Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Distinctive lung function trajectories from age 10 to 26 years in men and women and associated early life risk factors - a birth cohort study.

Pre-bronchodilator lung function including forced vital capacity (FVC), forced expiratory flow in 1 second (FEV1), their ratio (FEV1/FVC), and forced expiratory flow 25-75% (FEF25-75) measured at age 10, 18, and 26 years in the Isle of Wight birth cohort was analyzed for developmental patterns (trajectories). Early life risk factors before the age of 10 years were assessed for the trajectories. METHOD: Members of the birth cohort (1989/90) were followed at age 1, 2, 4, 10, 18, and 26 years. Allergic sensitization and questionnaire data were collected. Spirometry tests were performed and evaluated according to the American Thoracic Society (ATS) criteria at 10, 18, and 26 years. To identify developmental trajectories for FVC, FEV1, FEV1/FVC, and FEF25-75 from 10 to 26 years, a finite mixture model was applied to the longitudinal lung function data, separately for males and females. Associations of early life factors with the respective lung function trajectories were assessed using log-linear and logistic regression analyses. RESULTS: Both high and low lung function trajectories were observed in men and women. FVC continued to grow beyond 18 years in men and women, whereas FEV1 peaked at age 18 years in female trajectories and in one male trajectory. For the FEV1/FVC ratios and FEF25-75 most trajectories appeared highest at age 18 and declined thereafter. However, the low FEV1/FVC trajectory in both sexes showed an early decline at 10 years. Lower birth weight was linked with lower lung function trajectories in males and females. Eczema in the first year of life was a risk factor for later lung function deficits in females, whereas the occurrence of asthma at 4 years of age was a risk factor for later lung function deficits in males. A positive skin prick test at age four was a risk for the low FEV1 trajectory in females and for the low FEV1/FVC trajectory in males. CONCLUSION: Men and women showed distinctive lung function trajectories and associated risk factors. Lower lung function trajectories can be explained by not achieving maximally attainable function at age 18 years and by a function decline from 18 to 26 years.

Asociación entre deterioro del flujo espiratorio máximo y prevalencia de enfermedades cardiovasculares y metabólicas en población adulta chilena: hallazgos preliminares de la Cohorte del Maule (MAUCO) / Peak expiratory flow and prevalence of cardiovascular and metabolic diseases in a Chilean adult population: preliminary findings from the Maule Cohort (MAUCO)

Introducción: La enfermedad respiratoria crónica determina alta morbimortalidad y frecuencia de comorbilidades cardiometabólicas. Evaluamos la asociación entre flujo espiratorio máximo (FEM) y algunas condiciones cardiometabólicas en adultos de una zona semirural, en la medición basal de la cohorte MAUCO (MAUle COhort). Material y Método: Estudio transversal (3.465 adultos, 40-74 años). Se midió el flujo espiratorio máximo (FEM) (mini-Wright, estándar ATS) utilizándose valores de Gregg y Nunn (FEM deteriorado ≤ 80% del teórico). Se obtuvo autorreporte/mediciones de hipertensión arterial (HTA), enfermedad cerebrovascular (ECV), infarto al miocardio (IAM), diabetes mellitus 2 (DM2), presión arterial, glicemia, colesterol, peso y talla. Actividad física y tabaquismo se evaluaron por encuesta, previa aprobación Ética. Se calcularon medidas de asociación, prevalencia y Odds Ratio (OR). Resultados: Muestra de 63,9% de mujeres edad media 55 (± 9) años, escolaridad media 9 (± 4) años. 84,7% tuvo exceso de peso, 81,5% inactividad física 29,4% fumadores actuales. Prevalencia de FEM bajo: 50,6% (IC 95% 48,9-52,3). El autorreporte fue: ACV 2,2% IAM 3,3, sospecha de hipertensión 24% y DM2 2,7%. Los OR crudos fueron significativos en mujeres que autorreportaron HTA, ECV, IAM y autorreporte/sospecha de DM2, y en hombres con autorreporte de ECV, sospecha de DM2 y autorreporte/sospecha de HTA. La asociación se mantuvo post-ajuste en mujeres para autorreporte de IAM y deterioro moderado (OR = 2,49) y severo del FEM (OR = 2,60) y en hombres para sospecha de DM2 y deterioro leve (OR = 5,24) y severo del FEM (OR = 6,19). Conclusiones: FEM resultó significativamente asociado con las enfermedades cardiometabólicas seleccionadas, con efecto sexo- específico para IAM (mujeres) y sospecha de DM2 (hombres). Se constata alta prevalencia de FEM alterado, y de enfermedades cardiometabólicas crónicas en la población estudiada.

Introduction: Chronic respiratory diseases determine high morbimortality and cardiometabolic comorbidities. We evaluated the association between peak expiratory flow (PEF) and cardiometabolic conditions in adults in a semi-rural area, in the baseline of MAUCO cohort (MAUle COhort). Material and Method: Cross-sectional study (3,465 adults, 40-74 years). Peak expiratory flow (PEF) (mini-Wright, ATS standard) was measured (Gregg & Nunn; impaired PEF ≤ 80% predicted). Self-reported/measured hypertension (HT), cerebrovascular disease (CVD), myocardial infarction (AMI), diabetes mellitus 2 (DM2), blood pressure, glycemia, cholesterol, weight and height were obtained. Physical activity and smoking were surveyed, after Ethical approval. Association's measures, prevalence and Odds Ratio (OR) were calculated. Results: Sample of 63.9% of women, mean age 55 (± 9) years, schooling 9 (± 4) years. 84.7% had overweight, 81.5%physical inactivity 29.4% smokers. Low PEF: 50.6% (48.9-52.3). Self-reported was: CVD 2.2% AMI 3.3%, suspicion of hypertension 24% and DM2 2.7%. Crude OR`s were significant for women by self-reported hypertension, stroke, AMI and self-reported/suspicion DM2; in men for self-reported CVD, suspected DM2 and self-reported/suspected hypertension. The association remained post-adjusted in women self-reported AMI -moderate deterioration (OR = 2.49) and severe PEF (OR = 2.60) and in men suspected DM2 and mild (OR = 5.24) and severe deteriorated PEF (OR = 6.19). Conclusions: PEF was significantly associated with cardiometabolic diseases; sex- specific findings for AMI (women) and suspicion of DM2 (men). High prevalence of altered PEF and chronic cardiometabolic diseases were detected among the studied population.

