Effectiveness of a multistep Pseudomonas aeruginosa eradication treatment protocol in children with cystic fibrosis in Brazil.

OBJECTIVE: Although various strategies have been proposed for eradicating Pseudomonas aeruginosa in patients with cystic fibrosis (CF), only a few employ multistep treatment in children colonized by that pathogen for the first time. The aim of this study was to describe the effectiveness of a three-phase eradication protocol, initiated after the first isolation of P. aeruginosa, in children with CF in Brazil. METHODS: This was a retrospective real-life study in which we reviewed the medical records of pediatric CF patients in whom the eradication protocol was applied between June of 2004 and December of 2012. The three-phase protocol was guided by positive cultures for P. aeruginosa in airway secretions, and the treatment consisted of inhaled colistimethate and oral ciprofloxacin. Success rates were assessed after each phase, as well as cumulatively. RESULTS: During the study period, 47 episodes of P. aeruginosa colonization, in 29 patients, were eligible for eradication. Among the 29 patients, the median age was 2.7 years, 17 (59%) were male, and 19 (65%) had at least one F508del allele. All 29 patients completed the first phase of the protocol, whereas only 12 and 6 completed the second and third phases, respectively. Success rates for eradication in the three treatment phases were 58.6% (95% CI: 40.7-74.5), 50.0% (95% CI: 25.4-74.6), and 66.7% (95% CI: 30.0-90.3), respectively. The cumulative success rate was 93.1% (95% CI: 78.0-98.1). Treatment failure in all three phases occurred in only 2 patients. CONCLUSIONS: In this sample of patients, the multistep eradication protocol was effective and had a high success rate.

Brazilian guidelines for the diagnosis and treatment of cystic fibrosis.

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

Brazilian guidelines for the diagnosis and treatment of cystic fibrosis / Diretrizes brasileiras de diagnóstico e tratamento da fibrose cística

ABSTRACT 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.

Follow-up on pediatric patients with bronchiolitis obliterans treated with corticosteroid pulse therapy.

BACKGROUND: Bronchiolitis obliterans (BO) is a rare but severe disease in children. Currently, there is no consensus on the treatment for BO with respect to the systemic use of corticosteroids. Here we report on the follow-up of children with a diagnosis of BO who were treated with corticosteroid pulse therapy. METHODS: Forty patients fulfilling the BO diagnosis criteria were treated with methylprednisolone pulse therapy in monthly cycles until clinical improvement. After the pulse therapy began, we analyzed the clinical and laboratory data at intervals. Statistical analyses were performed using non-parametric tests to compare repeated measures (Friedman, Wilcoxon) or paired nominal data (McNemar) (α = 5%). RESULTS: The frequency of wheezing exacerbations and hospitalizations was reduced (p = 0.0042 and p < 0.0001, respectively) and oxygen saturation improved (p = 0.0002) in the pulse therapy-treated patients. Prolonged oral corticosteroid therapy was discontinued in 83% of these patients. The mean Z-score length for age improved from -1.08 to -0.63, and the mean Z-score weight for age improved from -0.91 to -0.59. The adverse effects during the infusion were temporary and none were serious. CONCLUSIONS: Our data suggest that pulse corticotherapy could be a safe alternative to prolonged systemic oral corticotherapy in children with BO, thus minimizing the adverse effects of the oral therapy. New prospective controlled studies are required to confirm this proposition.

Sweat conductivity: an accurate diagnostic test for cystic fibrosis?

