Función pulmonar: función pulmonar en fibrosis quística / Lung function in cystic fibrosis

La fibrosis quística (FQ) es una enfermedad hereditaria autosómica recesiva, causada por la mutación del gen que codifica la proteína CFTR (cystic fibrosis transmembrane conductance regulator), afecta varios órganos, pero la enfermedad pulmonar es la primera causa de morbimortalidad. El diagnóstico a través del screening neonatal (SNN) y los nuevos tratamientos moduladores del CFTR han aumentado el interés por pesquisar y monitorizar la función pulmonar antes del inicio de los síntomas para lograr un tratamiento adecuado y oportuno con una mejor calidad de vida. Existen numerosas formas de medir la función pulmonar según la edad, colaboración y recursos disponibles. En este artículo se resumen las pruebas clásicas y las más novedosas, como técnicas de imágenes, en la búsqueda de marcadores precoces de daño pulmonar, herramientas con los que cada centro de fibrosis quística debiera contar en la era de tratamientos moduladores del CFTR, que están cambiando el pronóstico de los pacientes con esta enfermedad.

Cystic fibrosis (CF) is an autosomal recessive inherited disease, caused by mutation of the gene encoding the CFTR protein (cystic fibrosis transmembrane conductance regulator), affects several organs, but lung disease is the first cause of morbidity and mortality. Diagnosis through neonatal screening (NNS) and new CFTR modulating treatments have increased interest in screening and monitoring lung function before the onset of symptoms to achieve adequate and timely treatment with a better quality of life. There are numerous ways to measure lung function based on age, collaboration, and available resources. This article summarizes the classic and the most innovative tests, which have emerged from imaging techniques in the search for early markers of lung damage, tools that each cystic fibrosis center should have in the era of CFTR modulating treatments, which are changing the prognosis of patients with this disease.

Ultrasound findings of pubertal development in girls with cystic fibrosis and their association with clinical outcomes and Tanner staging

ABSTRACT Objective: Patients with cystic fibrosis (CF) have a high incidence of pubertal and growth delay. In girls with CF, pubertal delay has an important psychological impact. Still, only a few studies have explored the occurrence of pubertal delay in girls with CF. The aims of this study were to compare the pubertal development of girls with CF compared with healthy controls regarding Tanner staging and pelvic ultrasound and, in girls with CF, correlate the findings with those of spirometry, body mass index, Shwachman-Kulczycki score (SKS), and genotyping. Subjects and methods: This was a cross-sectional, case-control study including 35 girls with CF aged 6-17 years and following up at the Pediatric Pulmonology Outpatient Clinic of a tertiary hospital. These patients were compared with 59 healthy controls who had undergone pelvic ultrasound as part of another study conducted by the same group. Girls with CF were consecutively enrolled in the study during their annual routine check-up visit. Data collected in the CF group included spirometry and anthropometric results, SKS values, bone age, occurrence of current cystic fibrosis-related diabetes (CFRD) and Pseudomonas aeruginosa colonization, history of meconium ileus, genotype, ultrasound parameters, and Tanner stage. Results: Pelvic ultrasound findings and Tanner stage reflected less pubertal development in girls with CF compared with healthy controls. Pubertal stage in patients with CF who presented CFRD (3.17 ± 1.16), had chronic colonization by Pseudomonas aeruginosa (3.10 ± 1.10), or were homozygous for the F508del mutation (1.91 ± 1.30) was more delayed than in controls (3.41 ± 1.41). Tanner stage correlated with age at menarche, bone age, and anthropometric and ultrasound data. Conclusions: Girls with CF presented a delay in pubertal development evaluated by Tanner stage and ultrasound parameters, which was more evident in the presence of comorbidities.