La utilidad de los medidores de flujo espiratorio máximo en el diagnóstico de la gravedad del asma / Utility of peak expiratory flow meters for the diagnosis of asthma severity

OBJETIVO: revisar la evidencia disponible sobre la utilidad de los medidores de flujo espiratorio máximo (FEM) en el diagnóstico de la gravedad del asma. MÉTODO: se realizó una revisión narrativa de los artículos publicados en las bases de datos: Medline, Cinhal y Cochrane Library Plus con los siguientes términos libres de búsqueda: "asma", "flujo espiratorio máximo (FEM)" y "educación". Limitados en idioma: inglés o español, en población mayor de 18 años y publicados en los últimos diez años (2008-2018). RESULTADOS: se encontraron 49 artículos en la búsqueda (37 Pubmed, 1 Cinhal, 11 Cochrane Library). Se seleccionaron 19 artículos. El uso del flujo espiratorio máximo es una forma objetiva de medir y evaluar el grado de obstrucción al flujo aéreo en una situación de exacerbación asmática. A partir de la Guía Española para el Manejo del Asma se empezaron a construir los conocidos planes de acción del paciente y la implantación de su uso, puesto que es relativamente sencillo y fácil que la enfermera consiga la colaboración del paciente en su uso habitual. CONCLUSIÓN: los medidores de flujo espiratorio máximo resultan útiles en el diagnóstico de la gravedad del asma. El papel de la enfermera es muy importante para conseguir que el paciente sea capaz de llevar un buen control de su enfermedad y en llevar a cabo un buen manejo de los dispositivos de medición de flujo espiratorio máximo

OBJECTIVE: to explore the attitude and feelings of Nursing students towards care at death, as well as differences according to demographical characteristics, previous experience with death, and clinical practices completed. METHOD: a descriptive cross-sectional study on Nursing students from Universities of Galicia, through the validated FATCOD-S scale. Other variables were: age, gender, school, academic course, residential environment at childhood, previous experience with end of life, and if they had already completed clinical practices. An open question was included regarding their feelings towards the subject of the study. Bivariate analysis was conducted through Student's t, ANOVA or Mann-Whitney's U tests, and Spearman Correlation Coefficient. RESULTS: there were answers by 463 students. The overall mean score in the FATCOD scale was 98.1. Students in their 1st year who were ≤20-year-old presented statistically lower values than older students, both in Factor I (p= 0.014) and in Factor II (p= 0.04); they had higher scores in both factors (p= 0.02) if they declared having had previous experiences. An increasing gradient was found between the scores in both factors and the academic year (p< 0.001). In terms of feelings, four categories were identified: sadness and anxiety when faced with death; lack of experience and/or training; satisfaction and personal pride; and empathy, respect and relief. CONCLUSIONS: nursing students in Galicia presented a positive attitude towards end-of-life care. Age and previous experience represented key factors, as well as having completed clinical practices

El consumo máximo de oxígeno predice los ingresos recurrentes por insuficiencia cardiaca con fracción de eyección conservada / Peak exercise oxygen uptake predicts recurrent admissions in heart failure with preserved ejection fraction

Introducción y objetivos. La insuficiencia cardiaca con fracción de eyección conservada (IC-FEc) es un síndrome muy prevalente con alto riesgo de morbilidad y mortalidad. Hasta la fecha, la evidencia acerca del papel del consumo máximo de oxígeno (VO2máx) para predecir la carga de morbilidad en la IC-FEc es escasa. El objetivo de este estudio es evaluar la relación entre el VO2máx y el riesgo de ingresos recurrentes de los pacientes con IC-FEc. Métodos. A un total de 74 pacientes con IC-FEc sintomáticos y clínicamente estables, se les realizó una prueba de esfuerzo cardiopulmonar entre junio de 2012 y mayo de 2016. Se utilizó el método de regresión binomial negativa para determinar la asociación entre el porcentaje de VO2máx predicho (%VO2máx-p) y los ingresos recurrentes. Las estimaciones del riesgo se informaron como tasas de incidencia. Resultados. La media de edad era 72,5 ± 9,1 años, el 53% eran mujeres y todos los pacientes estaban en clase funcional II-III de la New York Heart Association. La media de VO2máx y la mediana de %VO2máx-p fueron 10 ± 2,8 ml/min/kg y el 60% (47-67) respectivamente. Durante un seguimiento medio de 276 [intervalo intercuartílico, 153-1.231] días, se registraron 84 hospitalizaciones por cualquier causa de 31 pacientes (41,9%). También se determinó un total de 15 muertes (20,3%). En un análisis multivariable, teniendo en cuenta la mortalidad como evento terminal, el %VO2máx-p mantuvo la asociación independiente y lineal con el riesgo de ingresos recurrentes. Así, y modelado como continuo, una disminución del 10% del %VO2máx-p aumentó en un 32% el riesgo de ingresos recurrentes (IRR = 1,32; IC95%, 1,03-1,68; p = 0,028). Conclusiones. En los pacientes de edad avanzada con IC-FEc sintomáticos, el %VO2máx-p predice los ingresos recurrentes por todas las causa (AU)

