Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. Methodology: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. Results: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. Conclusions: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug. (AU)

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease.

INTRODUCTION: Elexacaftor/tezacaftor/ivacaftor (ETI) was used through the early access programme in Spain from December 2019 in cystic fibrosis (CF) patients with homozygous or heterozygous F508del mutation with advanced lung disease. METHODOLOGY: Multicentre, ambispective, observational, study in which 114 patients in follow-up in 16 national CF units were recruited. Clinical data, functional tests, nutritional parameters, quality of life questionnaires, microbiological isolates, number of exacerbations, antibiotic treatments and side effects were collected. The study also compared patients with homozygous and heterozygous F508del mutations. RESULTS: Of the 114 patients, 85 (74.6%) were heterozygous for F508del mutation, and the mean age was 32.2±9.96 years. After 30 months of treatment, lung function measured by FEV1% showed improvement from 37.5 to 48.6 (p<0.001), BMI increased from 20.5 to 22.3 (p<0.001), and all isolated microorganisms decreased significantly. The total number of exacerbations was also significantly reduced from 3.9 (±2.9) to 0.9 (±1.1) (p<0.001). All items in the CFQ-R questionnaire showed improvement, except for the digestive domain. Oxygen therapy use decreased by 40%, and only 20% of patients referred for lung transplantation remained on the active transplant list. ETI was well-tolerated, with only 4 patients discontinuing treatment due to hypertransaminemia. CONCLUSIONS: ETI decreases the number of exacerbations, increases lung function and nutritional parameters, decrease in all isolated microorganisms, for 30 months of treatment. There is an improvement in the CFQ-R questionnaire score except for the digestive item. It is a safe and well-tolerated drug.

The U-Shaped Relationship Between Eosinophil Count and Bronchiectasis Severity: The Effect of Inhaled Corticosteroids.

BACKGROUND: Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis RESEARCH QUESTION: Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? STUDY DESIGN AND METHODS: This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/µL), (2) low number of eosinophils (51-100/µL), (3) normal number of eosinophils (101-300/µL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/µL). RESULTS: Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/µL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/µL, 488 patients (52.6%) with 101-300 eosinophils/µL, and 153 patients (16.5%) with > 300 eosinophils/µL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/µL. INTERPRETATION: A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group.

Peripheral Neutrophil-to-Lymphocyte Ratio in Bronchiectasis: A Marker of Disease Severity.

Most patients with bronchiectasis have a predominantly neutrophilic inflammatory profile, although other cells such as lymphocytes (as controllers of bronchial inflammation) and eosinophils also play a significant pathophysiological role. Easy-to-interpret blood biomarkers with a discriminative capacity for severity or prognosis are needed. The objective of this study was to assess whether the peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with different outcomes of severity in bronchiectasis. A total of 1369 patients with bronchiectasis from the Spanish Registry of Bronchiectasis were included. To compare groups, the sample was divided into increasing quartiles of NLR ratio. Correlations between quantitative variables were established using Pearson's P test. A simple linear regression (with the value of exacerbations as a quantitative variable) was used to determine the independent relationship between the number and severity of exacerbations and the NLR ratio. The area under the curve (AUC)-ROC was used to determine the predictive capacity of the NLR for severe bronchiectasis, according to the different multidimensional scores. Mean age: 69 (15) years (66.3% of women). The mean NLR was 2.92 (2.03). A higher NLR was associated with more severe bronchiectasis (with an especially significant discriminative power for severe forms) according to the commonly used scores (FACED, E-FACED and BSI), as well as with poorer quality of life (SGRQ), more comorbidities (Charlson index), infection by pathogenic microorganisms, and greater application of treatment. Furthermore, the NLR correlated better with severity scores than other parameters of systemic inflammation. Finally, it was an independent predictor of the incident number and severity of exacerbations. In conclusion, the NLR is an inexpensive and easy-to-measure marker of systemic inflammation for determining severity and predicting exacerbations (especially the most severe) in patients with bronchiectasis.

Usefulness of Muscle Ultrasonography in the Nutritional Assessment of Adult Patients with Cystic Fibrosis.

