Fibrosis quística: epidemiología, clínica, diagnóstico y tratamiento / Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis and treatment

La fibrosis quística es una enfermedad genética y multisistémica. La principal comorbilidad en la edad adulta es la afectación respiratoria, con la presencia de bronquiectasias, infección bronquial crónica y obstrucción al flujo aéreo. Hasta hace una década los tratamientos estaban dirigidos a favorecer el drenaje de secreciones, reducir las exacerbaciones respiratorias, controlar la infección bronquial crónica y enlentecer el deterioro funcional, pero con la llegada de los moduladores del gen cystic fibrosis transmembrane conductance regulator (CFTR) el paradigma de la fibrosis quística se ha modificado. Este novedoso tratamiento da un paso más frente al tratamiento de esta enfermedad, es capaz de mejorar la producción de proteína CFTR defectuosa y aumentar su expresión en la superficie celular, para así conseguir un mejor funcionamiento del intercambio iónico fluidificando las secreciones respiratorias y reduciendo la obstrucción al flujo aéreo. Además, en la actualidad hay diferentes líneas de investigación orientadas a corregir el defecto genético causante de la fibrosis quística (AU)

Cystic fibrosis is a genetic and multisystemic disease. The main comorbidity in adulthood is respiratory involvement, with the presence of bronchiectasis, chronic bronchial infection and airflow obstruction. Until a decade ago, treatments were aimed at favoring secretion drainage, reducing respiratory exacerbations, controlling chronic bronchial infection and slowing functional deterioration, but with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the cystic fibrosis paradigm has changed. This novel treatment goes a step further in the management of this disease, it is able to improve the production of defective CFTR protein and increase its expression on the cell surface, thus achieving a better functioning of ion exchange, fluidizing respiratory secretions and reducing airflow obstruction. In addition, there are currently different lines of research aimed at correcting the genetic defect that causes cystic fibrosis (AU)

Cystic fibrosis: Epidemiology, clinical manifestations, diagnosis and treatment. / Fibrosis quística: epidemiología, clínica, diagnóstico y tratamiento.

Cystic fibrosis is a genetic and multisystemic disease. The main comorbidity in adulthood is respiratory involvement, with the presence of bronchiectasis, chronic bronchial infection and airflow obstruction. Until a decade ago, treatments were aimed at favoring secretion drainage, reducing respiratory exacerbations, controlling chronic bronchial infection and slowing functional deterioration, but with the advent of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the cystic fibrosis paradigm has changed. This novel treatment goes a step further in the management of this disease, it is able to improve the production of defective CFTR protein and increase its expression on the cell surface, thus achieving a better functioning of ion exchange, fluidizing respiratory secretions and reducing airflow obstruction. In addition, there are currently different lines of research aimed at correcting the genetic defect that causes cystic fibrosis.

Recommendations for the Implementation of the Self-Administration of Alpha-1 Antitrypsin.

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT. Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3). Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support. Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation.

Real Life With Tezacaftor and Ivacaftor in Adult Patients With Cystic Fibrosis: Spanish Multicenter Study

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Treatment of Pulmonary Disease of Cystic Fibrosis: A Comprehensive Review.

Cystic fibrosis (CF) is a genetic disease that causes absence or dysfunction of a protein named transmembrane conductance regulatory protein (CFTR) that works as an anion channel. As a result, the secretions of the organs where CFTR is expressed are very viscous, so their functionality is altered. The main cause of morbidity is due to the involvement of the respiratory system as a result of recurrent respiratory infections by different pathogens. In recent decades, survival has been increasing, rising by around age 50. This is due to the monitoring of patients in multidisciplinary units, early diagnosis with neonatal screening, and advances in treatments. In this chapter, we will approach the different therapies used in CF for the treatment of symptoms, obstruction, inflammation, and infection. Moreover, we will discuss specific and personalized treatments to correct the defective gene and repair the altered protein CFTR. The obstacle for personalized CF treatment is to predict the drug response of patients due to genetic complexity and heterogeneity of uncommon mutations.

Effect of Sex Differences on Computed Tomography Findings in Adults With Cystic Fibrosis: A Multicenter Study / Efecto de las diferencias de sexo en los hallazgos en la tomografía axial computerizada en adultos con fibrosis quística: un estudio multicentro

Background: The survival of women with cystic fibrosis (CF) is lower than that of men by approximately 5 years. While various factors have been put forward to account for this discrepancy, no specific reasons have been established. Our hypothesis was that anatomical-structural involvement is more pronounced in women with CF than in men and that this is reflected in thoracic HRCT findings.Material and methods: We performed a prospective multicentre study, in which adult patients were consecutively included over 18 months. Chest HRCT was performed, and findings were scored by 2 thoracic radiologists using the modified Bhalla system. We also studied respiratory function, applied the CFQR 14+ questionnaire, and collected clinical variables.Results: Of the 360 patients followed up in the participating units, 160 were eventually included. Mean age was 28 years, and 47.5% were women. The mean±SD global score on the modified Bhalla score was 13.7±3.8 in women and 15.2±3.8 in men (p=0.024). The highest scores were observed for sacculations, bronchial generations, and air trapping in women. Women had lower BMI, %FEV1, %FVC, and %DLCO. Similarly, the results for the respiratory domain in CFQR 14+ were worse in women, who also had more annual exacerbations.Conclusions: This is the first study to provide evidence of the implication of sex differences in HRCT findings in patients with CF. Women with CF present a more severe form of the disease that results in more frequent exacerbations, poorer functional and nutritional outcomes, deterioration of quality of life, and greater structural damage. (AU)