Introduction and objectives. Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent syndrome with an elevated risk of morbidity and mortality. To date, there is scarce evidence on the role of peak exercise oxygen uptake (peak VO2) for predicting the morbidity burden in HFpEF. We sought to evaluate the association between peak VO2 and the risk of recurrent hospitalizations in patients with HFpEF. Methods. A total of 74 stable symptomatic patients with HFpEF underwent a cardiopulmonary exercise test between June 2012 and May 2016. A negative binomial regression method was used to determine the association between the percentage of predicted peak VO2 (pp-peak VO2) and recurrent hospitalizations. Risk estimates are reported as incidence rate ratios. Results. The mean age was 72.5 ± 9.1 years, 53% were women, and all patients were in New York Heart Association functional class II to III. Mean peak VO2 and median pp-peak VO2 were 10 ± 2.8 mL/min/kg and 60% (range, 47-67), respectively. During a median follow-up of 276 days [interquartile range, 153-1231], 84 all-cause hospitalizations in 31 patients (41.9%) were registered. A total of 15 (20.3%) deaths were also recorded. On multivariate analysis, accounting for mortality as a terminal event, pp-peak VO2 was independently and linearly associated with the risk of recurrent admission. Thus, and modeled as continuous, a 10% decrease of pp-peak VO2 increased the risk of recurrent hospitalizations by 32% (IRR, 1.32; 95%CI, 1.03-1.68; P = .028). Conclusions. In symptomatic elderly patients with HFpEF, pp-peak VO2 predicts all-cause recurrent admission (AU)

Propuesta de ecuaciones predictivas de capacidad inspiratoria y flujo espiratorio máximo considerando mediciones torácicas: un estudio piloto / Proposal of predictive equations of inspiratory capacity and maximum spiratory flow considering thoracic measurements: a pilot study

RESUMEN: El objetivo del siguiente estudio fue determinar si las mediciones de tórax provocan modificaciones en las ecuaciones predictivas de capacidad inspiratoria (CI) y flujo espiratorio máximo (FEM). Se evaluaron 24 sujetos de sexo masculino entre 18 y 26 años, todos estudiantes sedentarios de la Universidad Católica del Maule, Chile. Se les realizó antropometría corporal básica (peso y talla corporal) y específica de tórax, diámetro antero-posterior (DAT) y transverso (DTT) de tórax y perímetro mesoesternal (PME). Posterior a esto, se evaluó la función ventilatoria a través de pletismografía corporal. Para estimar las ecuaciones de regresión lineal se utilizó el método de mínimos cuadrados relacionando la CI y FEM. La comparación entre el valor predicho establecido y nuestra propuesta fue comparado utilizando la prueba t de student o U de Mann-Whitney según correspondiera, considerándose un nivel de significancia estadística de p<0,05. Los resultados indican que para la propuesta de la ecuación de FEM se consideró el DTT y PME, logrando diferencias significativas con los valores de Knudson et al. Por tanto, se concluye que las mediciones de DTT a VR y PME a CPT influyeron en la ecuación predictiva de FEM en estudiantes sedentarios.

SUMMARY: The aim of the following study was to determine if chest measurements cause changes in the predictive equations of inspiratory capacity (IC) and peak expiratory flow (PEF). Twenty- four male subjects between 18 and 26 years old, all sedentary students of the Universidad Catolica del Maule, Chile, were evaluated. They were subjected to basic body anthropometry (weight and body size) and chest specificity, anteroposterior diameter (APD) and transverse (TTD) of the thorax and mesosternal perimeter (MSP). After this, the ventilatory function was evaluated through body plethysmography. To estimate the linear regression equations, the least squares method were used, relating IC and PEF. The comparison between the established predicted value and our proposal was compared using the student t-test or Mann-Whitney U test as appropriate, considering a level of statistical significance of p <0.05. The results indicate that the TTD and MSP were considered for the proposal of the PEF equation, achieving significant differences with the values o f Knudson et al. Therefore, it is concluded that measurements of TTD to RV and MSP to TPC influenced the predictive equation of PEF in sedentary students.

Flujo espiratorio máximo: caracterización en un estudio en población adulta chilena; resultados basales de la cohorte del Maule (MAUCO) / Peak expiratory flow rate: characterization study in Chilean adult population; baseline results of the Maule cohort (MAUCO)

Resumen Introducción: Las enfermedades respiratorias crónicas tienen alta prevalencia en países en desarrollo, en poblaciones rurales y deprivadas. El flujo espiratorio máximo (FEM) obtenido mediante espiración forzada tiene uso clínico y de investigación. Describimos valores de medición del FEM en la medición basal de un estudio de cohorte en curso (Cohorte del Maule-MAUCO). Material y Método: Diseño transversal en 3.465 adultos (40-74 años) con registros de FEM (ATS). (Flujómetro Mini-Wright), usando valores de Gregg y Nunn. Valores < 80% del predicho se consideraron disminuidos. Se obtuvo sexo, edad, nivel educacional, actividad física y tabaquismo; se calculó índice de masa corporal (IMC) usando mediciones antropométricas. Resultados: La muestra tuvo 63,9% de mujeres; edad media de 55 (± 9) años, escolaridad de 9 (± 4) años; sobrepeso y obesidad fueron 43,1% y 41,5%: 81,5% fueron inactivos y 29,4% fumadores actuales. El valor medio de FEM fue 330 (± 80) L/min (mujeres) y 460 (± 119) L/min (hombres): el FEM disminuido alcanzó el 50,6% ([48,9-52,3]) con diferencias según edad, educación, IMC y actividad física. Conclusiones: Se observó alta prevalencia de FEM disminuido con variaciones según sexo, edad, escolaridad, IMC e inactividad física. Como otros estudios latinoamericanos, los valores bajos también fueron altamente prevalentes, sugiriendo sobreestimación de valores predichos al usar valores de Gregg & Nunn. Estos resultados sugieren la conveniencia de estudiar factores ambientales locales.