BACKGROUND: Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. Sweat conductivity is widely used although still considered a screening test. METHODS: This was a prospective, cross-sectional, diagnostic research conducted at the laboratory of the Instituto da Criança of the Hospital das Clínicas, São Paulo, Brazil. Sweat chloride (quantitative pilocarpine iontophoresis) and sweat conductivity tests were simultaneously performed in patients referred for a sweat test between March 2007 and October 2008. Conductivity and chloride cut-off values used to rule out or diagnose CF were <75 and ≥90 mmol/L and <60 and ≥60 mmol/L, respectively. The ROC curve method was used to calculate the sensitivity, specificity, positive (PPV) and negative predictive value (NPV), as well as the respective 95% confidence intervals and to calculate the area under the curve for both tests. The kappa coefficient was used to evaluate agreement between the tests. RESULTS: Both tests were performed in 738 children, and CF was ruled out in 714 subjects; the median sweat chloride and conductivity values were 11 and 25 mmol/L in these populations, respectively. Twenty-four patients who had received a diagnosis of CF presented median sweat chloride and conductivity values of 87 and 103 mmol/L, respectively. Conductivity values above 90 mmol/L had 83.3% sensitivity, 99.7% specificity, 90.9% PPV and 99.4% NPV to diagnose CF. The best conductivity cut-off value to exclude CF was <75 mmol/L. Good agreement was observed between the tests (kappa: 0.934). CONCLUSIONS: The sweat conductivity test yielded a high degree of diagnostic accuracy and it showed good agreement with sweat chloride. We suggest that it should play a role as a diagnostic test for CF in the near future.

Fibrose cística na clínica pediátrica / Cystic fibrosis in Pediatrics

A fibrose cística (FC) é uma doença de herança autossômica recessiva, que atinge as glândulas exócrinas, envolvendo múltiplos órgãos e evoluindo de forma crônica e progressiva. A mutação ocorre no gene CFTR (cystic fibrosis transmembrane condutance regulator), que codifica a proteína de membrana também denominada CFTR, um canal de cloro que participa da regulação do transporte de eletrólitos e água na superfície celular. Acima de 1.900 mutações já foram descritas. Deve-se ressaltar, na apresentação clínica, a presença de doença pulmonar obstrutiva e supurativa recorrente ou crônica, diarreia/esteatorreia, dificuldade no ganho de peso/crescimento ou desnutrição e desidratação hiponatrêmica. Porém o diagnóstico deve ser também considerado em diversas outras possíveis apresentações clínicas. O teste do suor continua sendo o exame de referência para o diagnóstico da doença, estando alterado em cerca de 98% dos casos. A triagem neonatal positiva deve ser um sinal de alerta ao pediatra para o diagnóstico de FC, mas, muitas vezes, trata-se de falso-positivo. O tratamento é complexo e deve ser feito em centro de referência, por equipe multiprofissional. Manter bom estado nutricional, associado a bom controle da doença pulmonar, utilizando-se das inúmeras terapêuticas hoje existentes possibilita melhor prognóstico e sobrevida. Diversas novas perspectivas terapêuticas se encontram em estudo, possibilitando melhor prognóstico, melhor qualidade de vida e possivelmente, em alguns anos, a cura da doença...

A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study / El impacto de primer ano de tratamiento con dornasa alfa en los parametros clinicos de pacientes con fibrosis quistica: resultado de estudio brasileno multicentrico / O impacto de primeiro ano de tratamento com dornase alfa nos parametros clinicos de pacientes com fibrose cistica: estudo multicentrico brasileiro

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 ...

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 ...

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 ...

A first-year dornase alfa treatment impact on clinical parameters of patients with cystic fibrosis: the Brazilian cystic fibrosis multicenter study.

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 (VEF(1)), in forced vital capacity (FVC), in oxygen saturation (SpO(2)), 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.

Six minute walk test Z score: correlations with cystic fibrosis severity markers.

BACKGROUND: The six-minute-walk-test (6MWT) has been increasingly used in cystic fibrosis (CF) patients. However, few studies in children have correlated 6MWT with current parameters used to evaluate CF severity. Moreover, no study transformed the values of distance walked from meters into Z scores to avoid bias like age and gender, which are sources of 6MWT variability. METHODS: A cross-sectional descriptive study was performed to analyze the correlations (Spearman) among forced expiratory volume in one second (FEV(1)), body mass index (BMI), chest radiography (CXR), chest tomography (CT), and 6MWT Z score (Z-6MWT). Clinically stable CF patients, aged 6-21 years, were included. RESULTS: 34 patients, 14F/20M, mean age 12.1±4.0 years were studied. The mean Z-6MWT was -1.1±1.106. The following correlations versus Z-6MWT were found: FEV(1) (r=0.59, r(2)=0.32, p=0.0002), BMI Z score (r=0.42, r(2)=0.17, p=0.013), CXR (r=0.34, r(2)=0.15, p=0.0472) and CT (r=-0.45, r(2)=0.23, p=0.0073). CONCLUSIONS: In conclusion there was a significant, but poor, correlation between the six minute walk test Z score and the cystic fibrosis severity markers currently in use.