Background: Muscle ultrasonography of the quadriceps rectus femoris (QRF) is a technique on the rise in the assessment of muscle mass in application of nutritional assessment. The aim of the present study is to assess the usefulness of muscle ultrasonography in patients with cystic fibrosis, comparing the results with other body composition techniques such as anthropometry, bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), and handgrip strength (HGS). At the same time, we intend to assess the possible association with the nutritional and respiratory status. Methods: This was a prospective observational study in adult patients with cystic fibrosis in a clinically stable situation. Muscle ultrasonography of the QRF was performed, and the results were compared with other measures of body composition: anthropometry, BIA, and DXA. HGS was used to assess muscle function. Respiratory parameters were collected, and nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria. Results: A total of 48 patients were included, with a mean age of 34.1 ± 8.8 years. In total, 24 patients were men, and 24 patients were women. Mean BMI was 22.5 ± 3.8 kg/m2. Mean muscular area rectus anterior (MARA) was 4.09 ± 1.5 cm2, and mean muscular circumference rectus was 8.86 ± 1.61 cm. A positive correlation was observed between the MARA and fat-free mass index (FFMI) determined by anthropometry (r = 0.747; p < 0.001), BIA (r = 0.780; p < 0.001), and DXA (r = 0.678; p < 0.001), as well as muscle function (HGS: r = 0.790; p < 0.001) and respiratory parameters (FEV1; r = 0.445, p = 0.005; FVC: r = 0.376, p = 0.02; FEV1/FVC: r = 0.344, p = 0.037). A total of 25 patients (52.1%) were diagnosed with malnutrition according to GLIM criteria. Differences were observed when comparing the MARA based on the diagnosis of malnutrition (4.75 ± 1.65 cm2 in normo-nourished vs. 3.37 ± 1.04 in malnourished; p = 0.014). Conclusions: In adults with cystic fibrosis, the measurements collected by muscle ultrasound of the QRF correlate adequately with body composition techniques such as anthropometry, BIA, DXA, and handgrip strength. Muscle ultrasound measurements, particularly the MARA, are related to the nutritional status and respiratory function of these patients.

Impact of the SARS-CoV-2 Virus Pandemic on Patients with Bronchiectasis: A Multicenter Study.

BACKGROUND: Infection by SARS-CoV-2 has unquestionably had an impact on the health of patients with chronic respiratory airway diseases, such as COPD and asthma, but little information is available about its impact on patients with bronchiectasis. The objective of the present study was to analyze the effect of the SARS-CoV-2 pandemic on the state of health, characteristics, and clinical severity (including the number and severity of exacerbations) of patients with non-cystic fibrosis bronchiectasis. METHODS: This study was multicenter, observational, and ambispective (with data collected before and during the SARS-CoV-2 pandemic), and included 150 patients diagnosed with non-cystic fibrosis bronchiectasis. RESULTS: A significant drop was observed in the number and severity of the exacerbations (57% in all exacerbations and 50% in severe exacerbations) in the E-FACED and BSI multidimensional scores, in the pandemic, compared with the pre-pandemic period. There was also a drop in the percentage of sputum samples positive for pathogenic microorganisms in general (from 58% to 44.7%) and, more specifically, Pseudomonas aeruginosa (from 23.3% to 13.3%) and Haemophilus influenzae (from 21.3% to 14%). CONCLUSIONS: During the SARS-CoV-2 period, a significant reduction was observed in the exacerbations, severity, and isolations of pathogenic microorganisms in patients with bronchiectasis.

Impact of Chronic Bronchial Infection by Staphylococcus aureus on Bronchiectasis.

