Reliability of blood eosinophil count in steady-state bronchiectasis.

RATIONALE: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. OBJECTIVES: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. METHODS AND MEASUREMENTS: Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. MAIN RESULTS: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. CONCLUSIONS: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

Assessment of body composition in cystic fibrosis: agreement between skinfold measurement and densitometry / Evaluación de la composición corporal en adultos con fibrosis quística: concordancia entre la densitometría y la antropometría

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), 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 (AU)

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 (IMC) era < 18,5 kg/m2. Se diagnosticó desnutrición por masa libre de grasa (FFM) cuando el FFMI era < 17 kg/m2 en los hombres y < 15 kg/m2 en las mujeres (FFMI: masa libre de grasa en kg/estatura en m2). Resultados: se estudiaron cuarenta y un pacientes (veintidós mujeres (53,7 %), con una edad media de 29,8 años (rango intercuartílico, 20,9-33,7) y un IMC de 21,6 (19,8-23,0). Solo cuatro (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; además, dieciséis (39,1 %) pacientes presentaban malnutrición del FFMI, con el 20,8 % de varones y el 61,8 % de mujeres afectados. 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) (AU)

Real-life cost-effectiveness of benralizumab in patients with severe asthma.

BACKGROUND: Availability of clinically effective and cost-effective treatments for severe asthma would be beneficial to patients and national healthcare systems. The aim of this study was to evaluate clinical outcomes and healthcare expenditure after incorporating benralizumab into the standard treatment of refractory eosinophilic asthma. METHODS: This was a cross-sectional multicentre study of consecutive patients with refractory eosinophilic asthma who received treatment with benralizumab during at least 12 months. Patient follow-up was performed in specialised severe asthma units. The main effectiveness parameters measured were: the avoidance of one asthma exacerbation, a 3-point increase in the asthma control test (ACT) score, and the difference in utility scores (health-related quality of life) between a 1-year baseline treatment and 1-year benralizumab treatment. The health economic evaluation included direct costs and incremental cost-effectiveness ratios (ICERs). RESULTS: After 1 year of treatment with benralizumab, patients with refractory eosinophilic asthma showed an improvement in all the effectiveness parameters analysed: improvement of asthma control and lung function, and decrease in the number of exacerbations, oral corticosteroid (both as corticosteroid courses and maintenance therapy), and inhaled corticosteroid use. The total annual cost per patient for the baseline and benralizumab treatment periods were €11,544 and €14,043, respectively, reflecting an increase in costs due to the price of the biological agent but a decrease in costs for the remaining parameters. The ICER was €602 per avoided exacerbation and €983.86 for every 3-point increase in the ACT score. CONCLUSIONS: All the pharmacoeconomic parameters analysed show that treatment with benralizumab is a cost-effective option as an add-on therapy in patients with refractory eosinophilic asthma.

Pseudomonas aeruginosa and lung function decline in patients with bronchiectasis.

OBJECTIVES: The objective of this study was to analyse lung function decline over time in bronchiectasis, along with the factors associated with it. METHODS: Spirometry was measured every year in this observational, prospective study in 849 patients from the Spanish Bronchiectasis Registry (RIBRON). The main outcome was the decline in the rate of forced expiratory volume during the first second (FEV1). To be included in this study, patients needed a baseline assessment and at least one subsequent assessment. FEV1 decline was analysed using a mixed-effects linear regression model adjusted for clinically significant variables. RESULTS: We recruited 849 bronchiectasis patients with at least two annual lung function measurements (follow-up range 1-4 years). A total of 2262 lung function tests were performed (mean 2.66 per patient, range 2-5). Mean baseline FEV1 was 1.78 L (standard deviation (SD) 0.76; 71.3% predicted). Mean age was 69.1 (SD 15.4) years; 543 (64% women. The adjusted rates of FEV1 decline were -0.98% predicted/year (95% confidence interval (CI) -2.41 to -0.69) and -31.6 (95% CI -44.4 to -18.8) mL. The annual FEV1 decline was faster in those patients with chronic bronchial infection by Pseudomonas aeruginosa (-1.37% (52.1 mL) vs -0.37% (-24.6 mL); p < 0.001), greater age, increased number of severe exacerbations in the previous year and higher baseline FEV1 value. DISCUSSION: In patients with bronchiectasis, the annual rate of FEV1 decline was -31.6 mL/year and it was faster in older patients and those with chronic bronchial infection by P. aeruginosa, increased number of previous severe exacerbations and higher baseline FEV1 value.

