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.

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.

Sex differences between women and men with COPD: A new analysis of the 3CIA study.

BACKGROUND: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females. METHODS: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis. RESULTS: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV1%, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69-1.96) and 1.73 (1.50-2.00), respectively. CONCLUSIONS: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients.

Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data.

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system.

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

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.

Compassionate Use of Lumacaftor/Ivacaftor in Cystic Fibrosis: Spanish Experience.

BACKGROUND: The most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs. METHODS: We conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1<40%, chosen from CF units country-wide. For the purposes of the study, they were treated with lumacaftor/ivacaftor 200/125mg two tablets twice a day on a compassionate use programme throughout 2016. The primary endpoint was measured in all of the sample patients. Data were analysed from ppFEV1 at baseline and was measured every 6 months. RESULTS: The mean age was 26.65 (range of 10-45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9kg/m2. We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p=0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p=0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment. CONCLUSIONS: While treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found.

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)

Compassionate Use of Lumacaftor/Ivacaftor in Cystic Fibrosis: Spanish Experience / Uso compasivo de lumacaftor/ivacaftor en fibrosis quística: experiencia española

Background: The most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs. Methods: We conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1 < 40%, chosen from CF units country-wide. For the purposes of the study, they were treated with lumacaftor/ivacaftor 200/125 mg two tablets twice a day on a compassionate use programme throughout 2016. The primary endpoint was measured in all of the sample patients. Data were analysed from ppFEV1 at baseline and was measured every 6 months. Results: The mean age was 26.65 (range of 10-45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9 kg/m2. We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p = 0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p = 0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment. Conclusions: While treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found

Introducción: La mutación causante de fibrosis quística (FQ) más frecuente es la deltaF508 (F508del), presente en el 28% de los pacientes españoles con FQ. Aunque la literatura sobre estudios en vida real en pacientes de FQ homocigotos para F508del tratados con lumacaftor/ivacaftor es escasa, pone de manifiesto la necesidad de contar con mejores estrategias para prevenir los efectos adversos (EA) relacionados con el tratamiento, así como del desarrollo de nuevos fármacos. Métodos: Se realizó un estudio observacional, retrospectivo multicéntrico para describir los efectos del tratamiento con lumacaftor/ivacaftor en vida real en España. Se incluyeron 20 pacientes con FQ, edad superior a los 6 años y ppFEV1 < 40%, procedentes de unidades de FQ de todo el país. Para los fines del estudio, fueron tratados con 2 comprimidos de lumacaftor/ivacaftor 200/125 mg/2 veces al día como parte de un programa de uso compasivo a lo largo de 2016. El criterio de valoración primario se midió en las muestras de todos los pacientes. Los datos de ppFEV1 se analizaron al inicio y cada 6 meses. Resultados: La mediana de edad fue de 26,65 (rango: 10-45), mientras que la mediana de ppFEV1 antes del tratamiento fue del 32,4% y la mediana del IMC 19,9 kg/m2. No se encontraron diferencias al analizar los cambios de ppVEF1 e IMC desde el inicio y durante el tratamiento con lumacaftor/ivacaftor. Sin embargo, se estableció una asociación moderada entre los días requeridos de antibiótico intravenoso y el uso de lumacaftor/ivacaftor (p = 0,001). De hecho, con lumacaftor/ivacaftor, los pacientes requirieron 5,8 días de tratamiento intravenoso con antibiótico, comparado con los 14,9 días previos al estudio. Además, el número de exacerbaciones pulmonares graves que requirieron hospitalización fue estadísticamente menor con lumacaftor/ivacaftor (p = 0,003). Por último, el 75% de la muestra presentó EA, lo cual supuso la discontinuación del tratamiento en un 35% de los casos. Conclusión: El tratamiento con lumacaftor/ivacaftor mejoró el número de exacerbaciones pulmonares severas, pero no supuso mejora ni en el ppFEV1 ni el IMC

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