Diagnóstico pré-natal de fibrose cística / Prenatal diagnosis of cystic fibrosis

A fibrose cística é caracterizada pelo desequilíbrio na concentração de cloro e sódio nas células, mudando a viscosidade das secreções. Uma das primeiras manifestações clínicas consiste em obstrução intestinal perinatal, consequência do mecônio anormalmente espesso. Até 50% dos recém-nascidos com íleo meconial apresentam alguma lesão intestinal associada, como volvo ou perfuração. O caso apresenta uma gestante de 31 semanas, com história pregressa de filha com fibrose cística, que foi encaminhada ao serviço de ultrassom de urgência queixando-se de redução de movimentação fetal. Ao ultrassom, o feto apresentava dilatação em alças intestinais, intestino delgado hiperecogênico e ascite. O parto foi realizado em dois dias e o neonato foi submetido à laparotomia, identificando-se vólvulo de segmento jejunoileal e necrose em segmento intestinal. Com o presente relato, ressalta-se a importância da triagem e do acompanhamento das pacientes com fator de risco, durante o pré-natal, visando ao melhor prognóstico neonatal.(AU)

Cystic fibrosis is characterized by imbalance in the concentration of sodium and chlorine in the cells, changing the viscosity of the secretions. One of the first clinical manifestations consists of perinatal intestinal obstruction, a consequence of abnormally thick meconium. Up to 50% of newborns with meconium ileus have some associated intestinal lesion, such as volvulus or perforation. The case presents a pregnant woman of 31 weeks, a previous history of a daughter with cystic fibrosis, referred to the emergency ultrasound service complaining of reduced fetal movement. At ultrasound, the fetus presented dilation in intestinal loops, hyperechogenic small intestine and ascites. Delivery was performed in two days and the neonate underwent laparotomy, identifying jejunoileal segment volvulus and intestinal segment necrosis. With the present report, the importance of screening and monitoring of patients with a risk factor during prenatal care is emphasized, aiming at a better neonatal prognosis.(AU)

High-resolution computed tomography findings in young infants with cystic fibrosis detected by newborn screening

OBJECTIVE: High-resolution computed tomography (HRCT) allows the early detection of pathological changes in the lung structure, and reproducible scoring systems can be used to quantify chest computed tomography (CT) findings in patients with cystic fibrosis (CF). The aim of the study was to describe early HRCT findings according to a validated scoring system in infants with CF diagnosed by newborn screening (NBS). METHODS: This cross-sectional study included infants with CF diagnosed by NBS who were born between January 2013 and January 2017 and who underwent HRCT scanning within the first year after diagnosis when they were clinically stable. The CT scans were evaluated using the modified Bhalla score. RESULTS: Thirty-two subjects underwent HRCT scanning. The mean total-modified Bhalla score was 3.6±2.1, and 93.8% of the scans were abnormal. Pseudomonas aeruginosa airway colonization was associated with increased modified Bhalla score values. Bronchial wall thickening was the most common feature (90.6%), followed by bronchial collapse/consolidation (59.4%), mosaic attenuation/perfusion (50%), bronchiectasis (37.5%) and mucus plugging (15.6%). Bronchial wall thickening was diffuse in most of the patients. CONCLUSION: A substantial proportion of infants diagnosed with CF after detection by NBS already showed evidence of lung disease. P. aeruginosa colonization was associated with increased Bhalla scores, highlighting the importance of this CF pathogen in early structural lung disease. The presence of bronchial wall thickening at such a young age may reflect the presence of airway inflammatory processes. The detection and quantification of structural abnormalities with the modified Bhalla score may aid in the identification of lung disease before it is clinically apparent.

