broncodilatador foi semelhante nos três grupos, com uma média de 2,9 no grupo placebo; 2,7 no grupo prednisona; e 2,5 no grupo budesonida. Em geral, as drogas estudadas foram bem toleradas, com efeitos colaterais semelhantes ao placebo. A administração de dose única de budesonida inalatória associada ao salbutamol, na crise moderada de asma, promoveu melhora clínica comparável à da prednisona oral. A recuperação da saturação transcutânea da hemoglobina foi mais rápida com prednisona. OBJECTIVE: To investigate the efficacy of a single dose of inhaled budesonide as compared to oral prednisone in patients with acute asthma. METHODS: Randomized double-blind, double-dummy and placebo-controlled clinical trial. Forty-nine children aged 2 to 7 years with acute asthma were randomized in three groups after receiving nebulized salbutamol (0.15 mg/kg). Group I received placebo both as tablets and nebulization, group II was treated with a single dose of oral prednisone (1 mg/kg) and inhaled placebo, and group III received a single dose of placebo tablet and nebulized budesonide (2 mg). Patients were evaluated in terms of symptom score and transcutaneous hemoglobin saturation. Nebulized salbutamol was repeated in case of increasing symptom score or lower saturation. RESULTS: Progressive clinical improvement was observed in all three groups. However, a significant increase in hemoglobin saturation was observed after 2 hours with prednisone, 4 hours with budesonide, and 24 hours with placebo. CONCLUSION: A combination of single-dose nebulized budesonide and salbutamol may be as effective as oral prednisone to improve symptom severity, but the latter increases hemoglobin saturation in exacerbation of asthma.

BACKGROUND: Several factors influence the pulmonary function values considered normal. In children of short stature, there are difficulties in interpreting the pulmonary function. OBJECTIVE: To assess spirometric values in children and adolescents with short stature and to identify a correction factor to adequately predict the expected values for this population. METHOD: A prospective selection of 77 patients was made, all with short stature and no respiratory disease. These patients were submitted to spirometry, transcutaneous hemoglobin oxygen saturation, chest perimeter measurement, and immediate hypersensitivity testing. Bone age was assessed by wrist X-rays. The data obtained by spirometry (FVC, FEV1, and FEF25-75%) were compared with those of Polgar and Promadhat (1971), predicted in three ways: a) by actual height; b) by height estimated at the 50th percentile for chronological age (CA); c) by height estimated at the 50th percentile for bone age (BA). RESULTS: The mean height was 133.3 ± 13.2 cm, and the deficit in relation to the third percentile was 5.4 ± 6.0 cm. The values obtained for FVC, FEV1, FEF25-75%, were significantly higher than those predicted by actual height. The mean FEV1 obtained was 2.42 ± 0.71 L, and the predicted (actual height) was 2.10 ± 0.64 L; according to the height estimated by BA and CA, the values were 2.27 and 2.86 L, respectively. The mean FVC1 was 2.20 ± 0.6 L, and the predicted was 1.90 ± 0.55 L. With the height estimated for bone age and chronologic age, the predicted values were 2.10 and 2.60 L, respectively. CONCLUSION: Children and adolescents with short stature have higher spirometric values than predicted for their actual height. These findings suggest that the height estimated at the 50th percentile for bone age can be used to evaluate pulmonary function.

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. Nosso objetivo foi avaliar a reprodutibilidade do Asthma Control Questionnaire 7 (ACQ-7) em asmáticos e comparar os resultados com os critérios de controle da Global Initiative for Asthma (GINA). Foram avaliados 52 pacientes em duas visitas com intervalo de 15 dias entre si. Os pacientes responderam o ACQ-7, realizaram espirometria e foram avaliados clinicamente para verificar o controle da asma de acordo com a GINA nas duas visitas. Em relação ao ACQ-7, o ponto de corte para asma não controlada foi definido em 1,5. Os resultados de ACQ-7 demonstraram boa reprodutibilidade, com coeficiente de correlação de 0,73. O ACQ-7 identificou um maior número de pacientes com asma não controlada em relação aos critérios da GINA; segundo os critérios GINA, 47 pacientes (90,4%) tinham asma parcialmente controlada.