The objective of the study was to analyze the factors associated with chronic bronchial infection (CBI) due to methicillin-susceptible Staphylococcus aureus (SA) and assess the clinical impact on severity, exacerbations, hospitalizations, and loss of lung function compared to patients with no isolation of PPMs in a large longitudinal series of patients from the Spanish bronchiectasis registry (RIBRON). Material and methods: A prospective, longitudinal, multicenter study was conducted with patients included in the RIBRON registry between January 2015 and October 2020. The inclusion criteria were an age of 18 years or older and an initial diagnosis of bronchiectasis. Patients recorded in the registry had a situation of clinical stability in the absence of an exacerbation in the four weeks before their inclusion. All patients were encouraged to provide a sputum sample at each visit for microbiological culture. Annual pulmonary function tests were performed according to the national spirometry guidelines. Results: A total of 426 patients were ultimately included in the study: 77 patients (18%) with CBI due to SA and 349 (82%) who did not present any isolation of PPMs in sputum. The mean age was 66.9 years (16.2), and patients 297 (69.7%) were female, with an average BMI of 25.1 (4.7) kg/m2 and an average Charlson index of 1.74 (1.33). The mean baseline value of FEV1 2 L was 0.76, with a mean FEV1% of 78.8% (23.1). One hundred and seventy-two patients (40.4%) had airflow obstruction with FEV1/FVC < 0.7. The mean predictive FACED score was 1.62 (1.41), with a mean value of 2.62 (2.07) for the EFACED score and 7.3 (4.5) for the BSI score. Patients with CBI caused by SA were younger (p < 0.0001), and they had a lower BMI (p = 0.024) and more exacerbations in the previous year (p = 0.019), as well as in the first, second, and third years of follow-up (p = 0.020, p = 0.001, and p = 0.018, respectively). As regards lung function, patients with CBI due to SA had lower levels of FEV1% at the time of inclusion in the registry (p = 0.021), and they presented more frequently with bronchial obstruction (p = 0.042). A lower age (OR: 0.97; 95% CI: 0.94−0.99; p < 0.001), lower FEV1 value% (OR: 0.98; 95% CI: 0.97−0.99; p = 0.035), higher number of affected lobes (OR: 1.53; 95% CI: 1.2−1.95; p < 0.001), and the presence of two or more exacerbations in the previous year (OR: 2.33; 95% CI: 1.15−4.69; p = 0.018) were observed as independent factors associated with CBI due to SA. The reduction in FEv1% in all patients included in the study was −0.31%/year (95% CI: −0.7; −0.07) (p = 0.110). When the reduction in FEv1% is analyzed in the group of patients with CBI due to SA and the group without pathogens, we observed that the reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in the first group and −0.02% (95% CI: −0.07, −0.01) (p = 0.918) in the second group. According to a linear regression model (mixed effects) applied to determine which factors were associated with a more pronounced reduction in FEv1% in the overall group (including those with CBI due to SA and those with no PPM isolation), age (p = 0.0019), use of inhaled corticosteroids (p = 0.004), presence of CBI due to SA (p = 0.007), female gender (p < 0.001), and the initial value of FEV1 (p < 0.001) were significantly related. Conclusions: Patients with non-CF bronchiectasis with CBI due to SA were younger, with lower FEV1% values, more significant extension of bronchiectasis, and a higher number of exacerbations of mild to moderate symptoms than those with no PPM isolation in respiratory secretions. The reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in patients with CBI caused by SA.

Blood Neutrophil Counts Define Specific Clusters of Bronchiectasis Patients: A Hint to Differential Clinical Phenotypes.

We sought to investigate differential phenotypic characteristics according to neutrophil counts, using a biostatistics approach in a large-cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 1034 patients who met the inclusion criteria were clustered into two groups on the basis of their blood neutrophil levels. Using the Mann-Whitney U test to explore potential differences according to FACED and EFACED scores between the two groups, a neutrophil count of 4990 cells/µL yielded the most balanced cluster sizes: (1) above-threshold (n = 337) and (2) below-threshold (n = 697) groups. Patients above the threshold showed significantly worse lung function parameters and nutritional status, while systemic inflammation levels were higher than in the below-threshold patients. In the latter group, the proportions of patients with mild disease were greater, while a more severe disease was present in the above-threshold patients. According to the blood neutrophil counts using biostatistics analyses, two distinct clinical phenotypes of stable patients with non-CF bronchiectasis were defined. Patients falling into the above-threshold cluster were more severe. Severity was characterized by a significantly impaired lung function parameters and nutritional status, and greater systemic inflammation. Phenotypic profiles of bronchiectasis patients are well defined as a result of the cluster analysis of combined systemic and respiratory variables.

Systemic Inflammatory Biomarkers Define Specific Clusters in Patients with Bronchiectasis: A Large-Cohort Study.

