Patient care in cystic fibrosis centers: a real-world analysis in Brazil.

OBJECTIVE: To analyze the characteristics of cystic fibrosis (CF) care centers (CFCCs) in Brazil. METHODS: A questionnaire was sent to the coordinators of all 51 registered CFCCs between May and September of 2021. RESULTS: The response rate was 100%. Southeastern Brazil is the region where most of the CFCCs in the country are located (21 centers; 41%), followed by the southern and northeastern regions (11 centers each; 21.5%), the central-western region (6; 12%), and the northern region (2; 4%). A total of 4,371 patients with CF were cared for in Brazil during the study period, ranging from 7 to 240 patients per center (mean, 86 patients/center; median, 75 patients/center); 2,197 patients (50%) were cared for in centers in the southeastern region of the country, particularly in the state of São Paulo (33%), the remaining patients being treated in southern Brazil (1,014 patients, 23%), northeastern Brazil (665 patients, 15%), central-western Brazil (354 patients, 8%), and northern Brazil (141 patients, 4%). Overall, 47 centers (92%) reported having an incomplete multidisciplinary team; 4 (8%) lacked essential team members; 6 (12%) lacked a physical therapist; 5 (10%) lacked a dietitian; 17 (33%) lacked outpatient nursing care; 13 (25%) lacked outpatient social work services; 14 (27%) lacked a psychologist; and 32 (63%) lacked a clinical pharmacist. Seven CFCCs (14%) in the northern and northeastern regions of Brazil reported that the quality of newborn screening for CF was poor. All centers reported having difficulties in accessing CF medications. CONCLUSIONS: Brazilian CFCCs experience multiple problems, including inadequate staffing, infrastructure, testing, and medication supply. There is an urgent need to regulate the implementation of CF referral centers and an appropriate network structure for the diagnosis and follow-up of CF patients using optimal treatment recommendations.

Patient care in cystic fibrosis centers: a real-world analysis in Brazil / Assistência ao paciente em centros de fibrose cística: análise do mundo real no Brasil

ABSTRACT Objective: To analyze the characteristics of cystic fibrosis (CF) care centers (CFCCs) in Brazil. Methods: A questionnaire was sent to the coordinators of all 51 registered CFCCs between May and September of 2021. Results: The response rate was 100%. Southeastern Brazil is the region where most of the CFCCs in the country are located (21 centers; 41%), followed by the southern and northeastern regions (11 centers each; 21.5%), the central-western region (6; 12%), and the northern region (2; 4%). A total of 4,371 patients with CF were cared for in Brazil during the study period, ranging from 7 to 240 patients per center (mean, 86 patients/center; median, 75 patients/center); 2,197 patients (50%) were cared for in centers in the southeastern region of the country, particularly in the state of São Paulo (33%), the remaining patients being treated in southern Brazil (1,014 patients, 23%), northeastern Brazil (665 patients, 15%), central-western Brazil (354 patients, 8%), and northern Brazil (141 patients, 4%). Overall, 47 centers (92%) reported having an incomplete multidisciplinary team; 4 (8%) lacked essential team members; 6 (12%) lacked a physical therapist; 5 (10%) lacked a dietitian; 17 (33%) lacked outpatient nursing care; 13 (25%) lacked outpatient social work services; 14 (27%) lacked a psychologist; and 32 (63%) lacked a clinical pharmacist. Seven CFCCs (14%) in the northern and northeastern regions of Brazil reported that the quality of newborn screening for CF was poor. All centers reported having difficulties in accessing CF medications. Conclusions: Brazilian CFCCs experience multiple problems, including inadequate staffing, infrastructure, testing, and medication supply. There is an urgent need to regulate the implementation of CF referral centers and an appropriate network structure for the diagnosis and follow-up of CF patients using optimal treatment recommendations.

