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PurposeCystic fibrosis (CF) is a multisystem genetic disease caused by dysfunction of the epithelial anionic channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Decreased mucociliary clearance because of thickened mucus is part of the pulmonary disease pathophysiology. It is controversial if the thickened airway surface liquid (ASL) is caused by the deficient chloride secretion and excessive sodium (through ENaC) and water hyperabsorption from the periciliar fluid or by the lack of bicarbonate secretion with relative acidification of the ASL. Correlations between the magnitude of in vivo chloride conductance with phenotypic characteristics and CF genotype can help to elucidate these mechanisms and direct to new treatments.MethodsNasal potential difference was measured in 28 CF patients (age from 0.3 to 28 year) and correlated with pulmonary function, pancreatic phenotype, pulmonary colonization and genotype severity.ResultsThe CFTR-chloride conductance was better in older patients (r = 0.40; P = 0.03), in patients with better pulmonary function (r = 0.48; P = 0.01), and was associated with genotype severity. Higher chloride diffusion in the presence of a favorable chemical gradient was associated with Pseudomonas aeruginosa negativity (P

Objective: To test the hypothesis that disease severity in patients with cystic fibrosis (CF) is correlated with an increased risk of sleep apnea.Methods: A total of 34 CF patients underwent clinical and functional evaluation, as well as portable polysomnography, spirometry, and determination of IL-1β levels.Results: Mean apnea-hypopnea index (AHI), SpO2 on room air, and Epworth Sleepiness Scale score were 4.8 ± 2.6, 95.9 ± 1.9%, and 7.6 ± 3.8 points, respectively. Of the 34 patients, 19 were well-nourished, 6 were at nutritional risk, and 9 were malnourished. In the multivariate model to predict the AHI, the following variables remained significant: nutritional status (β = −0.386; p = 0.014); SpO2 (β = −0.453; p = 0.005), and the Epworth Sleepiness Scale score (β = 0.429; p = 0.006). The model explained 51% of the variation in the AHI.Conclusions: The major determinants of sleep apnea were nutritional status, SpO2, and daytime sleepiness. This knowledge not only provides an opportunity to define the clinical risk of having sleep apnea but also creates an avenue for the treatment and prevention of the disease. ResumoObjetivo: Testar a hipótese de que a gravidade da doença em pacientes com fibrose cística (FC) correlaciona-se com maior risco de apneia do sono.Métodos: Um total de 34 pacientes com FC foram submetidos a avaliação clínica e funcional, polissonografia portátil, espirometria e dosagem de IL-1β.Resultados: As médias do índice de apneia e hipopneia (IAH), da SpO2 em ar ambiente e da pontuação na Escala de Sonolência de Epworth foram de 4,8 ± 2,6, 95,9 ± 1,9% e 7,6 ± 3,8, respectivamente. Dos 34 pacientes, 19 eram eutróficos, 6 apresentavam risco nutricional e 9 apresentavam desnutrição. No modelo multivariado para prever o IAH, permaneceram significativos o estado nutricional (β = −0,386; p = 0,014), a SpO2 (β = −0,453; p = 0,005) e a pontuação na Escala de Sonolência de Epworth (β = 0,429; p = 0,006). O modelo explicou 51% da variação do IAH.Conclusões: Os maiores determinantes de apneia do sono foram o estado nutricional, a SpO2 e a sonolência diurna. Esse conhecimento representa não somente uma oportunidade de definir o risco clínico de apresentar apneia do sono, mas também de atuar na prevenção e tratamento da doença.

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: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the intervention. OBJETIVO: Relatar el impacto clínico del primer año de tratamiento con dornasa alfa conforme a la franja de edad, en una cohorte de pacientes brasileños con fibrosis quística (FC). MÉTODOS: El presente estudio analizó datos de 152 pacientes elegibles, de 16 centros de referencia para FC, los que contestaron a los cuestionarios clínicos y realizaron pruebas laboratoriales, al inicio del tratamiento con la dornasa alfa (T0) y después de 6 (T2) y 12 (T4) meses de la intervención. Se analizaron 3 grupos etarios: 6-11, 12-13 e >14 años de edad. Se evaluaron las pruebas pulmonares, la microbiología de vías aéreas, las atenciones de emergencia, hospitalizaciones y tratamientos emergenciales y de rutina. Las estadísticas descriptivas, pruebas t y chi-cuadrado y ANOVA fueron usadas cuando pertinentes. RESULTADOS: El tratamiento regular se basó en la fisioterapia respiratoria, ejercicios regulares, encimas pancreáticas, vitaminas, broncodilatadores, corticosteroides y antibióticos. En los 6 meses anteriores al estudio (fase T0), las hospitalizaciones por exacerbación pulmonar ocurrieron en 38, 10 y 61,4%, respectivamente, para las tres franjas de edad analizadas. En el grupo 6-11 años, hubo reducción significativa de atenciones de emergencia después de 1 año de tratamiento. No hubo modificaciones significativas de volumen espiratorio forzado en el 1er segundo (VEF1), capacidad vital forzada (CVF), saturación de oxígeno (SpO)2 e índice de Tiffeneau, en todos grupos. El escore de Schwachman-Kulczychi mejoró significativamente en el grupo de más edad. Los últimos 6 meses de tratamiento, la colonización crónica o intermitente por P. aeruginosa fue detectada en el 75, 71,4 y 62,5%, respectivamente, mientras que por S. aureus ocurrió en 68,6, 66,6 y 41,9% de los casos en cada grupo de edad. CONCLUSIONES: La intervención con dornasa alfa resultó en mantenimiento de los parámetros pulmonares y fue asociada a la reducción significativa de visitas a la emergencia por exacerbación pulmonar en el grupo de 6 a 11 años de edad, con mejora del escore clínico en el grupo >14 años de edad, al final de un año de estudio. OBJETIVO: Relatar o impacto clínico do primeiro ano de tratamento com dornase alfa de acordo com a faixa etária, numa coorte de pacientes brasileiros com fibrose cística (FC). MÉTODOS: O presente estudo analisou dados de 152 pacientes elegíveis, de 16 centros de referência para FC, os quais responderam aos questionários clínicos e realizaram testes laboratoriais, ao início do tratamento com dornase alfa (T0) e após seis (T2) e 12 (T4) meses da intervenção. Analisaram-se três grupos etários: seis a 11, 12 a 13 e >14 anos de idade. Avaliaram-se os testes pulmonares, a microbiologia de vias aéreas, os atendimentos de emergência, as hospitalizações e os tratamentos emergenciais e rotineiros. O teste t de Student, o qui-quadrado e a análise de variância foram usados quando pertinentes. RESULTADOS: O tratamento baseou-se em fisioterapia respiratória, exercícios regulares, enzimas pancreáticas, vitaminas, broncodilatadores, corticosteroides e antibióticos. Nos seis meses anteriores ao estudo (fase T0), as hospitalizações por exacerbação pulmonar ocorreram em 38,0, 10,0 e 61,4%, respectivamente para as três faixas etárias analisadas. No grupo de seis a 11 anos, houve redução significativa de atendimentos de emergência após um ano de tratamento. Não houve modificações significativas de volume expiratório forçado no primeiro segundo (VEF1), capacidade vital forçada (CVF), saturação de oxigênio (SpO)2 e índice de Tiffeneau em todos os grupos. O escore de Shwachman-Kulczychi melhorou significativamente no grupo de mais idade. Nos últimos seis meses de tratamento, a colonização crônica ou intermitente por P.aeruginosa foi detectada em 75,0, 71,4 e 62,5%, respectivamente, enquanto a colonização por S.aureus ocorreu em 68,6, 66,6 e 41,9% dos casos em cada grupo etário. CONCLUSÕES: A intervenção com dornase alfa resultou em manutenção dos parâmetros pulmonares e associou-se à redução significativa de visitas à emergência por exacerbação pulmonar no grupo de seis a 11 anos de idade, com melhora do escore clínico no grupo >14 anos de idade ao final de um ano de estudo.

