Seguridad y efectividad del tratamiento con elexacaftor, tezacaftor e ivacaftor en adultos con fibrosis quística / Safety and effectiveness of treatment with elexacaftor, tezacaftor and ivacaftor in adults with cystic fibrosis

Introducción La fibrosis quística (FQ) es una enfermedad causada por mutaciones en el gen localizado en el cromosoma 7 que codifica la proteína reguladora de la conductancia transmembrana de la FQ. Varios ensayos han demostrado la eficacia y seguridad de la combinación ELE/TEZ/IVA en los pacientes que tienen al menos una mutación F508del. El objetivo principal del estudio fue evaluar la seguridad a los 3 y 6 meses del tratamiento con ELE/TEZ/IVA en pacientes adultos con FQ. Métodos Se trata de un estudio transversal, prospectivo y unicéntrico de vida real en el que se incluyeron pacientes adultos de la unidad multidisciplinar de FQ del Hospital Universitario Ramón y Cajal que cumplían criterios para recibir tratamiento con ELE/TEZ/IVA. Se registraron las características demográficas y clínicas de todos los pacientes. Durante el tiempo del estudio, se llevaron a cabo 3 visitas (basal, a los 3 y a los 6 meses). Se registraron los efectos secundarios y la evolución de la función hepática durante el tiempo de seguimiento. Resultados A los 3 meses del inicio del tratamiento se observó una mejoría estadísticamente significativa de la función pulmonar, el IMC, las exacerbaciones pulmonares y el nivel de energía, así como en todas las categorías del cuestionario CFQ-R excepto en el dominio digestivo. Esta mejoría se mantuvo, pero no se incrementó, a los 6 meses en todas las variables, excepto en el IMC, donde sí se observaron diferencias entre los 3 y 6 meses de tratamiento. Conclusiones En la cohorte estudiada, el tratamiento con ELE/TEZ/IVA tiene un buen perfil de seguridad y produce un mejoría precoz en la función pulmonar, el IMC, la calidad de vida y el «nivel de energía» de los pacientes adultos con FQ, que se mantiene a los 6 meses de tratamiento (AU)

Introduction Cystic fibrosis (CF) is a disease caused by mutations in the gene located on chromosome 7 that encodes the CF transmembrane conductance regulator protein. Several trials have demonstrated the efficacy and safety of the ELE/TEZ/IVA combination in patients who have at least one F508del mutation. The main objective of the study was to evaluate the safety at 3 and 6 months of treatment with ELE/TEZ/IVA in adult patients with CF. Methods This is a real-life, prospective, single-center, cross-sectional study that included adult patients from the CF multidisciplinary unit. The demographic and clinical characteristics of all patients were recorded. During the time of the study, 3 visits were carried out (baseline, at 3 and at 6 months). Side effects were recorded during the follow-up time. Results 3 months after the start of treatment, a statistically significant improvement was observed. of lung function, BMI, pulmonary exacerbations and energy level, as well as in all the categories of the CFQ-R questionnaire except in the digestive domain. This improvement was maintained, but not increased at 6 months in all variables, except BMI, where differences were observed between 3 and 6 months of treatment. Conclusions In the cohort studied, treatment with ELE/TEZ/IVA has a good safety profile. and produces an early improvement in lung function, BMI, quality of life and the “energy level” of adult patients with CF, which is maintained at 6 months of treatment (AU)

[Safety and effectiveness of treatment with elexacaftor, tezacaftor and ivacaftor in adults with cystic fibrosis]. / Seguridad y efectividad del tratamiento con elexacaftor, tezacaftor e ivacaftor en adultos con fibrosis quística.

INTRODUCTION: Cystic fibrosis (CF) is a disease caused by mutations in the gene located on chromosome 7 that encodes the CF transmembrane conductance regulator protein. Several trials have demonstrated the efficacy and safety of the ELE/TEZ/IVA combination in patients who have at least one F508del mutation. The main objective of the study was to evaluate the safety at 3 and 6 months of treatment with ELE/TEZ/IVA in adult patients with CF. METHODS: This is a real-life, prospective, single-center, cross-sectional study that included adult patients from the CF multidisciplinary unit. The demographic and clinical characteristics of all patients were recorded. During the time of the study, 3 visits were carried out (baseline, at 3 and at 6 months). Side effects were recorded during the follow-up time. RESULTS: 3 months after the start of treatment, a statistically significant improvement was observed. of lung function, BMI, pulmonary exacerbations and energy level, as well as in all the categories of the CFQ-R questionnaire except in the digestive domain. This improvement was maintained, but not increased at 6 months in all variables, except BMI, where differences were observed between 3 and 6 months of treatment. CONCLUSIONS: In the cohort studied, treatment with ELE/TEZ/IVA has a good safety profile. and produces an early improvement in lung function, BMI, quality of life and the "energy level" of adult patients with CF, which is maintained at 6 months of treatment.