OBJECTIVE: To report clinical presentation, diagnostic procedures and treatment of patients with anomalous subclavian artery. SUBJECTS: Fifteen patients with anomalous subclavian artery followed up at the Department of Pediatrics, Hospital de Clínicas da Universidade Federal do Paraná. RESULTS: Age at diagnosis varied from birth to eight years, and 10/15 were female. Nine presented with respiratory symptoms (cough, pneumonia, stridor, wheezing). Eleven had gastrointestinal symptoms (vomiting and choking). Six patients have both respiratory and digestive symptoms. Diagnosis was suggested by barium swallow in 14/15; confirmed in 10 by arteriography or helicoidal tomography with vascular reconstruction. In fourteen cases, the anomalous subclavian was at the right side and in one at the left side. Frequent associations were gastroesophageal reflux (6/15), cardiac septum defect and Down syndrome (3/15). Surgical repair was undertaken in eight, two of whom had chylothorax in the immediate post operative period. CONCLUSION: Although anomalous subclavian artery is mostly asymptomatic, it should be looked for in children with respiratory symptoms, mainly cough and choking. The chief investigation tool is barium swallow, and surgical repair is needed when symptoms are present.

OBJETIVO: Determinar se os nebulizadores de pacientes com fibrose cística são fonte de contaminação microbiana e verificar se a técnica e a frequência de desinfecção dos nebulizadores é apropriada. MÉTODOS: Estudo de corte transversal observacional, sem grupo controle. Foram coletadas amostras de 28 pacientes com fibrose cística, no domicílio do paciente, sem aviso prévio sobre o motivo da visita. Foram colhidas três amostras por paciente: do reservatório do nebulizador, da máscara/bocal e do próprio paciente (swab da orofaringe/escarro). As amostras foram acondicionadas adequadamente e levadas para análise. Os pacientes, seus pais ou responsáveis preencheram um questionário sobre métodos de limpeza e desinfecção dos nebulizadores. RESULTADOS: Foram obtidas 84 amostras dos 28 pacientes. Destes, 15 (53,5%) eram do gênero masculino. A mediana de idade foi de 11 anos (variação: 1-27 anos). Dos 28 pacientes, 15 apresentaram culturas de escarro/orofaringe positivas. As bactérias encontradas com maior frequencia foram Streptococcus aureus (8/15) e Pseudomonas aeruginosa (4/15). A cultura obtida dos nebulizadores identificou diversos patógenos, sem nenhum predominante. Não houve associações entre os resultados das culturas obtidas dos nebulizadores e aquelas dos pacientes em 27 casos (96,7%). A limpeza e a desinfecção não eram realizadas de forma adequada em 22 casos (78,6%). CONCLUSÕES: Nesta amostra de pacientes, apesar das técnicas de desinfecção inadequadas, os nebulizadores não foram uma fonte de contaminação microbiana OBJECTIVE: To determine whether nebulizers are a source of microbial contamination in patients with cystic fibrosis, as well as whether the technique and frequency of disinfection of these devices is appropriate. METHODS: This was a cross-sectional, uncontrolled observational study. Samples were collected from 28 patients with cystic fibrosis. Samples were collected at the homes of the patients, who were not previously informed of the purpose of the visit. Three samples were collected from each patient: one from the nebulizer chamber, one from the mask/mouthpiece, and one from the patient (oropharyngeal swab /sputum). The samples were properly stored and taken for analyses. The patients, their parents, or their legal guardians completed a questionnaire regarding nebulizer cleaning and disinfecting methods. RESULTS: We collected 84 samples from the 28 patients. Of those 28 patients, 15 (53.5%) were male. The median age of the patients was 11 years (range, 1-27 years). Of the 28 patients, 15 presented with positive oropharyngeal swab /sputum sample cultures. The most common bacterial isolates were Staphylococcus aureus (in 8 patients) and Pseudomonas aeruginosa (in 4 patients). Although the samples obtained from the nebulizers presented with various pathogens in culture, no specific species predominated. In 27 cases (96.7%), there were no associations between the samples obtained from the nebulizers and those obtained from the patients in terms of the results of the cultures. Cleaning and disinfection of nebulizers were inappropriate in 22 cases (78.6%). CONCLUSIONS: In this sample of patients, despite the inappropriate disinfection techniques, nebulizers were not found to be a source of microbial contamination