Real-life experience with benralizumab during 6 months.

BACKGROUND: Benralizumab is a monoclonal antibody that binds to the human interleukin-5 (IL-5) receptor (IL-5R), thereby preventing IL-5 from binding to its receptor and inhibiting differentiation and maturation of eosinophils in the bone marrow. Because of its recent marketing approval, sufficient real-life evidence is lacking to confirm the efficacy and safety data from clinical trials. The purpose of this study was to evaluate the efficacy and safety of benralizumab for the treatment of severe refractory eosinophilic asthma in a real-world cohort of patients. METHODS: This was a cross-sectional multicentre study of consecutive patients with severe refractory eosinophilic asthma who received treatment with benralizumab during at least 6 months. Patient follow-up was performed in specialised severe asthma units. RESULTS: A total of 42 patients were enrolled and treated with benralizumab. Asthma control, as measured by the asthma control test (ACT), improved in all patients both at 3 months of treatment compared with baseline (13.9 ± 4 vs 20.1 ± 3.7, p < 0.001) and at 6 months of treatment compared with the results obtained at 3 months (20.1 ± 3.7 vs 21 ± 2.7, p = 0.037). Similarly, the number of emergency department visits decreased both at 3 months compared with baseline (1 [IR:0.7] vs 0 [IR:0.75], p < 0.001) and at 6 months compared with the results at 3 months (0 [IR:0.75] vs 0 [IR:0], p = 0.012). Reductions in the number of oral corticosteroid cycles, percentage of corticosteroid-dependent patients, and mean daily dose of oral or inhaled corticosteroid were also evidenced. Finally, mean lung function improvement was 291 mL (p < 0.001), and FEV1% improved both at 3 months compared with baseline (64.4 ± 9.3 vs 73.1 ± 9.1, p < 0.001) and at 6 months compared to 3 months (73.1 ± 9.1 vs 76.1 ± 12, p = 0.002). Side effects were mild and did not lead to treatment discontinuation. CONCLUSIONS: This study confirms the efficacy and safety of benralizumab in a real-life setting with improved asthma control and lung function, and a reduced oral and inhaled corticosteroid use as well as fewer emergency department visits. In addition to a rapid initial improvement, it appears that patients continue to improve during the first 6 months of treatment.

Osteopenia and Osteoporosis in Patients with Bronchiectasis: Association with Respiratory Parameters, Body Composition, Muscle Strength and Bone Remodeling Biomarkers.

The prevalence of osteopenia/osteoporosis has not been sufficiently studied in people with bronchiectasis not due to cystic fibrosis (BC), nor has its relationship with other variables (clinical, body composition and bone turnover and inflammation markers) been sufficiently studied. Our aim was to determine the prevalence of osteopenia and osteoporosis and related factors in patients with BC. We did a cross-sectional study in people with BC in a clinically stable state. Spirometric parameters, annual exacerbations and analysis with bone turnover markers (BTM) and inflammation markers were evaluated. Densitometry (DXA) was performed for body composition, bone mineral density (BMD) and handgrip strength. 123 patients were studied (65% women, mean age 49.6 ± 18.8, Body Mass Index (BMI) 24.8 ± 4.7 kg/m2). 62.8% and 62.5% of men and women, respectively, had normal bone mineral density, 30.2% and 22.2% osteopenia and 7% and 15% osteoporosis. 52 patients (56.2%) had low fat-free mass: 68.9% women and 28.6% men. Patients with decreased bone mass had significantly lower muscle strength, maximum expiratory volume in the first second (FEV1%), vitamin D, higher levels of C-terminal telopeptide of type 1 collagen (CTX) and total osteocalcin and underarboxylated osteocalcin (ucOC). We observed significant and negative correlations between BMD and the number of serious exacerbations per year CTX and undercarboxylated osteocalcin. We observed significant positive correlations between BMD, fat free mass index (FFMI) and handgrip dynamometry. The study suggest that the prevalence of osteoporosis was high in relation to the demographic characteristics. Respiratory parameters, body composition, muscle strength and bone remodeling markers were associated with a lower bone mineral density.