Introduction: Chronic respiratory (CRD) diseases show high prevalence in developing countries, rural and deprived populations. Peak expiratory flow rate (PEFR) is a functional measurement obtained through forced expiratory used for clinical and research purposes. We described PEFR in a rural setting in an ongoing cohort study (Maule Cohort-MAUCO). Material and Method: Cross-sectional design in 3,465 adults (40-74 years) with PEFR ATS standard records (Mini-Wright flowmeter) using Gregg and Nunn values. PEFR ≤ 80% predicted were considered decreased. Sex, age, educational level, physical activity and tobacco smoking were obtained. Body mass index (BMI) was calculated based on anthropometrical measurements. Main Results: Sample had 63.9% of women; mean age of 55 (± 9) years, schooling of 9 (± 4) years. Overweight and obesity were 43.1% and 41.5%. Physical inactivity was 81.5% and 29.4% were current smokers. PEFR mean value was 330 (± 80) L/min (women) and 460 (± 119) L/min (men): Decreased PEFR was 50.6% ([48.9-52.3]) with significant differences by age, schooling, BMI and physical activity. Conclusions: High prevalence of decreased PEFR was observed: PEFR showed variations according to sex, age, schooling, BMI and physical activity. As other Latin-American studies show, low values were also highly prevalent, suggesting that Gregg & Nunn overestimated PEFR values. These results suggests the convenience of studying local environmental factors.

A 28-day, randomized, double-blind, placebo-controlled, parallel group study of nebulized revefenacin in patients with chronic obstructive pulmonary disease.

BACKGROUND: Revefenacin is a once-daily long-acting muscarinic antagonist (LAMA) in clinical development for the treatment of patients with chronic obstructive pulmonary disease (COPD). In a dose-ranging study, nebulized once-daily revefenacin had a long duration of action in patients after 7 days' administration of doses up to 700 µg. In this multiple-dose study, the bronchodilation efficacy and adverse events profile were characterized in patients administered nebulized revefenacin once daily for 28 days. METHODS: A total of 355 COPD patients (mean age 62 years, mean forced expiratory volume in 1 s [FEV1] 44% of predicted) were randomized in a double-blind, placebo-controlled parallel group study. Inhaled corticosteroids as well as short-acting bronchodilators were permitted. Once-daily treatments (44, 88, 175 or 350 µg revefenacin or matching placebo) were administered by a standard jet nebulizer, for 28 days. The primary endpoint was change from baseline in D28 trough FEV1, and secondary endpoints included weighted mean FEV1 over 0 to 24 h and rescue medication (albuterol) use. Safety evaluations included adverse events, laboratory assessments, electrocardiograms and 24-h Holter profiles. RESULTS: Revefenacin (88, 175 and 350 µg) significantly improved D28 trough FEV1 over placebo (187.4, 166.6 and 170.6 mL, respectively, all p < 0.001); 44 µg produced a sub-therapeutic response. At doses ≥88 µg, more than 80% of patients achieved at least a 100-mL increase from baseline FEV1 in the first 4 h post dose compared with 33% of placebo patients. For doses ≥88 µg, D28 24 h weighted mean differences from placebo for FEV1 were numerically similar to respective trough FEV1 values, indicating bronchodilation was sustained for 24 h post dose. Doses ≥88 µg reduced the average number of albuterol puffs/day by more than one puff/day. The 350 µg dose did not demonstrate additional efficacy over that observed with 175 µg revefenacin. Revefenacin was generally well tolerated, with minimal reports of systemic anti-cholinergic effects. CONCLUSIONS: These data suggest that 88 and 175 µg revefenacin are appropriate doses for use in longer-term safety and efficacy trials. Revefenacin offers the potential for the first once-daily LAMA for nebulization in patients with COPD who require or prefer a nebulized drug delivery option. TRIAL REGISTRATION: ClinicalTrials.gov NCT02040792 . Registered January 16, 2014.

Asociación de la masa muscular determinada mediante DEXA con los resultados espirométricos de individuos sanos / Relationship of Muscle Mass Determined by DEXA with Spirometric Results in Healthy Individuals

Introducción: La cantidad de masa muscular podría ser un factor determinante que explicara la variabilidad de los resultados de la espirometría en individuos del mismo sexo y edad y de características antropométricas similares. El objetivo de este estudio es determinar si existe asociación entre los resultados espirométricos de individuos sanos y su masa muscular estimada mediante absorciometría de rayosX (DEXA). Métodos: Se estudió una muestra de 161 mujeres y 143 varones sanos, no fumadores, de 18 a 77 años. En cada sujeto se registraron los resultados de una espirometría y los valores de la masa magra total y regional obtenidos mediante DEXA. Se realizó un análisis descriptivo de las variables y un análisis de regresión para estudiar las relaciones entre variables espirométricas y masa magra, corrigiendo los efectos que pudieran ejercer la edad y el índice de masa corporal (IMC). Resultados: En ambos sexos todas las variables de masa magra se correlacionan de forma positiva y significativa con las variables espirométricas, siendo estas relaciones mayores en los varones. Al ajustar estas correlaciones de forma parcial por la edad y el IMC, lo que mejor explica las variables espirométricas es la masa magra en las extremidades inferiores en varones, y la masa magra del tronco en mujeres. Conclusiones: En los varones, la masa muscular en las extremidades inferiores es la que más se asocia a los resultados espirométricos. En las mujeres es la masa muscular del tronco. En ambos sexos la masa muscular influye principalmente sobre el volumen espiratorio forzado en el primer segundo (FEV1) (AU)