A fibrose cística, que já foi considerada uma doença da infância, é agora também uma doença do adulto. O aumento da longevidade resultou em mais problemas médicos relacionados com a idade e com a própria doença. O crescente número de adultos com fibrose cística resultou em aumento da necessidade de cuidados médicos. Essa necessidade tem sido suprida por um crescente número de pneumologistas de adultos e outros especialistas. O objetivo dessa revisão é sumarizar o conhecimento corrente sobre o diagnóstico e tratamento no adulto com fibrose cística. Na maioria dos casos, o diagnóstico é sugerido por manifestações de doença sinopulmonar crônica e insuficiência pancreática exócrina, e, então, confirmado por um teste do suor positivo. Pacientes adultos podem, entretanto, apresentar suficiência pancreática e características clínicas atípicas, às vezes, associadas com teste do suor normal ou limítrofe. Em tais casos, a possibilidade de realizar pesquisa de mutações para fibrose cística e de medir a diferença de potencial nasal pode ser de utilidade diagnóstica. A abordagem terapêutica padrão para a doença pulmonar inclui: antibióticos, higiene das vias aéreas, exercício, mucolíticos, broncodilatadores, oxigênio, agentes anti-inflamatórios e suporte nutricional. A utilização adequada dessas terapias resulta em mais pacientes com fibrose cística sobrevivendo na vida adulta com uma aceitável qualidade de vida.Once considered a childhood disease, cystic fibrosis is now also a disease of adults. Increased longevity has resulted in the aging of the cystic fibrosis population. The consequent age-related medical problems among adults with cystic fibrosis have increased medical care needs. These needs are being met by a growing number of non-pediatric pulmonologists and other non-pediatric specialists. The objective of this review was to summarize the current knowledge about diagnosis and treatment in adult cystic fibrosis. In most cases, the diagnosis is suggested by manifestations of chronic sinopulmonary disease and exocrine pancreatic insufficiency. The diagnosis is confirmed by a positive sweat test result. Adult patients may, however, present pancreatic sufficiency and atypical clinical features, sometimes in combination with normal or borderline sweat test results. In such cases, identifying cystic fibrosis mutations and measuring nasal potential difference can have diagnostic utility. The standard therapeutic approach to pulmonary disease includes the use of antibiotics, airway clearance, exercise, mucolytics, bronchodilators, oxygen therapy, anti-inflammatory agents and nutritional support. Appropriate application of these therapies results in most cystic fibrosis patients surviving into adulthood with an acceptable quality of life.

Burkholderia pseudomallei is rarely isolated from cystic fibrosis patients outside known areas of endemicity. We report the recovery of B. pseudomallei from the sputum of a cystic fibrosis patient who lives in Brazil. We highlight the importance of careful attention to unusual nonfermentative gram-negative rods in cystic fibrosis patients.

The combination of factors, such as abnormal viscosity of the paranasal sinus secretions, decreased sinus drainage, and impaired mucociliary clearance may account for the establishment of a suitable and opportune environment for the colonization of bacteria in the paranasal sinuses of patients with cystic fibrosis. AIM: The goal of the present study was to assess the bacteriology of the middle meatus aspirate in patients diagnosed whit cystic fibrosis. MATERIAL AND METHODS: Through a cross-sectional prospective study, a sample consisting of 23 patients evaluated for 2 years, was assessed. Firstly, we established the relationship between the middle meatus culture and the maxillary sinus x-ray. In second, we studied the relationship between the middle meatus aspirate bacteriology and the sputum bacteriology. RESULTS: In total, 42 aspirates of the middle meatus were carried out. In 17 (73.91%) of the 23 patients, the aspirates were negative; and in 6 (26.08%) they were positive. Out of the 42 aspirates,31 (78.8%) were negative, and 11 (26.2%) were positive. The presence of Pseudomonas aeruginosa was observed in 18.18% of the positive cultures, and Staphylococcus aureus was observed in 27.28%. CONCLUSION: The great majority of the middle meatus aspirates of the patients with cystic fibrosis were negative.

A prospective study was conducted in Brazil to evaluate antimicrobial resistance patterns and molecular epidemiology of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients with chronic lung infection. All isolates were obtained between May 2009 and June 2010 from 75 patients seen in four reference centers in Brazil: HCPA (20 patients) and HEOM (15 patients), located in southern and northeastern Brazil, respectively; IFF (20 patients) and HUPE (20 patients), both in southwestern Brazil. Antimicrobial susceptibility testing, PCR for detection of carpapenemases, and pulsed-field gel electrophoresis (PFGE) were performed in 274 isolates. A total of 224 PFGE types were identified and no clones were found circulating among the centers or within the same center. Despite the chronic infection, most patients were colonized by intermittent clones. Only three patients (4%) maintained the same clone during the study. The resistance rates were lower than 30% for the majority of antimicrobials tested in all centers and only 17% of isolates were multiresistant. Isolates (n = 54) with reduced susceptibility to imipenem and/or meropenem presented negative results for blaSPM-1, blaIMP-1, blaVIM , and blaKPC genes. Our results indicate an unexpected low level of antimicrobial resistance and a high genotypic diversity among P. aeruginosa from Brazilian chronic CF patients.

Objetivo do estudo: Avaliar o padrão da evolução dos fluxos e volumes pulmonares dinâmicos dos pacientes com fibrose cística (FC), assim como analisar a relação entre a gravidade do comprometimento ventilatório com a idade, sexo, genótipo e colonização pulmonar. Material e método: Na Unidade de Pneumologia Infantil e Serviço de Pneumologia do Hospital de Clínicas de Porto Alegre, foram avaliadas 243 espirometrias de 52 pacientes portadores de FC maiores de quatro anos realizadas no período de 1987 a 1999. Do prontuário médico foram extraídas informações sobre idade ao diagnóstico, pesquisa genética, colonização brônquica e os valores absolutos e percentuais para fluxos e volumes da melhor espirometria de cada ano. Resultados: A idade dos pacientes variou de quatro a 26 anos (média = 13,04 ± 4,82). Dos 52 pacientes, 49 (94%) tiveram pelo menos uma cultura de escarro com P. aeruginosa, 45 (86%) com S. aureus e 13 (25%) com B. cepacia. Na avaliação inicial dos quatro aos seis anos (n = 40), os valores médios da CVF e do VEF1 foram de 114,24% e 112,25%, respectivamente. A média da CVF manteve-se acima do normal até os 18 anos, quando apresentou queda súbita para 67,2% (p = 0,0002). A média do VEF1 atingiu valores abaixo de 80% aos dez anos, estando em 50% aos 18 anos (p < 0,00001). A relação VEF1/CVF%, índice mais sensível de obstrução, mostrou-se diminuída já na primeira avaliação, sendo 85% entre os quatro e seis anos, com declínio lento progressivo, chegando a 63% aos 18 anos. Os valores médios do FEF50, FEF75 e FMEF inicialmente foram normais (94%, 80% e 90%, respectivamente), mostraram queda maior e mais precoce, estatisticamente significativa, atingindo valores médios aos 18 anos de 37%, 12,5% e 19%, respectivamente. Embora houvesse tendência para fluxos terminais mais baixos para as meninas, as diferenças não tiveram valor estatístico. Também não foram detectadas correlações estatisticamente significativas entre a função pulmonar e o germe colonizador da via aérea ou o genótipo. Conclusão: O padrão evolutivo das alterações funcionais pulmonares encontrado nos pacientes está de acordo com o descrito na literatura, onde predomina o distúrbio ventilatório obstrutivo com redução precoce dos fluxos terminais e acometimento tardio da CVF.Objectives: To evaluate the evolution pattern of dynamic pulmonary flow and volume in cystic fibrosis patients and analyze the relation between the severity of ventilatory attacks and age, gender, genotype and pulmonary colonization. Methods: At the Pediatric Pulmonary Unit and Pulmonary Service of Hospital de Clínicas of Porto Alegre, 243 spirometries performed between 1987 and 1999 in 52 cystic fibrosis patients older than four years of age were reviewed. From the patients' medical records the following informations were extracted: age at diagnosis, genetic data, bronchial colonization and absolute as well as percent values of the flows and volumes of the best annual spirometry. Results: The age of the patients ranged from four to 26 years (mean = 13.04 ± 4.82). Out of the 52 patients, 49 (94%) had at least one sputum culture with P. aeruginosa, 45 (86%) with S. aureus and 13 (25%) with B. cepacia. At initial evaluation, that included patients four to six years old (n = 40), mean values for FVC and FEV1 were 114.24% and 112.25%, respectively. Mean FVC remained above baseline until 18 years of age, when it abruptly dropped to 67.2% (p = 0.0002). Mean FEV1 values dropped to less than 80% at ten years and was 50% at 18 years (p < 0.00001). The FEV1/FVC% relationship, the most obstruction sensitive index, was observed to be reduced as early as initial evaluation. It was 85% between four and six years and gradually decreased to 63% at 18 years. The mean values of FEF50, FEF75 and FMEF were initially normal (94%, 80% and 90%, respectively), showed a greater and earlier statistically significant decline, and reached to 37%, 12.5% and 19%, respectively, at 18 years. Although a tendency to lower terminal flow was seen in the girls, the differences were not statistically significant. Significant correlations between pulmonary function and the airway colonizator or genotype were not detected statistic. Conclusion: The evolution pattern of pulmonary function alterations found in these patients is consistent with those reported in the literature, where obstructive ventilatory disorders with early terminal flow reduction and late FVC onset predominate.