Diferencias en los marcadores de estrés oxidativo entre pacientes con enfermedad pulmonar obstructiva crónica según fenotipo agudizador y no agudizador / Differences in biomarkers of oxidative stress between patients with chronic obstructuve pulmonary disease according to the exacerbator and non-exacerbator phenotypes

Objetivo: en las agudizaciones de los pacientes con EPOC los marcadores de estrés oxidativo suelen estar elevados. Nuestro objetivo fue analizar si existen diferencias en estos marcadores entre pacientes con EPOC estable según fenotipo agudizador y no agudizador y la influencia de factores de confusión como la edad y el sexo. Método: se analizaron pacientes remitidos a una consulta monográfica de EPOC. Tras realizar una historia clínica detallada se clasificaron como agudizadores los que habían presentado dos o más agudizaciones en el año previo o habían tenido ingreso hospitalario. Se realizaron una espirometria y una extracción de sangre, cuantificando el estado total antioxidante del suero y los grupos tioles totales (sistemas antioxidantes no enzimáticos), la actividad superóxido dismutasa (sistema antioxidante enzimático) y las especies reactivas del ácido tiobarbitúrico(TBARS), los hidroperóxidos lipídicos, los productos avanzados de oxidación proteica y los productos finales de glicosilación avanzada como productos de oxidación. Resultados: se incluyeron 50 pacientes con fenotipo agudizador y 57 no agudizadores (edad media de 63 ± 7 años; 73% hombres). Se observaron valores superiores de TBARS en el fenotipo no agudizador, con significación estadística, a expensas de los pacientes mayores de 65 años y de sexo masculino. También se observó una tendencia a valores superiores de superóxido dismutasas en el fenotipo no agudizador. Conclusiones: existen pocas diferencias en los parámetros relacionados con el estrés oxidativo entre pacientes agudizadores y no agudizadores en fase estable. Encontramos valores más elevados de TBARSen pacientes no agudizadores, probablemente por causas no directamente relacionadas con la EPOC

Objective: In exacerbations of patients with COPD, the biomarkers of oxidative stress are often high. Our objective was to analyze whether there are any differences between these biomarkers in patients with stable COPD according to the exacerbator and non-exacerbator phenotypes and the influence of confounding factors such as age and gender. Method: Patients referred to a COPD consultation unit were analyzed. After taking a detailed clinical history, those who had two or more exacerbations in the previous year or hospital admission were classified as the exacerbator phenotype. Spirometry was performed and blood drawn, quantifying the total antioxidant status of serum and total thiol groups (non-enzymatic antioxidant systems), superoxide dismutase activity (enzymatic antioxidant system) and thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, advanced oxidation protein products and advanced glycation end products as oxidation products. Results: Fifty patients with the exacerbator phenotype and 57 with the non-exacerbator phenotype were included (mean age of 63 ± 7 years; 73% male). Statistically significantly higher TBARS values were observed in the group with the nonexacerbated phenotype, at the expense of male patients over 65 years of age. A trend towards higher superoxide dismutase values was also observed in the non-exacerbated phenotype. Conclusions: There are few differences in oxidative stressrelated parameters between exacerbated and non-exacerbated patients at a stable stage. We found higher TBARS values in non-exacerbated patients, probably due to causes not directly related to COPD

Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients.

BACKGROUND: Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients. METHODS: This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis. RESULTS: A total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49-5.84; p = 0.002), greater severity of asthma (OR, 2.43; 95% CI, 1.29-4.57; p = 0.006), at least one previous episode of pneumonia (OR, 2.42; 95% CI, 1.03-5.69; p = 0.044), and lower levels of FeNO (OR, 0.98; 95% CI, 0.97-0.99; p = 0.016). The NOPES score was developed on the basis of these variables (FeNO[cut off point 20.5 ppb], Pneumonia, Expectoration and asthma Severity), and it ranges from 0 to 4 points, where 0 means "no risk" and 4 corresponds to "high risk". The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%. CONCLUSIONS: Almost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma.