Differential phenotypic characteristics using data mining approaches were defined in a large cohort of patients from the Spanish Online Bronchiectasis Registry (RIBRON). Three differential phenotypic clusters (hierarchical clustering, scikit-learn library for Python, and agglomerative methods) according to systemic biomarkers: neutrophil, eosinophil, and lymphocyte counts, C reactive protein, and hemoglobin were obtained in a patient large-cohort (n = 1092). Clusters #1-3 were named as mild, moderate, and severe on the basis of disease severity scores. Patients in cluster #3 were significantly more severe (FEV1, age, colonization, extension, dyspnea (FACED), exacerbation (EFACED), and bronchiectasis severity index (BSI) scores) than patients in clusters #1 and #2. Exacerbation and hospitalization numbers, Charlson index, and blood inflammatory markers were significantly greater in cluster #3 than in clusters #1 and #2. Chronic colonization by Pseudomonas aeruginosa and COPD prevalence were higher in cluster # 3 than in cluster #1. Airflow limitation and diffusion capacity were reduced in cluster #3 compared to clusters #1 and #2. Multivariate ordinal logistic regression analysis further confirmed these results. Similar results were obtained after excluding COPD patients. Clustering analysis offers a powerful tool to better characterize patients with bronchiectasis. These results have clinical implications in the management of the complexity and heterogeneity of bronchiectasis patients.

Assessment of body composition in cystic fibrosis: agreement between skinfold measurement and densitometry.

Introduction: Introduction: few studies have evaluated body composition (BC) through different techniques, and the degree of agreement between them in adults with cystic fibrosis (CF). Objectives: to describe BC using techniques to assess nutritional status and to test their concordance in CF. Methods: a cross-sectional study in CF patients in a clinically stable situation. Nutritional assessment was performed using skinfold measurement (SM) and densitometry (DXA). Fat-free mass index (FFMI) was also determined. The diagnosis of malnutrition was established if body mass index (BMI) < 18.5 kg/m2. Fat-free mass (FFM) malnutrition was diagnosed when FFMI was < 17 kg/m2 in males and < 15 kg/m2 in females (FFMI: fat-free mass in kg/height in m2). Results: forty-one patients were studied (twenty-two females, 53.7 %); median age was 29.8 (interquartile range, 20.9-33.7); BMI was 21.6 (19.8-23.0). Only four (9.8 %) patients had a BMI < 18.5. By DXA, FFM (kg) results were: median, 52.8 (47.8-56.9) with FFMI of 17.9 (16.7-19.3) in males and 36.7 (33.1-38.9) in females, FFMI of 14.7 (14.2-15.8). Twenty (48.6 %) patients presented FFM malnutrition, with 16.7 % of males and 59.1 % of females being affected. By SM, the FFMI was 18.7 (17.2-20.0) in males and 14.9 (14.2-15.8) in females; moreover, sixteen (39.1 %) patients presented malnutrition of FFM, with 20.8 % of males and 61.8 % of females being affected. For FFM (kg), a high concordance was obtained between SM and DXA (intraclass correlation coefficient of 0.950); likewise when they were compared by applying the ESPEN criteria for FFM malnutrition. However, when the techniques were compared to classify malnutrition according to FFMI, the kappa coefficient was only moderate (k = 0.440). The mean difference between FFM by DXA and SM was +1.44 ± 0.62 kg in favor of SM, with greater dispersion as FFM increased. Conclusions: the prevalence of FFM malnutrition is high in adult CF patients, despite a normal BMI, especially in females. Notwithstanding the good statistical agreement between SM and DXA, concordance was moderate. Therefore, DXA remains the technique of choice, and SM may be used when the former is not available.

