O impacto da Covid-19 na rotina de cuidados das crianças e adolescentes com fibrose cística / The impact of Covid-19 on the care routine of children and adolescents with cystic fibrosis

A Covid-19 é uma infecção respiratória aguda, potencialmente grave e que rapidamente se tornou uma pandemia sem precedentes na contemporaneidade, podendo ser entendida como um dos maiores desafios sanitários da humanidade neste século. A Covid-19 trouxe enormes preocupações à comunidade envolvida nos cuidados dos pacientes com fibrose cística (FC), que é uma doença rara, crônica e multissistêmica, que leva a grandes danos aos pulmões, pâncreas e outros órgãos. O tratamento da FC é composto por uma rotina diária de medicações, dieta e fisioterapia, que auxiliam na manutenção de uma boa condição pulmonar e nutricional, melhorando a expectativa e a qualidade de vida. Diante da complexidade do tratamento, ele é realizado em centros de referência e por equipe multiprofissional. A adoção do isolamento social que foi necessária para evitar a disseminação da Covid-19, interrompeu e/ou adiou os atendimentos possibilitando o agravamento dos quadros de saúde dos pacientes com FC. O objetivo desse estudo foi investigar as alterações provocadas pela pandemia da Covid-19 na rotina de cuidados das crianças e adolescentes com FC. Assim realizou-se um estudo transversal considerando as respostas a partir do levantamento online, nos meses de novembro e dezembro de 2021, com os responsáveis por crianças e adolescentes com FC que são acompanhadas no Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF). Participaram do estudo 75 responsáveis. Observou-se que as restrições impostas pela pandemia intensificaram as dificuldades já vividas pelas crianças e adolescentes com FC e trouxeram rupturas na trajetória de cuidado à saúde, medos, incertezas e profundos desgastes físicos e psicológicos. A perda de renda durante a pandemia, as dificuldades para realização de exames em geral e a falta de suplementos calóricos foram associados a piora do quadro pulmonar e/ou nutricional dos pacientes com FC, assim como alterações no sono e no humor. Diante dos resultados apresentados conclui-se que o fortalecimento de políticas públicas se faz necessário para ampliação do acesso aos benefícios sociais e redes de apoio psicológico aos pacientes com FC e suas famílias a fim garantir suporte material e afetivo no cenário pós pandêmico para a conservação do estado de saúde dos pacientes. A consulta remota foi uma ferramenta fundamental para o gerenciamento da FC durante a pandemia da Covid-19, sendo possível manter a continuidade dos cuidados mesmo com o distanciamento social, tendo grande adesão por parte dos pacientes, no entanto para se obter êxito na teleconsulta é necessário que os pacientes tenham acesso a tecnologias apropriadas e os profissionais de saúde prestem informações de fácil compreensão. (AU)

Covid-19 is an acute, potentially serious respiratory infection that has rapidly become an unprecedented pandemic in contemporary times and can be understood as one of the greatest health challenges facing humanity in this century. Covid-19 has brought enormous concern to the community involved in the care of patients with cystic fibrosis (CF), which is a rare, chronic and multisystem disease that leads to major damage to the lungs, pancreas and other organs. Treatment for CF consists of a daily routine of medication, diet and physiotherapy, which help to maintain a good pulmonary and nutritional condition, improving life expectancy and quality of life. Given the complexity of the treatment, it is carried out in reference centers and by a multi-professional team. The adoption of social isolation, which was necessary to prevent the spread of Covid-19, has interrupted and/or postponed treatment, making it possible for CF patients' health conditions to worsen. The aim of this study was to investigate the changes caused by the Covid-19 pandemic in the care routine of children and adolescents with CF. Thus, a cross-sectional study was carried out considering the responses from the online survey, in the months of November and December 2021, with the guardians of children and adolescents with CF who are monitored at the Fernandes Figueira National Institute for Women's, Children's and Adolescents' Health (IFF). Seventy-five caregivers took part in the study. It was observed that the restrictions imposed by the pandemic intensified the difficulties already experienced by children and adolescents with CF and brought disruptions to the health care path, fears, uncertainties and profound physical and psychological stress. The loss of income during the pandemic, the difficulties in carrying out tests in general and the lack of calorie supplements were associated with a worsening of the pulmonary and/or nutritional condition of CF patients, as well as changes in sleep and mood. In view of the results presented, it can be concluded that public policies need to be strengthened in order to increase access to social benefits and psychological support networks for CF patients and their families, in order to guarantee material and emotional support in the post pandemic scenario for the preservation of patients' state of health. The remote consultation was a fundamental tool for managing CF during the Covid-19 pandemic, making it possible to maintain continuity of care even with social distancing, with great adherence on the part of patients. However, in order for teleconsultation to be successful, it is necessary for patients to have access to appropriate technologies and for health professionals to provide information that is easy to understand. (AU)

Repercussões Clínicas da Gameterapia no Manejo do Indivíduo com Fibrose Cística / Clinical repercussions of game therapy in the management of individuals with cystic fibrosis

Introdução: A gameterapia (GT) tem sido utilizada como método para estimular a prática de atividade física em indivíduos com fibrose cística (FC), podendo proporcionar melhora no sistema cardiorrespiratório e na adesão ao tratamento. Objetivo: analisar as repercussões clínicas da gameterapia no manejo de pacientes com FC. Métodos:Conduziu-se uma revisão sistemática de literatura nas seguintes bases de dados: PubMed, Embase, Scopus e MEDLINE via Ovid, utilizando-se os descritores:"Cystic fibrosis","video games" e seus cognatos, por meio da qual se incluíram estudos que descrevessem as repercussões do uso da GT em indivíduos com FC. Resultados: Foram identificados 293 estudos, sendo 7 selecionados ao final. Em 6 estudos, a frequência cardíaca alcançada durante a GT apresentou-se dentro dos padrões recomendados para treinamento. A avaliação do consumo máximo de oxigênio (VO2máx) foi realizada em 3 publicações, e este parâmetro apresentou níveis mais elevados em comparação ao identificado no teste de caminhada de seis minutos. Os consoles mais utilizados foram Nintendo Wii TM e Xbox 360 ™ e a intensidade na realização dos exercícios com a GT esteve entre moderada e intensa. A adesão dos indivíduos quanto a esse recurso também foi verificada, e a GT apresentou-se mais aceitável que outros e foi considerada lúdica. Conclusão: a GT se mostra uma intervenção capaz de gerar respostas fisiológicas que correspondem às necessidades de treinamento, além de maior adesão e satisfação dos indivíduos com FC em sua realização (AU),