Introduction: Muscle mass maybe a determining factor in the variability of spirometry results in individuals of the same sex and age who have similar anthropometric characteristics. The aim of this study was to determine the association between spirometric results from healthy individuals and their muscle mass assessed by dual energy X-ray absorptiometry (DEXA). Methods: A sample of 161 women and 144 men, all healthy non-smokers, was studied. Ages ranged from 18 to 77 years. For each subject, spirometry results and total and regional lean mass values obtained by full body DEXA were recorded. A descriptive analysis of the variables and a regression analysis were performed to study the relationship between spirometric variables and lean body mass, correcting for age and body mass index (BMI). Results: In both sexes all muscle mass variables correlated positively and significantly with spirometric variables, and to a greater extent in men. After partial adjustment of correlations by age and BMI, the factor which best explains the spirometric variables is the total lean body mass in men, and trunk lean body mass in women. Conclusions: In men, muscle mass in the lower extremities is most closely associated with spirometric results. In women, it is the muscle mass of the trunk. In both sexes muscle mass mainly affects FEV1 (AU)

Peak oxygen uptake prediction in overweight and obese adults / Predicción del consumo pico de oxígeno en adultos con sobrepeso y obesidad

Peak oxygen uptake ( VO2peak) is an important risk predictor for cardiovascular mortality and morbidity. The main aim of this study was to develop equations for estimating VO2peakin sedentary and active overweight and obese subjects. The second objective was to compare the newly created equations with the standard equations that are widely used. One hundred and twenty-nine overweight and obese subjects (57 males), aged 18-50 years, were randomized into two groups: development group (n = 94) and validation group (n= 35). Individuals performed a modified Bruce protocol before (sedentary) and after (active) a 24-week weight loss program. Body composition was measured by bioelectrical impedance analysis. Stepwise multiple regression models were performed; the following factors: age, body weight (BW ), lean body mass percentage (%LBM), and time of effort test (TIME) were included in the model. Four equations were developed: with and without effort test data for sedentary and active subjects. In the validation group, equations with and without TIME underestimated VO2peakvalues in sedentary (p= 0.002 and p= 0.008, respectively), but not in active subjects. Furthermore, the equations derived from this study presented the greatest determination coefficients and the lowest values for the standard errors of estimate, for both development and validation groups. The following equation presented the highest determination coefficient, using effort test data for active subjects: VO2peak(L/min) = -5.017 + (0.040×BW ) + (0.127×TIME) + (0.046×%LBM) + (-0.010×AGE). The predicted VO2peakvalues using the Bruce equation were significantly lower than the measured values in active participants (p = 0.046); whereas those predicted by ACSM’s equation were significantly higher in comparison to the measured O2peak levels in sedentary and active subjects (p<0.001), for both groups. In conclusion, equations developed in this study were adequate to predict VO2peakin overweight and obese subjects, whilst the most commonly used equations in the literature, ACSM and Bruce, reported an inaccurate estimation of VO2pea

El consumo de oxígeno pico (VO2peak) es un predictor importante de riesgo cardiovascular. El principal objetivo de este estudio fue desarrollar ecuaciones para estimar el VO2peak en sujetos con sobrepeso y obesidad, tanto sedentarios como activos. El objetivo secundario fue comparar las ecuaciones desarrolladas con ecuaciones ampliamente utilizadas. Ciento veintinueve sujetos con sobrepeso y obesidad (57 varones), de entre 18 y 50 años, fueron aleatoriamente divididos en dos grupos: de desarrollo (n=94) y de validación (n=35). Los sujetos realizaron un protocolo de Bruce modificado antes (sedentario) y tras un programa de pérdida de peso de 24 semanas (activo). La composición corporal se midió con impedancia bioeléctrica. Se realizaron modelos de regresión múltiple por pasos y los siguientes factores fueron incluidos en el modelo: edad, peso corporal (PC), porcentaje de masa magra (%MM) y tiempo máximo en la prueba de esfuerzo (TIEMPO). Fueron desarrolladas cuatro ecuaciones: con y sin dato de prueba de esfuerzo para sedentarios y activos. En el grupo de validación, las ecuaciones con y sin TIEMPO subestimaron los valores de VO2peak en sedentarios (p = 0,002 y p = 0,008, respectivamente), pero no en sujetos activos. Por otra parte, nuestras ecuaciones presentaron los mayores coeficientes de determinación y los valores más bajos en errores estándar de estimación, tanto para el grupo de desarrollo como para el grupo de validación. La ecuación con el coeficiente de determinación más alto fue la desarrollada para los sujetos activos con datos de prueba de esfuerzo: O2peak (L/min) = -5,017 + (0,040×PC) + (0,127×TIEMPO) + (0,046×%MM) + (0,010×EDAD). La ecuación de Bruce calculó valores de O2peak significativamente menores que los valores medidos en sujetos activos (p = 0,046); mientras que los valores predichos por la ecuación de ACSM fueron significativamente mayores en comparación con los valores de VO2peak medidos, tanto en sedentarios como en activos (p <0,001), para ambos grupos. En conclusión, las ecuaciones desarrolladas en este estudio fueron adecuadas para predecir VO2peak en sujetos con sobrepeso y obesidad, mostrando una mayor precisión que otras ecuaciones utilizadas en la literatura

Pulmonary Function and Incidence of Selected Respiratory Diseases Depending on the Exposure to Ambient PM10.

It is essential in pulmonary disease research to take into account traffic-related air pollutant exposure among urban inhabitants. In our study, 4985 people were examined for spirometric parameters in the presented research which was conducted in the years 2008-2012. The research group was divided into urban and rural residents. Traffic density, traffic structure and velocity, as well as concentrations of selected air pollutants (CO, NO2 and PM10) were measured at selected areas. Among people who live in the city, lower percentages of predicted values of spirometric parameters were noticed in comparison to residents of rural areas. Taking into account that the difference in the five-year mean concentration of PM10 in the considered city and rural areas was over 17 µg/m³, each increase of PM10 by 10 µg/m³ is associated with the decline in FEV1 (forced expiratory volume during the first second of expiration) by 1.68%. These findings demonstrate that traffic-related air pollutants may have a significant influence on the decline of pulmonary function and the growing rate of respiratory diseases.

Relación entre el grado de extensión del enfisema y alteraciones morfológicas musculares periféricas en pacientes con EPOC / Relationship between the degree to which emphysema has extended and morphological changes in peripheral musclesin patients with COPD

Nuestro objetivo fue evaluar si existían diferencias en distintos parámetros basales según la prevalencia de enfisema y analizar las alteraciones estructurales y morfológicas de la fibra muscular periférica del paciente EPOC frente al sujeto sano y las posibles diferencias según el predominio enfisematoso que presente. Para ello, estudiamos a 19 pacientes varones (edad 65 ± 3,2) diagnosticados de EPOC (FEV1 44,6 ± 13,2 en % del teórico) y 8 sujetos sanos no fumadores. En base a los resultados de la TC de alta resolución, 10 pacientes fueron considerados con 'predominio enfisema' (PE) y 9 sin 'predominio enfisema' (NPE). Se realizó una estimación de la fuerza muscular por el test de una repetición máxima (Test 1RM), test de esfuerzo máximo, submáximo y prueba de paseo de los 6 minutos, valoración del índice de la disnea basal (IDB) y calidad de vida (CRDQ) y biopsia del vasto lateral del músculo cuádriceps. Los pacientes con PE presentan a esfuerzo máximo una significativa menor carga de trabajo y consumo de oxígeno máximo (VO- 2peak de 55,1 ± 12,6 versus 60,5 ± 15,9) y una menor fuerza muscular periférica (1RM) en tres de los cinco ejercicios realizados. No existían diferencias en el test de endurance ni en la distancia paseada. Tampoco existían diferencias significativas entre los dos grupos en las distintas categorías ni en el total del CRDQ. Sin embargo, los pacientes con PE puntuaban significativamente peor en todos los dominios del IDB (IDB focal score de 4,5 ± 1,4 versus 5,8 ± 3,5). Los pacientes con EPOC presentan en el músculo cuádriceps un menor porcentaje de fibras tipo I (33,5 ± 10,3 versus 51,8 ± 3,6) y mayor porcentaje de fibras tipo II (3,2 ± 1,3 versus 1 ± 0,4) con respecto al sujeto sano y una menor relación capilar/fibra e inferior densidad capilar. El descenso en el porcentaje en la fibras tipo I es significativamente mayor en el paciente EPOC con PE (30,9 ± 8,9 versus 35,7 ± 6,2). En conclusión, los pacientes con EPOC con PE refieren significativamente menor capacidad de esfuerzo máximo, mayor disnea y menor fuerza muscular periférica que los pacientes EPOC con NPE. Los pacientes con EPOC presentan en el músculo cuádriceps un menor porcentaje de fibras tipo I y mayor porcentaje de fibras tipo II con respecto al sujeto sano y esta alteración en el porcentaje de las fibras del músculo periférico es significativamente mayor en el paciente EPOC con PE

Our aims were to assess whether there are differences in different baseline parameters depending on the prevalence of emphysema, and analyze the structural and morphological alterations of peripheral muscle fibers in COPD patients compared to healthy subjects and differences according to the present dominance emphysema. We studied 19 male patients (age 65 ± 3.2) diagnosed with COPD (FEV1 44.6 ± 13.2%) and 8 healthy nonsmokers. Based on the results of the high resolution CT, 10 patients were considered to have 'predominant emphysema' (PE) and 9 without 'predominant emphysema' (NPE).An estimate of muscle strength test is performed by the one repetition maximum (1RM Test), maximal exercise test, submaximal test and walk 6 minutes, assessment of baseline dyspnea index (BDI) and quality of life (CRDQ) and biopsy of the vastus lateralis of the quadriceps muscle. Patients with PE presented a significantly lower maximum stress load and maximum oxygen consumption (VO2peak 55.1 ± 12.6 versus 60.5 ± 15.9) and had a lower peripheral muscle strength (1RM) in three five exercises. There were no differences in the endurance test or walking distance. There are no significant differences between groups in different categories or the total CRDQ. However, patients with PE score significantly worse in all domains of the IDB (IDB focal score of 4.5 ± 1.4 versus 5.8 ± 3.5). Patients with COPD quadriceps muscle in a lower percentage of type I (33.5 ± 10.3 versus 51.8 ± 3.6) and higher percentage of type II fibers (3.2 ± 1.3 versus 1 ± 0.4) compared to the healthy subject and a lower capillary/fiber ratio and capillary density lower. The decline in the percentage of type I fibers was significantly higher in COPD patients with PE (30.9 ± 8.9 versus 35.7 ± 6.2). In conclusion, patients with COPD with PE refer significantly lower maximal exercise capacity, more dyspnea and lower peripheral muscle strength that COPD patients with NPE.COPD patients have a lower percentage of type I fibers and greater percentage of type II fiber for healthy subject and this alteration in the percentage of fibers peripheral muscle is significantly higher in the COPD patient with PE

Estudio de la función muscular periférica y de la capacidad de ejercicio en pacientes con síndrome de apneas hipopneas del sueño / Peripheral muscle function study and the exercise capacity in patients with Sleep Apnea Syndrome