Introducción: Introducción: pocos estudios han evaluado la composición corporal (BC) mediante diferentes técnicas y el grado de concordancia entre ellas en adultos con fibrosis quística (FQ). Objetivos: describir la BC mediante técnicas de evaluación nutricional y comprobar su concordancia en la FQ. Métodos: estudio transversal de adultos con FQ en situación de estabilidad clínica. La evaluación nutricional se realizó mediante medición de pliegues cutáneos (SM) y densitometría (DXA). También se determinó el índice de masa libre de grasa (FFMI). El diagnóstico de desnutrición se estableció si el índice de masa corporal era < 18,5 kg/m2. Se diagnosticó desnutrición por masa libre de grasa (FFM) cuando el FFMI era < 17 kg/m2 en 4 hombres y < 15 kg/m2 en mujeres (FFMI: masa libre de grasa en kg/estatura en m2). Resultados: se estudiaron 41 pacientes (22 mujeres (53,7 %), con una edad media de 29,8 años (rango intercuartílico, 20,9-33,7) e IMC de 21,6 (19,8-23,0). Solo 4 (9,8 %) pacientes tenían un IMC < 18,5. Mediante DXA, los resultados de FFM (kg) fueron (mediana y RIC): 52,8 (47,8-56,9) con FFMI de 17,9 (16,7-19,3) en los varones y 36,7 (33,1-38,9) en las mujeres con FFMI de 14,7 (14,2-15,8). Veinte (48,6 %) pacientes presentaban desnutrición del FFM, con el 16,7 % de varones y el 59,1 % de mujeres afectados. Mediante el SM, el FFMI fue de 18,7 (17,2-20,0) en los varones y de 14,9 (14,2-15,8) en las mujeres. En el caso de la FFM (kg), se obtuvo una alta concordancia entre el SM y la DXA (coeficiente de correlación intraclase de 0,950); igualmente cuando se compararon las técnicas aplicando los criterios ESPEN para la desnutrición de la FFM. Sin embargo, cuando se compararon las técnicas para clasificar la malnutrición según el FFMI, el coeficiente kappa fue solo moderado (coeficiente kappa = 0,440). La diferencia media entre el FFM por DXA y el SM fue de +1,44 ± 0,62 kg a favor del SM, con mayor dispersión a medida que aumenta el FFM. Conclusiones: la prevalencia de la malnutrición por FFM es elevada en pacientes adultos con FQ, a pesar de presentar un IMC normal, especialmente en el caso de las mujeres. A pesar de existir una buena correlación estadística entre el SM y la DXA, la concordancia fue moderada. Por lo tanto, la DXA sigue siendo la técnica de elección y el SM puede ser una alternativa cuando la DXA no esté disponible.

Validation of a Spanish version of the Leicester Cough Questionnaire in cystic fibrosis.

Cough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George's Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach's α 0.81-0.93). The test-retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was -0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations.

Handgrip Strength: Associations with Clinical Variables, Body Composition, and Bone Mineral Density in Adults with Cystic Fibrosis.

BACKGROUND: Loss of fat-free mass (FFM) is associated with an increase in morbidity and mortality in cystic fibrosis (CF) patients. Handgrip strength (HGS) measures muscle function and may be associated with clinical parameters with prognostic value. Our objectives were to evaluate muscle strength through HGS in CF patients and to determine if there are any associations with respiratory clinical variables, FFM, and bone mineral density (BMD). METHODS: A cross-sectional study conducted in clinically stable patients. We evaluated muscle function through HGS, respiratory function-forced expiratory volume in 1 s (FEV1) (%), forced vital capacity (FVC) (%), bronchorrhea, annual exacerbations, and body composition (FFM and FFM index, FFMI: fat-free mass in kg/height in m2) and Bone Mineral Density (BMD) through densitometry (DXA). RESULTS: The study included 53 CF patients (58.5% females, mean age 28.3 ± 8.1, body mass index (BMI) 21.7 ± 3.4). The mean values for dynamometry were 40.2 ± 8.1 kg in males and 23.1 ± 7.0 kg in women, being 20.8% below the 10th percentile. Patients with lower muscle strength showed significantly more exacerbations and lower FEV1% and FVC%, as well as lower BMI, worse BMD (g/cm2), T-score, and Z-score. A significant and positive correlation was found between the mean and maximum dynamometry values and age, FVC%, BMI, FFMI, FFM (kg), and BMD. CONCLUSIONS: For adults with CF, HGS is a practical tool for assessment of health status. Low values reflect poor nutritional status and are associated with poor respiratory function, low fat-free mass and low bone mineral density.

Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity.

Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann-Whitney U test and eosinophil count threshold: 100 cells/µL) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.

Differences in Nutritional Status and Inflammatory Biomarkers between Female and Male Patients with Bronchiectasis: A Large-Cohort Study.