RESUMO Objetivo: Analisar as características dos centros de tratamento de fibrose cística (CTFC) no Brasil. Métodos: Entre maio e setembro de 2021, um questionário foi enviado aos coordenadores de todos os 51 CTFC registrados. Resultados: A taxa de resposta foi de 100%. O Sudeste do Brasil é a região onde está a maioria dos CTFC do país (21 centros; 41%), seguida pelas regiões Sul e Nordeste (11 centros cada; 21,5%), Centro-Oeste (6; 12%) e Norte (2; 4%). No total, 4.371 pacientes com fibrose cística (FC) foram atendidos no Brasil durante o período do estudo, variando de 7 a 240 pacientes por centro (média de 86 pacientes/centro; mediana de 75 pacientes/centro); 2.197 pacientes (50%) foram atendidos em centros da região Sudeste, particularmente no estado de São Paulo (33%), e os demais receberam atendimento nas regiões Sul (1.014 pacientes, 23%), Nordeste (665 pacientes, 15%), Centro-Oeste (354 pacientes, 8%) e Norte (141 pacientes, 4%). Do total de CTFC, 47 (92%) relataram que a equipe multidisciplinar estava incompleta; em 4 centros (8%), as equipes multidisciplinares careciam de membros essenciais; 6 centros (12%) careciam de fisioterapeuta; 5 (10%) careciam de dietista; 17 (33%) careciam de cuidados ambulatoriais de enfermagem; 13 (25%) careciam de serviços ambulatoriais de assistência social; 14 (27%) careciam de psicólogo e 32 (63%) careciam de farmacêutico clínico. Sete CTFC (14%) nas regiões Norte e Nordeste relataram que a qualidade da triagem neonatal de FC era ruim. Todos os centros relataram dificuldades de acesso a medicamentos para FC. Conclusões: Os CTFC brasileiros enfrentam múltiplos problemas: pessoal inadequado, infraestrutura inadequada, testes inadequados e fornecimento inadequado de medicamentos. Há uma necessidade urgente de regulamentar a implantação de centros de referência em FC e de uma rede adequada para o diagnóstico e acompanhamento de pacientes com FC com base nas recomendações para o tratamento ideal da doença.

Chloride Conductance, Nasal Potential Difference and Cystic Fibrosis Pathophysiology.

PURPOSE: Cystic 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. METHODS: Nasal 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. RESULTS: The 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 < 0.05). More negative NPDmax was associated with pancreatic insufficiency (P < 0.01) as well with genotype severity, but not with the pulmonary function. CONCLUSIONS: The anion permeability through CFTR, mainly chloride, but bicarbonate as well, is the most critical factor in CF airway pathophysiology. Treatments primarily directed to correct CFTR function and/or airway acidity are clearly a priority.

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.

Infecção respiratória na fibrose cística e tratamento / Cystic fibrosis respiratory infection and treatment

Fibrose cística é uma doença multissistêmica e complexa, que exige tratamento contínuo. A doença pulmonar é o principal determinante da sua evolução. Alterações na composição da secreção das vias aéreas levam ao desenvolvimento de doença pulmonar progressiva com infecção respiratória crônica por germes peculiares à doença. Esquemas de antibioticoterapia para tratamento das exacerbações pulmonares, erradicação de bactérias ou de supressão da infecção crônica constituem parte importante do tratamento, com repercussão significativa na melhora dos sintomas, da função pulmonar e da qualidade de vida dos pacientes com fibrose cística.

Cystic fibrosis is a complex multisystemic disease that requires lifelong treatment. Pulmonary disease is the major prognostic determinant. The altered airway surface liquid leads to the development of progressive pulmonary disease with chronic respiratory infection by specific germs. Antibiotic strategies for treatment of pulmonary disease exacerbations, bacterial eradication or chronic infection suppression play an important role in the treatment, contributing to the improvement of symptoms, lung function and the quality of life of Cystic Fibrosis patients.

Diferença de potencial nasal: um novo teste para diagnóstico de fibrose cística / Nasal potential difference: a new test for cystic fibrosis diagnosis

Introdução: Fibrose Cística (FC) é uma doença cujo diagnóstico é essencialmente clínico, confirmada por dosagem de cloro no suor acima de 60 mEq/L e/ou identificação das mutações do CFTR causadoras da doença nos dois alelos. Casos atípicos necessitam ser investigados através do exame da diferença de potencial nasal (DPN). Na FC a DPN é mais negativa, há maior despolarização com o amiloride e pouca resposta ao isoproterenol. Objetivo: Determinar os valores da DPN para portadores de FC e grupos controle. Métodos: A DPN foi medida em 24 portadores de FC, 19 portadores de outras doenças não FC e 18 sadios e foram determinadas a média e desvio-padrão da DPN máxima, 8 amil, 8ØCl, 8iso, 8Cl, 8amil+iso e index DPN. Resultados: A média da DPN máxima foi -32 mV no grupo FC, -14 mV no grupo Não FC e -16 mV no grupo Sadio (P<0,0001). No grupo FC a média do 8 amil foi -18 mV, no grupo Não FC -6 mV e no grupo Sadio -7mV (P<0,0001). No grupo FC a média do 8Cl foi 4mV, 17mV no grupo Não FC e 11mV no grupo Sadio. A média do index 8 amil + iso foi - 16mV e o index DPN foi 0,85 no grupo FC, comparado com -0,6 mV e 0,26 no grupo Não FC e -2mV e 0,23 no grupo Sadio. Conclusões: O teste da DPN pode claramente diferenciar o grupo FC, com valores semelhantes aos descritos na literatura, possibilitando seu emprego futuro como teste diagnóstico complementar nos casos atípicos de FC.