Objetivo do estudo: Avaliar o padrão da evolução dos fluxos e volumes pulmonares dinâmicos dos pacientes com fibrose cística (FC), assim como analisar a relação entre a gravidade do comprometimento ventilatório com a idade, sexo, genótipo e colonização pulmonar. Material e método: Na Unidade de Pneumologia Infantil e Serviço de Pneumologia do Hospital de Clínicas de Porto Alegre, foram avaliadas 243 espirometrias de 52 pacientes portadores de FC maiores de quatro anos realizadas no período de 1987 a 1999. Do prontuário médico foram extraídas informações sobre idade ao diagnóstico, pesquisa genética, colonização brônquica e os valores absolutos e percentuais para fluxos e volumes da melhor espirometria de cada ano. Resultados: A idade dos pacientes variou de quatro a 26 anos (média = 13,04 ± 4,82). Dos 52 pacientes, 49 (94%) tiveram pelo menos uma cultura de escarro com P. aeruginosa, 45 (86%) com S. aureus e 13 (25%) com B. cepacia. Na avaliação inicial dos quatro aos seis anos (n = 40), os valores médios da CVF e do VEF1 foram de 114,24% e 112,25%, respectivamente. A média da CVF manteve-se acima do normal até os 18 anos, quando apresentou queda súbita para 67,2% (p = 0,0002). A média do VEF1 atingiu valores abaixo de 80% aos dez anos, estando em 50% aos 18 anos (p < 0,00001). A relação VEF1/CVF%, índice mais sensível de obstrução, mostrou-se diminuída já na primeira avaliação, sendo 85% entre os quatro e seis anos, com declínio lento progressivo, chegando a 63% aos 18 anos. Os valores médios do FEF50, FEF75 e FMEF inicialmente foram normais (94%, 80% e 90%, respectivamente), mostraram queda maior e mais precoce, estatisticamente significativa, atingindo valores médios aos 18 anos de 37%, 12,5% e 19%, respectivamente. Embora houvesse tendência para fluxos terminais mais baixos para as meninas, as diferenças não tiveram valor estatístico. Também não foram detectadas correlações estatisticamente significativas entre a função pulmonar e o germe colonizador da via aérea ou o genótipo. Conclusão: O padrão evolutivo das alterações funcionais pulmonares encontrado nos pacientes está de acordo com o descrito na literatura, onde predomina o distúrbio ventilatório obstrutivo com redução precoce dos fluxos terminais e acometimento tardio da CVF. Objectives: To evaluate the evolution pattern of dynamic pulmonary flow and volume in cystic fibrosis patients and analyze the relation between the severity of ventilatory attacks and age, gender, genotype and pulmonary colonization. Methods: At the Pediatric Pulmonary Unit and Pulmonary Service of Hospital de Clínicas of Porto Alegre, 243 spirometries performed between 1987 and 1999 in 52 cystic fibrosis patients older than four years of age were reviewed. From the patients' medical records the following informations were extracted: age at diagnosis, genetic data, bronchial colonization and absolute as well as percent values of the flows and volumes of the best annual spirometry. Results: The age of the patients ranged from four to 26 years (mean = 13.04 ± 4.82). Out of the 52 patients, 49 (94%) had at least one sputum culture with P. aeruginosa, 45 (86%) with S. aureus and 13 (25%) with B. cepacia. At initial evaluation, that included patients four to six years old (n = 40), mean values for FVC and FEV1 were 114.24% and 112.25%, respectively. Mean FVC remained above baseline until 18 years of age, when it abruptly dropped to 67.2% (p = 0.0002). Mean FEV1 values dropped to less than 80% at ten years and was 50% at 18 years (p < 0.00001). The FEV1/FVC% relationship, the most obstruction sensitive index, was observed to be reduced as early as initial evaluation. It was 85% between four and six years and gradually decreased to 63% at 18 years. The mean values of FEF50, FEF75 and FMEF were initially normal (94%, 80% and 90%, respectively), showed a greater and earlier statistically significant decline, and reached to 37%, 12.5% and 19%, respectively, at 18 years. Although a tendency to lower terminal flow was seen in the girls, the differences were not statistically significant. Significant correlations between pulmonary function and the airway colonizator or genotype were not detected statistic. Conclusion: The evolution pattern of pulmonary function alterations found in these patients is consistent with those reported in the literature, where obstructive ventilatory disorders with early terminal flow reduction and late FVC onset predominate.

O tratamento medicamentoso da fibrose cística (alfa dornase, suplementos pancreáticos, antibióticos orais e inalatórios) são fornecidos pela Secretaria da Saúde do Estado do Rio Grande do Sul como parte de sua responsabilidade na Política Nacional Assistência Farmacêutica do governo central para acesso a medicamentos especiais dirigido a indivíduos que tenham um diagnóstico confirmado. Para ter acesso ao tratamento os pacientes devem seguir os passos descritos no texto. The pharmacological treatment of Cystic Fibrosis (alpha-dornase, pancreatic enzymes, oral and inhaled antibiotics) has been delivered by the State Health Board of Rio Grande do Sul as part of its responsibility on the National Drugs Policy from the central government to permit access to special treatments for those who have a confirmed diagnosis. In order to access the treatment patients must follow the steps described in the text.

OBJETIVO: Avaliar a concentração da elastase-1 (EL-1) fecal em pacientes pediátricos com fibrose cística, portadores da mutação ∆F508. MÉTODOS: Estudo transversal com amostras colhidas consecutivamente de 51 pacientes com idade entre 4 meses e 17 anos (média 9,11±4,74), sendo 32 (62,8%) pacientes do sexo masculino. Houve coleta de dados clínico-demográficos e do tipo de mutação. A insuficiência pancreática exócrina foi definida pela atividade da EL-1 fecal < 200 µg/g. A quantificação da EL-1 foi realizada pelo método ELISA monoclonal (ScheBo Biotech AG, Germany). A suplementação pancreática foi utilizada em 46 (90,2%) pacientes. RESULTADOS: Quarenta e um (80,4%) pacientes apresentaram insuficiência pancreática (EL-1 fecal < 100 µg/g), sendo 17 (41,5%) homozigotos, 14 heterozigotos (34,1%) e 10 sem ∆F508 (24,4%). Ao considerar a mutação, houve associação estatisticamente significativa entre os homozigotos e a concentração da EL-1 fecal < 100 µg/g (p = 0,010). Todos os pacientes considerados insuficientes pancreáticos (n = 41) pelo teste utilizavam suplemento pancreático. Dez (19,6%) apresentaram EL-1 fecal > 200 µg/g, e 5/10 (50%) utilizavam enzimas. CONCLUSÕES: A atividade de EL-1 fecal < 100 µg/g, indicativa de insuficiência pancreática, apresentou-se em 17/17 (100%) dos homozigotos, conforme o esperado, sendo menos frequente nos heterozigotos para ∆F508 e nos pacientes com ausência dessa mutação. Não houve relação entre a concentração da EL-1 fecal com idade e sexo dos pacientes. O teste foi padronizado, é de fácil execução e poderá ser utilizado para avaliação da função pancreática dos pacientes com fibrose cística. OBJECTIVE: To assess the concentration of faecal elastase-1 (EL-1) in pediatric patients with cystic fibrosis with mutation ∆F508. METHODS: Cross-sectional study with samples collected consecutively from 51 patients aged 4 months to 17 years old (mean 9.11±4.74); 32 (62.8%) patients were male. Clinical-demographic data were collected, as well as data on the type of mutation. Exocrine pancreatic insufficiency was established by the activity of faecal EL-1 < 200 µg/g. EL-1 was quantified through the monoclonal ELISA method (ScheBo Biotech AG, Germany). Pancreatic supplements were used in 46 (90.2%) patients. RESULTS: Forty-one (80.4%) patients presented with pancreatic insufficiency (EL-1 fecal < 100 µg/g): 17 (41.5%) were homozygous, 14 were heterozygous (34.1%) and 10 were non-∆F508 (24.4%). Regarding the mutation, there was a statistically significant association of homozygosity with faecal EL-1 concentration < 100 µg/g (p = 0.010). All patients considered to be pancreatic insufficient (n = 41) by the test were using pancreatic supplements. Ten (19.6%) presented faecal EL-1 > 200 µg/g, and 5/10 (50%) used enzymes. CONCLUSIONS: The activity of faecal EL-1 < 100 µg/g, indicating pancreatic insufficiency, was observed in 17/17 (100%) of homozygous patients, as expected, and was less frequent in patients who were heterozygous for ∆F508 and in patients without the mutation. There was no association of faecal EL-1 concentration with age and sex of patients. The test was standardized, is easy to execute, and can be used to assess the pancreatic status of patients with cystic fibrosis.