El objetivo del estudio fue evaluar la composición corporal, la función muscular y la capacidad de ejercicio en pacientes con Síndrome de Apneas-Hipopneas del Sueño (SAHS) moderado-severo. Material y métodos: Se trata de un estudio observacional descriptivo. Se realizó una poligrafía domiciliaria a 25 pacientes, de los que 16 fueron diagnosticados de SAHS moderado severo (IAH >15) constituyendo el grupo de estudio, mientras que el resto (IAH< 5), formaron el grupo control. Se evaluó la fuerza muscular periférica mediante test de una repetición máxima, 1RM, la capacidad de ejercicio mediante test de esfuerzo cardiopulmonar, se realizó un test de marcha de 6 min, se calculó la composición corporal y valoró la calidad de vida mediante el cuestionario SF36. Resultados: Nuestros hallazgos principales mostraron que los pacientes con SAHS tenían un menor VO2max de p50 (p25-p75) 19,6 [15,7 - 23,7] vs grupo control 26,2 [18 - 29,1] (n.s.) y menor Wmax (carga máxima alcanzada durante el esfuerzo) 69,5 [53,2 - 77,5] vs 81 [72,7 - 90,7] p = 0,029. Menor fuerza muscular periférica 1RM hombros 32 [22 - 38] vs 34 [19 - 40,5] (n.s), 1RM cuádriceps 33 [22,5 - 48,5] vs 36 [20 - 42,5] (n.s.) y menor distancia recorrida en test 6 min 579 [524 - 613,5] vs 594 [552,7 - 623,7], (n.s.). Los pacientes SAHS tenían mayor grasa corporal con un peso graso en Kg 31,25 (23,1 - 44,2) vs 21,4 (18,5 - 28,5) P = 0,015. Conclusiones: En nuestro grupo de pacientes con SAHS, se demuestra una peor tolerancia al ejercicio en comparación con pacientes sanos con características antropométricas similares. Esto no parece estar relacionado con la fuerza muscular de las extremidades, sino que podría deberse a otros factores, como la obesidad e incluso el desentrenamiento

The aim of the study was to assess body composition, muscle function and exercise capacity in patients with moderate to severe Obstructive Sleep Apnea (OSA). Methods: This is an observational descriptive study. A home sleep monitoring was performed in 25 patients. 16 were diagnosed with moderate-severe (AHI >15) SAHS and constituted the study group, whereas the rest (AHI< 5) formed the control group. Peripheral muscle strength was assessed with the one repetition maximum (1RM) test, exercise capacity by means of a cardiopulmonary exercise test and the 6 minutes walking test; body composition was calculated by impedanciometry, and quality of life was assessed with the SF36 questionnaire. Results: Our main findings showed that patients with OSA had lower VO2max of P50 (P25- P75) 19.6 [15.7 - 23.7] vs control group 26.2 [18 - 29.1] (ns), and lower Wmax 69.5 [53.2 - 77.5] vs 81 [72.7 - 90.7] p = 0.029. OSA patients had lower peripheral muscle strength: 1RM shoulders 32 [22 - 38] vs 34 [19 - 40.5] (ns), 1RM quadriceps 33 [22.5 - 48.5] vs 36 [20 - 42.5] (ns), and less distance in 6 min walking test 579 [524 - 613.5] vs 594 [552.7 - 623.7] (ns). The OSA patients had a greater body fat weight 31.25 (23.1 - 44.2) vs 21.4 (18.5 - 28.5) P = 0.015. Conclusions: Our patients with OSA demonstrated a worse exercise tolerance compared to healthy patients with similar anthropometric characteristics. This does not appear to be related to muscle strength in the limbs, but could be due to other factors such as obesity and even detraining

Evaluación de flujos y volúmenes dinámicos en pacientes con compromiso muscular respiratorio / Dynamic flows and volumes evaluation in patients with respiratory muscle impairment

Spirometry measures the forced expiratory volumes and flows. In patients with neuromuscular disease, these are altered since there is some respiratory muscle involvement. The usefulness of this test is based on the interpretation of the shape of the flow / volume loop and values of spirometric variables. In patients with neuromuscular disease, Forced Vital Capacity is the most used especially for its prognosis value.

La espirometría mide volúmenes y flujos espiratorios forzados. En los pacientes con enfermedad neuromuscular (ENM) estos se ven alterados debido al compromiso muscular respiratorio. La utilidad de este examen se basa en la interpretación de la forma de la curva flujo/volumen y los valores de las variables espirométricas. En los pacientes con ENM la Capacidad Vital Forzada es la más utilizada ya que otorga valor pronóstico.

Influence of weather and atmospheric pollution on physical activity in patients with COPD.

RATIONALE: Information concerning how climate and atmospheric pollutants affects physical activity in COPD patients is lacking and might be valuable in determining when physical activity should be encouraged. METHODS: Seventy-three stable COPD patients recorded on daily diary cards worsening of respiratory symptoms, peak expiratory flow rate, hours spent outside the home and the number of steps taken per day. Pedometry data was recorded on 16,478 days, an average of 267 days per patient (range 29-658). Daily data for atmospheric PM10 and ozone (O3) were obtained for Bloomsbury Square, Central London from the Air Quality Information Archive databases. Daily weather data were obtained for London Heathrow from the British Atmospheric Data Archive. RESULTS: Colder weather below 22.5 °C, reduced daily step count by 43.3 steps day per °C (95% CI 2.14 to 84.4; p = 0.039) and activity was lower on rainy than dry days (p = 0.002) and on overcast compared to sunny days (p < 0.001). Daily step count was 434 steps per day lower on Sunday than Saturday (p < 0.001) and 353 steps per day lower on Saturday than Friday (p < 0.001). After allowance for these effects, higher O3 levels decreased activity during the whole week (-8 steps/ug/m3; p = 0.005) and at weekends (-7.8 steps/ug/m3; p = 0.032). Whilst, during the week PM10 reduced activity (p = 0.018) but not during the weekend. CONCLUSIONS: Inactivity of COPD patients is greatest on cold, wet and overcast days and at the weekends. This study also provides evidence of an independent effect of atmospheric pollution at high levels.