Uso da ultrassonografia para avaliar a espessura muscular e a gordura subcutânea em crianças e adolescentes com fibrose cística / The use of ultrasonography to evaluate muscle thickness and subcutaneous fat in children and adolescents with cystic fibrosis

RESUMO Objetivo: Comparar a espessura muscular e a gordura subcutânea entre pacientes com fibrose cística (FC) e controles saudáveis e correlacionar os achados ultrassonográficos com variáveis nutricionais, clínicas e de função pulmonar. Métodos: Foram incluídos sujeitos (6 a 18 anos) com o diagnóstico de FC e indivíduos saudáveis. Foram realizadas medidas antropométricas, avaliação ultrassonográfica da espessura muscular e da gordura subcutânea do tríceps, quadríceps e da região do gastrocnêmio, além da quantificação das pregas cutâneas. O percentual de gordura corporal foi estimado pelas pregas cutâneas. Osindivíduos com FC também tiveram a função pulmonar avaliada por espirometria. Resultados: Foram incluídos 39 pacientes com FC e 45 controles. Ossujeitos com FC apresentaram do índice de massa corporal menor (p=0,011). Acomposição corporal e a espessura muscular foram similares entre os grupos. Apenas a circunferência da panturrilha (p=0,023) e o diâmetro do fêmur (p<0,001) foram menores nos pacientes com FC. Embora sem diferença na comparação dos achados ultrassonográficos da gordura subcutânea, os pacientes com FC apresentaram redução das dobras cutâneas do tríceps (p=0,0031) e do quadríceps (p=0,019). Além disso, observaram-se correlações fracas e moderadas da espessura do quadríceps pelo ultrassom com a capacidade vital forçada (CVF) e massa magra, respectivamente. Também houve correlações moderadas das pregas cutâneas do tríceps, quadríceps e gastrocnêmio com a gordura subcutânea avaliada pela ultrassonografia. Conclusões: Pacientes com FC apresentaram menor espessura da gordura subcutânea. A espessura muscular se correlacionou com a CVF e os parâmetros nutricionais, e a ultrassonografia apresentou correlação positiva com as pregas cutâneas.

ABSTRACT Objective: To compare muscle thickness and subcutaneous fat in cystic fibrosis (CF) patients and healthy controls using ultrasonography (US), and to correlate US findings with nutritional, clinical and functional variables. Methods: Patients aged 6 to 18 years old with a diagnosis of CF and healthy controls were included. Participants underwent anthropometric measurements, an ultrasonographic evaluation of muscle thickness and subcutaneous fat in the triceps, quadriceps, and gastrocnemius regions, and skinfold thickness measurements. Body fat percentage was estimated using skinfold measurement. Subjects with CF also underwent a pulmonary function assessment using spirometry. Results: We studied 39 CF patients and 45 controls. Alower body mass index was observed in CF patients (p=0.011). Body composition and muscle thickness were similar between the groups. Only calf (p=0.023) circumference and femur diameter (p<0.001) were lower in CF patients. Although there were no significant between-group differences in the comparison of US measurements of subcutaneous fat, CF patients exhibited decreased skinfold thickness in the triceps (p=0.031) and quadriceps (p=0.019). Moreover, there were weak and moderate correlations of US quadricep thickness with forced vital capacity (FVC) and lean mass, respectively. Moderate correlations of the triceps, quadriceps and gastrocnemius between US subcutaneous fat and skinfold measurements were found. Conclusions: Patients with CF presented a reduction in subcutaneous fat content. Muscle thickness correlated with FVC and nutritional parameters. In addition, US findings correlated positively with skinfold measurements.

Avaliação em pacientes com fibrose cística a partir da utilização de escores radiográficos / Assessing cystic fibrosis patients through radiological scores