Background & aims: Malnutrition is related with pulmonary disease. The aim was to analyze the association of lung function respectively to nutritional status, identified pulmonary pathogens and socioeconomic condition of patients attending a pediatric CF reference center. Methods: Cross-sectional study performed with CF patients aged 6 to 18 years attending a CF-Center in southern Brazil. Nutritional status, plasma albumin level and pulmonary bacterial colonization were assessed. The outcome studied was forced expiratory volume in 1 second (FEV1). Results: Eighty-five patients were included in this study. FEV1 was significantly associated with body mass index (BMI) percentiles, plasma albumin level and methicillin resistant Staphylococcus aureus (MRSA) pulmonary colonization. Regression analysis showed that BMI below the 10th percentile was associated with a 25.58% drop in FEV1, and plasma albumin levels equal to or lower than 4.1 mg/dL was associated with 18.6% FEV1 reduction. FEV1 was 14.4% lower in the MRSA infected patients. Plasma albumin of 4.25 mg/dL predicted FEV1 of 60% with 76.9% sensitivity and 72.2% specificity, and 85.7% accuracy. The socioeconomic status was not association with pulmonary function. Conclusion: BMI below the 10th percentile and albumin below 4.1 mg/dL were predictors of low FEV1. Chronic MRSA infection was associated with lower FEV1. Longitudinal studies may better complement these results. Objetivos: Analizar la asociación entre la función pulmonar y tres factores: el estado nutricional, el estado de patógenos pulmonares y el estado socio-económico de pacientes en un centro de referencia en atención a pacientes pediátricos con fibrosis quística. Métodos: Se realizó un estudio longitudinal en pacientes con fibrosis quística, de 6 a 18 años atendidos en un centro de fibrosis quística del Sur del Brasil. Fueron evaluados: estado nutricional, niveles de albúmina plasmática y colonización bacteriana pulmonar. El principal resultado estudiado fue el volumen espiratorio forzado en el 1 segundo (FEV1). Resultados: Fueron incluidos en este estudio 85 pacientes. El FEV1 se mostró significativamente correlacionado con percentiles del Índice de Masa Corporal (IMC), albúmina plasmática y colonización pulmonar por Staphylococcus aureus resistente a meticilina (SARM). El análisis de regresión mostró que el IMC abajo del percentil 10 estuvo asociado con una disminución del 25,58% en el FEV1, y que niveles de albúmina plasmática iguales o menores a 4,1 mg/dL se correlacionaron on una reducción de 18,6% del FEV1. El FEV1 fue 14,4% menos en los pacientes infectados por SARM. La albúmina plasmática de 4,25 mg/dL predijo un FEV1 de 60% con una sensibilidad de 76,9% una especificidad de 72,2% y presición de 85,7%. El estado socioeconómico no tuvo asociación con la función pulmonar. Conclusiones: El IMC debajo del percentil 10 y albúmina plasmática menor que 4,1 mg/dL fueron predictivos de un bajo FEV1 . La infección crónica de SARM mostró asociación con un menor FEV1.

Background & aims: Malnutrition is related with pulmonary disease. The aim was to analyze the association of lung function respectively to nutritional status, identified pulmonary pathogens and socioeconomic condition of patients attending a pediatric CF reference center. Methods: Cross-sectional study performed with CF patients aged 6 to 18 years attending a CF-Center in southern Brazil. Nutritional status, plasma albumin level and pulmonary bacterial colonization were assessed. The outcome studied was forced expiratory volume in 1 second (FEV1). Results: Eighty-five patients were included in this study. FEV1 was significantly associated with body mass index (BMI) percentiles, plasma albumin level and methicillin resistant Staphylococcus aureus (MRSA) pulmonary colonization. Regression analysis showed that BMI below the 10th percentile was associated with a 25.58% drop in FEV1, and plasma albumin levels equal to or lower than 4.1 mg/dL was associated with 18.6% FEV1 reduction. FEV1 was 14.4% lower in the MRSA infected patients. Plasma albumin of 4.25 mg/dL predicted FEV1 of 60% with 76.9% sensitivity and 72.2% specificity, and 85.7% accuracy. The socioeconomic status was not association with pulmonary function. Conclusion: BMI below the 10th percentile and albumin below 4.1 mg/dL were predictors of low FEV1. Chronic MRSA infection was associated with lower FEV1. Longitudinal studies may better complement these results.

To determine the repeatability of the 6-minute walk test (6MWT) in adolescents and adults with cystic fibrosis (CF).This was a prospective cross-sectional study. We included consecutive patients agesor=15 years attending an adult CF program. The patients underwent the 6MWT, pulmonary function tests, and clinical evaluation. The second 6MWT was performed following a rest period of 60 min.Thirty-one patients were included. The mean+/-SD age was 23.5+/-6.7 y, and the mean FEV1 was 61+/-28% of predicted. The mean+/-SD walked distance in the first 6MWT was 583.6+/-68.6 m and in the second 6MWT was 590.0+/-72.2 m. The mean difference between the first and second 6MWT was -6.5 m, with limits of agreement between -74.9 m and 61.9 m, and the coefficient of variation was 4.3%. The mean oxygen desaturation in the first 6MWT was 2.5+/-4.5%, and in the second test it was 1.8+/-4.0%. The mean difference between the first and second test was 0.6%, and the coefficient of variation was 104%.Although the 6MWT distance was reproducible, the wide limits of agreement exceeded the minimum important difference for this test. These findings indicate that, in the routine evaluation of CF patients, at least two 6MWTs are required on any testing occasion to obtain a reliable estimate of the 6MWT distance.

Malnutrition is related with pulmonary disease. The aim was to analyze the association of lung function respectively to nutritional status, identified pulmonary pathogens and socioeconomic condition of patients attending a pediatric CF reference center.Cross-sectional study performed with CF patients aged 6 to 18 years attending a CF-Center in southern Brazil. Nutritional status, plasma albumin level and pulmonary bacterial colonization were assessed. The outcome studied was forced expiratory volume in 1 second (FEV1).Eighty-five patients were included in this study. FEV1 was significantly associated with body mass index (BMI) percentiles, plasma albumin level and methicillin resistant Staphylococcus aureus (MRSA) pulmonary colonization. Regression analysis showed that BMI below the 10th percentile was associated with a 25.58% drop in FEV1, and plasma albumin levels equal to or lower than 4.1 mg/dL was associated with 18.6% FEV1 reduction. FEV1 was 14.4% lower in the MRSA infected patients. Plasma albumin of 4.25 mg/dL predicted FEV1 of 60% with 76.9% sensitivity and 72.2% specificity, and 85.7% accuracy. The socioeconomic status was not association with pulmonary function.BMI below the 10th percentile and albumin below 4.1 mg/dL were predictors of low FEV1. Chronic MRSA infection was associated with lower FEV1. Longitudinal studies may better complement these results.