Game therapy (GT) has been used as a method to encourage the practice of physical activity in individuals with cystic fibrosis (CF), which may provide improvement in the cardiorespiratory system and treatment adherence. Objective: analyze the clinical repercussions of game therapy in the management of patients with CF. Methods: A systematic review of the literature was carried out in the following databases: PubMed, Embase, Scopus and MEDLINE via Ovid, using the descriptors: "Cystic fibrosis", "video games" and their cognates, through which they included Studies describing the repercussions of the use of GT in individuals with CF were sought. Results: 293 studies were identified, seven of which were selected at the end. In six studies, the heart rate reached during the TG was within the recommended standards for training. The assessment of maximum oxygen consumption (VO2max) was performed in three publications, and this parameter showed higher levels compared to that identified in the six-minute walk test. The most used consoles were Nintendo WiiTM and Xbox 360™and the intensity in carrying out the exercises with the TG was moderate and intense. The individuals' adherence to this resource was also verified, and the GT was more acceptable than others and was considered playful. Conclusion: TG proves to be an intervention capable of generating physiological responses that correspond to training needs and greater adherence and satisfaction of individuals with CF in its performance (AU).

Espirometria e oscilometria de impulso durante internação por exacerbação pulmonar aguda em escolares com fibrose cística / Spirometry and impulse oscillometry during acute pulmonary exacerbation hospitalization in children with cystic fibrosis

RESUMO: Objetivo: avaliar o comportamento de parâmetros do sistema respiratório durante internação para antibioticoterapia intravenosa (AIV) como tratamento da exacerbação pulmonar aguda (EPA) em escolares com fibrose cística (FC). Métodos: estudo do tipo analítico observacional, before-after, realizado no Hospital Infantil Joana de Gusmão, Florianópolis ­ Santa Catarina. Foram incluídas crianças com diagnóstico de FC, entre seis e 15 anos, em internação para tratamento da exacerbação pulmonar aguda, no início (T1), durante (T2) e ao final (T3) da internação foi conduzida avaliação de escores específicos de EPA, dados antropométricos e realizada avaliação dos parâmetros do sistema respiratório pelo sistema de oscilometria de impulso (IOS) e espirometria. Foram obtidos, em prontuário, dados de colonização bacteriana, genótipo, gravidade da doença (Escore de Schwachman-Doershuk-ESD) e espirometria mais recente em estabilidade clínica. Aplicou-se o teste Shapiro-Wilk para análise da distribuição dos dados e os testes ANOVA de medidas repetidas, teste de Friedman, teste T pareado e Wilcoxon, com nível de significância de 5%. Resultados: participaram 16 crianças/adolescentes (68.8% meninas, 12.88±1.67anos). Houve aumento dos parâmetros da espirometria e dados antropométricos (p<0.005) no T3, bem como redução dos escores de EPA e do X5 (p<0.005) no T3. Conclusão: os dados apresentados nesse trabalho mostram melhora dos escores de EPA, dados antropométricos, parâmetros da espirometria e do parâmetro de recolhimento elástico do IOS (X5).RESUMODescritores: Fibrose cística, Exacerbação dos sintomas, Testes de função pulmonar, Mecânica respiratória. (AU)

ABSTRACT: Objective: Evaluate the respiratory system parameters of children with cystic fibrosis (CF) during hospitalization for acute pulmonary exacerbation (APE) treatment. Methods: observational study before-after that occurred at the CF reference center. There were included children with cystic fibrosis (CF) between six to 15 years old hospitalized due to APE. The registration of the APE clinical scores, anthropometric data, and respiratory system (IOS and spirometry) evaluation occurred at the beginning (T1), during (T2), and at the end (T3) of the hospitalization. There were registered pathogens, genetic mutation, disease severity (Schwachman-Doershuk Score), and the most recent spirometry when they were clinically stable. The Shapiro-Wilk test was applied to analyze data distribution, and the repeated measure ANOVA, Friedman test, Tpaired test, and Wilcoxon test were performed to compare data, with a significance level set at 5%. Results: sixteen children/adolescents participated in the study (68.8% girls, 12.88±1.67 years old). The spirometric parameters, X5 parameter, and anthropometric data increased (p<0.005) and the APE scores decreased (p<0.005) at T3. Conclusion: APE scores, anthropometric data, spirometric parameters, and IOS elastic recoil parameter (X5) improved at the end of hospitalization.ABSTRACTKeywords: Cystic fibrosis, Symptom flare up, Respiratory function tests, Respiratory mechanics.1. Universidade do Estado de Santa Catarina ­ UDESC ­ Florianópolis, (SC) ­ Brasil https://doi.org/10.11606/issn.2176-7262.rmrp.2022.183755Tayná Castilho1, Renata Maba Gonçalves Wamosy1, Camila Isabel Santos Schivinski1Este é um artigo publicado em acesso aberto (Open Access) sob a licença Creative Commons Attribution, que permite uso, distribuição e reprodução em qualquer meio, sem restrições, desde que o trabalho original seja corretamente citado. (AU)

Actualización en fibrosis quística - fagoterapia: ¿es el futuro para tratar bacterias multirresistentes? / Phage therapy: is the future to treat multiresistant bacteria?

Las infecciones respiratorias representan una morbilidad y mortalidad significativas, con aumento progresivo de la resistencia a los antibióticos. La escasez de nuevos antibióticos disponibles y la pérdida de eficacia de los antiguos, ha impulsado a investigar otras alternativas de tratamiento. La terapia con bacteriófagos (fagos) representa uno de esos enfoques, la que ha demostrado ser eficaz contra una variedad de patógenos bacterianos, incluidas las cepas resistentes a los medicamentos. La administración puede ser tópica, intravenosa o inhalada, esta última requiere preparaciones estables de fagos y sistemas adecuados para proporcionar partículas que accedan al árbol respiratorio. En esta comunicación se revisan diversos aspectos de los bacteriófagos, los que podrían ser de gran utilidad para el tratamiento de las infecciones pulmonares en pacientes con diagnóstico de fibrosis quística.