We hypothesized that systemic inflammatory and nutritional parameters may differ between male and female patients with non-CF bronchiectasis. In a large patient cohort from the Spanish Online Bronchiectasis Registry (RIBRON), clinical features, systemic inflammatory and nutritional parameters were analyzed in male and female patients with bronchiectasis. Lung function, disease severity using several scores, nutritional status, systemic inflammatory parameters, and multivariate regression analyses were performed to identify differences between male and female patients in the target variables. The number of female patients included in the registry was greater than male patients and they had a less severe disease as measured by all three indices of disease severity, a lower degree of airway obstruction, worse diffusion capacity and airway trapping, better nutritional parameters, and lower levels of inflammatory biomarkers. Multivariate regression analysis evidenced that strong relationships were found between female gender and the following variables: total numbers of leukocytes and neutrophils, hemoglobin, hematocrit, creatinine, and body mass index (BMI). Multivariate regression analyses evidenced that nutritional parameters and inflammatory biomarkers may be reliable indicators of gender-related differences in patients with non-CF bronchiectasis. These findings deserve further attention in follow-up investigations in which the potential predictive value of those biomarkers should be thoroughly explored.

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)

Validity of Self-rating Screening Scales for the Diagnosis of Depression and Anxiety in Adult Patients With Bronchiectasis / Validez de las escalas de autoevaluación para el diagnóstico de depresión y ansiedad en pacientes adultos con bronquiectasias

Background: There are no previous studies aimed at assessing the validity of the screening scales for depression and anxiety in adult patients with bronchiectasis.Aims: To analyze the psychometric properties of Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI) and Hamilton Anxiety Scale and to evaluate the concordance for the diagnosis of depression and anxiety between these screening scales and the structured clinical interview in adult patients with bronchiectasis.Method: Cross sectional study. 52 patients with bronchiectasis completed HADS, BDI and Hamilton Anxiety Scale; afterwards, were individually interviewed by a mental health care professional using the structured Mini International Neuropsychiatric Interview (MINI), which evaluates for depression and anxiety according to DSM-IV criteria.Results: Based on MINI, 18 subjects (34.6%) had a diagnosis of depression and 25 (48.1%) had anxiety. Optimal cut-off values to detect depression were ≥9 for the HADS-D (sensitivity 0.833, specificity 0.971, AUC 0.962 [95% CI 0.918–1]), and 17 for BDI (sensitivity 0.889, specificity 0.912, AUC 0.978 [95% CI 0.945–1]). Optimal cut-off values to detect anxiety were ≥4 for the HADS-A (sensitivity 0.960, specificity 0.593, AUC 0.833 [95% CI 0.723–0.943]), and 17 for Hamilton Anxiety Scale (sensitivity 0.800, specificity 0.852, AUC 0.876 [95% CI 0.781–0.970]). (AU)

Contexto global: No existen estudios previos dirigidos a la evaluación de las escalas de detección de la depresión y de la ansiedad en pacientes adultos con bronquiectasias.Objetivos: Analizar las propiedades psicométricas de la escala de ansiedad y depresión hospitalaria (HADS, por sus siglas en inglés), el inventario de depresión de Beck (BDI, por sus siglas en inglés) y la escala de ansiedad de Hamilton, y evaluar la concordancia para el diagnóstico de la depresión y la ansiedad entre estas escalas de detección y la entrevista clínica estructurada en pacientes adultos con bronquiectasias.Método: Estudio transversal. Cincuenta y dos pacientes con bronquiectasias completaron la HADS, el BDI y la escala de ansiedad de Hamilton; posteriormente, un psiquiatra profesional de la salud mental les entrevistó individualmente utilizando la entrevista estructurada denominada Minientrevista neuropsiquiátrica internacional (MINI), que evalúa la depresión y la ansiedad siguiendo los criterios del DSM-IV.Resultados: Basándonos en la MINI, 18 sujetos (el 34,6%) fueron diagnosticados de depresión y 25 de ellos (el 48,1%) presentaba ansiedad. Los valores de corte óptimos para detectar depresión fueron ≥9 para la HADS-D (sensibilidad: 0,833; especificidad: 0,971; ABC: 0,962 [IC 95%: 0,918-1]) y 17 para el BDI (sensibilidad: 0,889; especificidad: 0,912; ABC: 0,978 [IC 95%: 0,945-1]). Los valores de corte óptimos para detectar ansiedad fueron ≥4 para la HADS-A (sensibilidad: 0,960; especificidad: 0,593; ABC: 0,833 [IC 95%: 0,723-0,943]) y 17 para la escala de ansiedad de Hamilton (sensibilidad: 0,800; especificidad: 0,852; ABC: 0,876 [IC 95%: 0,781-0,970]). (AU)

C-Reactive Protein Concentration in Steady-State Bronchiectasis: Prognostic Value of Future Severe Exacerbations. Data From the Spanish Registry of Bronchiectasis (RIBRON) / Concentración de la proteína C reactiva en las bronquiectasias en fase estable: valor pronóstico de futuras exacerbaciones graves. Datos del registro español de pacientes con bronquiectasias (RIBRON)

BACKGROUND: Both systemic inflammation and exacerbations have been associated with greater severity of bronchiectasis. Our objective was to analyze the prognostic value of the peripheral concentration of C-reactive protein (CRP) for the number and severity of exacerbations in patients with bronchiectasis. METHODS: Patients from the Spanish Bronchiectasis Registry (RIBRON) with valid data on their CRP value (in a clinically stable phase) and valid data on exacerbations during the first year of follow-up were included. A logistic regression analysis was used to evaluate the prognostic value of the CRP concentration (divided into tertiles) with the presence of at least one severe exacerbation or at least two mild-moderate exacerbations during the first year of follow-up. RESULTS: 802 patients (mean age: 68.1 [11.1 years], 65% female) were included. Of these, 33.8% and 13%, respectively, presented ≥ 2 mild-moderate exacerbations or at least one severe exacerbation during the first year of follow-up. The mean value of the CRP was 6.5 (17.6 mg/L). Patients with a CRP value between 0.4 and 2.7 mg/L (second tertile) and ≥ 2.7 mg/L (third tertile) presented a 2.9 (95%CI: 1.4-5.9) and 4.2 (95% CI: 2.2-8.2) times greater probability, respectively, of experiencing a severe exacerbation than those with < 0.4 mg/L (control group), regardless of bronchiectasis severity or a history of previous exacerbations. However, the CRP value did not present any prognostic value for the number of mild-moderate exacerbations. CONCLUSIONS: The CRP value was associated with a greater risk of future severe exacerbations but not with mild or moderate exacerbations in patients with steady-state bronchiectasis

CONTEXTO GENERAL: Tanto la inflamación sistémica como las exacerbaciones se han asociado con una mayor gravedad de las bronquiectasias. Nuestro objetivo fue analizar el valor de la concentración en sangre periférica de proteína C reactiva (PCR) para predecir el número y la gravedad de las exacerbaciones en pacientes con bronquiectasias. MÉTODOS: Se incluyeron pacientes del Registro Español de Pacientes con Bronquiectasias (RIBRON) con datos válidos sobre sus niveles de PCR (en fase clínicamente estable) y datos válidos sobre exacerbaciones durante el primer año de seguimiento. Se utilizó un análisis de regresión logística para evaluar el valor pronóstico de la concentración de PCR (dividida en terciles) con la presencia de al menos una exacerbación grave o al menos dos exacerbaciones leves-moderadas durante el primer año de seguimiento. RESULTADOS: Se incluyeron 802 pacientes (edad media: 68,1 [11,1] años, 65% mujeres). De ellos, el 33,8% y el 13%, respectivamente, presentaron ≥ 2 exacerbaciones leves-moderadas o al menos una exacerbación grave durante el primer año de seguimiento. El valor medio de la PCR fue de 6,5 (17,6) mg/L. Los pacientes con un valor de PCR entre 0,4 y 2,7 mg/L (segundo tercil) y ≥ 2,7 mg/L (tercer tercil) presentaron 2,9 veces (IC 95%: 1,4-5,9) y 4,2 veces (IC 95%: 2,2-8,2) más probabilidad, respectivamente, de experimentar una exacerbación grave que aquellos con < 0,4 mg/L (grupo de control), independientemente de la gravedad de las bronquiectasias o de presentar antecedentes de exacerbaciones previas. Sin embargo, el valor de la PCR no presentó ninguna utilidad pronóstica para el número de exacerbaciones leves-moderadas. CONCLUSIONES: El valor de la PCR se asoció a un mayor riesgo de exacerbaciones graves en el futuro, pero no a las exacerbaciones leves o moderadas en pacientes con bronquiectasias en fase estable

RIBRON: el registro español informatizado de bronquiectasias. Caracterización de los primeros 1.912 pacientes / RIBRON: The spanish Online Bronchiectasis Registry. Characterization of the First 1912 Patients

INTRODUCCIÓN: El Registro Español de Bronquiectasias de la SEPAR (RIBRON) comenzó como una plataforma longitudinal de recogida de datos de pacientes con esta enfermedad. El objetivo del presente estudio es describir tanto su funcionamiento, como analizar las características de los pacientes con bronquiectasias según el sexo. MÉTODOS: Entre febrero de 2015 y 2019, fueron incluidos 1.912 pacientes adultos diagnosticados de bronquiectasias procedentes de 43 centros. Todos los pacientes presentaron al menos datos completos de 79 variables básicas necesarias y controladas mediante una auditoria externa. RESULTADOS: Edad media fue de 67,6 años (15,2), el 63,9% mujeres. El síntoma más común fue la tos productiva en el 78,3%, que fue mucopurulenta-purulenta en el 45,9%. La etiología más frecuente fue la postinfecciosa en el 40,4%, siendo idiopáticas en el 18,5%. Pseudomonas aeruginosa fue el microorganismo más frecuentemente aislado con el 40,4%, el 25,6% en forma de infección crónica. El número anual de agudizaciones leve-moderadas/graves fue de 1,62 (1,9)/0,59 (1,3). El 50% de los pacientes presentaron obstrucción al flujo aéreo (el 17% grave). La localización más frecuente fueron los lóbulos inferiores. El valor medio del FACED /E-FACED/BSI fue de 2,06 (1,7)/2,67 (2,2)/7,8 (4,5), respectivamente. El 66,7% de los pacientes tomaban corticoides inhalados, el 19,2% macrólidos y el 19,5% antibióticos inhalados. Las mujeres presentaron un perfil de menor gravedad que los varones en términos clínico-funcionales y etiológicos, pero semejante perfil infeccioso, radiológico y terapéutico. CONCLUSIONES: RIBRON representa un excelente mapa de las características de las bronquiectasias en nuestro país. Dos tercios de los pacientes son mujeres que presentaron unas características propias, de menor gravedad de la enfermedad

INTRODUCTION: The SEPAR Spanish Bronchiectasis Registry (RIBRON) began as a platform for the collection of longitudinal data on patients with this disease. The objective of this study is to describe its operation and to analyze the characteristics of bronchiectasis patients according to sex. METHODS: A total of 1912 adult patients diagnosed with bronchiectasis in 43 centers were included between February 2015 and 2019. All patients had complete data consisting of at least 79 basic required variables, controlled by an external audit. RESULTS: Mean age was 67.6 (15.2) years; 63.9% were women. The most common symptom was productive cough (78.3%) which was mucopurulent-purulent in 45.9% of cases. The most common etiology was post-infectious (40.4%), while 18.5% were idiopathic. Pseudomonas aeruginosa was the most frequently isolated microorganism (40.4%), of which 25.6% were associated with chronic infection. The annual number of mild-to-moderate/severe exacerbations was 1.62 (1.9)/0.59 (1.3). Half of the patients (50%) presented with airflow obstruction (17% severe). The most frequent radiological localization was lower lobes. The average FACED/E-FACED/BSI values were 2.06 (1.7)/2.67 (2.2)/7.8 (4.5), respectively. Overall, 66.7% of patients were taking inhaled corticosteroids, 19.2% macrolides, and 19.5% inhaled antibiotics. Women presented a less severe profile than men in clinical and functional terms, and a similar infectious, radiological and therapeutic profile. CONCLUSIONS: RIBRON represents an excellent map of the characteristics of bronchiectasis in our country. Two thirds of patients are women who presented lower disease severity as a specific characteristic