Objetivo: O angioedema hereditário é uma doença genética, de herança autossômica dominante caracterizada pela deficiência quantitativa e qualitativa do inibidor de C1 resultando em edema de vários órgãos. O presente estudo tem como objetivo uma revisão da literatura, visando atualização do diagnóstico, classificação e tratamento desta patologia.Método: Revisão da literatura recente de artigos originais e diretrizes nacionais e internacionais.Resultados: As manifestações clínicas de angioedema hereditário são dor abdominal, vômitos, diarreia e edema de membros, face, laringe e genitais. O diagnóstico se faz por anamnese, exame físico e exames laboratoriais, entre eles dosagem sérica de C4 e do inibidor da C1-esterase. A classificação é baseada na deficiência ou não da enzima C1 esterase. A abordagem terapêutica segue orientações gerais para evitar fatores desencadeantes, medicamentos para o manejo das crises e tratamento profilático. Andrógenos atenuados são utilizados para tratamento preventivo e antifibrinolíticos e plasma fresco são empregados nas crises. Novas drogas inibidoras de bradicinina e concentrados de C1 derivados de plasma têm sido utilizados no tratamento e prevenção das crises. Conclusões: O angioedema hereditário é doença grave, com alta morbidade e mortalidade. O diagnóstico correto desta condição pelos profissionais da saúde é essencial para seu manejo adequado.

OBJECTIVES: To assess bacterial colonization prospectively in patients with cystic fibrosis identified by neonatal screening. To assess susceptibility to antimicrobials and to perform the molecular typing of Staphylococcus aureus strains isolated from the oropharynx of patients during the study. METHODS: Twenty-five cystic fibrosis patients receiving regular treatment at the Cystic Fibrosis Outpatient Clinic of Hospital de Clinicas of Universidade Federal do Parana Brazil, were included in the study. All patients were identified by trypsin-like immunoreactivity and their diagnosis was confirmed by two or more sweat tests. Oropharyngeal swabs were collected and cultured according to routine methods; bacterial colonies were phenotypically identified and their susceptibility to antimicrobials was tested. S. aureus isolates were submitted to molecular typing using pulsed-field gel electrophoresis. RESULTS: Out of 234 oropharyngeal swabs, S. aureus was the most frequently isolated strain (76% of patients, 42% of swabs), followed by Pseudomonas aeruginosa (36% of patients, 16% of swabs) and Haemophilus spp. (76% of patients; 19% of swabs). Seventy-three isolates were obtained from 19 patients colonized with S. aureus, of which 18 were oxacillin-resistant (24.6%), isolated from two patients, with the same electrophoretic profiles as that of the Brazilian clone. The remaining oxacillin-sensitive isolates were distributed into 18 electrophoretic profiles. CONCLUSION: There was higher prevalence of S. aureus, with earlier isolation than other pathogens. Multi-sensitive isolates were distributed into different clones, characterizing non-transmissibility among community-acquired strains. The isolated oxacillin-resistant S. aureus showed identical electrophoretic profiles, probably acquired in hospital. P. aeruginosa was not so frequent in the studied population.

OBJECTIVE: To correlate sweat conductivity by Wescor with quantitative sodium determination in the same sample. METHODS: We analyzed 206 sweat samples, being 31 obtained from patients with cystic fibrosis (CF). Sweat was collected by quantitative pilocarpine iontophoresis in the Macroduct system for 30 minutes. Samples were immediately determined by Sweat-Chek analyzer (Wescor) and sodium quantification with a flame photometer. RESULTS: In non-CF subjects sweat (n=175), mean conductivity and quantitative sodium were 41mmol/L (16-75mmol/l) and 36mEq/ l (12-75mEq/l) respectively. In CF subjects (n=31), mean values of conductivity and sodium were 119mmol/L (84-155mmol/l) and 113mEq/l (80 - 146mEq/l) respectively. None of CF patients showed values lower than 80mmol/L. There was a correlation between sweat conductivity and sodium determination (r= + 0.99; p0.0001). CONCLUSION: Sweat conductivity by Wescor simplifies the analysis with lower volumes and is well correlated to sodium concentration.