Respiratory infections represent a significant morbidity and mortality, with a progressive increase in resistance to antibiotics. The scarcity of new antibiotics available and the loss of efficacy of the old ones has prompted investigation of other treatment alternatives. Bacteriophage (phage) therapy represents one such approach that has been shown to be effective against a variety of bacterial pathogens, including resistant strains to medications. Administration can be topical. Intravenous or inhaled, the latter requiring stable preparations of phages and adequate systems to provide particles that will access the respiratory tree. In this communication various aspects of bacteriophages and their clinical utility are reviewed, which could be very useful for the treatment of pulmonary infections in patients diagnosed with cystic fibrosis.

Brazilian Guidelines for Nutrition in Cystic Fibrosis

ABSTRACT Objective To develop a scientific consensus on nutrition in cystic fibrosis. Methods Sixteen coordinators elaborated relevant questions on nutritional therapy in cystic fibrosis, which were divided into six sections: nutritional assessment, nutritional recommendations, nutritional intervention, dietary counseling, special situations and enzyme replacement, and gastrointestinal manifestations. Two to three specialists in the field were responsible for each section and obtaining answers formulated based on standardized bibliographic searches. The available literature was searched in the PubMed®/MEDLINE database, after training and standardization of search strategies, to write the best level of evidence for the questions elaborated. Issues related to disagreement were discussed until a consensus was reached among specialists, based on the current scientific literature. Results Forty-two questions were prepared and objectively answered, resulting in a consensus of nutritional therapy in cystic fibrosis. Conclusion This work enabled establishing a scientific consensus for nutritional treatment of cystic fibrosis patients.

Diabetes de inicio precoz en pacientes con fibrosis quística, a propósito de 3 casos / Early-onset diabetes in patients with cystic fibrosis, about 3 cases

INTRODUCCIÓN. La diabetes es la complicación extrapulmonar más frecuente en adultos con fibrosis quística. Existen escasas publicaciones de diabetes relacionada a la fibrosis quística en preescolares a nivel mundial. En Chile se desconoce su prevalencia. MÉTODO. Reportamos una serie de tres casos de niños con fibrosis quística (FQ) y diagnóstico de diabetes a muy temprana edad. RESULTADOS. Caso 1: Niño de 8 años, con diagnóstico de fibrosis quística a los 3 meses de vida por test de sudor y estudio genético p.Phe508del /-. Presenta hiperglicemia no cetósica desde los 6 meses de edad, con colonización traqueal de Staphylococcus Aureus (SA) y Pseudomona Aeruginosa (PA) y debut de diabetes a los 2 años 1 mes. Caso 2: Niño de 16 años, a los 7 meses de vida se diagnostica FQ por test de sudor y estudio genético p.Phe508del /-. Presenta colonización traqueal por SA y múltiples infecciones por PA. A los 5 años 7 meses se diagnostica diabetes presentando cetosis al debut. Caso 3: Niño de 13 años, con diagnóstico de FQ a los 7 meses de vida mediante test de sudor y estudio genético p.Phe508del/-. Presenta colonización traqueal por SA y múltiples infecciones por PA, se realiza diagnóstico de diabetes a los 2 años 7 meses de edad. DISCUSIÓN: La diabetes asociada a fibrosis quística es una complicación frecuente en adultos con fibrosis quística, pero puede presentarse desde edades tempranas. Se debe tener alto nivel de sospecha para el diagnóstico oportuno y óptimo manejo.

INTRODUCTION: Diabetes is the most common extra pulmonary complication in adults with cystic fibrosis (CF). There are few reports of diabetes related to (CF) in preschool children worldwide. Prevalence in Chile is unknown. MÉTODO: We report ta serie of three cases of children with CF and diagnosis of diabetes at an early age. Case 1: Boy 8 year old, CF diagnosed at the age of 3 months by sweat test and genetic study p.Phe508del/-. He presented non-ketotic hyperglycemia since he was 6 months old, with tracheal colonization of Staphylococcus Aureus (SA) and Pseudomona Aeruginosa (PA) , and diagnosis of diabetes at the age of 2 years 1 month. Case 2: Boy patient, 16 years old, with diagnosis of CF at the of age 7 months by sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple PA infections. At the age 5 years 7 months, diabetes is diagnosed, presenting ketosis at the beginning. Case 3: Boy 13 years diagnosed with CF at the age of 7 months, presented sweat test and genetic study p.Phe508del/-. He presents tracheal colonization by SA and multiple infections. DISCUSSION: CF related diabetes is common in adults with cystic fibrosis, but it can be diagnosed in early childhood. A high level of suspicious is required for a proper and timely diagnosis

Guía de diagnóstico y tratamiento de pacientes con fibrosis quística. Actualización / Guideline for the diagnosis and treatment of patients with cystic fibrosis. Update

La presente revisión de la "Guía de diagnóstico y tratamiento de pacientes con fibrosis quística"publicada en el año 2014 tiene como objetivo actualizar el conocimiento acerca de varios aspectos relacionados con el manejo clínico de la enfermedad, según los avances científicos publicados y en desarrollo en los últimos años. Solo se tratarán aquí tópicos nuevos y aquellos que, a la luz de la investigación, requieren ser modificados, por lo que el contenido de la anterior guía permanece vigente en el resto de las cuestiones.Los aspectos actualizados se dan en el diagnóstico de la enfermedad por los cambios realizados en el test del sudor, la pesquisa neonatal y la biología molecular, la actualización de estudios de seguimiento, como el índice de aclaramiento pulmonar y la resonancia magnética nuclear, y modificaciones con respecto al área nutricional (diabetes secundaria a fibrosis quística) y el tratamiento kinésico y de rehabilitación pulmonar

The present revision of the Guide for the diagnosis and treatment of patients with cystic fibrosis published in 2014 aims to update the knowledge about various aspects related to the clinical management of the disease, according to the scientific advances published and in development in recent years. Only new topics will be discussed here and those that, in light of the research, require modification, so the content of the previous guide remains valid in the rest of the aspects.The updated aspects range over the diagnosis of the disease due to the changes made in the sweat test, the neonatal screening and molecular biology, the update of follow-up studies, such as the Lung Clearance Index and the Nuclear Magnetic Resonance, and modifications regarding the nutritional area (diabetes secondary to cystic fibrosis) and the physiotherapy treatment and pulmonary rehabilitation.

