Effects of exercise-related dynamic hyperinflation and expiratory airflow limitation on lung kinematics and cardiocirculatory responses pre- and post-bronchodilatation in patients with moderate-to-severe COPD

• Grant number: 06/06529-0
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2007
• End date: July 31, 2010
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: José Alberto Neder Serafini
• Grantee: José Alberto Neder Serafini
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are centrally related to exercise intolerance in patients with COPD. However, there is mounting evidence that the kinetics of EFL-DH during exercise is markedly heterogeneous. Therefore, the cardiocirculatory effects of EFL-DH - and the exercise response to acute bronchodilation - may vary according to specific patterns of recruitment of the chest wall compartiments (rib cage and/or abdominal). In particular, it could be anticipated that the combination of an active expiratory abdominal recruitment plus a lenghtened expiratory time would decrease cardiac preload and increase its afterload. These abnormalities, in turn, would present with deleterious consequences on exercise-related central and peripheral haemodynamic adjustments. Objective: This study aims to investigate, pre- and post-bronchodilatation, the kinetics of EFL-DH and lung kinematics as related to central and peripheral haemodynamics during whole-body exercise in non-hypoxaemic patients with moderate-to-severe COPD. Material and Methods: In a prospective and cross-over study, 10 EFL- and 20 non EFL-limited patients (post-bronchodilator FEV1 30-60% predicted)will be submitted to 2 constant work rate (WR) exercise tests at 70% of peak WR (post-bronchodilator or placebo) with measurements of: (i) breath-by-breath operational lung volumes and lung kinematics (optoelectronic plethysmography or OEP), (ii)presence and severity of EFL (negative expiratory pressure), (iii) ventilatory work and power as calculated by continuous integration of volume (OEP), flow (pneumotachography) and esophageal pressures (esophageal baloon connected to differential pressure transducers); (iv) arterialized blood gases and (v) central and peripheral haemodynamic adjustments (cardioimpedance and near infrared spectroscopy, respectively). Relevance: The present study will test an integrative hypothesis about the multifactorial determinants of exercise pathophysiology in COPD. In this context, a seminal demonstration of the deleterious consequences of pulmonary-mechanical adjustments upon cardiocirculatory responses would change our current understanding of the exercise limiting mechanisms in this patient population. (AU)