Shwachman-Kulczycki score still useful to monitor cystic fibrosis severity.

INTRODUCTION: The Shwachman-Kulczycki score was the first scoring system used in cystic fibrosis to assess disease severity. Despite its subjectivity, it is still widely used. OBJECTIVE: To study correlations among forced expiratory volume in one second (FEV1), chest radiography, chest computed tomography, 6-minute walk test, and Shwachman-Kulczycki score in patients with cystic fibrosis and to test whether the Shwachman-Kulczycki score is still useful in monitoring the severity of the disease. METHODS: A cross-sectional prospective study was performed to analyze the correlations (Spearman). Patients with clinically stable cystic fibrosis, aged 3-21 years, were included. RESULTS: 43 patients, 19F/24M, mean age 10.5 + 4.7 years, with a median Shwachman-Kulczycki score of 70 were studied. The median Brasfield and Bhalla scores were 17 and 10, respectively. The mean Z score for the 6-minute walk test was -1.1 + 1.106 and the mean FEV1 was 59 + 26 (as percentage of predicted values). The following significant correlations versus the Shwachman-Kulczycki score were found: FEV1 (r = 0.76), 6-minute walk test (r = 0.71), chest radiography (r = 0.71) and chest computed tomography (r = -0.78). When patients were divided according to FEV1, a statistically significantly correlation with the Shwachman-Kulczycki score was found only in patients with FEV1 <70% (r = 0.67). CONCLUSIONS: The Shwachman-Kulczycki score remains an useful tool for monitoring the severity of cystic fibrosis, adequately reflecting the functional impairment and chest radiography and tomography changes, especially in patients with greater impairment of lung function. When assessing patients with mild lung disease its limitations should be considered and its usefulness in such patients should be evaluated in larger populations.

Shwachman-Kulczycki score still useful to monitor cystic fibrosis severity

INTRODUCTION: The Shwachman-Kulczycki score was the first scoring system used in cystic fibrosis to assess disease severity. Despite its subjectivity, it is still widely used. OBJECTIVE: To study correlations among forced expiratory volume in one second (FEV1), chest radiography, chest computed tomography, 6-minute walk test, and Shwachman-Kulczycki score in patients with cystic fibrosis and to test whether the Shwachman-Kulczycki score is still useful in monitoring the severity of the disease. METHODS: A cross-sectional prospective study was performed to analyze the correlations (Spearman). Patients with clinically stable cystic fibrosis, aged 3-21 years, were included. RESULTS: 43 patients, 19F/24M, mean age 10.5 + 4.7 years, with a median Shwachman-Kulczycki score of 70 were studied. The median Brasfield and Bhalla scores were 17 and 10, respectively. The mean Z score for the 6-minute walk test was -1.1 + 1.106 and the mean FEV1 was 59 + 26 (as percentage of predicted values). The following significant correlations versus the Shwachman-Kulczycki score were found: FEV1 (r = 0.76), 6-minute walk test (r = 0.71), chest radiography (r = 0.71) and chest computed tomography (r = -0.78). When patients were divided according to FEV1, a statistically significantly correlation with the Shwachman-Kulczycki score was found only in patients with FEV1 <70 percent (r = 0.67). CONCLUSIONS: The Shwachman-Kulczycki score remains an useful tool for monitoring the severity of cystic fibrosis, adequately reflecting the functional impairment and chest radiography and tomography changes, especially in patients with greater impairment of lung function. When assessing patients with mild lung disease its limitations should be considered and its usefulness in such patients should be evaluated in larger populations.