Clinical outcomes of cystic fibrosis patients with hemoptysis treated with bronchial artery embolization / Desfechos clínicos de pacientes com fibrose cística e hemoptise tratada por meio de embolização arterial brônquica

ABSTRACT Objective: Massive hemoptysis is one of the most serious complications in patients with cystic fibrosis (CF). This study aimed to evaluate the hemoptysis-free period following bronchial and non-bronchial artery embolization (BAE/non-BAE) in CF patients and to investigate predictors of recurrent bleeding and mortality by any cause. Methods: This was a retrospective cohort study of CF patients ≥ 16 years of age undergoing BAE/non-BAE for hemoptysis between 2000 and 2017. Results: We analyzed 39 hemoptysis episodes treated with BAE/non-BAE in 17 CF patients. Hemoptysis recurrence rate was 56.4%. Of the sample as a whole, 3 (17.6%) were hemoptysis-free during the study period, 2 (11.8%) underwent lung transplantation, and 3 (17.6%) died. The median hemoptysis-free period was 17 months. The median hemoptysis-free period was longer in patients with chronic infection with Pseudomonas aeruginosa (31 months; 95% CI: 0.00-68.5) than in those without that type of infection (4 months; 95% CI: 1.8-6.2; p = 0.017). However, this association was considered weak, and its clinical significance was uncertain due to the small number of patients without that infection. Conclusions: BAE appears to be effective in the treatment of hemoptysis in patients with CF.

RESUMO Objetivo: A hemoptise maciça é uma das complicações mais graves em pacientes com fibrose cística (FC). O objetivo deste estudo foi avaliar o período livre de hemoptise após a embolização arterial brônquica/não brônquica (EAB/não EAB) em pacientes com FC e investigar preditores de sangramento recorrente e mortalidade por qualquer causa. Métodos: Trata-se de um estudo retrospectivo de coorte de pacientes com FC com idade ≥ 16 anos submetidos a EAB/não EAB para o tratamento de hemoptise entre 2000 e 2017. Resultados: Foram analisados 39 episódios de hemoptise tratada por meio de EAB/não EAB em 17 pacientes com FC. A taxa de recidiva da hemoptise foi de 56,4%. Do total de pacientes, 3 (17,6%) permaneceram sem hemoptise durante o estudo, 2 (11,8%) foram submetidos a transplante de pulmão e 3 (17,6%) morreram. A mediana do período sem hemoptise foi de 17 meses. A mediana do período sem hemoptise foi maior em pacientes com infecção crônica por Pseudomonas aeruginosa (31 meses; IC95%: 0,00-68,5) do que naqueles sem esse tipo de infecção (4 meses; IC95%: 1,8-6,2; p = 0,017). No entanto, essa associação foi considerada fraca, e sua importância clínica foi considerada incerta em virtude do pequeno número de pacientes sem essa infecção. Conclusões: A EAB parece ser eficaz no tratamento de hemoptise em pacientes com FC.

Diabetes relacionada con la fibrosis quística / Cystic fibrosis-related diabetes

Los avances en el campo de la fibrosis quística han aumentado la esperanza de vida de estos pacientes, por lo que cada vez es más prevalente la Diabetes Relacionada con la Fibrosis Quística (DRFQ) y sus complicaciones. La DRFQ se asocia a mayor morbimortalidad, deterioro de la función pulmonar y del estado nutricional. Por lo mismo, el manejo óptimo de esta patología depende de un diagnóstico precoz, tratamiento individualizado y vigilancia de las complicaciones diabéticas. El screening de DRFQ debe realizarse anualmente a partir de los 10 años, mediante una Prueba de Tolerancia a la Glucosa Oral (PTGO), lo cual permite el diagnóstico. El manejo de esta patología tiene por objetivo estabilizar y mejorar la función pulmonar y el estado nutricional y metabólico de los pacientes. Actualmente, la insulina es el tratamiento farmacológico de elección para controlar la hiperglicemia y el esquema de uso debe ser individualizado para cada persona. En caso de enfermedades agudas pueden existir mayores requerimientos de insulina. Además, se deben tener consideraciones especiales en cuanto a la dieta y la insuficiencia pancreática exocrina que presentan estos pacientes. Para la vigilancia de complicaciones microvasculares se debe realizar una monitorización anual a partir de los 5 años desde el diagnóstico de DRFQ. Debido a la complejidad de estos pacientes, para alcanzar el mejor cuidado posible se necesita un enfoque multidisciplinario con distintos profesionales de la salud coordinados, incluyendo en la toma de decisiones al paciente y su familia.

Advances made in the field of cystic fibrosis have increased the life expectancy of these patients, which is why Cystic Fibrosis-Related Diabetes (CFRD) and its complications are becoming more and more prevalent. CFRD is associated with increased morbidity and mortality, lower lung function and inadequate weight maintenance. Therefore, the optimal management of this pathology depends on an early diagnosis, individualized treatment and monitoring of diabetic complications. For CFRD, routine screening with an Oral Glucose Tolerance Test (OGTT) should be carried out yearly from the age of 10, which allows to diagnose it. The treatment goals in CFRD are to stabilize and improve lung function and obtain adequate weight gain. Currently, insulin is the pharmacological treatment of choice to control hyperglycemia and the insulin regimen must be personalized for each person. In acute illnesses, there may be higher insulin requirements. In addition, special considerations must be taken regarding diet and exocrine pancreatic insufficiency that these patients present. For the surveillance of microvascular complications, annual monitoring should be carried out 5 years after the diagnosis of CFRD. Due to the complexity of these patients, in order to achieve the best possible care, a multidisciplinary approach is needed with different coordinated health professionals, including the patients and their family in the decision-making process.