Reliability of the maximal oxygen uptake following two consecutive trials by indirect calorimetry / Confiabilidad del consumo máximo de oxigeno evaluado en pruebas de esfuerzo consecutivas mediante calorimetría indirecta

Background: The maximal oxygen uptake (VO2máx) assessment by indirect calorimetry is the most reliable method to determine VO2máx, but when repeated tests are conducted, the results have been controversial. Aim: To determine the reliability of the maximal oxygen uptake (VO2máx) in healthy adults following two consecutive trials with 10 min rest between trials using the Bruce protocol. Methods: Participants were 6 males apparently healthy physically active (Mean age=23,4±1,3 years), who performed twice the Bruce protocol and after reaching their VO2máx in the first trial they stepped down the treadmill and rested seated on a chair during 10 min. Results: The data analysis showed high reproducibility values between tests, indicated by the correlation coefficient Pearson product moment and R squared with confidence intervals at 95% (CI95%), the correlation of the maximum oxygen consumption was VO2máx =0.907 with a R2 =0.823, the maximum heart rate was HRmáx=0.786, with R2 =0.618 and the rate of ventilation and carbon dioxide elimination was VE/VCO2 =0.868, with an R2 =754. No adverse effects were reported during the 10 min rest between trials. Conclusion: Resting 10 min between consecutive maximal exercise tests using Bruce protocol treadmill tests does not affect VO2máx in healthy young adults. It is feasible and reliable to perform maximal treadmill tests in a single session without adverse effects for the participant (AU)

Introducción: La evaluación del con consumo máximo de oxígeno (VO2máx) por calorimetría indirecta es el método más confiable aun sin embargo los resultados al determinar el VO2máx cuando se realizan pruebas repetidas han resultado controversiales. Objetivo: Determinar la confiabilidad del consumo máximo de oxígeno (VO2máx) obtenido mediante dos pruebas de esfuerzo consecutivas utilizando el protocolo de Bruce en sujetos sanos que descansaron 10 min entre cada prueba. Método: En el estudio participaron 6 adultos jóvenes de género masculino, físicamente activos con una edad promedio de 23,4±1,3 años, los sujetos realizaron dos pruebas de esfuerzo mediante el protocolo de Bruce y al alcanzar el VO2máx, entre la primera y la segunda prueba, se bajaron del ergometro y reposaron sentados en una silla durante 10 minutos. Resultados: Los datos obtenidos mostraron alta reproducibilidad de los valores entre las pruebas, indicado por el coeficiente de correlación producto momento de Pearson y el R cuadrado con intervalos de confianza al 95% (IC95%), la correlación del consumo máximo de oxígeno de fue VO2máx=0.907, con un R2 =0.823, la frecuencia cardiaca máxima fue FCmáx=0.786, con un R2 =0.618 y la tasa de ventilación y eliminación de dióxido de carbono fue VE/VCO2 =0.868, con un R2 =754. Conclusión: No se observaron efectos adversos durante el periodo de descanso de 10 minutos entre pruebas. En conclusión, descansar 10 minutos entre pruebas de esfuerzo máximas consecutivas utilizando el protocolo de Bruce no afecta el VO2máx en sujetos jóvenes y aparentemente sanos. Repetir una prueba máxima en una misma sesión es posible, confiable y no se presentan efectos adversos (AU)

The receptor for advanced glycation end-products supports lung tissue biomechanics.

The receptor for advanced glycation end-products (RAGE) and its soluble forms are predominantly expressed in lung but its physiological importance in this organ is not yet fully understood. Since RAGE acts as a cell adhesion molecule, we postulated its physiological importance in the respiratory mechanics. Respiratory function in a buffer-perfused isolated lung system and biochemical parameters of the lung were studied in young, adult, and old RAGE knockout (RAGE-KO) mice and wild-type (WT) mice. Lungs from RAGE-KO mice showed a significant increase in the dynamic lung compliance and a decrease in the maximal expiratory air flow independent of age-related changes. We also determined lower mRNA and protein levels of elastin in lung tissue of RAGE-KO mice. RAGE deficiency did not influence the collagen protein level, lung capillary permeability, and inflammatory parameters (TNF-α, high-mobility group box protein 1) in lung. Overexpressing RAGE as well as soluble RAGE in lung fibroblasts or cocultured lung epithelial cells increased the mRNA expression of elastin. Moreover, immunoprecipitation studies indicated a trans interaction of RAGE in lung epithelial cells. Our findings suggest the physiological importance of RAGE and its soluble forms in supporting the respiratory mechanics in which RAGE trans interactions and the influence on elastin expression might play an important role.

Inhaled tobramycin effectively reduces FEV1 decline in cystic fibrosis. An instrumental variables analysis.

RATIONALE: The efficacy of inhaled tobramycin on chronic Pseudomonas aeruginosa infections in patients with cystic fibrosis (CF) has been established in clinical trials. However, little is known about its clinical effectiveness on lung function outside randomized controlled trial settings; conventional analysis of existing registry data has heretofore been confounded by treatment selection bias. OBJECTIVE: To determine effectiveness of inhaled tobramycin on FEV1 decline in patients with chronic P. aeruginosa infections using observational data from the Cystic Fibrosis Foundation Patient Registry. METHODS: Patient-level tobramycin use was measured at first chronic P. aeruginosa infection (n = 13,686 patients; age, 6-21 yr). Decline in FEV1 2 years after infection was estimated for patients treated with tobramycin and compared with untreated patients. Multiple linear regressions with confounder adjustment and propensity scores were used to estimate mean FEV1 decline for each group. Because care is organized by centers, we used center-specific prescription rates as an instrument to reduce treatment-by-condition bias. MEASUREMENTS AND MAIN RESULTS: Using center-level prescribing rates, instrumental variables analysis showed less FEV1 decline for patients who received tobramycin when first eligible compared with those who did not receive tobramycin (difference, 2.55% predicted; 95% confidence interval, 0.16-4.94; P = 0.0366). CONCLUSIONS: Inhaled tobramycin is effective in reducing lung function decline among patients 6 to 21 years of age with CF. Because CF care is organized by center, using center-specific prescription rates as an instrumental variable is a feasible approach to using the Cystic Fibrosis Foundation Patient Registry to determine treatment effectiveness. More generally, this approach can correct for treatment-by-condition bias arising from observational studies.