Description of rare mutations and a novel variant in Brazilian patients with Cystic Fibrosis: a case series from a referral center in the Bahia State.

Knowledge of the genetic profile of Cystic Fibrosis (CF) contributes to a better understanding of the genotype/phenotype relationship, particularly in mixed populations such as in Brazil. To describe clinical data of CF patients with rare or not yet observed CFTR gene mutations in Brazil. It was a case series of CF patients followed-up at a referral center. Clinical and laboratory data were obtained through medical records. Molecular analysis of the mutations was performed by conventional methods and/or by next-generation sequencing. Ten patients were studied, seven had five pathogenic mutations without previous description in Brazil (Q1100P, Y109C, A107P, E1409K and K162E), one of which has not yet been reported in patients with CF (A107P). Among the seven patients, three (two siblings) had the second mutant allele of rare occurrence among Brazilians patients (G1069R and 2307insA). Three other patients also had at least one rare variant (V201M, S466X and G1069R). The age of the CF diagnosis ranged from 1 to 190 months in the ten cases and the main clinical manifestations were respiratory symptoms and difficulty in gaining weight. All but one patient presented clinical and/or laboratory data compatible with pancreatic insufficiency. The identification of rare or not yet described CFTR mutations in patients with CF in Brazil highlights the high genetic heterogeneity in this population. Knowledge of the genotypic profile of Brazilian CF patients can contribute to the development of specific mutation panels for the genetic investigation targeting each region of the country, as well as helping to understand the complex genotype/phenotype relationship, especially in mixed populations.

Celiac Disease and Cystic Fibrosis: Challenges to Differential Diagnosis.

Cystic fibrosis and celiac disease were considered a single clinical entity for many years. Differentiation between the diseases occurred some time in the 1930s of the 20th Century. Both diseases may present the intestinal malabsorption syndrome and similar clinical manifestations that contribute to difficulties with clinical distinction. We describe a report of two patients with initial diagnosis of cystic fibrosis, who were subsequently diagnosed with celiac disease. These case reports emphasize the possibility of false positivity being shown in the sweat test in CD, which may result in delayed diagnosis and inadequate management of this disease.

Infectious etiology and indicators of malabsorption or intestinal injury in childhood diarrhea. / Etiología infecciosa e indicadores de malabsorción o daño intestinal en diarrea infantil

INTRODUCTION: The multifactorial etiology of gastroenteritis emphasizes the need for different laboratory methods to identify or exclude infectious agents and evaluate the severity of diarrheal disease. OBJECTIVE: To diagnose the infectious etiology in diarrheic children and to evaluate some fecal markers associated with intestinal integrity. MATERIALS AND METHODS: The study group comprised 45 children with diarrheal disease, tested for enteropathogens and malabsorption markers, and 76 children whose feces were used for fat evaluation by the traditional and acid steatocrit tests. RESULTS: We observed acute diarrhea in 80% of the children and persistent diarrhea in 20%. Of the diarrheic individuals analyzed, 40% were positive for enteropathogens, with rotavirus (13.3%) and Giardia duodenalis (11.1%) the most frequently diagnosed. Among the infected patients, occult blood was more evident in those carrying pathogenic bacteria (40%) and enteroviruses (40%), while steatorrhea was observed in infections by the protozoa G. duodenalis (35.7%). Children with diarrhea excreted significantly more lipids in feces than non-diarrheic children, as determined by the traditional (p<0.0003) and acid steatocrit (p<0.0001) methods. Moreover, the acid steatocrit method detected 16.7% more fecal fat than the traditional method. CONCLUSIONS: Childhood diarrhea can lead to increasingly severe nutrient deficiencies. Steatorrhea is the hallmark of malabsorption, and a stool test, such as the acid steatocrit, can be routinely used as a laboratory tool for the semi-quantitative evaluation of fat malabsorption in diarrheic children.