OBJETIVO: Identificar os fatores preditores de dessaturação de oxigênio durante o teste de caminhada de seis minutos (TC6) em pacientes com fibrose cística (FC). MÉTODOS: Estudo transversal e prospectivo em pacientes com FC clinicamente estáveis com idade superior a 10 anos. Os pacientes foram submetidos à avaliação nutricional, teste oral de tolerância à glicose, testes de função pulmonar, exame radiológico do tórax e TC6. RESULTADOS: Foram incluídos 88 pacientes (43 femininos e 45 masculinos) com média de idade de 19,9 ± 7,2 anos e média de VEF1 de 65,4 ± 28,4%. Observamos que 75 pacientes apresentaram-se sem dessaturação de oxigênio (SD) e 13 com dessaturação (CD). Os pacientes do grupo CD apresentaram maior média de idade (p = 0,004), pior escore clínico (p < 0,001), pior escore radiológico (p < 0,001), maior frequência de intolerância à glicose (p = 0,004), menor frequência de infecção bacteriana por Staphylococcus aureus sensível à meticilina (p < 0,001), maior frequência de infecção por S. aureus resistente à meticilina (p = 0,016) e por Pseudomonas aeruginosa (p = 0,008) e menor valor médio de SpO2 em repouso (p < 0,001) e de VEF1 (p < 0,001) do que os pacientes do grupo SD. Na análise de regressão logística, SpO2 em repouso (OR = 0,305, p < 0,001) e VEF1 (OR = 0,882, p = 0,025) se associaram com a dessaturação de oxigênio no TC6. Os parâmetros que maximizaram o valor preditivo para dessaturação de oxigênio foram SpO2 em repouso < 96% e VEF1 < 40%. Nessa amostra, 15% dos pacientes com FC com mais de 10 anos apresentaram dessaturação de oxigênio no TC6. CONCLUSÕES: Os parâmetros SpO2 em repouso < 96% e VEF1 < 40% contribuem como preditores de dessaturação no TC6. OBJECTIVE: To identify the predictive factors of oxygen desaturation during the six-minute walk test (6MWT) in patients with cystic fibrosis (CF). METHODS: Prospective cross-sectional study involving clinically stable patients with CF aged > 10 years. The patients were submitted to nutritional evaluations, oral glucose tolerance tests, pulmonary function tests, chest X-rays and 6MWTs. RESULTS: The study included 88 patients (43 females and 45 males; mean age, 19.9 ± 7.2 years; mean FEV1, 65.4 ± 28.4%). We observed oxygen desaturation in 13 patients (OD+ group) and no oxygen desaturation in 75 (ODµ group). In comparison with ODµ group patients, OD+ group patients presented higher mean age (p = 0.004), worse clinical score (p < 0.001), worse radiological score (p < 0.001), higher incidence of glucose intolerance (p = 0.004), lower incidence of methicillin-sensitive Staphylococcus aureus infection (p < 0.001), higher incidence of methicillin-resistant S. aureus infection (p = 0.016), higher incidence of Pseudomonas aeruginosa infection (p = 0.008), lower mean resting SpO2 (p < 0.001) and lower mean FEV1 (p < 0.001). In the logistic regression analysis, oxygen desaturation during the 6MWT correlated with resting SpO2 (OR = 0.305, p < 0.001) and FEV1 (OR = 0.882, p = 0.025). The parameters maximizing the predictive value for oxygen desaturation were resting SpO2 < 96% and FEV1 < 40%. In this sample, 15% of the patients with CF aged > 10 years presented oxygen desaturation during the 6MWT. CONCLUSIONS: Resting SpO2 < 96% and FEV1 < 40% can predict oxygen desaturation during the 6MWT.

To identify the predictive factors of oxygen desaturation during the six-minute walk test (6MWT) in patients with cystic fibrosis (CF).Prospective cross-sectional study involving clinically stable patients with CF agedor = 10 years. The patients were submitted to nutritional evaluations, oral glucose tolerance tests, pulmonary function tests, chest X-rays and 6MWTs.The study included 88 patients (43 females and 45 males; mean age, 19.9 + or - 7.2 years; mean FEV(1), 65.4 + or - 28.4%). We observed oxygen desaturation in 13 patients (OD+ group) and no oxygen desaturation in 75 (ODmicro group). In comparison with ODmicro group patients, OD+ group patients presented higher mean age (p = 0.004), worse clinical score (p0.001), worse radiological score (p0.001), higher incidence of glucose intolerance (p = 0.004), lower incidence of methicillin-sensitive Staphylococcus aureus infection (p0.001), higher incidence of methicillin-resistant S. aureus infection (p = 0.016), higher incidence of Pseudomonas aeruginosa infection (p = 0.008), lower mean resting SpO(2) (p0.001) and lower mean FEV(1) (p0.001). In the logistic regression analysis, oxygen desaturation during the 6MWT correlated with resting SpO(2) (OR = 0.305, p0.001) and FEV(1) (OR = 0.882, p = 0.025). The parameters maximizing the predictive value for oxygen desaturation were resting SpO(2)96% and FEV(1)40%. In this sample, 15% of the patients with CF agedor = 10 years presented oxygen desaturation during the 6MWT.Resting SpO(2)96% and FEV(1)40% can predict oxygen desaturation during the 6MWT.

A fibrose cística, que já foi considerada uma doença da infância, é agora também uma doença do adulto. O aumento da longevidade resultou em mais problemas médicos relacionados com a idade e com a própria doença. O crescente número de adultos com fibrose cística resultou em aumento da necessidade de cuidados médicos. Essa necessidade tem sido suprida por um crescente número de pneumologistas de adultos e outros especialistas. O objetivo dessa revisão é sumarizar o conhecimento corrente sobre o diagnóstico e tratamento no adulto com fibrose cística. Na maioria dos casos, o diagnóstico é sugerido por manifestações de doença sinopulmonar crônica e insuficiência pancreática exócrina, e, então, confirmado por um teste do suor positivo. Pacientes adultos podem, entretanto, apresentar suficiência pancreática e características clínicas atípicas, às vezes, associadas com teste do suor normal ou limítrofe. Em tais casos, a possibilidade de realizar pesquisa de mutações para fibrose cística e de medir a diferença de potencial nasal pode ser de utilidade diagnóstica. A abordagem terapêutica padrão para a doença pulmonar inclui: antibióticos, higiene das vias aéreas, exercício, mucolíticos, broncodilatadores, oxigênio, agentes anti-inflamatórios e suporte nutricional. A utilização adequada dessas terapias resulta em mais pacientes com fibrose cística sobrevivendo na vida adulta com uma aceitável qualidade de vida. Once considered a childhood disease, cystic fibrosis is now also a disease of adults. Increased longevity has resulted in the aging of the cystic fibrosis population. The consequent age-related medical problems among adults with cystic fibrosis have increased medical care needs. These needs are being met by a growing number of non-pediatric pulmonologists and other non-pediatric specialists. The objective of this review was to summarize the current knowledge about diagnosis and treatment in adult cystic fibrosis. In most cases, the diagnosis is suggested by manifestations of chronic sinopulmonary disease and exocrine pancreatic insufficiency. The diagnosis is confirmed by a positive sweat test result. Adult patients may, however, present pancreatic sufficiency and atypical clinical features, sometimes in combination with normal or borderline sweat test results. In such cases, identifying cystic fibrosis mutations and measuring nasal potential difference can have diagnostic utility. The standard therapeutic approach to pulmonary disease includes the use of antibiotics, airway clearance, exercise, mucolytics, bronchodilators, oxygen therapy, anti-inflammatory agents and nutritional support. Appropriate application of these therapies results in most cystic fibrosis patients surviving into adulthood with an acceptable quality of life.

Once considered a childhood disease, cystic fibrosis is now also a disease of adults. Increased longevity has resulted in the aging of the cystic fibrosis population. The consequent age-related medical problems among adults with cystic fibrosis have increased medical care needs. These needs are being met by a growing number of non-pediatric pulmonologists and other non-pediatric specialists. The objective of this review was to summarize the current knowledge about diagnosis and treatment in adult cystic fibrosis. In most cases, the diagnosis is suggested by manifestations of chronic sinopulmonary disease and exocrine pancreatic insufficiency. The diagnosis is confirmed by a positive sweat test result. Adult patients may, however, present pancreatic sufficiency and atypical clinical features, sometimes in combination with normal or borderline sweat test results. In such cases, identifying cystic fibrosis mutations and measuring nasal potential difference can have diagnostic utility. The standard therapeutic approach to pulmonary disease includes the use of antibiotics, airway clearance, exercise, mucolytics, bronchodilators, oxygen therapy, anti-inflammatory agents and nutritional support. Appropriate application of these therapies results in most cystic fibrosis patients surviving into adulthood with an acceptable quality of life.

To study correlations among pulmonary function, chest radiology and clinical status in cystic fibrosis.A retrospective cross-sectional study was performed to evaluate chest X-rays and clinical charts of patients treated at the Hospital de Clínicas de Porto Alegre. Spirometry findings, Shwachman-Kulczycki (S-K) scores and Brasfield scores were analyzed.The final sample consisted of 40 patients (mean age 9.72 +/- 3.27). The following mean S-K scores were obtained: total, 80.87 +/- 10.24; general activity, 24.75 +/- 1.1; physical examination, 18.87 +/- 4.59; nutrition, 21.87 +/- 4.18; radiology, 15.37 +/- 5.23. The mean Brasfield score was 18.2 +/- 4. The pulmonary function test results, in percentage of predicted, were as follows: forced vital capacity (FVC), 82.99 +/- 14.36%; forced expiratory volume in one second (FEV1), 83.62 +/- 18.26%; and forced expiratory flow between 25 and 75% of FVC (FEF25-75), 74.63 +/- 2.53%. The S-K score correlated moderately with FVC, whereas it correlated strongly with FEV1 and FEF25-75. The Brasfield score correlated strongly with the S-K total and radiology score, whereas it correlated moderately with pulmonary function. Physical examination correlated moderately with FVC, FEV1 and FEF25-75; as did nutrition with FEF25-75; and radiology with FEV1 and FEF25-75. General activity was the domain that had the greatest influence on the total S-K score.These two scoring systems are complementary, correlating with each other, as well as with pulmonary function tests. The radiology domain of the S-K scoring system is a good alternative to the Brasfield score.

Objetivo do estudo: Avaliar o padrão da evolução dos fluxos e volumes pulmonares dinâmicos dos pacientes com fibrose cística (FC), assim como analisar a relação entre a gravidade do comprometimento ventilatório com a idade, sexo, genótipo e colonização pulmonar. Material e método: Na Unidade de Pneumologia Infantil e Serviço de Pneumologia do Hospital de Clínicas de Porto Alegre, foram avaliadas 243 espirometrias de 52 pacientes portadores de FC maiores de quatro anos realizadas no período de 1987 a 1999. Do prontuário médico foram extraídas informações sobre idade ao diagnóstico, pesquisa genética, colonização brônquica e os valores absolutos e percentuais para fluxos e volumes da melhor espirometria de cada ano. Resultados: A idade dos pacientes variou de quatro a 26 anos (média = 13,04 ± 4,82). Dos 52 pacientes, 49 (94%) tiveram pelo menos uma cultura de escarro com P. aeruginosa, 45 (86%) com S. aureus e 13 (25%) com B. cepacia. Na avaliação inicial dos quatro aos seis anos (n = 40), os valores médios da CVF e do VEF1 foram de 114,24% e 112,25%, respectivamente. A média da CVF manteve-se acima do normal até os 18 anos, quando apresentou queda súbita para 67,2% (p = 0,0002). A média do VEF1 atingiu valores abaixo de 80% aos dez anos, estando em 50% aos 18 anos (p < 0,00001). A relação VEF1/CVF%, índice mais sensível de obstrução, mostrou-se diminuída já na primeira avaliação, sendo 85% entre os quatro e seis anos, com declínio lento progressivo, chegando a 63% aos 18 anos. Os valores médios do FEF50, FEF75 e FMEF inicialmente foram normais (94%, 80% e 90%, respectivamente), mostraram queda maior e mais precoce, estatisticamente significativa, atingindo valores médios aos 18 anos de 37%, 12,5% e 19%, respectivamente. Embora houvesse tendência para fluxos terminais mais baixos para as meninas, as diferenças não tiveram valor estatístico. Também não foram detectadas correlações estatisticamente significativas entre a função pulmonar e o germe colonizador da via aérea ou o genótipo. Conclusão: O padrão evolutivo das alterações funcionais pulmonares encontrado nos pacientes está de acordo com o descrito na literatura, onde predomina o distúrbio ventilatório obstrutivo com redução precoce dos fluxos terminais e acometimento tardio da CVF. Objectives: To evaluate the evolution pattern of dynamic pulmonary flow and volume in cystic fibrosis patients and analyze the relation between the severity of ventilatory attacks and age, gender, genotype and pulmonary colonization. Methods: At the Pediatric Pulmonary Unit and Pulmonary Service of Hospital de Clínicas of Porto Alegre, 243 spirometries performed between 1987 and 1999 in 52 cystic fibrosis patients older than four years of age were reviewed. From the patients’ medical records the following informations were extracted: age at diagnosis, genetic data, bronchial colonization and absolute as well as percent values of the flows and volumes of the best annual spirometry. Results: The age of the patients ranged from four to 26 years (mean = 13.04 ± 4.82). Out of the 52 patients, 49 (94%) had at least one sputum culture with P. aeruginosa, 45 (86%) with S. aureus and 13 (25%) with B. cepacia. At initial evaluation, that included patients four to six years old (n = 40), mean values for FVC and FEV1 were 114.24% and 112.25%, respectively. Mean FVC remained above baseline until 18 years of age, when it abruptly dropped to 67.2% (p = 0.0002). Objectives: To evaluate the evolution pattern of dynamic pulmonary flow and volume in cystic fibrosis patients and analyze the relation between the severity of ventilatory attacks and age, gender, genotype and pulmonary colonization. Methods: At the Pediatric Pulmonary Unit and Pulmonary Service of Hospital de Clínicas of Porto Alegre, 243 spirometries performed between 1987 and 1999 in 52 cystic fibrosis patients older than four years of age were reviewed. From the patients’ medical records the following informations were extracted: age at diagnosis, genetic data, bronchial colonization and absolute as well as percent values of the flows and volumes of the best annual spirometry. Results: The age of the patients ranged from four to 26 years (mean = 13.04 ± 4.82). Out of the 52 patients, 49 (94%) had at least one sputum culture with P. aeruginosa, 45 (86%) with S. aureus and 13 (25%) with B. cepacia. At initial evaluation, that included patients four to six years old (n = 40), mean values for FVC and FEV1 were 114.24% and 112.25%, respectively. Mean FVC remained above baseline until 18 years of age, when it abruptly dropped to 67.2% (p = 0.0002).

Sixty-one cystic fibrosis patients admitted for check-up or antibiotic treatment were enrolled for genetic and clinical evaluation. Genetic analysis was performed on blood samples stored on neonatal screening cards using PCR techniques to determine the presence of delta F508 mutations. Clinical evaluation included Shwachman and Chrispin-Norman scores, age at onset of symptoms and diagnosis, spirometry, awake and sleep pulse oximetry, hyponychial angle measurement and presence of chronic Pseudomonas aeruginosa colonization. Eighteen patients (29.5%) were homozygous for the delta F508 mutation, 26 (42.6%) had one delta F508 mutation and 17 (27.9%) were noncarriers, corresponding to a 50.8% prevalence of the mutation in the whole population. Analysis by the Kruskal-Wallis test for comparison of genetic status with continuous variables or by the chi-square test and logistic regression for dichotomous variables showed no significant differences between any two groups for alpha = 0.05. We conclude that genetic status in relation to the delta F508 mutation is not associated with pulmonary status as evaluated by the above variables.

Sixty-one cystic fibrosis patients admitted for check-up or antibiotic treatment were enrolled for genetic and clinical evaluation. Genetic analysis was performed on blood samples stored on neonatal screening cards using PCR techniques to determine the presence of DF508 mutations. Clinical evaluation included Shwachman and Chrispin-Norman scores, age at onset of symptoms and diagnosis, spirometry, awake and sleep pulse oximetry, hyponychial angle measurement and presence of chronic Pseudomonas aeruginosa colonization. Eighteen patients (29.5%) were homozygous for the DF508 mutation, 26 (42.6%) had one DF508 mutation and 17 (27.9%) were noncarriers, corresponding to a 50.8% prevalence of the mutation in the whole population. Analysis by the Kruskal-Wallis test for comparison of genetic status with continuous variables or by the chi-square test and logistic regression for dichotomous variables showed no significant differences between any two groups for a = 0.05. We conclude that genetic status in relation to the DF508 mutation is not associated with pulmonary status as evaluated by the above variables