Introducción: La supervivencia de las mujeres con fibrosis quística (FQ) es menor que la de los varones, en aproximadamente 5 años. Si bien se han presentado varios factores para explicar esta discrepancia, no se han establecido razones específicas. Nuestra hipótesis fue que el compromiso anatómico-estructural es más pronunciado en las mujeres con FQ que en los varones, y que esto se refleja en los hallazgos de la TCAR torácica.Materiales y métodos: Realizamos un estudio prospectivo multicéntrico, en el que los pacientes adultos se fueron incluyendo consecutivamente durante 18 meses. Se realizó un TCAR de tórax, y 2 radiólogos torácicos evaluaron los hallazgos utilizando la escala de Bhalla modificada. También estudiamos la función respiratoria, aplicamos el cuestionario CFQR 14+ y recogimos ciertas variables clínicas.Resultados: De los 360 pacientes en seguimiento en las unidades participantes, finalmente se incluyeron 160. La edad media fue de 28 años, y el 47,5% eran mujeres. La puntuación global media±DE en la escala de Bhalla modificada fue de 13,7±3,8 en mujeres y de 15,2±3,8 en varones (p=0,024). Las puntuaciones más altas se observaron para las saculaciones o abscesos, las generaciones bronquiales y el atrapamiento de aire en mujeres. Las mujeres tenían un IMC, % FEV1, % FVC y % DLCO más bajos. Del mismo modo, los resultados para el dominio respiratorio en el CFQR 14+ fueron peores en las mujeres, que también tenían más exacerbaciones anuales.Conclusiones: Este es el primer estudio que proporciona evidencia de la implicación de las diferencias de sexo en los hallazgos de la TCAR en pacientes con FQ. Las mujeres con FQ presentan una forma más grave de la enfermedad que resulta en exacerbaciones más frecuentes, peores resultados funcionales y nutricionales, deterioro de la calidad de vida y mayor daño estructural. (AU)

Effect of Sex Differences on Computed Tomography Findings in Adults With Cystic Fibrosis: A Multicenter Study.

BACKGROUND: The survival of women with cystic fibrosis (CF) is lower than that of men by approximately 5 years. While various factors have been put forward to account for this discrepancy, no specific reasons have been established. Our hypothesis was that anatomical-structural involvement is more pronounced in women with CF than in men and that this is reflected in thoracic HRCT findings. MATERIAL AND METHODS: We performed a prospective multicentre study, in which adult patients were consecutively included over 18 months. Chest HRCT was performed, and findings were scored by 2 thoracic radiologists using the modified Bhalla system. We also studied respiratory function, applied the CFQR 14+ questionnaire, and collected clinical variables. RESULTS: Of the 360 patients followed up in the participating units, 160 were eventually included. Mean age was 28 years, and 47.5% were women. The mean±SD global score on the modified Bhalla score was 13.7±3.8 in women and 15.2±3.8 in men (p=0.024). The highest scores were observed for sacculations, bronchial generations, and air trapping in women. Women had lower BMI, %FEV1, %FVC, and %DLCO. Similarly, the results for the respiratory domain in CFQR 14+ were worse in women, who also had more annual exacerbations. CONCLUSIONS: This is the first study to provide evidence of the implication of sex differences in HRCT findings in patients with CF. Women with CF present a more severe form of the disease that results in more frequent exacerbations, poorer functional and nutritional outcomes, deterioration of quality of life, and greater structural damage.

Predictive value of the modified Bhalla score for assessment of pulmonary exacerbations in adults with cystic fibrosis.

OBJECTIVES: The objective of this study was to analyze the predictive value of the modified Bhalla score in high-resolution computed tomography (HRCT) for assessment of pulmonary exacerbations (PEx) in cystic fibrosis (CF) patients. We also describe the relationship between this score and pulmonary function test results. METHODS: We performed a multicenter and prospective study where adult patients with CF were included consecutively over 18 months. All patients underwent HRCT with acquisition in inspiration and expiration. The results were analyzed by an expert radiologist who assigned a modified Bhalla score value. Lung function was also assessed, and clinical variables were collected. Follow-up lasted approximately 1 year, and PEx were registered. RESULTS: The study population comprised 160 subjects selected from 360 CF patients monitored in the participating CF units. The mean age was 28 years, 47.5% were women, and mean forced expiratory volume in 1 s (FEV1) was 67.5%. The mean global modified Bhalla score was 14.5 ± 0.31 points. Pulmonary function test (PFT) results and the modified Bhalla score correlated well, mainly forced vital capacity (FVC) and FEV1. We constructed a statistical model based on the overall Bhalla score to predict the number of PEx. CONCLUSIONS: The overall modified Bhalla score can predict future PEx in CF patients. This useful tool can help to prevent PEx in higher risk patients. KEY POINTS: • Pulmonary function test results and the modified Bhalla score correlated well with FVC and FEV1. • The total modified Bhalla score can predict the number of exacerbations in adult CF patients. • Our findings highlight the need to establish a unified protocol for chest HRCT during the follow-up of adult patients with CF in order to anticipate possible complications and determine their impact on pulmonary function.