Introducción. La etiología multifactorial de la gastroenteritis enfatiza la necesidad de usar diferentes métodos de laboratorio para identificar o excluir agentes infecciosos y evaluar la gravedad de la enfermedad diarreica. Objetivo. Diagnosticar la etiología infecciosa de la diarrea en niños y evaluar algunos marcadores fecales asociados con la integridad intestinal. Materiales y métodos. Se estudiaron 45 niños con enfermedad diarreica, en los cuales se evaluaron la presencia de enteropatógenos y los marcadores de malabsorción. Se analizaron las muestras fecales de 76 niños, mediante las pruebas de esteatocrito tradicional y esteatocrito ácido, para la cuantificación de la grasa. Resultados. Se observó diarrea aguda en el 80 % de los niños y diarrea persistente en el 20 %. De los individuos con diarrea, el 40 % fue positivo para enteropatógenos; los más diagnosticados fueron rotavirus (13,3 %) y Giardia duodenalis (11,1 %). Entre los pacientes infectados, la sangre oculta fue más evidente en aquellos portadores de bacterias patógenas (40 %) o enterovirus (40%), mientras que la esteatorrea se observó en infecciones por el protozoo G. duodenalis (35,7 %). Los niños con diarrea excretaron significativamente más lípidos en las heces que aquellos sin diarrea, según lo determinado por los métodos de esteatocrito tradicional (p<0,0003) y esteatocrito ácido (p<0,0001). Conclusiones. La diarrea infantil puede provocar deficiencias graves de nutrientes. La esteatorrea es distintiva de la malabsorción intestinal y puede detectarse mediante la estimación del esteatocrito ácido. Esta prueba podría utilizarse de forma rutinaria como una herramienta de laboratorio para la evaluación semicuantitativa de la malabsorción de grasas en niños con diarrea.

Five-year performance analysis of a cystic fibrosis newborn screening program in northeastern Brazil.

OBJECTIVE: To analyze the performance of the cystic fibrosis (CF) newborn screening (NBS) program over its first five years in a Brazilian northeastern state. METHOD: A population-based study using a screening algorithm based on immunoreactive trypsinogen (IRT)/IRT. Data were retrieved from the state referral screening center registry. The program performance was evaluated using descriptive indicators such as the results of an active search, coverage, newborn's age at the time of blood sampling, the time between sample collection and its arrival at the laboratory, and the child's age at diagnosis of disease. RESULTS: The public CF screening program covered 82.6% of the 1,017,576 births that occurred, with an accumulated five-year incidence of 1:20,767 live births. The median (25th-75th) age at diagnosis was 3.5 (2.3-7.3) months. The sampling before 7 days of life for the first IRT (IRT1) increased between 2013 and 2017 from 42.2 to 48.3%. Around 5% of IRT1 samples and 30% of the second samples were collected after 30 days of life. In the first and second stages of screening, 23.6% and 19.9% of the infants, respectively, were lost to follow-up. In both stages of screening, the samples were retained at the health units for a median (25th-75th) of 9.0 (7.0-13.0) days. CONCLUSIONS: The coverage by the CF-NBS program was satisfactory as compared to other Brazilian state rates and the percentage of IRT1 samples collected within the first week of life increased progressively. However, time of samples retention at the health units, inappropriate sampling, inherent methodological problems, and loss of follow-up need to improve.

Telehealth for children and adolescents with chronic pulmonary disease: systematic review.

OBJECTIVE: To revise the impact of telehealth on the quality of life, reduction in pulmonary exacerbations, number of days using antibiotics, adherence to treatment, pulmonary function, emergency visits, hospitalizations, and the nutritional status of individuals with asthma and cystic fibrosis. DATA SOURCE: Four databases were used, MEDLINE, LILACS, Web of Science and Cochrane, as well as manual searches in English, Portuguese and Spanish. Randomized clinical trials, published between January 2010 and December 2020, with participants aged 0 to 20 years, were included. DATA SYNTHESIS: Seventy-one records were identified after the removal of duplicates; however, twelve trials were eligible for synthesis. Included trials utilized: mobile phone applications (n=5), web platforms (n= 4), mobile telemedicine unit (n=1), software with an electronic record (n=1), remote spirometer (n=1), and active video games platform (n=1). Three trials used two tools, including telephone calls. Among the different types of interventions, improvement in adherence, quality of life, and physiologic variables were observed for mobile application interventions and game platforms compared to usual care. Visits to the emergency department, unscheduled medical appointments, and hospitalizations were not reduced. There was considerable heterogeneity among studies. CONCLUSIONS: The findings suggest that better control of symptoms, quality of life, and adherence to treatment can be attributed to the technological interventions used. Nevertheless, further research is needed to compare telehealth with face-to-face care and to indicate the most effective tools in the routine care of children with chronic lung diseases.

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

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

Human bocavirus in very young infants hospitalized with acute respiratory infection in northeast Brazil.