Dornase alfa improves the health-related quality of life among Brazilian patients with cystic fibrosis--a one-year prospective study.

SUMMARY BACKGROUND: Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction. PATIENTS AND METHODS: One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T(0)), and at 3 (T(1)), 6 (T(2)), 9 (T(3)), and 12 (T(4)) months of follow-up. Eighteen patients were excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis. RESULTS: After 1 year of follow-up, there was significant improvement in respiratory symptoms (T(4) - T(0) = 8.1; 95% confidence interval (95% CI) = [2.1;14.0]; effect size (ES) = 0.35; P < 0.001), Emotional Functioning (T(4) - T(0) = 5.6; 95% CI = [1.1;10.1]; ES = 0.31; P < 0.05), Social Functioning (T(4) - T(0) = 6.0; 95% CI = [1.3;11.7]; ES = 0.31; P < 0.05), Body Image (T(4) - T(0) = 11.9; 95% CI = [4.1;19.7]; ES = 0.42; P < 0.05), and Treatment Burden (T(4) - T(0) = 5.3; 95% CI = [0.3;10.3]; ES = 0.24; P < 0.05) domains in the younger group. A significant improvement in Role Functioning (T(4) - T(0) = 6.1; 95% CI = [1.1;11.1]; ES = 0.40; P < 0.05), Body Image (T(4) - T(0) = 12.6; 95% CI = [3.5;21.7]; ES = 0.46; P < 0.05), and Weight (T(4) - T(0) = 11.7; 95% CI = [1.8;21.6]; ES = 0.40; P < 0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T(4) - T(0) = 5.5; 95% CI = [1.5;9.4]; ES = 0.30; P < 0.05), Respiratory Symptoms (T(4) - T(0) = 7.6; 95% CI = [3.9;11.4]; ES = 0.48; P < 0.05), and Weight (T(4) - T(0) = 10.1; 95% CI = [1.6;18.6]; ES = 0.26; P < 0.05) domains. CONCLUSION: The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment.

Emergência de Enterococcus faecium resistente à vancomicina em paciente com fibrose cística e infecção crônica por Staphylococcus aureus resistente à meticilina após tratamento com vancomicina inalatória / Emergence of vancomycin-resistant Enterococcus faecium after use of inhaled vancomycin in a cystic fibrosis patient chronically infected with methicillin-resistant Staphylococcus aureus

Os autores descrevem um caso de emergência de patógenos multiresistentes em paciente com fibrose cística tratada com vancomicina inalada. Paciente do sexo feminino de dez anos de idade, com fibrose cística cronicamente infectada por Staphylococcus aureus resistente à meticilin, com piora progressiva da doença pulmonar. Foi submetida a tratamento com vancomicina por via inalatória com melhora clínica, mas o complexo B. cepacia foi isolado no escarro e Enterococcus faecium resistente à vancomicina, em cultura de swab retal durante o tratamento. Os autores concluíram que o uso da vancomicina por via inalatória deve ser evitado em pacientes com fibrose cística, pois isso pode contribuir com o aparecimento de Enterococcus sp. resistente à vancomicina e, portanto, aumentar o risco de aparecimento de cepas de Staphylococcus aureus resistente à vancomicina.

Caso clínico: síndrome de Kartagener / Kartagener syndrome: case report / La síndrome de Kartagener: relato de caso

Objetivo: descrever um caso da síndrome de Kartagener e alertar os pediatras para o diagnóstico da discinesia ciliar primária. Relato do caso:paciente de 17 anos, sexo feminino, que apresentava desde o primeiro ano de vida, tosse, secreção nasal, otorréia, sibilância e 15 episódios de pneumonia. Os exames de imagem mostraramsinusopatia maxilar bilateral, situs inversus totalis, bronquiectasias nas bases pulmonares, áreas de condensação e bronquiolectasias difusas com aspecto de “árvore em brotamento”. A espirometria mostrou distúrbio obstrutivo leve, sem resposta a broncodilatador. As duas dosagensde cloro no suor e as imunoglobulinas séricas foram normais. O teste de triagem para avaliação do transporte mucociliar (teste da sacarina)teve resultado alterado (40 min), caracterizando a discinesia ciliar. Com base nesse resultado, a presença de situs inversus, bronquiectasias e sinusopatia crônica, foi estabelecido o diagnóstico da síndrome de Kartagener. Conclusão: a suspeita de discinesia ciliar é facilitada quando ocorre o situs inversus, o que caracteriza a síndrome de Kartagener. Porém, deve-se atentar para o fato de que a maioria dos casos de discinesia ciliar não têm essa má formação associada.