Doenças raras na agenda da inovação em saúde: avanços e desafios na fibrose cística / Rare diseases on the agenda for innovation in health: progress and challenges with cystic fibrosis / Enfermedades raras en la agenda de la innovación en salud: avances y desafíos en la fibrosis quística

Resumo: O presente artigo se propõe a discutir as muitas complexidades envolvidas na incorporação de novas tecnologias em saúde para doenças raras, tomando como foco central da discussão o caso da fibrose cística. Tal escolha acontece por ser essa uma doença rara, genética, autossômica recessiva, considerada a mais comum entre as doenças raras. Também por ser uma doença que tem se beneficiado imensamente dos investimentos em pesquisa no campo da biologia molecular, feitos principalmente nos Estados Unidos, mas também em grupos de pesquisa europeus que resultaram no registro e comercialização de quatro novos medicamentos. Esses novos fármacos atuam, pela primeira vez, no defeito básico da fibrose cística. Numa perspectiva que entende as doenças raras como um campo de pesquisa tecido entre muitos outros, o presente texto tenta problematizar, com base em uma perspectiva mais centrada nas pessoas com fibrose cística, a dualidade de testemunhar de longe a molecularizaçao da vida, o surgimento de medicamentos de última geração que interrompem, em nível molecular, a cascata de erros e portanto sintomas e evolução de sua doença. O texto busca trazer para o debate os vários elementos que atravessam a complexa realidade local dos pacientes brasileiros com fibrose cística, num contexto global de inovação tecnológica e de quebra de paradigma em seus tratamentos. Baseando-se no campo das doenças raras, passando pela apresentação da fibrose cística em tempos da medicina de precisão, aliado a discussões sobre biopolíticas num contexto de inovação em saúde e medicamentos de alto custo, o artigo tenta dar visibilidade aos desafios e possibilidades do tempo presente.

Abstract: The article proposes to discuss the many complexities involved in the incorporation of new health technologies for rare diseases, with a central focus on the case of cystic fibrosis. Cystic fibrosis was chosen because it is a autosomal recessive genetic disorder, considered the most common of the rare diseases. The disease has also benefited greatly from investments in research in the field of molecular biology, mainly in the United States, but also among European research groups, which resulted in the registration and marketing of four new drugs. These new drugs act for the first time on the basic defect in cystic fibrosis. From a perspective that views rare diseases as a field of research woven among many others, the article aims to problematize cystic fibrosis from a more person-centered approach, the duality of witnessing from afar the molecularization of life, the emergence of last-generation drugs that interrupt, at the molecular level, the cascade of errors and thus the symptoms and evolution of the disease. The article aims to bring various elements to the debate that traverse the complex local reality of Brazilian cystic fibrosis patients in a global context of technological innovation and with a break in the treatment paradigm. Based on the field of rare diseases, including the presentation of cystic fibrosis in the age of precision medicine, alongside discussions on biopolitics in a context of health innovation and high-cost drugs, the article aims to shed light on the current challenges and possibilities.

Resumen: El presente artículo se propone discutir las diversas complejidades implicadas en la incorporación de nuevas tecnologías en salud para enfermedades raras, centrando la discusión en el caso de la fibrosis quística. Tal elección se produce por ser esta una enfermedad rara, genética, autosómica recesiva, considerada la más común entre las enfermedades raras. También por ser una enfermedad que se ha beneficiado inmensamente de las inversiones en investigación en el campo de la biología molecular, realizadas no sólo en los Estados Unidos, sino también en grupos de investigación europeos que resultaron en el registro y comercialización de cuatro nuevos medicamentos. Estos nuevos fármacos actúan, por la primera vez, en el defecto básico de la fibrosis quística. Desde una perspectiva que entiende las enfermedades raras, como un campo de investigación tejido entre muchos otros, el presente texto intenta problematizar, a partir de una perspectiva más centrada en las personas con fibrosis quística, la dualidad de testimoniar de lejos la molecularización de la vida, el surgimiento de medicamentos de última generación que interrumpen, a nivel molecular, la cascada de errores y por tanto síntomas y evolución de su enfermedad. El texto busca presentar en el debate los diferentes elementos que atraviesan la compleja realidad local de los pacientes brasileños con fibrosis quística, en un contexto global de innovación tecnológica y de quiebra de paradigma en sus tratamientos. A partir del campo de las enfermedades raras, pasando por la presentación de la fibrosis quística en tiempos de la medicina de precisión, junto a discusiones sobre biopolíticas en un contexto de innovación en salud y medicamentos de alto coste, el artículo intenta dar visibilidad a los desafíos y posibilidades del tiempo presente.

Treatment adherence among children and adolescents in a cystic fibrosis reference center / Adesão ao tratamento da fibrose cística entre crianças e adolescentes de um centro de referência

ABSTRACT 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.

RESUMO Objetivo: Avaliar o grau de adesão ao tratamento (AT) autorreferida e pesquisar sua associação com variáveis clínicas e sociodemográficas em pacientes com fibrose cística (FC) de um centro de referência e comparar o grau de AT autorreferida com o presumido pela equipe multidisciplinar. Métodos: Estudo transversal, incluindo crianças e adolescentes com FC entre zero e 20 anos. Foram realizadas entrevistas com os adolescentes maiores de 14 anos ou com os responsáveis dos mais jovens, utilizando-se formulário padronizado. Profissionais do centro preencheram outro formulário com suas impressões da AT dos pacientes. Registraram-se dados clínicos por meio da revisão de prontuários. A AT foi considerada satisfatória se o índice de adesão global (IAG) fosse igual ou superior a 80%. Resultados: Foram incluídos 53 pacientes, com mediana de idade de 112 meses. O IAG médio foi de 83,2%. Os índices de adesão à terapêutica (IAT) médios para alfadornase, enzimas pancreáticas, tobramicina inalatória de uso contínuo, suplementos vitamínicos, suplementos nutricionais e orientações dietéticas foram, respectivamente, 86,1; 96,6; 78,6; 88,1; 51,8 e 78%. Crianças com idade inferior a 14 anos apresentaram melhor AT (p=0,021). As correlações entre a AT autorreferida e a presumida pelos profissionais variaram de 0,117 a 0,402, sendo maiores para a psicologia e a nutrição. Conclusões: A taxa global de AT foi elevada, principalmente para menores de 14 anos. Houve correlação positiva entre a AT autorreferida e as avaliações da psicologia (p=0,032) e da nutrição (p=0,012).