A cross-sectional study was carried out over a period of 12 months to investigate the occurrence of human bocavirus (HBoV) infection in infants hospitalized for respiratory infections in a teaching hospital in Salvador, Brazil, and to describe the clinical manifestations of this infection. Nasopharyngeal aspirates were collected from the children and immunofluorescence and polymerase chain reaction were performed to investigate the presence of respiratory viruses. HBoV was detected in 4 out of 66 patients. Two of the HBoV-positive infants were co-infected with other viruses. The principal clinical findings in HBoV-positive children were: nasal obstruction, catarrh, cough, fever and dyspnea. This study revealed HBoV infection in children aged <2 months, suggesting that the infection may occur at a very early age.

TREATMENT ADHERENCE AMONG CHILDREN AND ADOLESCENTS IN A CYSTIC FIBROSIS REFERENCE CENTER.

OBJECTIVE: To evaluate the level of self-referenced treatment adherence (TA) and its association with clinical and sociodemographic variables in patients with cystic fibrosis assisted at a reference center, as well as compare the level of self-referenced TA with that presumed by the multidisciplinary team. METHODS: This is a cross-sectional study that included children and adolescents aged between 0-20 years with cystic fibrosis. Adolescents older than 14 years or their guardians, when younger than 14 years old, were interviewed using a standardized questionnaire. Professionals from the multidisciplinary clinic filled out another form with their impressions of the patients' TA. Clinical and laboratory data were obtained in the medical records. The TA was considered satisfactory if the total adherence index (TAI) was equal or higher than 80%. RESULTS: 53 patients were included with a median age of 112 months. The mean TAI was 83.2%. The mean TAIs for dornase alfa, pancreatic enzymes, continued use of inhaled tobramycin, vitamins supplements, nutritional supplements and dietary orientation was respectively: 86.1; 96.6; 78.6; 88.1; 51.8 and 78%. Children younger than 14 years presented better TA (p=0.021). The correlation between the self-referenced TA and the one presumed by the multidisciplinary team ranged from 0,117 to 0.402, being higher for Psychology and Nutrition professionals. CONCLUSIONS: The TAI was high particularly among children younger than 14 years. There was a positive correlation between the self-referenced TA and the one presumed by the Psychology (p=0.032) and the nutrition (p=0.012) professionals.

Reference values for spirometry in Brazilian children.

OBJECTIVE: To generate reference values for spirometry in Brazilian children 3-12 years of age and to compare those values with the values employed in the equations currently in use in Brazil. METHODS: This study involved healthy children, 3-12 years of age, recruited from 14 centers (primary data) and spirometry results from children with the same characteristics in six databases (secondary data). Reference equations by quantile regressions were generated after log transformation of the spirometric and anthropometric data. Skin color was classified as self-reported by the participants. To determine the suitability of the results obtained, they were compared with those predicted by the equations currently in use in Brazil. RESULTS: We included 1,990 individuals from a total of 21 primary and secondary data sources. Of those, 1,059 (53%) were female. Equations for FEV1, FVC, the FEV1/FVC ratio, FEF between 25% and 75% of the FVC (FEF25-75%) and the FEF25-75%/FVC ratio were generated for white-, black-, and brown-skinned children. The logarithms for height and age, together with skin color, were the best predictors of FEV1 and FVC. The reference values obtained were significantly higher than those employed in the equations currently in use in Brazil, for predicted values, as well as for the lower limit of normality, particularly in children with self-reported black or brown skin. CONCLUSIONS: New spirometric equations were generated for Brazilian children 3-12 years of age, in the three skin-color categories defined. The equations currently in use in Brazil seem to underestimate the lung function of Brazilian children 3-12 years of age and should be replaced by the equations proposed in this study.

Cystic fibrosis: when neonatal screening is unsatisfactory for early diagnosis / Fibrose cística: quando a triagem neonatal é insatisfatória para o diagnóstico precoce

