William H. Thompson

Controlled trial of inhaled fluticasone propionate in moderate to severe COPD

Inhaled corticosteroids are often used in the treatment of stable chronic obstructive pulmonary disease (COPD), however, studies of these agents have had mixed results. Previous trials have often excluded subjects with bronchodilator response, have failed to evaluate effect on gas exchange, and have usually looked at only post- rather than prebronchodilator forced expiratory volume (FEV). Our objective was to better assess the efficacy of topical corticosteroids in the treatment of COPD. We used a prospective, randomized, double-blinded, placebo-controlled, crossover study at the Outpatient Department, Department of Veterans Affairs Medical Center. Thirty-six COPD patients with a mean (± SD) FEV1 of 1.10 ± 0.43 L, with or without significant bronchodilator response participated in the study. Subjects received a 3-month course of inhaled fluticasone propionate (220 mg/puff) or identical-appearing placebo by metered-dose inhaler at 2 puffs twice daily, followed by crossover to the alternative inhaler for an additional 3 months. Fluticasone treatment resulted in a higher prebronchodilator FEV1 (1.17 ± 0.08 L [mean ± SEM] versus 1.07 ± 0.08 L, p = 0.001), a higher PaO2 (66.6 ± 1.4 mmHg versus 63.6 ± 1 .6 mmHg, p = 0.002), and a better dyspnea score on the chronic respiratory questionnaire (3.70 ± 0.18 versus 3.47 ± 0.19, p = 0.03). A trend towards fewer exacerbations with fluticasone did not quite meet statistical significance (p = 0.11). Inhaled fluticasone over 3 months improved prebronchodilator airflow obstruction and oxygenation while decreasing dyspnea in moderate to severe COPD. Postbronchodilator FEV1 was not significantly changed.

Bronchovascular Responses to Intravenous Contrast Media for Helical CT Pulmonary Angiography

CT angiography is now commonly used for the diagnosis of pulmonary embolism, but the contrast media used for imaging produces various hemodynamic changes. In this study, we investigated the bronchovascular and hemodynamic responses to intravenous iopromide, a non-ionic contrast agent used for pulmonary CT angiograms, in anesthetized, mechanically ventilated sheep (n = 6). Bronchial blood flow and cardiac output were measured with ultrasonic flow probes. Systemic and pulmonary arterial pressures were continuously monitored. Injections of 0.9% NaCl (120 ml over 30 s) or iopromide (300 mg/ml, 120 ml over 30 s) were given in random order in a peripheral vein with an angiogram infuser and hemodynamic changes were determined. After these parameters returned to baseline, the left pulmonary artery (LPA) was occluded with a snare and the animals were allowed to stabilize. Injections of NaCl and iopromide were repeated in random order as before. There were no significant hemodynamic effects with infusion of NaCl. With intact pulmonary vasculature, NaCl and iopromide did not cause significant changes in arterial blood gases, however, cardiac output (QT, L/min), mean systemic and pulmonary arterial pressures (PSA and PPA, Torr) increased and bronchovascular resistance (BVR, Torr × min/ml), decreased. Following LPA ligation, pH and PO2 significantly decreased over baseline, whereas PCO2 increased. After LPA ligation, iopromide produced a greater decrease in BVR as compared with preligation intact pulmonary vasculature. In conclusion, iopromide caused rapid hemodynamic changes and decreased BVR, likely secondary to osmolar stress. Bronchovascular effects were more pronounced after pulmonary arterial occlusion.