Consenso chileno para la atención integral de niños y adultos con fibrosis quística / Chilean consensus for the integral care of children and adults with cystic fibrosis

Cystic Fibrosis (CF) is the most frequent hereditary disease in whites, with a reserved prognosis. Since 2003, Chile began a comprehensive National Cystic Fibrosis Program, directed by the Respiratory Health Unit of the Ministry of Health. To date, the main results of the Program record a significantly longer survival (average 27 years) and a significant reduction in the age of diagnosis of patients admitted from 2006 onwards. Access to Chilean Explicit Health Guarantees, the implementation of neonatal screening in some regions of the country, the organization and setting up of CF-trained teams of various specialties, has contributed to improving results. Although the main manifestations are of the respiratory and digestive system, the multisystemic nature of CF makes it necessary to know the different aspects involved in its management, in order to optimize the results of the treatment and the resources invested, both in the public and private sectors. This document is a review and an update on the main aspects of the diagnosis, monitoring and treatment of the respiratory and non-respiratory manifestations of CF.

La Fibrosis Quística (FQ) es la enfermedad hereditaria de pronóstico reservado más frecuente en raza blanca. Desde el año 2003, Chile inicia un Programa Nacional de Fibrosis Quística, de carácter integral, dirigido por la Unidad de Salud Respiratoria del Ministerio de Salud. Hasta la fecha, los principales resultados del Programa registran una significativa mayor sobrevida (promedio 27 años) y una significativa reducción en la edad de diagnóstico de los pacientes ingresados desde 2006 en adelante. El acceso a la canasta GES (Garantías Explícitas en Salud), la implementación del tamizaje neonatal en algunas regiones del país, la organización y la constitución de equipos entrenados en FQ de diversas especialidades, ha contribuido a mejorar los resultados. Si bien las principales manifestaciones son del aparato respiratorio y digestivo, el carácter multisistémico de la FQ obliga a conocer los distintos aspectos involucrados en su manejo, a fin de optimizar los resultados del tratamiento y los recursos invertidos, tanto en el sector público como privado. Este documento es una revisión y actualización sobre los principales aspectos del diagnóstico, seguimiento y tratamiento de las manifestaciones respiratorias y no respiratorias de la FQ.

Adherence to inhalation therapy and quality of life in children with cystic fibrosis: a cross-sectional study

Introduction: Inhalation therapy is a crucial part of the cystic fibrosis (CF) treatment regimen. Drugs that assist in mucociliary clearance and inhaled antibiotics are used by most patients. Methods: This is a cross-sectional study where patients with CF and their caregivers answered questionnaires regarding their adherence to inhalation therapy and QoL. Demographic, spirometric, and bacteriological data, as well as S-K scores and hospitalization frequencies were also collected. Results: We included 66 patients in this study; participants had a mean age of 12.3 years and Z-scores of -1.4 for forced expiratory volume in 1 second and 48.6 for body mass index. Patients were divided into 2 groups according to their self-reported adherence to inhalation therapy: high adherence (n = 46) and moderate/low adherence (n = 20). When comparing both groups, there was no statistically significant differences in age, sex, family income, and S-K score (p > 0.05). The high-adherence group had had shorter hospitalization periods in the previous year (p = 0.016) and presented better scores in the following domains of the QoL questionnaire: emotion (p = 0.006), eating (p = 0.041), treatment burden (p = 0.001), health perception (p = 0.001), and social (p = 0.046). Conclusions: A low self-reported adherence to inhalation therapy recommendations was associated with longer hospitalizations in the previous year and with a decrease in QoL in pediatric patients with CF. (AU)

Adesão de adolescentes com fibrose cística a terapia de reposição enzimática: fatores associados / Adherence of adolescents with cystic fibrosis to enzyme replacement therapy: associated factors

Resumo O objetivo deste artigo é avaliar a prevalência e os fatores associados à adesão a terapia de reposição enzimática em adolescentes com Fibrose cística. Estudo transversal, descritivo e observacional. Foram coletados dados sociodemográficos e clínicos. Os instrumentos utilizados para avaliar adesão foram: questionário de Morisky-Green e a dispensação de medicação na farmácia e para os fatores associados, entrevista com questionário estruturado. Foram entrevistados 44 adolescentes. Segundo o método de análise de dispensação da farmácia e o questionário de Morisky-Green, encontramos uma adesão de 45,5% e 11,4%, respectivamente. A maior adesão foi observada naqueles com diagnóstico precoce e a menor nos adolescentes mais velhos e nas meninas. Os fatores com a maior prevalência de não adesão foram: não levar as enzimas ao comer fora de casa, tomar enzimas somente nas grandes refeições, função pulmonar normal, com obstrução grave e muito grave. A prevalência de adesão a enzima foi pequena. Informações relacionadas à doença e ao tratamento devem ser aprimoradas, principalmente em adolescentes mais velhos e com comprometimento da função pulmonar, com criação de estratégias e estudos longitudinais para identificar fatores que interferem na adesão.

Abstract This article sets out to evaluate the prevalence and factors associated with adherence to enzyme replacement therapy among adolescents with cystic fibrosis. It is a cross-sectional, descriptive and observational study. Sociodemographic and clinical data were collected. The instruments used to assess adherence were: the Morisky-Green questionnaire and medication dispensation at the pharmacy, and interviews with structured questionnaires for the associated factors. Forty-four adolescents were interviewed. According to the method of the pharmacy medication dispensation analysis and the Morisky-Green questionnaire, the adherence of 45.5% and 11.4% was found, respectively. The higher adherence was observed in those with early diagnosis and the lowest in older adolescents and girls. The factors with the highest prevalence of non-adherence were: not taking enzymes when eating out of the home; only taking enzymes with major meals; normal lung function; with severe and very severe obstruction. The prevalence of adhesion to enzymes was low. Information related to the disease and treatment should be improved, especially among older adolescents and with impairment of lung function, with the creation of strategies and longitudinal studies to identify factors that interfere with adherence.