Abstract Introduction: cystic fibrosis newborn screening must enable its earlier diagnosis, which may enhance outcomes. This study was a series case of delayed-diagnosis children submitted to cystic fibrosis newborn screening. Description: fourteen children were included; eight (57.1%) were due to false-negative screening, while six (42.9%) were due to processing errors. Two samples collected after 30 days of life were incorrectly classified as negative, and four infants with a positive test could not be located due to screening processing errors. Cystic fibrosis diagnosis was confirmed at a median (IQR) age of 5.3 (4.2-7.4) months. Poor nutritional status was the most prevalent clinical sign at diagnosis, being present in 78.6% of infants. The mean (SD) weight-for-length and length-for-age Z-scores were -3.46 (0.84) and -3.99 (1.16), respectively. Half of the children had Pseudo-Bartter syndrome, and 42.9% had breathing difficulties. Twelve children (85.7%) required hospitalization, with a median (IQR) length of stay of 17.0 (11.5-26.5) days. Discussion: newborn screening had some faults, from incorrect collections to inefficient active search. Early identification of these children in which screening was unsatisfactory is essential, emphasizing the importance and efforts to not miss them. In the case of a failed test, healthcare professionals must be prepared to recognize the main symptoms and signs of the disease.

Resumo Introdução: a triagem neonatal para fibrose cística deve contribuir para diagnóstico precoce e melhor prognóstico da doença. O estudo é uma série de casos com lactentes submetidos à triagem, porém com diagnóstico tardio da doença. Descrição: quatorze crianças foram incluídas; oito (57,1%) com triagem falso-negativo e seis (42,9%) com erros processuais na triagem neonatal. Duas amostras foram coletadas tardiamente, sendo incorretamente classificadas como negativas e quatro lactentes com triagem positiva não foram localizados, por erros na busca ativa. Confirmou-se o diagnóstico da fibrose cística com idade mediana (IIQ) de 5,3 (4,2-7,4) meses. O Comprometimento nutricional precoce foi o sinal clínico mais prevalente ao diagnóstico, presente em 78,6% das crianças. Os Z escores médios (SD) do peso para altura e altura para idade foram -3,46 (0,84) e -3,99 (1,16), respectivamente. Metade das crianças teve síndrome de Pseudo-Bartter e 42,9% dificuldade respiratória. Doze crianças (85,7%) precisaram hospitalização com tempo mediano de permanência de 17 dias. Discussão: a triagem neonatal para fibrose cística apresentou falhas, desde testes falso-negativos, coletas incorretas, até problemas com a busca ativa. Entretanto, o diagnóstico ágil é essencial e os profissionais de saúde devem reconhecer os sintomas e sinais precoces da doença, mesmo quando a triagem neonatal não for satisfatória.

[Impact of hospitalization on breastfeeding practices in a pediatric hospital in Salvador, Bahia State, Brazil]. / Impacto da internação na prática do aleitamento materno em hospital pediátrico de Salvador, Bahia, Brasil.

This cross-sectional study enrolled 97 inpatients at a teaching hospital in Salvador, Bahia, Brazil, to determine breastfeeding prevalence in infants less than 4 months of age hospitalized due to respiratory infection, and to evaluate the impact of hospitalization on breastfeeding. Patients' mothers were interviewed, and a standardized questionnaire was completed. After hospital discharge, medical records were reviewed and information on the infant's feeding practices during hospitalization was recorded. Exclusive breastfeeding was observed in 57.1% of patients, but it was interrupted in 35.4%, with the introduction of infant formula during hospitalization. Mean duration was not associated with the introduction of complementary feeding in the hospital. In the bivariate analysis, early interruption of exclusive breastfeeding was associated with higher maternal schooling and lower family income. Prevalence of exclusive breastfeeding was low. Hospitalization contributed to early interruption of exclusive breastfeeding in 35.4% of infants, possibly due to inadequate hospital infrastructure and insufficient support from health professionals to maintain exclusive breastfeeding.

Hepatobiliary disease in children and adolescents with cystic fibrosis.

OBJECTIVES: The aims of the study were to determine the frequency of hepatobiliary disease in patients with cystic fibrosis and to describe the sociodemographic, clinical, and laboratory profile of these patients. METHODS: This was a retrospective, descriptive, and analytical study of 55 patients diagnosed with cystic fibrosis, aged between 3 months and 21 years, followed-up from January 2008 to June 2016 in a referral center. Medical records were consulted and sociodemographic, clinical and laboratory data, including hepatobiliary alterations, imaging studies, genetic studies, liver biopsies, and upper digestive endoscopies were registered. RESULTS: Hepatobiliary disease was diagnosed in 16.4% of the patients and occurred as an initial manifestation of cystic fibrosis in 55.6% of these cases. The diagnosis of hepatopathy occurred before or concomitantly with the diagnosis of cystic fibrosis in 88.9% of the children. All patients with hepatobiliary disease were considered non-white, with a predominance of females (77.8%) and median (IQR) of 54 (27-91) months. Compared with the group without hepatobiliary disease, children with liver disease had a higher frequency of severe mutations identified in the CFTR gene (77.8% vs. 39.6%, p=0.033) and severe pancreatic insufficiency (88.9% vs. 31.6%, p=0.007). CONCLUSION: The frequency of hepatobiliary disease was high, with a very early diagnosis of the disease and its complications in the studied series. A statistical association was observed between the occurrence of hepatobiliary disease and the presence of pancreatic insufficiency and severe mutations in the CFTR gene. It is emphasized that cystic fibrosis is an important differential diagnosis of liver diseases in childhood.