Impact of SARS-CoV-2 infection in patients with cystic fibrosis in Spain: Incidence and results of the national CF-COVID19-Spain survey.

BACKGROUND: Given the high incidence of confirmed infection by SARS-CoV-2 and mortality by COVID-19 in the Spanish population, its impact was analysed among persons with Cystic Fibrosis (CF) as a group at risk of a worse evolution. The possible causes of the incidence observed in them are explained and how CF Units have faced this health challenge is detailed. METHODS: Retrospective descriptive observational study, for which a Spanish CF Patients with Confirmed COVID-19 Registry is created, requesting information on number of people affected between 8 March-16 May 2020 and their clinical-demographic characteristics from the CF Units participating in the European Cystic Fibrosis Society Patient Registry (ECFSPR). The accumulated incidence is calculated, compared with that of the general population. Additionally, a survey (CF-COVID19-Spain) is carried out on prevention of SARS-CoV-2 infection, workings of CF Units and possible reasons for the incidence observed. RESULTS: COVID-19 was diagnosed in eight CF patients, one of whom had received a lung transplant. The accumulated incidence was 32/10000 in CF patients and 49/10000 in the general population. General death rate was 5.85/10000 while no CF patients included in the ECFSPR died. The characteristics of those affected and the results of the survey are described. CONCLUSIONS: Despite being considered a disease at high risk of severe COVID-19, the low incidence and mortality in CF patients in Spain contrasts with the figures for the general population. The possible factors that would explain such findings are discussed, with the help of the results of the CF-COVID19-Spain survey.

Estudio de una cohorte de paciente con fibrosis quística y Scedosporium spp / Study of a Cohort of Patients With Cystic Fibrosis and Isolation of Scedosporium spp

Introducción: En los últimos años se observa un aumento de la prevalencia de colonización e infección por Scedosporium spp. en pacientes con fibrosis quística (FQ). En el presente estudio se registra la frecuencia de aislamiento de Scedosporium spp. en una Unidad de FQ de adultos, analizándose las características de los pacientes y los factores predisponentes. Métodos: Se realizó un estudio observacional retrospectivo en 87 pacientes adultos con FQ en los que se valoró la presencia de cultivo positivo para Scedosporium spp. durante 5 años (enero de 2012-julio de 2017). Se recogieron las siguientes variables clínicas: edad, sexo, índice de masa corporal, genotipo, presencia de insuficiencia pancreática, colonizaciones bacterianas, función pulmonar, complicaciones, exacerbaciones y tratamiento, así como puntuación Bhalla modificada de la última tomografía computarizada axial de alta resolución. Los resultados se analizaron con el paquete estadístico IBM SPSS Statistics Version 22.0. Resultados: En un 25,3% de los pacientes se aisló Scedosporium spp. En el análisis bivariante se observó en estos enfermos más frecuencia de Pseudomonas aeruginosa, peor puntuación en la clasificación de Bhalla (destacando los ítems presencia de bronquiectasias, tapones mucosos y generaciones bronquiales), un descenso leve en la capacidad de difusión pulmonar (DLCO) y que recibían con más frecuencia antibioterapia inhalada. En el análisis multivariante de regresión logística únicamente el ítem generaciones bronquiales fue significativo. Conclusiones: Scedosporium spp. debe considerarse un patógeno oportunista emergente en pacientes con FQ del que se desconoce su implicación clínica, factores de riesgo o necesidad de tratamiento

Introduction: In recent years an increase in the prevalence of colonization and infection by Scedosporium spp. in patients with cystic fibrosis (CF) has been observed. In this article, we study the frequency of isolation of Scedosporium spp. in an adult CF Unit, analyzing characteristics of the patients and predisposing factors. Methods: A retrospective observational study was conducted in 87 adult CF patients in whom the presence of positive culture for Scedosporium spp. was tested for a 5-year period (January 2012-July 2017). We recorded the following clinical variables: age, sex, body mass index, genotype, presence of pancreatic insufficiency, bacterial colonization, lung function, other complications, exacerbations and treatment, and the modified Bhalla score from the last high-resolution computed tomography. Results were analyzed with IBM SPSS Statistics Version 22.0 software. Results: Scedosporium spp. was isolated in 25.3% of patients. In the bivariate analysis, these patients showed a higher rate of Pseudomonas aeruginosa infection, worse score in the Bhalla classification (highlighting the following items: bronchiectasis, mucus plugs and bronchial generations), a slight decrease in the lung diffusion capacity and more frequently received inhaled antibiotics. In the logistic regression multivariate analysis, only the bronchial generations item was significant. Conclusion: Scedosporium spp. must be considered an emerging opportunistic pathogen in patients with CF whose clinical involvement, risk factors or need for treatment is unknown