Investigating the Effects of Symbicort on the Ventilatory Kinematics in Patients With Obstructive Disease With Optoelectronic Plethysmography

This study will be a prospective, randomized, double blind, crossover interventional design. The crossover allows for equality in number of subjects assigned to each treatment and for subjects to be their own controls. Baseline spirometry will be taken prior to exercise test. Subjects will be prepared for OEP. All exercise will take place on an electromagnetically braked cycle ergometer. Throughout the protocol heart rate, blood pressure, O2 saturation, ventilation, and metabolic data will be recorded. A modified exercise induced asthma protocol will be used. Unlike prior studies, ventilatory kinematics (with isolated diaphragmatic function) will be monitored throughout exercise using biomechanical motion analysis (OEP). This OEP analysis involves compartmentalization of the chest into three sections; 1) pulmonary rib cage, 2) diaphragmatic rib cage, and 3) abdomen to determine the contribution of each component to total lung volume. By measuring the percent contribution of compartment, we are able to better understand its impact on respiration. OEP will be able to quantify and assess the distortion effects of dynamic hyperinflation and obstruction.

Twenty moderate to severe COPD patients will be recruited. Subjects will refrain from their usual inhaled medications for 24 hours prior to the testing session. All subjects will be asked to verify that this is acceptable with their pulmonologist prior to participation. Subjects will also be asked to have their short acting bronchodilators and other regular medications available to be taken if symptoms should occur. During the initial screening, subjects will be familiarized with all procedures. Then baseline pulmonary function testing, and baseline resting OEP measurements will be performed. The subjects will then be randomized to receive either budesonide/formoterol fumarate dihydrate (Symbicort) or a placebo of budesonide only (Entocort EC). At that time, they will receive treatment with either placebo or budesonide/formoterol fumarate dihydrate and after 45 minutes, they will repeat spirometry and OEP and submaximal exercise testing with OEP. After one week, subjects will be tested again and switched to the opposite treatment (i.e. if on budesonide/formoterol fumarate dihydrate initially then switch to placebo and vice versa). The one week washout period between tests will include a resumption of the usual medications. The subjects will refrain from their inhaled medications for 24 hours before the second testing session, but use all of their other usual medications.