Telehealth for children and adolescents with chronic pulmonary disease: systematic review / Telessaúde para crianças e adolescentes com doenças pulmonares crônicas: revisão sistemática

Abstract Objective: To revise the impact of telehealth on the quality of life, reduction in pulmonary exacerbations, number of days using antibiotics, adherence to treatment, pulmonary function, emergency visits, hospitalizations, and the nutritional status of individuals with asthma and cystic fibrosis. Data source: Four databases were used, MEDLINE, LILACS, Web of Science and Cochrane, as well as manual searches in English, Portuguese and Spanish. Randomized clinical trials, published between January 2010 and December 2020, with participants aged 0 to 20 years, were included. Data synthesis: Seventy-one records were identified after the removal of duplicates; however, twelve trials were eligible for synthesis. Included trials utilized: mobile phone applications (n=5), web platforms (n= 4), mobile telemedicine unit (n=1), software with an electronic record (n=1), remote spirometer (n=1), and active video games platform (n=1). Three trials used two tools, including telephone calls. Among the different types of interventions, improvement in adherence, quality of life, and physiologic variables were observed for mobile application interventions and game platforms compared to usual care. Visits to the emergency department, unscheduled medical appointments, and hospitalizations were not reduced. There was considerable heterogeneity among studies. Conclusions: The findings suggest that better control of symptoms, quality of life, and adherence to treatment can be attributed to the technological interventions used. Nevertheless, further research is needed to compare telehealth with face-to-face care and to indicate the most effective tools in the routine care of children with chronic lung diseases.

RESUMO Objetivo: Revisar o impacto da telessaúde na qualidade de vida, redução das exacerbações pulmonares, número de dias em uso de antibióticos, adesão ao tratamento, função pulmonar, visitas à emergência, hospitalizações e estado nutricional de indivíduos com asma e fibrose cística. Fontes de dados: Foram utilizadas quatro base de dados, sendo, MEDLINE, LILACS, Web of Science e Cochrane, além de pesquisas manuais nos idiomas inglês, português e espanhol. Foram incluídos ensaios clínicos randomizados, publicados no período de janeiro de 2010 a dezembro de 2020, com participantes de 0 a 20 anos. Síntese dos dados: Setenta e um registros foram identificados após a remoção das duplicatas e doze estudos foram elegíveis para síntese. Os ensaios utilizaram aplicativos para celular (n=5), plataformas da web (n= 4), unidade de telemedicina móvel (n=1), software com registro eletrônico (n=1), espirômetro remoto (n=1) e plataforma ativa de videogames (n=1). Três ensaios utilizaram duas ferramentas, incluindo chamadas telefônicas. Entre os diferentes tipos de intervenções, observou-se melhora na adesão, qualidade de vida e de variáveis fisiológicas para intervenções de aplicativos móveis e plataformas de jogos em comparação com os cuidados habituais. Visitas ao pronto-socorro, consultas médicas não agendadas e internações não foram reduzidas. Houve considerável heterogeneidade entre os estudos. Conclusões: Os achados sugerem que a melhora do controle dos sintomas, da qualidade de vida e da adesão ao tratamento podem ser atribuídos às intervenções tecnológicas utilizadas. No entanto, mais pesquisas são necessárias para comparar a telessaúde com o atendimento presencial e indicar as ferramentas mais efetivas na rotina de cuidados à população infantil com doenças crônicas pulmonares.

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

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

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

Incidence and treatment of methicillin-resistant S. aureus infection in cystic fibrosis patients: a cohort study.