Objective: to describe a case of Kartagener syndrome and alert pediatricians for the diagnosis of primary ciliary dyskinesia. Case report:a 17 year-old patient, female, presented since her first year of life cough, nasal secretion, otorrhea, sibilance and 15 episodes of pneumonia. Image exams have shown bilateral maxillary sinusopathy, situs inversus totalis, bronchiectasis at pulmonary bases, condensation areas and diffuse bronchiolectasis with “sprouting tree”aspect. The spirometry shown a light obstructive disorder without response to bronchodilator. Two chlorine exams in the sweat and the seric immunoglobulin were normal. The test to evaluatethe mucociliary transport (saccharin test) had altered result (40 minutes), characterizing the ciliary dyskinesia. Based on this result, and the presence of situs inversus, bronchiectasis and chronic sinusopathy, the diagnosis of Kartagener syndrome was established. Conclusion: the suspicion of ciliary dyskinesia is easier when a situs inversus, is found, which characterizes the Kartagener syndrome. However, it shall be no ticed that most of the ciliary dyskinesia cases does not present this malformation associated.

Objetivo: discrebir un caso síndrome de Kartagener y alertar los pediatras para el diagnostico de discinesia ciliar primaria. Relato del caso: una paciente de 17 años, presentaba desde el primeraño de vida toss, secreción nasal, otorrea, sibilancia em el pecho, con histórico de 15 episodios de neumonia. Los exames auxiliares de imagen mostaran sinusitis maxilar bilateral, situs inversus totalis, bronquiectasias nas bases pulmonares,áreas de condensación y ronquiectasias difusas, com aspecto de arbol en brote. La espirometria mostro distúrbio obstrutivo pequeño sin respuestaa lo broncodilatador. Los niveles de cloro en el suor y de las inmunoglobulinas sericas fuerannormales. Lo testigo de triage para evaluar el transporte mucociliar con sacarina tubo resultado alterado (40 minutos), caracterizando el diagnosticode síndrome de Kartagener. Conclusión: la sospecha de discinesia ciliar es facilitada cuando hay el situs inversus, que es caracteristico de la síndrome de Kartagener. Pero, es necessário atentara que circa de la mitad de los casos de discinesia ciliar non tiene esta ma-formación.

Discinesia ciliar primária: quando o pediatra deve suspeitar e como diagnosticar?: [revisão] / Primary ciliary dyskinesia: when the pediatrician must suspect and how to do the diagnosis?: [review]

OBJETIVO: Revisar a discinesia ciliar primária (DCP) quanto aos seus aspectos ultra-estruturais, discriminar os defeitos ciliares primários dos secundários, descrever o quadro clínico, os testes laboratoriais de triagem e de diagnóstico disponíveis, bem como seu manejo clínico. FONTE DE DADOS: Pesquisa nas bases de dados Medline, Lilacs e SciELO, no período de 1980 a 2007. SÍNTESE DOS DADOS: A DCP é uma doença autossômica recessiva que compromete a estrutura e/ou a função ciliar e, conseqüentemente, o transporte mucociliar. As manifestações clínicas envolvem o trato respiratório superior e inferior, com infecções recorrentes do ouvido médio, seios paranasais e pulmonares, que podem evoluir para bronquiectasias. Outras manifestações incluem situs inversus totalis e infertilidade masculina. O diagnóstico deve ser suspeitado pelos pediatras em várias situações: recém-nascidos de termo com desconforto respiratório sem causa aparente; neonatos portadores de dextrocardia; lactentes com tosse persistente e/ou infecções otorrinolaringológicas de repetição, excluindo-se as imunodeficiências e a fibrose cística; crianças com asma atípica e as com bronquiectasias sem causa definida. Os testes de triagem diagnóstica são os da sacarina e do óxido nítrico nasal. As avaliações do defeito ultra-estrutural e funcional exigem análise por microscopia eletrônica e da freqüência e formato da onda de batimento ciliar. CONCLUSÕES: A DCP, apesar da baixa prevalência, é pouco diagnosticada pelas dificuldades de estabelecer o diagnóstico definitivo do defeito ciliar devido à complexidade da investigação laboratorial e pela falta de reconhecimento da doença pelos médicos. A suspeita clínica e o diagnóstico precoce são fundamentais para reduzir a morbidade e prevenir o desenvolvimento de complicações.

