Abstract This is a descriptive cross-sectional study that aims to determine the distribution of the CFTR causing variant in a group of patients at a cystic fibrosis (CF) center in southern Brazil, as well as to describe causing variants that are treatable with mutation-specific drugs. Ninety-two patients from a CF reference center were assessed in this research, all of them with a clinical diagnosis of CF and both alleles identified with pathogenic variants. The most prevalent causing variants were F508del, R1162X, G542X, and N1303K. As for patients with a mutation-specific drug indication, 69.6 % were candidates for the use of Elexacaftor/Tezacaftor/Ivacaftor (Trikafta®), 44.6 % for the use of Tezacaftor/Ivacaftor (Symdeko®), and 35.9 % for the use of Lumacaftor/Ivacaftor (Orkambi®). For the use of Ivacaftor (Kalydeco®), only two patients (2.2 %) were candidates following the Brazilian agency approval. According to the FDA, 10 patients would be candidates for Ivacaftor (10.9 %). Causing variants of classes I and II, which are related to a major severity of the illness, were identified in 135 of 184 alleles (73.3 %). In this study, more than 2/3 of the patients were candidates for the use of CFTR modulators therapy.

RESUMO Objetivos: Caracterizar as principais mutações identificadas no cystic fibrosis transmembrane conductance regulator (CFTR) em um grupo de crianças e adolescentes de um centro multidisciplinar de tratamento de fibrose cística e sua associação com características clínicas e laboratoriais. Método: Estudo transversal descritivo que incluiu pacientes com fibrose cística que possuíam dois alelos identificados com mutação no CFTR. Dados clínicos, antropométricos, laboratoriais e de função pulmonar (espirometria) foram coletados de registros em prontuários e descritos com os resultados de genotipagem da amostra. Resultados: Foram incluídos 42 pacientes com fibrose cística. A mutação mais frequente foi a F508del, abrangendo 60 alelos (71,4%). A segunda mutação mais comum foi a G542X (seis alelos, 7,1%), seguida das mutações N1303K e R1162X (ambas com quatro alelos cada uma). Três pacientes (7,14%) apresentaram mutações de classes III e IV, e 22 pacientes (52,38%), homozigose para F508del. Trinta e três pacientes (78,6%) tinham insuficiência pancreática, 11 (26,2%) apresentaram íleo meconial e sete (16,7%) déficit nutricional. Dos pacientes do estudo, 59,52% seriam potenciais candidatos ao uso de fármacos moduladores de CFTR. Conclusões: As mutações do CFTR identificadas com mais frequência foram F508del e G542X, as quais são mutações pertencentes às classes II e I, respectivamente, e que, juntamente à classe III, conferem um fenótipo de fibrose cística com mais gravidade. Mais da metade (52,38%) da amostra apresentava F508del em homozigose, população candidata ao novo tratamento com Lumacaftor/Ivacaftor. Aproximadamente 7% dos pacientes apresentavam mutações de classes III e IV, sendo candidatos ao tratamento com Ivacaftor.

ABSTRACT Objectives: To characterize the main identified mutations on cystic fibrosis transmembrane conductance regulator (CFTR) in a group of children and adolescents at a cystic fibrosis center and its association with the clinical and laboratorial characteristics. Method: Descriptive cross-sectional study including patients with cystic fibrosis who had two alleles identified with CFTR mutation. Clinical, anthropometrical, laboratorial and pulmonary function (spirometry) data were collected from patients’ records in charts and described with the results of the sample genotyping. Results: 42 patients with cystic fibrosis were included in the study. The most frequent mutation was F508del, covering 60 alleles (71.4%). The second most common mutation was G542X (six alleles, 7.1%), followed by N1303K and R1162X mutations (both with four alleles each). Three patients (7.14%) presented type III and IV mutations, and 22 patients (52.38%) presented homozygous mutation for F508del. Thirty three patients (78.6%) suffered of pancreatic insufficiency, 26.2% presented meconium ileus, and 16.7%, nutritional deficit. Of the patients in the study, 59.52% would be potential candidates for the use of CFTR-modulating drugs. Conclusions: The mutations of CFTR identified more frequently were F508del and G542X. These are type II and I mutations, respectively. Along with type III, they present a more severe cystic fibrosis phenotype. More than half of the sample (52.38%) presented homozygous mutation for F508del, that is, patients who could be treated with Lumacaftor/Ivacaftor. Approximately 7% of the patients (7.14%) presented type III and IV mutations, therefore becoming candidates for the treatment with Ivacaftor.

Resumo Introdução: As lesões laríngeas agudas após a intubação parecem ser precursoras das lesões crônicas. Objetivo: Descrever a incidência e o tipo de lesões laríngeas agudas após extubação em Unidade de Terapia Intensiva Pediátrica (UTIP). Método: Estudo de coorte envolvendo crianças de 0 a 5 anos incompletos, com intubação por mais de 24 horas na UTIP de um hospital universitário. Nas primeiras 8 horas após extubação, uma nasofibrolaringoscopia à beira do leito foi realizada. Aqueles com anormalidades moderadas a graves foram submetidos a novo exame entre 7-10 dias após. Resultados: 177 pacientes foram incluídos, com idade mediana de 2,46 meses. O tempo médio de intubação foi de 8,19 dias. Setenta e três (41,2%) pacientes apresentaram alterações moderadas ou graves à laringoscopia, o restante mostrando apenas alterações leves ou exame normal. Durante o acompanhamento, 16 crianças do grupo lesões moderada a grave desenvolveram estenose subglótica. Um paciente do grupo laringoscopia normal teve estenose subglótica, somando-se uma incidência de 9,6% de lesões crônicas. Conclusão: A maioria das crianças do estudo desenvolveu lesões laríngeas agudas leves decorrentes da intubação endotraqueal, com melhora em alguns dias após a extubação.

ABSTRACT INTRODUCTION: Acute laryngeal lesions after intubation appear to be precursors of chronic lesions. OBJECTIVE: To describe the incidence and type of acute laryngeal lesions after extubation in a pediatric intensive care unit (PICU). METHODS: A cohort study involving children from birth to <5 years, submitted to intubation for more than 24 h in the PICU of an university hospital. In the first eight hours after extubation, a flexible fiberoptic laryngoscopy (FFL) was performed at the bedside. Those with moderate to severe abnormalities underwent a second examination seven to ten days later. RESULTS: 177 patients were included, with a median age of 2.46 months. The mean intubation time was 8.19 days. Seventy-three (41.2%) patients had moderate or severe alterations at the FFL, with the remaining showing only minor alterations or normal results. During follow-up, 16 children from the group with moderate to severe lesions developed subglottic stenosis. One patient from the normal FFL group had subglottic stenosis, resulting in an incidence of 9.6% of chronic lesions. CONCLUSION: Most children in the study developed mild acute laryngeal lesions caused by endotracheal intubation, which improved in a few days after extubation.