Objetivo: rever a fisiopatologia da doença pulmonar e analisar sua correspondência com a avaliação radiográfica do tórax com base em escores na fibrose cística. Métodos: o levantamento bibliográfico foi realizado a partir das informações disponibilizadas pelas bases de dados Medline, Highwire, LILACS e por pesquisa direta, utilizando os termos Cystic Fibrosis, chest x-ray, lung disease. Resultados: para a elaboração desta revisão narrativa foram selecionados 25 referências bibliográficas abordando a fisiopatologia da doença pulmonar, os fatores que podem influenciar a evolução da fibrose cística e os escores radiográficos utilizados para avaliação do estágio de gravidade da lesão pulmonar. Os escores permitem quantificar, objetivamente, os danos pulmonares detectados na radiografia de tórax. Os artigos originais das descrições dos escores demonstraram de forma individualizada os objetivos de cada um deles, ressaltando sua utilidade e limitações. Conclusão: o conhecimento da fisiopatologia da fibrose cística é fundamental para a compreensão dos escores radiográficos e, principalmente, para o conhecimento de suas limitações. Não há um escore ideal e perfeito, portanto, é necessário conhecer a fisiopatologia da doença e os escores existentes, para então optar pelo escore ou escores a serem utilizados em diferentes situações clínicas.

Objective: To review the pathophysiology of pulmonary disease with emphasis on radiographic evaluation of the chest through scores in cystic fibrosis. Methods: The literature review was performed from the information provided by Medline, Highwire, LILACS and direct search using the Cystic Fibrosis terms, chest x-ray, lung disease. Results: A total of 25 references in the no systematically review addressing the pathophysiology of pulmonary disease, the factors that can influence the course of cystic fibrosis and radiographic scores used to stage the assessment of severity of lung injury. The creation of scores enabled, objectively quantify the lung damage shown on chest radiography. Original articles descriptionsof scores showed individually the objectives of each one of them, pointing their values and their failures. Conclusions: The pathophysiology of cystic fibrosis is critical for the comprehension of radiographic scores, and especially to the knowledge of scoring limitations. There is not a perfect score, so it is necessary to know the pathophysiology of the disease and scores to choose the aproppriate score or scores in defferent clinical situations.

Escores clínicos e diagnósticos por imagem na fibrose cística / Clinical Scores and Diagnostic Imaging in Cystic Fibrosis

Objetivo: rever a literatura, verificando o papel da tomografia computadorizada de alta resolução (TCAR) do tórax no acompanhamento de crianças e adolescentes com fibrose cística. Método: o levantamento bibliográfico foi realizado a partir das informa- ções disponibilizadas pelas bases de dados Medline, MD Consult, Highwire, Medscape, LILACS e por pesquisa direta dos últimos 10 anos, utilizando-se os termos cysticfibrosis, tomography, spirometry e children. Resultados: foram selecionados 21 artigos originais em revisão não sistemática. A TCAR do tórax é um bom método, uma vez que é preconizada para a avaliação do parênquima pulmonar, devido às características do comprometimento pulmonar na fibrose cística. Permite a identificação das principais alterações relacionadas à fibrose cística: bronquiectasias, espessamento peribrônquico, plugs mucosos e hiperinsuflação/enfisema, além de consolidações, atelectasias e lesões bolhosas. Realizada na rotina para determinar as alterações estruturais pulmonares, a TCAR também tem indicação nos casos de piora clínica significativa, independentemente da idade do paciente. A questão sobre o melhor momento para sua realização também carece de estudos clínicos e normalmente é baseada em protocolos de serviços. Estudos comparativos entre a espirometria e o escore clínico-radiológico de Shwachman- -Kulczycki mostraram forte correlação positiva entre este e o volume expiratório forçado no primeiro segundo (VEF1) (r=0,75, P<0,001 e r=0,50, P≤0,01). Porém, enquanto a TCAR mostrou alterações estruturais significativas, a espirometria exibiu mínima progressão ou pouca melhora no padrão. Muita atenção deve ser dada à questão da radiação ionizante e à quantidade de radiação a que o paciente é exposto. Conclusão: não há ainda papel definido para a TCAR no acompanhamento aos pacientes com fibrose cística. À medida que técnicas de baixa dose são desenvolvidas, pode-se vislumbrar a TCAR como um excelente método de avaliação do comprometimento pulmonar dos jovens menores de seis anos e, por isso, impossibilitados de realizar as provas de função pulmonar. (AU)