Safety and tolerability of inhaled antibiotics in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is typically treated with inhaled antibiotics in clinical practice. However, there is a striking lack of standardised procedures for the preparation of noncommercial solutions. We used biochemical parameters to analyse the safety and tolerability of inhaled antibiotics in patients with bronchiectasis, and determined potential associations between the inhaled antibiotics used and adherence to the medications and quality of life. METHODS: We conducted a literature review, biochemical testing, and a pilot study of patients admitted to our hospital with noncystic fibrosis bronchiectasis. The MEDLINE database was searched for studies involving inhaled antibiotics to treat bronchiectasis. We analysed the pH, osmolality, and sodium and chloride ion concentrations of the antibiotics used. The pilot study included patients receiving inhaled antibiotic treatment. Demographic data, adherence, and quality of life were recorded and assessed. We determined potential associations between the study variables. RESULTS: The literature review identified 429 articles: 106 included precise instructions for diluting antibiotics, and 18 reported data on the biochemical parameters analysed. Laboratory results showed that some antibiotic dilutions were outside the range of tolerability, especially those involving dry powders for intravenous infusion, which must be diluted for their inhalation. Adherence was good in more than 80% of the patients, and higher in men and older patients. Men reported better quality of life. No associations were found between the antibiotics used and the other variables. CONCLUSION: Regarding the biochemical parameters analysed, there is a lack of information on the tolerability and biochemical safety of noncommercial dilutions of inhaled antibiotics used to treat bronchiectasis.

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.

Colitis ulcerosa y bronquiectasias: ¿el tratamiento con tofacitinib podría repercutir en los síntomas respiratorios? / Ulcerative Colitis and Bronchiectasis: Can Treatment with Tofacitinib Have an Impact on Respiratory Symptoms?

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COPD Assessment Test in Bronchiectasis: Minimum Clinically Important Difference and Psychometric Validation: A Prospective Study.

BACKGROUND: Health-related quality of life (QoL) is one of the most important end points in bronchiectasis (BE). However, the majority of health-related QoL questionnaires are time-consuming or not validated in BE. The COPD Assessment Test (CAT) is an easy-to-use questionnaire. The objective of this study was to perform a complete validation of the CAT in BE. METHODS: This was an observational, multicenter, prospective study in patients with BE. Psychometric properties of the CAT were measured: internal consistency (Cronbach α), repeatability (test-retest; intraclass correlation coefficient), discriminant validity (correlation with severity scores), convergent validity (correlation with some validated QoL questionnaire and other clinical variables of interest), longitudinal validity (measuring before and after each exacerbation during follow-up to determine the sensitivity to change and responsiveness), predictive validity to future exacerbations, and finally minimum clinically important difference. RESULTS: Ninety-six patients were included and followed up for 1 year. Their mean age was 62.2 (15.6) years (79.2% women). The CAT showed excellent internal consistency (α, 0.95) and repeatability (intraclass correlation coefficient, 0.95). The validity of the CAT was excellent in all the measures (almost all with a Pearson coefficient > 0.40) except for the correlations with severity scores (Pearson coefficient between 0.22 and 0.26). Sensitivity to change before and after exacerbations was set at between 5.4 and 5.8 points. A CAT value ≥ 10 points showed prognostic value for patients with more than one exacerbation, and finally the minimum clinically important difference was set at 3 points. CONCLUSIONS: The CAT presented excellent psychometric properties and is a questionnaire that is easy to use and interpret in patients with BE.

Infecciones respiratorias por micobacterias no tuberculosas / Respiratory infections due to nontuberculous mycobacterias

Las infecciones más frecuentes causadas por micobacterias no tuberculosas (MNT) son las pulmonares. Los microorganismos que causan con más frecuencia estas infecciones son Mycobacterium avium complex, Mycobacterium kansasii y Mycobacterium abscessuscomplex. Su incidencia ha aumentado en las 3 últimas décadas. Tras la identificación de una MNT en el tracto respiratorio, deben considerarse aspectos clínicos y radiológicos para determinar si los aislamientos son clínicamente relevantes. También deben investigarse las condiciones predisponentes que pudieran favorecer la infección. La enfermedad pulmonar por MNT se presenta de 3 formas clínicas: a) neumonitis por hipersensibilidad; b) forma fibrocavitaria, y c) forma nodular-bronquiectásica. El diagnóstico de enfermedad respiratoria por MNT no obliga a iniciar el tratamiento inmediatamente. Antes de iniciar el mismo deben considerarse otros factores, tales como edad, comorbilidades, esperanza de vida, debido a que los tratamientos son prolongados, con potenciales efectos secundarios y, en muchos casos, con escasa respuesta a los mismos (AU)

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment (AU)

Respiratory infections due to nontuberculous mycobacterias. / Infecciones respiratorias por micobacterias no tuberculosas.

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment.