Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

Expresión y localización del factor de transcripción Yin Yang 1 en el músculo cuádriceps en la enfermedad pulmonar obstructiva crónica / Yin Yang 1 expression and localisation in quadriceps muscle in COPD

Introducción: El Ying Yang 1 (YY1) es un factor de transcripción represor que inhibe la expresión génicamuscular y la miogénesis. Este factor no se ha investigado previamente este factor no se ha investigado enel músculo esquelético de pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Los objetivosdel presente estudio fueron investigar la expresión de YY1 y su localización en el músculo cuádricepsde pacientes con EPOC, comparado con individuos control sanos, emparejados por edad, y examinar larelación entre la expresión y localización de YY1 en las áreas transversales (AT) de las fibras muscularesdel cuádriceps en pacientes con EPOC.Pacientes y métodos: Se sometió a 15 pacientes con EPOC y a 8 individuos de control, emparejados poredad, a valoraciones de la función pulmonar y del cuádriceps y a una biopsia percutánea de este músculo.Mediante inmunofluorescencia se determinó el AT de las fibras musculares del cuádriceps las proporcionesde fibras y localización de YY1. YY1 se inmunoprecipitó a partir del músculo y sus niveles se evaluaronmediante inmunotransferencia.Resultados: Los niveles de YY1 se correlacionaron inversamente con el AT de las fibras de tipo IIx y de tipo Ien pacientes e individuos de control, aunque los niveles de YY1 no fueron significativamente diferentesentre ambos grupos. En los pacientes, pero no en los individuos control, se demostró la localizaciónnuclear de YY1.Conclusión: La expresión de YY1 se asocia a un AT más pequeña de las fibras del cuádriceps en pacientescon EPOC, en cuyo músculo también se observa una localización nuclear del factor, a diferencia de losindividuos control. La regulación de YY1 parece alterada en la EPOC y podría estar implicada en la atrofiamuscular relacionada con la enfermedad(AU)

Introduction: Yin Yang 1 (YY1) is a transcriptional repressor that inhibits muscle gene expression andmyogenesis. YY1 has not previously been investigated in the skeletal muscle of patients with COPD.The aims of this study were to investigate YY1 expression and localisation in the quadriceps muscle ofCOPD patients compared to healthy age-matched controls, and examine the relationship between YY1expression and localisation and quadriceps muscle fibre cross-sectional area (CSA) in COPD patients.Patients and methods: 15 COPD patients and 8 age-matched controls underwent lung and quadriceps function assessments and a percutaneous quadriceps biopsy. Quadriceps muscle fibre CSA and fibre proportions and YY1 localisation were determined by immunofluorescence. YY1 was immunoprecipitated from muscle and YY1 levels assessed by western blotting.