Bronquiectasias no fibrosis quística: desde la infancia a la adultez: enfoque diagnostico y terapéutico / Bronchiectasis no cystic fibrosis: from childhood to adult: diagnostic and therapeutic approach

Bronchiectasis is a suppurative lung disease with heterogeneous phenotypic characteristics. It is defined as abnormal dilation of the bronchi, losing the existing relationship between bronchial sizes and accompanying artery. According to their form, they can be cylindrical, varicose, saccular or cystic. According to its location, they could be diffuse or localized. The diagnosis of bronchiectasis is usually suspected in patients with chronic cough, mucopurulent bronchorrea, and recurrent respiratory infections. The etiology can be varied, being able to classify in cystic fibrosis bronchiectasis, when there is cystic fibrosis transmembrane regulator (CFTR) gene mutation and not cystic fibrosis, being post infectious the most frequent. Its relationship with childhood is unknown. Severe respiratory infections can predispose in a susceptible subject the so-called theory of the "vicious circle" and the development of these. Persistent bacterial bronchitis in children has been described as a probable cause of not cystic fibrosis bronchiectasis in adults. The treatment is based on the management of symptoms and the prevention of exacerbations. The evidence is poor and many treatments are extrapolated from cystic fibrosis bronchiectasis. We are going to describe the diagnostic and therapeutic approach of non-cystic fibrosis bronchiectasis in adults.

La bronquiectasia es una enfermedad pulmonar supurativa con características fenotípicas heterogéneas. Se define como la dilatación anormal de los bronquios, perdiendo la relación existente entre tamaño bronquial y arteria que acompaña. Según su forma, pueden ser clasificadas en cilíndricas, varicosas, saculares o quísticas y según su etiología presentarse de forma difusa o localizada. El diagnóstico de bronquiectasias se sospecha generalmente en pacientes con tos crónica, broncorrea mucosa, mucupurulenta e infecciones respiratorias recurrentes. La etiología es variada, pudiendo clasificarse en bronquiectasias fibrosis quística, aquellas que se encuentran en el contexto de la mutación del gen regulador transmembrana de fibrosis quística (CFTR) y no fibrosis quística, de etiologías diversas, siendo post infecciosas la gran mayoría. No se conoce con certeza su relación con la infancia, es sabido que infecciones respiratorias severas pueden predisponer en un sujeto susceptible, a la llamada teoría del "circulo vicioso" y el desarrollo de estas. La bronquitis bacteriana persistente en niños se ha descrito como una causa probable del desarrollo de bronquiectasias no fibrosis quística en adultos. El tratamiento se basa en el manejo de los síntomas y la prevención de las exacerbaciones. La evidencia es escasa y la mayoría de las terapias se han investigado en las bronquiectasias tipo fibrosis quística. En este trabajo se explicará el enfrentamiento diagnóstico y terapéutico de los adultos portadores de bronquiectasias no fibrosis quística.

Características de los cuidadores principales de niños y adolescentes con fibrosis quística / Characteristics of main caregivers of children and adolescents with cystic fibrosis

Introducción: Las investigaciones sobre los cuidadores han tomado importancia por los efectos negativos que provoca en las esferas físicas, psicológicas y sociales de estas personas, debido a su dedicación prolongada a la atención de enfermos cuyas dolencias les impiden totalmente su autocuidado. Objetivos: Referir las características de los cuidadores principales de pacientes pediátricos con fibrosis quística. Métodos: Estudio descriptivo de corte transversal realizado en el segundo semestre del 2016, con 54 cuidadoras principales de pacientes menores de 19 años, atendidos en los hospitales Pediátrico de Centro Habana, Juan Manuel Márquez, de Marianao, y el William Soler, de Boyeros. Resultados: Las cuidadoras son mujeres, madres en su mayoría, sin vínculo laboral, con nivel educativo medio superior, dedicadas al cuidado de los enfermos a tiempo completo, lo que interfiere su vida personal y social. Ante estas situaciones responden con mediana capacidad de afrontamiento y adaptación ante las situaciones que les generan estrés. Conclusiones: Las estrategias de afrontamiento utilizadas por las cuidadoras están afectadas pues no generan respuestas efectivas que les permita adaptarse y responder a las situaciones de forma óptima, por lo que se requiere reforzar los recursos que están utilizando. La meta de enfermería como ciencia y como disciplina es un factor muy importante para obtener esos recursos necesarios para mejorar la calidad de vida de los niños, adolescentes y sus cuidadores(AU)

Introduction: Research on caregivers has become important because of the negative effects this activity causes in the physical, psychological and social aspects of these people due to their prolonged dedication to the care of patients, whose illnesses prevent them from fully looking for themselves. Objective: To describe the characteristics of the main caregivers of pediatric patients with cystic fibrosis. Methods: A cross-sectional descriptive study conducted in the second semester of 2016, with 54 main caregivers of patients under 19 years old that were attended in Centro Habana Pediatric Hospital, Juan Manuel Márquez (Marianao´s municipality Pediatric Hospital), and William Soler (Boyeros municipality´s Pediatric Hospital). Results: Caregivers are women, mostly mothers, with no employment, with a medium superior level of education, who are devoted to caring for the sick patients full-time, and this interferes with their personal and social life. Given these situations, they respond with a medium capacity for coping and adapting to situations that generate stress. Conclusions: Coping strategies used by caregivers are affected because they do not generate effective responses that allow them to adapt and respond to situations in an optimal way, so it is necessary to reinforce the resources they are using. The goal of nursing as a science and as a discipline is a very important factor in obtaining those necessary resources to improve the quality of life of children, adolescents and their caregivers(AU)

Microbiological contamination of nebulizers used by cystic fibrosis patients: an underestimated problem / Contaminação microbiológica de nebulizadores usados por pacientes com fibrose cística: um problema subestimado

ABSTRACT Objective: Home nebulizers are routinely used in the treatment of patients with cystic fibrosis (CF). This study aims to evaluate the contamination of nebulizers used for CF patients, that are chronically colonized by Pseudomonas aeruginosa, and the association of nebulizer contamination with cleaning, decontamination and drying practices. Methods: A cross-sectional, observational, multicenter study was conducted in seven CF reference centers in Brazil to obtain data from medical records, structured interviews with patients/caregivers were performed, and nebulizer's parts (interface and cup) were collected for microbiological culture. Results: overall, 77 CF patients were included. The frequency of nebulizer contamination was 71.6%. Candida spp. (52.9%), Stenotrophomonas maltophilia (11.9%), non-mucoid P. aeruginosa (4.8%), Staphylococcus aureus (4.8%) and Burkholderia cepacia complex (2.4%) were the most common isolated pathogens. The frequency of nebulizers' hygiene was 97.4%, and 70.3% of patients reported cleaning, disinfection and drying the nebulizers. The use of tap water in cleaning method and outdoor drying of the parts significantly increased (9.10 times) the chance of nebulizers' contamination. Conclusion: Despite the high frequency hygiene of the nebulizers reported, the cleaning and disinfection methods used were often inadequate. A significant proportion of nebulizers was contaminated with potentially pathogenic microorganisms for CF patients. These findings support the need to include patients/caregivers in educational programs and / or new strategies for delivering inhaled antibiotics.