In Brazil the knowledge about methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients is scarce. This study aimed to determine the incidence of respiratory tract colonization and the identification rates after a standardized treatment. A retrospective cohort was performed highlighting the history of respiratory colonizations between January 2008 and June 2015. Patients under the age of 21 years with cystic fibrosis confirmed by sweat test or genetic study receiving care at the outpatient clinics of a Teaching Hospital were included. The treatment consisted of trimethoprim/sulfamethoxazole, rifampicin, nasal mupirocin and chlorhexidine 2%. The mean follow-up period was of 22.2 months and those with ≥3 negative cultures were considered free of methicillin-resistant Staphylococcus aureus. Forty-two patients were included. Methicillin-resistant Staphylococcus aureus was identified in six patients. Most patients had methicillin-sensitive S. aureus isolation prior to methicillin-resistant Staphylococcus aureus. Five children used the standardized treatment, none presented side effects. Only one child had a new isolation of methicillin-resistant Staphylococcus aureus during follow-up (after 20 months). The incidence of methicillin-resistant Staphylococcus aureus infection was high and occurred in young patients. The therapeutic regimen was effective, safe and being a good option to treat methicillin-resistant Staphylococcus aureus infection.

Perinatal tuberculosis: a diagnostic challenge.

Despite the high prevalence of tuberculosis in adults and children, the congenital and perinatal forms of tuberculosis are rare. In Brazil, there has been only one published case of congenital tuberculosis and two cases of the perinatal form of this disease. We report a case of perinatal tuberculosis presenting with pneumonia. Alcohol-acid-resistant bacilli were found in the gastric lavage. Diagnosis of this disease presentation requires a high index of suspicion.

Comparação de custos da terapia de reposição enzimática empírica com terapia guiada por diagnóstico laboratorial da insuficiência pancreática / Costs comparison of empirical enzymatic replacement therapy with laboratory diagnosis guided therapy of pancreatic insufficiency

Introdução: a fibrose cística, também conhecida como mucoviscidose, é uma doença genética cujas manifestações resultam da disfunção do gene cystic fibrosis transmembrane conductorance regulator. Cerca de 85% dos indivíduos com essa doença desenvolvem insuficiência pancreática exógena. Objetivo: comparar os custos da terapia de reposição enzimática empírica com a terapia de reposição enzimática empírica guiada pelo teste da elastase fecal, em indivíduos com fibrose cística, acompanhados em um centro de referência para assistência à doença. Metodologia: realizou-se um estudo descritivo e comparativo, que incluiu indivíduos de 0 a 21 anos, com fibrose cística. Coletaram-se dados referentes ao período de janeiro de 2016 a fevereiro de 2020, com registros clínicos, demográficos e laboratoriais. Inicialmente, com base em critérios clínicos, os participantes foram classificados como suficientes pancreáticos ou insuficientes pancreáticos. Após o resultado da dosagem da elastase fecal, o diagnóstico do status pancreático foi reavaliado. Realizouse a estimativa dos custos do teste da elas tase fecal por participante e da terapia por reposição enzimática empírica da insuficiência pancreática em indivíduos que, posteriormente, foram diagnostica dos como suficientes pancreáticos. Resultados: incluíram-se 50 participantes, com média de idade de 9,4 anos, sendo 52% do sexo masculino. Após o resultado da dosagem da elastase fecal, 7 participantes considerados insuficientes pancreáticos e foram reclassificados como suficientes pancreáticos. No período estudado, a economia média estimada, por participante suficiente pancreático, com a suspensão das enzimas, após resultado da elastase fecal, foi de R$ 6.770,13. Conclusão: a terapia de reposição enzimática empírica no tratamento da insuficiência pancreática pode levar a custos desnecessários. A medida de dosagem da elastase fecal contribui para decisão mais objetiva da avaliação da função pancreática.

Introduction: Cystic fibrosis, also known as mucoviscidosis, is a genetic disorder whose manifestations result from dysfunction of the cystic fibrosis transmembrane conductance regulator gene. About 85% of individuals with this disease develop exogenous pancreatic insufficiency. Objetivo: to compare the costs of empirical enzyme replacement therapy with fecal elastase test-guided empirical enzyme replacement therapy in individuals with cystic fibrosis followed up at a referral center for disease care. Methodology: a descriptive and comparative study was carried out, which included individuals aged 0 to 21 years, with cystic fibrosis. Data for the period from January 2016 to February 2020 were collected, with clinical, demographic and laboratory records. Initially, based on clinical criteria, participants were classified as pancreatic sufficient or pancreatic insufficient. After the result of the fecal elastase measurement, the diagnosis of pancreatic status was reassessed. Estimates were made of the costs of the fecal elastase test per participant and of the empiric enzyme replacement therapy for pancreatic insufficiency in individuals who were later diagnosed as pancreatic sufficient. Results: fifty participants were included, with a mean age of 9.4 years, 52% male. After the result of the fecal elastase measurement, 7 participants considered as pancreatic insufficient were reclassified as pancreatic sufficient. In the period studied, the estimated mean savings, per sufficient pancreatic participant, with the suspension of enzymes, after the result of fecal elastase, was R$ 6,770.13. Conclusion: empirical enzyme replacement therapy in the treatment of pancreatic insufficiency can lead to unnecessary costs. The measurement of fecal elastase dosage contributes to a more objective decision on the assessment of pancreatic function.

Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil.

Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.

A influência da idade e do genótipo sobre os níveis de cloreto do suor em uma população pediátrica com fibrose cística no estado da Bahia / The influence of age and genotype on sweat chloride levels in a pediatric population with cystic fibrosis in the state of Bahia

Introdução: a fibrose cística é a doença autossômica recessiva mais comum em populações caucasianas e a sua etiologia está associada a variantes patogênicas no gene CFTR. O teste do suor é considerado o padrão ouro para o diagnóstico dessa enfermidade. Estudos apontam que o genótipo do CFTR e a idade dos indivíduos influenciam as concentrações de cloreto no suor. Objetivos: pesquisar a correlação entre os níveis de cloreto no teste do suor e a idade ao diagnóstico de indivíduos com fibrose cística e comparar as concentrações iônicas do cloreto entre os sexos, diferentes faixas etárias e três grupos diversos de genótipos do CFTR. Metodologia: realizou-se um estudo de corte transversal, incluindo sujeitos de 0 a 20 anos, com diagnóstico confirmado de fibrose cística. Os indivíduos selecionados foram agrupados de acordo com as variáveis analisadas. Calcularam-se os valores descritivos das concentrações de íons cloreto de cada grupo. Utilizou-se o teste de Spearman para a análise da correlação entre a idade ao diagnóstico e os níveis de cloreto no suor. Resultados: 64 indivíduos foram incluídos no estudo, sendo 51,56% do sexo masculino. A mediana (Min ­ Max) da idade ao diagnóstico foi de 7 meses (1-206). Não foi observa da correlação entre a idade dos indivíduos ao diagnóstico e os níveis de cloreto no suor. As concentrações medianas de cloreto foram maiores nos escolares (106 mEq/l), no sexo feminino (102 mEq/l) e nos heterozigotos F508del/Classe I a III (108 mEq/l); e menores nos adolescentes (100 mEq/l) e nos heterozigotos F508del/Classes IV a VI (77 mEq/l). Conclusão: os níveis de cloreto no suor não apresentaram correlação com a idade dos indivíduos ao diagnóstico. A variação considerável dos níveis iônicos entre os grupos de diferentes genótipos corrobora que o teste do suor é um bom preditor da avaliação funcional do canal CFTR.

Introduction: cystic fibrosis is the most common autosomal recessive disorder in Caucasian populations and its etiology is associated with pathogenic variants in the CFTR gene. The sweat test is considered the gold standard for the diagnosis of the disease. Some studies suggest that CFTR genotype and age affect sweat chloride concentrations. Objectives: to investigate the correlation between sweat chloride levels and age at diagnosis of individuals with cystic fibrosis and to compare ionic chloride concentrations among sexes, different age groups and three distinct groups of CFTR genotypes. Methodology: a cross-sectional study was conducted, which included CF subjects from 0 to 20 years of age. The selected individuals were clustered on the variables in analysis. The description values for chloride ion concentrations in each group were calculated. The Spearman's test was used to analyze the correlation between the age at diagnosis and sweat chloride levels. Results: 64 individuals were included, 51,56% male. The median (Min ­ Max) age at diagnosis was 7 months (1-206). There was no correlation between the age at diagnosis and sweat chloride levels. The median of the chloride concentrations were higher for schoolchildren (106 mEq/l), females (102 mEq/l) and heterozygous F508del/Classes I to III (108 mEq/l), and reached the lowest values for teenagers (100 mEq/l) and heterozygous F508del/Classes IV to VI (77 mEq/l). Conclusion: sweat chloride levels did not correlate with the age of individuals at diagnosis. The substantial variation of ionic levels among groups of distinct genotypes corroborates that the sweat test is a good predictor for functional assessment of the CFTR channel.