OBJECTIVE: To review primary ciliary dyskinesia (PCD) and its ultrastructural aspects, to differentiate primary from secondary ciliary defects and to describe the clinical features, screening and diagnostic laboratorial tests, and the clinical management of this disorder. DATA SOURCES: A bibliographical search was obtained from Medline, Lilacs and SciELO databases, from 1980 to 2007. DATA SYNTHESIS: PCD is an autossomic recessive disorder with abnormal structure and/or function of the cilia, leading to reduced mucociliary clearance. The clinical manifestations include upper and lower respiratory tracts, with recurrent ear, sinus and lung infections that may progress to bronchiectasis. Situs inversus and male infertility are other clinical features of this disorder. PCD should be suspected by pediatricians in the following clinical situations: full term neonates with respiratory distress without apparent causes, presence of dextrocardia, infants with chronic cough and/or recurrent upper airways infections in the absence of immunodeficiency and cystic fibrosis, children with atypical asthma and bronchiectasis without a definitive cause. The diagnostic screening tests are the saccharine and nasal nitric oxide tests. Functional and ultrastructural evaluations demand an electronic microscopic analysis and the observation of the frequency and the pattern of the ciliary movement. CONCLUSIONS: Although the prevalence of PCD is low, the difficulties in establishing the diagnosis due to the complex investigations demanded and the unfamiliarity of the disease by physicians lead to underdiagnosis. Early diagnosis and treatment of PCD are essential to reduce the morbidity and to avoid complications.

Cystic fibrosis with normal sweat chloride concentration--case report.

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion of cystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10 kb C-->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels.

Cystic fibrosis with normal sweat chloride concentration: case report

Cystic fibrosis is a genetic disease usually diagnosed by abnormal sweat testing. We report a case of an 18-year-old female with bronchiectasis, chronic P. aeruginosa infection, and normal sweat chloride concentrations who experienced rapid decrease of lung function and clinical deterioration despite treatment. Given the high suspicion ofcystic fibrosis, broad genotyping testing was performed, showing a compound heterozygous with deltaF508 and 3849+10kb C->T mutations, therefore confirming cystic fibrosis diagnosis. Although the sweat chloride test remains the gold standard for the diagnosis of cystic fibrosis, alternative diagnostic tests such as genotyping and electrophysiologic measurements must be performed if there is suspicion of cystic fibrosis, despite normal or borderline sweat chloride levels

Teste de sacarina em crianças / The saccharin test (ST) in children

O teste de sacarina é um método simples, reprodutível e de baixo custo que avalia o transporte mucociliar nasal. É usado como triagem diagnóstica na discinesia ciliar primária. Objetivo do estudo - Estabelecer valores médios para o teste de sacarina em populaçäo de crianças brasileiras aparentemente normais e compará-los com os citados na literatura. Local - A pesquisa foi realizada em duas escolas de Säo Paulo, SP. Participantes - Duzentos e trinta e oito crianças (134 M/104f), entre 10,8 e 16,8 anos, foram estudadas após autorizaçäo familiar e após preenchimento de questionário sobre antecendentes alérgicos, doenças respiratórias e tabagismo passivo. Resultados - Após análise dos questionários a populaçäo...