A combinação de fatores como viscosidade das secreções dos seios paranasais, diminuição da drenagem sinusal e comprometimento do transporte mucociliar podem ser responsáveis pela criação de um ambiente propício e adequado para a colonização de bactérias nos seios paranasais de pacientes com fibrose cística. OBJETIVO: Analisar a bacteriologia do aspirado do meato médio de pacientes portadores de fibrose cística. MATERIAL E MÉTODO: Através de um estudo prospectivo de delineamento transversal, avaliou-se uma amostra composta de 23 pacientes, avaliados durante 2 anos. Realizaram-se relações entre a cultura do meato médio e a avaliação radiológica do seio maxilar e a avaliação clínica. Secundariamente, estudou-se a relação da bacteriologia do aspirado do meato médio e a do escarro. RESULTADOS: No total foram realizadas 42 aspirações do meato médio. Em 17 (73,91%) dos 23 pacientes, as culturas foram negativas e, em 6 (26,08%), positivas. Das 42 aspirações, 31 (73,8%) foram negativas e 11 (26,2%), positivas. A presença de Pseudomonas aeruginosa foi observada em 18,18% das culturas positivas e o Staphylococcus aerus em 27,28%. CONCLUSÃO: A maioria das culturas do aspirado do meato médio de pacientes com fibrose cística foi negativa. The combination of factors, such as abnormal viscosity of the paranasal sinus secretions, decreased sinus drainage, and impaired mucociliary clearance may account for the establishment of a suitable and opportune environment for the colonization of bacteria in the paranasal sinuses of patients with cystic fibrosis. AIM: The goal of the present study was to assess the bacteriology of the middle meatus aspirate in patients diagnosed whit cystic fibrosis. MATERIAL AND METHODS: Through a cross-sectional prospective study, a sample consisting of 23 patients evaluated for 2 years, was assessed. Firstly, we established the relationship between the middle meatus culture and the maxillary sinus x-ray. In second, we studied the relationship between the middle meatus aspirate bacteriology and the sputum bacteriology. RESULTS: In total, 42 aspirates of the middle meatus were carried out. In 17 (73.91%) of the 23 patients, the aspirates were negative; and in 6 (26.08%) they were positive. Out of the 42 aspirates,31 (78.8%) were negative, and 11 (26.2%) were positive. The presence of Pseudomonas aeruginosa was observed in 18.18% of the positive cultures, and Staphylococcus aureus was observed in 27.28%. CONCLUSION: The great majority of the middle meatus aspirates of the patients with cystic fibrosis were negative.

O teste da diferença de potencial nasal (DPN) é um exame que mede a diferença bioelétrica através do epitélio nasal, a qual resulta do transporte iônico transepitelial dos íons sódio (Na+), pelo canal ENaC (Epitelial Na+ Channel), e cloro (Cl-), pelo canal CFTR(Cystic Fibrosis Transmembrane Conductance Regulator). DPN tem sido utilizada como teste de auxilio diagnóstico em doenças associadas à disfunção do CFTR, como a Fibrose Cística (FC). FC é uma doença genética autossômica recessiva causada por mutações que afetam o funcionamento do canal CFTR (e secundariamente do ENaC) e levam a manifestações em diversos órgãos. Normalmente a dosagem de cloro no suor acima de 60 mEq/L ou a identificação de mutações nos dois alelos confirmam diagnóstico de FC. Porém, existem casos atípicos com exames considerados inconclusivos onde as características eletrofisiológicas decorrentes da disfunção do CFTR devem ser demonstradas para estabelecimento do diagnóstico. A identificação correta destes casos é importante para instituição do tratamento adequado e definição do prognóstico. O objetivo principal deste trabalho foi padronizar a técnica da DPN para sua futura aplicação como ferramenta diagnóstica através da determinação dos seus valores de referência, de sensibilidade, de especificidade e de concordância entre os resultados das duas narinas. Secundariamente, objetivamos analisar as relações entre a presença de função residual do CFTRe a concentração de cloro no suor, fenótipo pancreático, presença de Pseudomonas aeruginosa, função pulmonar e genótipo na amostra de pacientes comFC. Foi realizado um estudo transversal com realização da DPN em um grupo de pacientes com FC (n=29, idade:15±6 anos) e dois grupos controle: não=FC (n=19, idade: 15 ± 10 anos) e sadios (n=19, idade: 17 ± 8 anos). Os resultados demonstraram que os valores da DPN são significativamente diferentes no grupo FC (FC: DPNmax: -34 ± 9mV, Δamil: -20 ± 9mV, ΔCl: 4 ± 5mV, Δamilo-iso: -19 ± 9 mV e indiceDPN: 0.85 ± 0.23; não-FC:DPNmax: -14 ± 5mV, Δamil: -6 ± 3mV, ΔCl: 17 ± 9mV, Δamilo-iso: -1 ± 4 mV e indiceDPN: 0.11 ± 0.11) e sadios: DPNmax: -15 ± 4mV, Δamil: -6 ± 3mV, ΔCl: 11 ± 7mV, Δamilo-iso: -2 ± 4 mV e indiceDPN: 0.20±0.14),com sensibilidade e especificidade de 95-96% e concordância de resultado entre as duas narinas maior para a DPNmax (r=0,934). A função residual da CFTR não mostrou relação com nenhum dos parâmetros fenotípicos avaliados. Somente mostrou relação com a gravidade do genótipo. Entretanto, foi observada relação entre os parâmetros que avaliam a hiperfunção do ENaC existente na FC e o fenótipo. Concluímos com este trabalho que foi possível reproduzir e padronizar esta técnica da DPN e demonstrar que o fenótipo da FC está mais relacionado à alteração do transporte do íon sódio através do ENaC do que à presença de função residual da CFTR. Nasal potential difference test (NPD) is a test that measures the bioelectrical difference across the nasal epithelium, which results from transepithelial ion transport of sodium (Na+), by ENaC channels (Epitelial Na+ Channel) and chloride (Cl-), by CFTR (Cystic Fibrosis Transmembrane Conductance Regulator).NPD has been used as a diagnostic tool in CFTR related disorders, such as Cystic Fibrosis (CF). CF is an autosomal recessive genetic disease caused by mutations that affect the function of the CFTR channel (andsecondarily of the EnaC)and lead to manifestations in various organs. Normally sweat chloride concentration > 60 mEq / L and identification of two CFTR mutations confirm the CF diagnosis. However there are atypical cases with inconclusive sweat chloride or genetic where the electrophysiological characteristics induced by CFTR dysfunction has to be demonstrated for diagnosis. The correct identification of these cases is important for institution of appropriate treatment and definition of prognosis. The objective of this study was to standardize the NPD for its future application as a diagnostic tool through the determination of reference values, sensibility and specificity and agreement of the results between both examined nostrils. Secondarily, we analyzed the relations between residual CFTR function and sweat chloride concentration, pancreatic phenotype, Pseudomonas aeruginosa positivity, pulmonary function and genotype in the sample of CF patients. It was a transversal study where the NPD was measured in a group of CF patients (n = 29, age: 15 ± 6 years) and two control groups: non-CF (n = 19, age: 15 ± 10 years) and healthy (n = 19, age: 17 ± 8 years). The results showed that NPD was significantly different in CF (NPDmax: -34 ± 9mV, Δamil: -20 ± 9mV, ΔCl: 4 ± 5mV, Δamilo-iso: -19 ± 9 mV e NPDindex: 0.85 ± 0.23; non-CF: NPDmax: -14 ± 5mV, Δamil: -6 ± 3mV, ΔCl: 17 ± 9mV, Δamilo-iso: -1 ± 4 mV and NPDindex: 0.11 ± 0.11) and healthy: NPDmax: -15 ± 4mV, Δamil: -6 ± 3mV, ΔCl: 11 ± 7mV, Δamilo-iso: -2 ± 4 mV and NPDindex: 0.20±0.14) with sensibility and specificity of 95-96% and agreement between both nostrils greater for NPDmax (r=0.934). The residual CFTR function did not show relation with all phenotypic parameters evaluated. It just showed relation with genotype severity. Indeed it was observed a relation between the parameters that assess the ENaC hyperfunction that occurs in CF and the phenotype. We concluded with this study that was possible to reproduce and to standardize the NPD and to demonstrate that the phenotype is more related to sodium transport alterations through ENaC than to the presence of residual CFTR function.

Introdução: A fibrose cística também conhecida como mucoviscidose, é uma doença genética autossômica recessiva, crônica, com manifestações sistêmicas, sendo o transplante pulmonar uma das alternativas para o tratamento quando a doença se apresenta em fase terminal. Objetivos: Avaliar a função pulmonar, condicionamento físico e qualidade de vida em pacientes com fibrose cística após trinta meses do transplante pulmonar seguido de um programa de reabilitação do cardiopulmonar. Metodologia: Estudo de coorte ambispectivo, foram estudados 8 pacientes com fibrose cística (5 mulheres 3 homens com média de idade 27 ± 4,62 anos) no período de dezembro de 2006 a dezembro de 2010. Havido perda de 2 pacientes ao longo do estudo. Foram analisados o teste de caminhada de seis minutos(TC6M), testes de função pulmonar e o questionário SF-36 no pré-transplante, pós-transplante imediato, pósreabilitação cardiopulmonar e após trinta meses após o transplante. Resultados: Tempo de lista de espera de 883 ± 571 dias tempo de internação total 30,14 ± 12,6 dias. Os pacientes apresentaram em média no pré-transplante VEF1 25,1% e CVF 38,4%, no pós transplante imediato VEF1 52,6% e CVF 54,6%. após reabilitação VEF1 60,8% e CVF 65,2% e 30 meses pós transplante VEF1 66,6% e CVF 67,2% . No TC6M a média de distância percorrida antes do transplante foi de 488 metros, pós-transplante imediato 510 metros, pós-reabilitação 603 metros e 30 meses pós-transplante 462 metros. Quanto à qualidade de vida os pacientes apresentaram melhora nos momentos pós-alta hospitalar e após reabilitação e piora em alguns domínios 30 meses após o transplante. Conclusão: O transplante de pulmão permanece sendo um procedimento de alto risco, no entanto, é uma estratégia terapêutica viável para pacientes com fibrose cística em estágio avançado da doença. Os dados encontrados no estudo sugerem uma tendência positiva a curto prazo na capacidade funcional e qualidade de vida, contudo a médio prazo perecem diminuir, enquanto a função pulmonar apresenta crescente melhora a curto e médio prazo. São necessários mais estudos com um maior número de pacientes para se afirmar com propriedade os benefícios a longo prazo do transplante de pulmão para essa população. Introduction: Cystic Fibrosis, also known as mucoviscidosis, is a chronic autosomal recessive genetic disorder with systemic manifestations, lung transplantation being one of the alternatives for treatment when the disease is in its terminal phase. Objective: Evaluate the lung function, physical conditions and the quality of life of the cystic fibrosis patient after 30 months from the lung transplantation following a rehabilitation program of cardiopulmonary therapy. Methodology: The study of the ambispective cohort, involved eight patients with cystic fibrosis (5 women and 3 men aged 27 ± 4.6 years) for the period from December 2006 to December 2010, two patients died during the study. Analysis was made of the Six Minutes Walk Test (6MWT), lung function and the SF-36 questionnaire for the pre-transplant, immediately post- transplant, post cardiopulmonary rehabilitation and 30 months after the transplant. Results: The waiting list was 883±571 days, hospitalization time totalled 30.14 ±12.6 days. The patients showed, on average, a pretransplant VEF1 25.1% and CVF 38.4%, immediately posttransplant VEF1 66.6% and CVF 54.6%, post cardiopulmonary rehabilitation VEF1 60.8% and CVF 65.2% end 30 months post-transplant VEF1 66.6% and CVF 67.2%. In the TC6M, the average distance done before the transplant was 488 meters, immediately post-transplant it was 510 meters, post cardiopulmonary rehabilitation it was 603 meters and 30 months after transplant it was 462 meters. The quality of life of the patients showed improvement from the moment of leaving the hospital and after rehabilitation but did deteriorate in some domains after 30 months from the transplant. Conclusion: The lung transplantation continues to be a high risk procedure, however it still is a therapeutic strategy available to patients with cystic fibrosis at the advance stage of the disease. The findings of the study suggest there is a positive trend in the short term functional capacity and quality of life in the medium term however perish decrease, while increasing lung function has improved in the short and medium term. Although it would require further study with a higher number of patients to affirm with confidence the benefit for the long term of lung transplants for this population.

Esse estudo transversal avaliou a saúde bucal de 36 pacientes com fibrose cística (FC). Um questionário foi aplicado para obter informações sobre autocuidados e outros aspectos que pudessem influenciar os resultados. Os exames, realizados por examinadora treinada e calibrada, foram placa visível (IPV), sangramento gengival (ISG), profundidade de sondagem (PS), perda de inserção (PI), exsudato à sondagem (SS), presença de sítios com cálculo dental, experiência de cárie (ceo/CPO-D + MBA) e número de dentes com sinais de anomalias no esmalte. Os resultados das variáveis clínicas foram comparados (P 12 anos os resultados foram: IPV (65,40±35,13% e 58,90±34,51%), ISG (14,00±21,61% e 26,51±27,09%) e presença de cálculo dental (21,59±28,96% e 11,97±9,29%), sem diferenças significativas entre os grupos. As médias de PS foram 1,30±0,32mm e 1,70±0,30mm (P=0,00) e de SS foram 3,89±9,92% e 7,72±20,04% (P=0,09). A média de PI, somente presente no grupo >12 anos, foi 0,15±0,35mm. Os valores do índice ceo/CPO-D+MBA foram 1,74±3,33/1,20±1,74 e 5,14±4,26, respectivamente. A presença de anomalias de esmalte variou de nenhum até todos os dentes com sinais, em ambos os grupos. A comparação dos grupos EC+ e EC- revelou que os valores do IPV (70,52±30,92% e 52±37,50%) e ISG (25,13±29,40% e 10,09±10,04%), não diferiram significativamente, ao contrário dos percentuais de cálculo, com valores de 9,97±10,06% e 28,86±32,05% nos grupos, respectivamente. Placa bacteriana (r=0,50; P=0,02), e preferência por alimentos doces (r=0,48; P=0,02) relacionaram-se positivamente com experiência cárie na dentição decídua, assim como o histórico de dor (r=0,48; P=0,03), que também teve relação positiva com a dentição permanente (r=0,52; P=0,02). Correlação positiva foi observada entre a perda de inserção e a percepção da gengiva já ter sangrado anteriormente (r=0,51; P=0,00). Os níveis de escolaridade da mãe e do pai relacionaram-se negativamente com a EC nas crianças FC (r=-0,57; r=-0,71). Conclusões: Nessa amostra, manifestações de cárie foram observadas a partir de sinais incipientes de perda mineral, sendo que a experiência de cárie foi semelhante àquela observada na população do sul do Brasil. A remoção de cálculo dental para tratamento da gengivite não deve ser priorizado no atendimento de pacientes císticos com atividade de cárie. Atenção odontológica deve ser direcionada à prevenção e ao tratamento da doença cárie. This cross-sectional study assessed the dental health of 36 cystic fibrosis (CF) patients. Questionnaire was applied to obtain information about self-care and other aspects that could influence the results. One trained and calibrated examiner evaluated the presence of visible plaque (VIP), gingival bleeding (GB), bleeding on probing (BOP), pocket depth (PD), clinical attachment loss (CAL), presence of supragingival calculus, dmf/DMF-T index modified by the presence of active white spots, and the presence of enamel defects. The results of the clinical variables were compared (P 12 years old were: VIP (65.40±35.13% and 58.90 ± 34.51%), GB (14.00±21.61% and 26.51% ± 27.09%) and presence of calculus (21.59±28.96% and 11.97±9.29%), without statistic differences between the groups. The mean value of PS was 1.30±0.32 mm and 1.70±0.30mm (P= 0.00) and BOP were 3.89± 9.92% and 20.04±7.72% (P= 0.09). The CAL mean value present in the group > 12 years old, was 0.15±0.35 mm. The values of the dmf/DMF-T modified index were 1.74 ±3.33 / 1.20 ± 1.74 and 5.14 ± 4.26, respectively. The presence of teeth with enamel defect, per individual, ranged from none to all teeth with signs in both groups. The analysis of the groups CE+ and CE- revealed that VIP (70.52±30.92% - 52.00±37.50%) and of GB (25.13±29.40% -10.09±10.04%), did not differ significantly. Differences were observed between the percentages of dental calculus (9.97±10.06% - 28.86±32.05%). Few significant correlations were observed between the findings. The presence of visible plaque (r= 0.50, P=0.02), and preference for sweet foods (r= 0.48, P=0.02) correlated positively with caries experience in primary dentition, as well as the history of pain (r= 0.48, P=0.03), and that also had positive correlation with the permanent dentition (r= 0.52, P=0.02). Positive correlation was also found between attachment loss and the perception of gingival bleeding by the patient (r= 0.51, P=0.00). Mother’s and father’s education were negatively correlated with CE+ in primary dentition (r= - 0.57, r= - 0.71). Conclusions: In the study, symptoms of decay were observed from the incipient signs of mineral loss, and the caries experience in the cystic patients sample were similar to those observed in the population from south of Brazil. In cystic patients with caries activity, the removal of dental calculus for the treatment of gingivitis should not take priority in the planning of dental care. Dental care should be directed to prevention and treatment of caries.