Efecto de la rehabilitación respiratoria asociada a suplementación nutricional sobre la actividad física en pacientes con bronquiectasias: estudio aleatorizado / The effect of pulmonary rehabilitation associated with nutritional supplementation on physical activity in patients with bronchiectasis: randomized trial

Introducción: la actividad física está fuertemente relacionada con la mortalidad y la situación respiratoria en patologías respiratorias como la enfermedad pulmonar obstructiva crónica (EPOC) y la fibrosis quística (FQ). Los programas de rehabilitación respiratoria (RR) han demostrado mejorar el grado de actividad física en pacientes con EPOC. No existen trabajos específicos en pacientes con bronquiectasias (BQ). Objetivos: comparar el efecto sobre la actividad física de la RR durante 12 semanas, comparado con RR más un suplemento hiperproteico enriquecido en beta-hidroxi-beta-metilbutirato (HMB) en pacientes con BQ no debidas a FQ. Material y métodos: estudio prospectivo aleatorizado, en el que se aplica un programa de RR estructurado a pacientes con BQ durante tres meses. A uno de los grupos, además, se le asoció un suplemento hiperproteico con HMB. Se valoró el grado de actividad física en situación basal, a los tres y seis meses mediante acelerómetro wGT3X (ActiGraph) y cuestionario IPAQ. Se analizaron los datos mediante una Anova de medidas repetidas (intención de tratar). Resultados: se incluyeron 30 pacientes con BQ no debidas a FQ (15 en cada rama) sin diferencias en variables clínicas entre los grupos. Después de la intervención, un porcentaje significativo de pacientes incrementaron la actividad física medida mediante el cuestionario IPAQ en el grupo suplementado a los 3 y 6 meses. No se observaron diferencias significativas en función del tipo de intervención. En ambos grupos se observó un discreto aumento de la actividad física de intensidad moderada medida por acelerómetro, a los 3 y 6 meses, pero no alcanzó significación estadística. Conclusiones: la RR, unida a suplementación nutricional en pacientes con BQ no debidas a FQ, aumentó el nivel de actividad física medida mediante el cuestionario IPAQ (a los 3 y 6 meses). Sin embargo, no alcanzó la significación estadística mediante acelerómetro. Son necesarios más estudios que evalúen la validez de los diferentes instrumentos de medida

Introduction: physical activity is closely related to mortality and respiratory status for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF).Pulmonary rehabilitation (PR) programs have been shown to improve the level of physical activity in COPD patients. There are no specific studies on patients with bronchiectasis. Objectives: study the effect of PR on physical activity over 12 weeks, in comparison with PR plus a hyperproteic supplement enriched in beta-hydroxy-beta-methylbutyrate (HMB) in patients with non CF bronchiectasis. Material and methods: prospective, randomized study in which a structured PR program is applied in bronchiectasis patients for three months. Additionally, one of the groups received a hyperproteic supplement with HMB. The degree of physical activity was evaluated at baseline and after three and six months using the wGT3X (ActiGraph) accelerometer and the IPAQ (International Physical Activity Questionnaire).Data was analyzed using a repeated measures ANOVA (intention to treat). Results: 30 patients with non-CF bronchiectasis (15 in each group)were included, without differences in clinical variables between groups. After intervention, a significant percentage of patients in the supplement group increased their average physical activity according to the IPAQ after 3 and 6 months. Significant differences depending on type of intervention were not observed. A slight increase in average moderate intensity physical activity measured by accelerometer was observed at 3 and 6 months, but it did not reach statistical significance. Conclusions: PR, along with nutritional supplements, in non-CF bronchiectasis patients increased the level of physical activity measured by the IPAQ (at 3 and 6 months).However, it did not reach statistical significance according to accelerometer measurements. Further studies are needed to evaluate the validity of the different measurement instruments

Predicting high risk of exacerbations in bronchiectasis: the E-FACED score.

BACKGROUND: Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. OBJECTIVE: Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. METHODS: The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. RESULTS: A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P<0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. CONCLUSION: E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score's simplicity and prognostic capacity for death.

Prevalence and factors associated with nontuberculous mycobacteria in non-cystic fibrosis bronchiectasis: a multicenter observational study.

BACKGROUND: Data on the prevalence of and factors associated with nontuberculous mycobacteria (NTM) in patients with non-cystic fibrosis (CF) bronchiectasis are limited. Our aim was to determine the prevalence and factors associated with isolation of NTM in this population. METHODS: We performed a multicenter observational study of historical cohorts comprising consecutive patients with non-CF bronchiectasis and at least 2 sputum samples cultured for mycobacteria over a period of 5 years. RESULTS: The study population included 218 adult patients (61.9 % women) with a mean (SD) age of 55.7 (16) years and a mean (SD) of 5.1 (3.3) cultures/patient. NTM was isolated from sputum in 18 patients (8.3 %). Of these, 5 patients (28 %) met the American Thoracic Society criteria for NTM disease. Mycobacterium avium complex was the most frequently isolated microorganism (9 patients, 4.1 %). The variables independently associated with isolation of NTM were FVC ≥ 75 % predicted (OR, 4.84; 95 % CI 1.47 to 15.9; p < 0.05), age ≥ 50 years (OR, 4.74; 95 % CI 1.25 to 17.97; p < 0.05), and body mass index (BMI) ≤ 23 kg/m(2) (OR, 2.97; 95 % CI 1.03-8.58; p < 0.05). Patients with these three characteristics had a 40 % probability of having at least one isolation of NMT. CONCLUSIONS: A significant number of patients with non-CF bronchiectasis are positive for the isolation of NTM. M. avium complex is the most frequently isolated mycobacteria. FVC ≥ 75 % predicted, age ≥ 50 years, and a BMI ≤ 23 kg/m(2) were independently associated with the presence of NTM in patients with non-CF bronchiectasis.

Depression and anxiety symptoms in Spanish adult patients with cystic fibrosis: associations with health-related quality of life.

BACKGROUND: Cystic fibrosis (CF) is a chronic disease with an impact on the quality of life. Self-reported symptoms of depression and anxiety were assessed in the Spanish cohort of the International Epidemiological Study on Depression and Anxiety in patients with CF (International Depression-Anxiety Epidemiological Study) and their relationship with health status and health-related quality of life (HRQoL) was evaluated. METHODS: This cross-sectional study recruited adult patients with CF at 10 Spanish centers. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Revised Cystic Fibrosis Questionnaire. Demographic and health data were recorded from medical charts. Logistic regression was used to determine the predictors of elevated symptoms of depression and anxiety (HADS≥8). RESULTS: Of the 336 participants recruited (mean age, 28.1years; 48.2% women), 41 (12.2%) had elevated depression-related scores, and 100 (29.7%) had elevated anxiety-related scores (HADS≥8). After adjusting for confounders, only less education, intravenous antibiotics, psychiatric medications and psychotherapy were significantly associated with elevated psychological symptoms. Specifically, regardless of lung function, patients who were depressed or anxious reported worse HRQoL. CONCLUSIONS: The prevalence of elevated symptoms of depression and anxiety was high in Spanish adult patients with CF, and these symptoms were associated with a decreased HRQoL.

Nutrición, fibrosis quística y aparato digestivo / Nutrition, cystic fibrosis and the digestive tract

La prevalencia de desnutrición en fibrosis quística es elevada aunque variable según los estudios. La detección de la misma debe realizarse mediante la combinación de diferentes métodos, en función de la disponibilidad de los mismos. No obstante, el criterio más sencillo y validado es medir en cada visita el peso (y la talla en niños) para calcular el índice de masa corporal y clasificar la desnutrición en criterios absolutos; en adultos, con valores menores a 18,5 kg/m2 y en niños, con percentiles del índice de masa corporal menores a 10. El empeoramiento del estado de nutrición guarda una relación directa con el descenso de los parámetros de función pulmonar y se ha propuesto como un factor predictor de morbilidad e incluso de mortalidad en personas con fibrosis quística, independientemente del grado de disfunción pulmonar. La insuficiencia pancreática exocrina está presente en aproximadamente el 70 al 90% de los pacientes con fibrosis quística y la correlación entre genotipo y fenotipo es alta. La mayoría de los pacientes con insuficiencia pancreática exocrina toleran una dieta alta en grasa si son tratados con enzimas pancreáticas a las dosis adecuadas. La prevalencia de diabetes aumenta con la edad alcanzando hasta el 40% de los casos en pacientes mayores de 30 años. La afectación hepática clínica es menos prevalente (aproximadamente afecta a 1/3 de los pacientes). Otras complicaciones intestinales como el íleo meconial, el reflujo gastroesofágico, la obstrucción del intestino distal o la colopatía fibrosante pueden condicionar también mal nutrición. En los pacientes con fibrosis quística se recomienda que la ingesta habitual aporte entre el 120 y 150% de las calorías recomendadas y que contenga alto contenido engrasas. Si no consiguen alcanzar o mantener los objetivos nutricionales previstos con las modificaciones de la dieta, se pueden adicionar suplementos artificiales, si bien la recomendación de su empleo no está avalado en evidencias científicas sólidas. Los preparados más empleados suelen ser poliméricos e hipercalóricos. Las indicaciones de soporte nutricional enteral por sonda (especialmente gastrostomía) o parenteral son similares a las empleadas en otras patologías. El control dietético y nutricional debe incluirse en un programa multidisciplinar que permita mejorar la capacidad funcional, la calidad de vida y reducir, al menos teóricamente, la morbi-mortalidad asociada a la malnutrición en estos pacientes

The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m2, and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlations high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients

Bronchiectasis in adult patients: an expression of heterozygosity for CFTR gene mutations?

While all patients with cystic fibrosis (CF) have mutations in both CFTR alleles, often only one CFTR change is detected in patients with other lung disorders. The aim of this study was to investigate whether heterozygosity for CFTR mutations could be a determinant risk factor in the development of bronchiectasis in adult patients. We have performed the CFTR gene analysis in a cohort of 55 bronchiectasis adult patients with unknown etiology. The 5T variant (TG)m and the M470V polymorphisms were also analyzed. A general population in which the same molecular analysis was previously performed was used as the control group. The mutational spectrum of patients was also compared with that found in our CF population. CFTR mutations/variants were found in 20 patients (36%), 14 with only one mutant gene (25%). All six patients colonized by Staphylococcus aureus presented with at least one CFTR change (p = 0.001). No statistical significance was observed between patients with and without mutations for other clinical features. The 5T variant was found in four patients. Additionally, 90% of patients with mutations had the more functional M470 allele (p < 0.001). These results suggest the involvement of the CFTR gene in bronchiectasis of unknown etiology in adult patients.

[Carbohydrate metabolic changes in cystic fibrosis]. / Alteraciones del metabolismo hidrocarbonado en la fibrosis quística.

OBJECTIVES: To assess the prevalence of impaired glucose tolerance and diabetes mellitus in a group of patients with cystic fibrosis and to compare insulin secretion, haemoglobin A1c, age, gender, genotype, and clinical status related variables between the groups with abnormal (impaired glucose tolerance and diabetes mellitus) and normal carbohydrate metabolism. PATIENTS AND METHODS: 66 patients with cystic fibrosis (age 1-38 years). Plasma glucose, insulin and C peptide determinations during an oral glucose tolerance test (OGTT) in 65 patients (one was previously known as diabetic). Based on the Expert Committee from the American Diabetes Association (1997), patients were classified as having impaired glucose tolerance and diabetes mellitus. Haemoglobin A1c, presence of delta F508 mutation, date of diagnosis and first sputum colonization, scores of National Institutes of Health, Schwachman and Chrispin-Norman, pancreatic enzyme intake, weight, body mass index, forced expiratory volume in one second and forced vital capacity determinations in every patient. Comparative analysis of these variables in both groups of patients was performed by Student test. RESULTS: Nine patients (13.6%) showed impaired tolerance glucose and one diabetes mellitus following OGTT, so we have two diabetics in our cystic fibrosis group (3.0%). When compared to cystic fibrosis patients with normal glucose tolerance, tolerance glucose and diabetes mellitus patients had significantly reduced basal insulin levels (8.6 [3.8] vs 15.0 [22.2] microU/ml; p < 0.0001), increased glucose stimulated insulin and C peptide levels (50.2 [19.3] vs 21.4 [19.3] microU/ml; p < 0.0001, and 9.0 [5.9] vs 4.4 [3.2] ng/ml; p < 0.0001), they were older (18.0 [7.5] vs 12.7 [7.3] years old; p < 0.05) and had longer time since diagnosis and since first sputum colonization. The remaining variables did not differ between the two groups. All patients with exocrine pancreatic sufficiency showed normal glucose tolerance. CONCLUSIONS: Abnormalities in carbohydrate metabolism were present in 16.6% of cystic fibrosis patients. These patients had reduced basal but increased glucose stimulated insulin levels. Age, time since diagnosis of cystic fibrosis, time since first sputum colonization and exocrine pancreatic insufficiency are the variables being associated with carbohydrate metabolism abnormalities.

Inhibition of ferrous-induced lipid peroxidation by dipyridamole, RA-642 and mopidamol in human lung tissue.

1. The in vitro production of ferrous-induced lipid peroxidation was 5.71 times higher in rat lung tissue than in human lung membranes. 2. The pyrimido-pyrimidine derivative RA-642 shows a more potent inhibition of ferrous-induced lipid peroxidation than dipyridamole; mopidamol had no effect. All the compounds showed higher anti-peroxidative effect in rat than in human lung tissue.