Rationale A negative association has been observed between Th1 and Th2 mediated diseases. The purpose of this study was to verify the frequency of atopy in patients with DM1. Methods The ISAAC written questionnaire was applied for in 90 outpatients with DM1 in order to establish the prevalence of asthma and rhinoconjunctivitis symptoms, and compare with those obtained from previous survey. Serum total IgE and specific IgE antibodies to D. pteronyssinus were determined by Pharmacia Immunocap®. A panel of six common aeroallergens was used for skin prick tests (SPT) in volar forearm surface. A positive SPT was considered if wheal cross diameters were ≥2mm. Results Ages ranged from 3 to 19 years (median 11.7) and 47 (52%) were male. The prevalence of wheezing in the past 12 months was 12.2%; 26.7% referred nose and eye symptoms in the past 12 months. In 2001 the frequency of these symptoms in 13-14 year-old schoolchildren of Curitiba was respectively 18.7% and 17%. A positive skin test and specific IgE levels ≥0.7 kU/L were observed in 29.5% and 31.3% respectively, with a significant association between them (p Conclusions Atopy does coexist with DM1 suggesting that Th1 and Th2 phenomenon are independent in those conditions. The frequency of rhinitis was higher than the frequency of asthma in DM1.

Background The prevalence of allergic conjunctivitis (AC) has not been established. Estimates suggest that ocular allergies affect 15 to 20% of the worldwide population yet most epidemiological studies encompasses nasal and ocular allergy symptoms together and have not been specific with respect to AC. The aim of this study was to verify the prevalence of ocular allergy symptoms in adolescents. Methods Adolescents were selected from a sample of schools and self-completed in classrooms a previously validated questionnaire on symptoms of AC. AC was considered when more than 3 episodes of ocular itching were reported in the past 12 months. Related symptoms as tearing, photophobia, foreign body sensation, impact on daily activities, and diagnosis of allergic conjunctivitis were analyzed. Results Questionnaires from 3120 adolescents (mean 13.3 ± 1.1 years) were analyzed. Ocular itching in the past 12 months occurred in 1,592 (51%). The most frequent associated symptom was tearing (74%) followed by photophobia (50.1%) and foreign body sensation (37.1%). The prevalence of allergic conjunctivitis was 20.7% affecting more females (56.1% vs 45.9%; P < 0.01). Moderate and severe interference in daily activities were reported by 66% and 21%, respectively. Diagnosis of AC was reported by 47% of them. Conclusions Symptoms of ocular allergy are common and cause great impact on daily activities in adolescents. Accessing risk factors and the allergic status of these patients should be the focus of future epidemiological studies on AC.

Results Forty two patients, male (45%), age mean 27.1±16.9 years. Symptoms started at median age 14 years (range 1 to 58ys.). Thirty seven (86%) had familial history of HAE. They had a median of 2 episodes/mo (range 0.2 to 30) lasting 3±1.7 days/episode. Edema of limbs, face, genital and laryngeal, abdominal pain, diarrhea and vomiting were seen in 73.8%, 52.4%, 23.8%, 17%, 81%, 24% and 38.1%, respectively. Twenty four (57%) had low C4 level, mean serum level of C4=12.7±10.6 mg/dL; 26 (62%) had low levels of C1 esterase inhibitor, 4 (9.5%) had low functional C1 esterase inhibitor and 12 (28.6%) had C1q deficiency and 3 (7.1%) had HAE type III confirmed. Fifteen (28.9%) were treated with Danazol 175±134 mg/day, 15 (28.9%) were using tranexamic acid as needed. No patient had Icatibant access.