Objective: To review the literature, verifying the role of high resolution computed tomography of the chest in the monitoring of children and adolescents with cystic fibrosis.Method: The bibliographic survey was based on information released by the Medline, MD Consult, Highwire, Medscape, LILACS, and direct search of the past 10 years, using the terms cysticfibrosis, tomography, spirometry and children. Results: We have selected 21 original articles on non-systematic review. The High Resolution Computed Tomography (HRCT) is a good method, since it is recommended to evaluate the lung parenchyma, due to the characteristics of lung impairment in cystic fibrosis. Allows identification of the main changes related to cystic fibrosis bronchiectasis, peribronchial thickening, mucus plugging and hyperinflation / emphysema, as well as consolidation, atelectasis, and bullae. Performed routinely to determine the structural abnormalities, HRCT is also indicated in cases of clinically significant worsening of the patient regardless of age. The question about the best time to perform it also lacks clinical studies and is usually based on service protocols. Comparative studies of spirometry and clinical-radiologic Shwachman-Kulczycki show that a strong positive correlation between this and FEV1 (r=0.75, P<0.001 and r=0.50, P≤ 0.01) but while HRCT showed significant structural changes spirometry showed minimal progression or improvement in the standard. Great attention should be given to the issue of ionizing radiation and the amount of radiation to which the patient is exposed. Conclusion: There is still a role for HRCT in monitoring patients with Cystic Fibrosis. As low-dose techniques are developed one can glimpse the HRCT as an excellent method for evaluation of pulmonary involvement of young pacient under the age of 6 years, and therefore unable to perform pulmonary function tests.

[3120+1kbdel8.6kb]+[p.N1303K] Genotype in an Emirati cystic fibrosis patient: indication of a founder mutation in Palestinian Arabs

Cystic fibrosis [CF] is the most common life-limiting autosomal recessive disorder in Caucasian population. The disease was initially considered to be rare in Middle Eastern countries. 95% of CF in Emirati families is due to two mutations only ' p.S549R[T>G] and p.F508del. We report here the case of a patient referred to CF and Respiratory Clinic at Tawam Hospital for cystic fibrosis transmembrane regulator [CFTR] gene screening to ascertain the diagnosis of CF, who was found to carry a unique genotype, signifying the importance of retrieving ancestral histories of patients with monogenic disorders

Morbidity and mortality data of cystic fibrosis patients

To identify factors that contributed to morbidity and mortality of cystic fibrosis [CF] population in the Kingdom of Saudi Arabia [KSA]. This retrospective chart review was carried out in King Faisal Specialist Hospital and Research Centre, Riyadh, KSA, during a 9 year period, November 1993 to November 2002, on confirmed CF patients, for demographic, clinical and mortality data. A total of 190 CF patients were diagnosed during the 9 years. One hundred and sixty-four [86%] patients are alive, 26 [14%] died. Ninety-nine [52%] were males and 91 [48%] were females. Age at diagnosis 2.8 +/- 3.5 years, and period of follow up 3 +/- 3 years. In 80% of patients, symptoms started <1 year of age. Sixty-five% of patients were in the mild to moderate malnutrition stage [<90th percentile], and 63% are in the mild to moderate stunted growth [<90th percentile]. Factors that contributed to early mortality are: calculated weight/height [p-value 0.01], low albumin level at follow up [0.001], high hematocrit [HCT] [p-values=0.0002], low mean corpuscular volume [MCV] [p-0.0002], low mean corpuscular hemoglobin concentration [MCHC] [p-value 0.001], early development of antibiotic resistance [p-value=< 0.01]. High HCT, low MCV, low MCHC and low albumin are factors related to poor prognosis and early death in CF patients. Iron supplement should be given to these patients even in the presence of normal hemoglobin. Early nutritional rehabilitation is needed to improve survival of our CF patients. Cohort isolation should be encouraged in CF centres. Early treatment of chronic pseudo colonization should be adopted to improve survival