Cystic Fibrosis (CF) is a disease whose diagnosis is essentially clinical, confirmed by measurement of sweatchloride above 60mEq / L and / or identification of CFTR mutations that cause disease in two alleles. Atypical cases need to be investigated by the nasal potential difference test (NPD). In CF the NPD is more negative, there is increased depolarization with amiloride (Eamil ) and a poor response to the isoproterenol (Eiso). Aim: To determine the values of NPD for CF patients and control groups. Methods: DPN was measured in 24 CF patients, 19 carriers of other diseases non-CF and 18 healthy and the mean plus standard deviation of NPD maximum, E amyl, EØCl, Eiso, ECl, E amil+iso and index NPD were determined. Results: NPD maximum in the FC group was -32 mV, -14 mV In the non-CF and-16mV in healthy group (p <0.0001). In the CF group the mean Eamil was - 18mV, -6mV in the non-FC group and -7mV in healthy (p <0.0001). The ECl mean was 4mV in CF group, 17mV in non-CF and 11mV in healthy. The average of the index E amil+iso was-16mV and DPN index was 0.85 in FC group compared with -0.6 mV and 0.26 in non-CF and -2mV, and 0.23 in healthy. Conclusions: The test of DPN can clearly distinguish the CF group, with values similar to those described in the literature, enabling their future use as a complementary diagnostic test in atypical cases of CF.

Evolução do estado nutricional de pacientes com fibrose cística em uso de suplementação nutricional por gastrostomia / Nutritional status of patientes with cystic fibrosis in use of nutritional supplementation by gastrostomy

Introdução: A nutrição tem papel essencial na sobrevida e qualidade de vida de pacientes com Fibrose Cística (FC). O objetivo desse estudo foi acompanhar a evolução do estado nutricional de pacientes com FC em uso de suplementação nutricional por gastrostomia. Métodos: Estudo longitudinal retrospectivo com todos os pacientes com FC e em uso de suplementação nutricional com dieta hipercalórica por gastrostomia em um centro de referência no sul do Brasil. Os pacientes foram acompanhados nos períodos de 6 meses antes, no momento da instalação da gastrostomia, 6 meses, 1 ano e 2 anos após o procedimento. Os parâmetros nutricionais utilizados foram escore Z para peso/idade e estatura/idade, percentil de índice de massa corpórea (PIMC), além de medidas de composição corporal. Foram obtidos dados de função pulmonar e de ingestão alimentar. Resultados: Foram avaliados dez pacientes, sendo sete (70%) do sexo masculino. A idade média da instalação da gastrostomia foi de 9,8 ± 3,8 anos. O ganho de peso foi de 8,35 Kg (P =0,007) e o de estatura de 16,2 cm (P <0,001). O PIMC passou de 14,2 para 27,1 no período de 2 anos e meio (P =0,282). Com relação à composição corporal houve aumento da reserva muscular e de gordura. Houve queda não significativa na função pulmonar ao longo do tempo. A média de calorias ofertadas comparada com a recomendação alimentar diária passou de 111,6 ± 24,6% para 157,7 ± 37,86% (P =0,048). Conclusão: A suplementação nutricional por gastrostomia resultou em significativo ganho de peso e estatura, bem como aumento da reserva muscular e de gordura, no entanto não houve melhora ou estabilização da função pulmonar nesse grupo de pacientes.

Background: Nutrition plays an essential role in the survival and quality of life of cystic fibrosis (CF) patients. The aim was to follow nutritional status of patients with CF in use of nutritional supplementation by gastrostomy. Methods: Retrospective longitudinal study including all patients with CF on nutritional supplementation by gastrostomy at a referral center in southern Brazil. Patients were followed up in periods of 6 months before the installation of gastrostomy, and then, 6 months, 1 year and 2 years after the procedure. The nutritional parameters used were Z scores for weight/age and height/age, percentile of body mass index (PBMI), and body composition measurements. Data of pulmonary function and food intake were recorded. Results: Ten patients were evaluated, of which seven (70%) were male. The average age when gastrostomy was made was 9.8 ±3.8 years. The weight earning was 8.35 Kg (P =0.007) and the height was 16.2 cm (P <0.001). The PBMI increased from 14.2 to 27.1 over two and a half years (P =0.282). In relation to body composition an increase of muscular and fat reserve was observed. There was no significant decline in pulmonary function over the time. Average calories offered compared with the Recommended Dietary Allowance increased from 111.6 ±24.6% to 157.7 ±37.86% (P =0.048). Conclusion: nutritional supplementation by gastrostomy resulted in significant weight and height gain, as well as increased muscle and fat reserves, however there wasn’t improvement or stabilization of pulmonary function in this group of patients.