RESUMO Objetivo: Nebulizadores caseiros são usados rotineiramente no tratamento de pacientes com fibrose cística (FC). Este estudo objetiva avaliar a contaminação de nebulizadores utilizados por pacientes de FC que estão cronicamente colonizados por Pseudomonas aeruginosa e a associação da contaminação do nebulizador com a higienização, esterilização e método de secagem. Métodos: Um estudo transversal, observacional, multicêntrico foi conduzido em sete centros de referência de FC no Brasil para obter dados de registros médicos; foram feitas entrevistas estruturadas com os pacientes/cuidadores e partes de nebulizadores (máscara e copo) foram coletados para cultura microbiológica. Resultados: No geral, 77 pacientes com FC foram incluídos. A frequência da contaminação do nebulizador foi de 71,6%. Candida spp. (52,9%), Stenotrophomonas maltophilia (11,9%), P. aeruginosa não mucoide (4,8%), Staphylococcus aureus (4,8%) e complexo Burkholderia cepacia (2.4%) foram os patógenos isolados mais comuns. A frequência de higienização dos nebulizadores foi de 97,4%, e 70,3% dos pacientes relata higienização, esterilização e secagem dos aparelhos. A lavagem com água da torneira e secagem das partes no tempo, em espaço aberto, aumentou significativamente (9 a 10 vezes) a chance de contaminação dos nebulizadores. Conclusões: Apesar dos relatos de frequente higienização dos nebulizadores, os métodos de limpeza e esterilização usados eram inadequados. Uma proporção significativa de nebulizadores foi contaminada com microrganismos potencialmente patogênicos para pacientes com FC. Estes resultados apoiam a necessidade de inclusão dos pacientes/cuidadores em programas educacionais e/ou novas estratégias para fornecimento de antibióticos inalatórios.

Caracterización espirométrica de pacientes con fibrosis quística / Spirometric caracterization of cystic fibrosis patients

INTRODUCCIÓN: El pronóstico de los pacientes con fibrosis quística (FQ) ha mejorado en forma notable. La evaluación de la progresión de la enfermedad se basa en la medición del Volumen Espirado al primer segundo (VEF1). OBJETIVOS: 1. Describir volúmenes y flujos espiratorios forzados y comparar su interpretación según diferentes patrones de referencia (Knudson, multiétnicas Global Lung Initiative, Gutiérrez); 2. Comparar evolución de VEF1 según diferentes patrones de referencia; 3. Describir respuesta a broncodilatador. PACIENTES Y MÉTODO: Estudio retrospectivo de fichas clínicas y espirometrías de pacientes con FQ controlados en Hospital Dr. Sótero del Río. Se obtuvo antecedentes demográficos, resultados de prueba de sudor, estudio genético, estudio bacteriológico. Se evaluó respuesta a broncodilatador (salbutamol 400 ugr), considerando significativo un aumento en 12% en el VEF1. El valor de cloro en sudor se obtuvo mediante método de Gibson y Cooke. Se registraron: Capacidad Vital Forzada (CVF), Volumen Espirado al primer segundo (VEF1) y relación VEF1/CVF. Para graficar la progresión del VEF1 en el tiempo y las curvas teóricas de GLI, Knudson y Gutiérrez, se utilizó el software de libre distribución R versión 3.3.1. RESULTADOS: Se incluyeron 14 pacientes, 7 varones, edad entre 6 y 24 años, mediana 15 años, me diana índice de masa corporal (IMC) 18,15 (rango 14,6-23,3), mediana cloro en sudor 76 mEq/l (rango 50,2- 119), 7 pacientes con al menos 1 mutación F508del. Al utilizar fórmulas predictivas multiétnicas y de Gutiérrez, el compromiso de la función pulmonar ocurría con anterioridad en relación al uso de ecuaciones de Knudson. Ninguno de los pacientes presentó respuesta significativa a broncodilatador. CONCLUSIÓN: El grupo de pacientes descritos presenta en su mayoría compromiso funcional respiratorio y no tiene respuesta a broncodilatador. La interpretación del compromiso funcional respiratorio varía según los valores teóricos utilizados.

INTRODUCTION: The prognosis of patients with cystic fibrosis (CF) has remarkably improved. The as sessment of the disease progression is based on the measurement of the FEV1 (Forced Expiratory Volume in one second). OBJECTIVES: 1. To describe forced expiratory flows and volumes and com pare their interpretation according to different reference standards (Knudson, Gutiérrez, and multi ethnic GLI); 2. To describe bronchodilator response. Patients and Method: The medical records and spirometries of all patients with CF controlled at the Dr. Sotero del Rio Hospital were reviewed. Demographic background, sweat test results, genetic study , and bacteriological study were obtained. In addition, Forced Vital Capacity (FVC) was recorded as well as FEV1 and FEV1/FVC ratio. RESULTS: Data from 14 patients, were analyzed, seven males, aged 6-24 years, median 15 years, median BMI 18.15 (range 14.6-23.3), median sweat chloride test 76 mEq/l (range 50,2-119 mEq/l), seven patients with at least one F508del mutation. Using multi-ethnic and Gutierrez predictive formulas, lung function involvement occurred previously in relation to the use of Knudson equations. None of the patients had a significant bronchodilator response. CONCLUSION: The group of patients descri bed mostly presents functional respiratory involvement and had no bronchodilator response. The interpretation of functional respiratory involvement varies according to the theoretical values used.