Nonequivalence of Inhaled and Nebulized Salbutamol in the Assessment of Endothelial Dysfunction

A noninvasive measure of global endothelial dysfunction may be obtained by pulse wave analysis (PWA) before and after administration of inhaled salbutamol. As some subjects may have difficulty using an inhaler, we determined whether equivalent doses of inhaled and nebulized salbutamol produced similar effects on a key measure obtained from PWA-the augmentation index (AIx). Twenty volunteers (11 with vascular risk factors and 9 healthy controls) underwent PWA at the right radial artery using SphygmoCor. Subjects were randomized to receive either 400 mu g inhaled salbutamol via spacer device or 2.5 mg nebulized salbutamol. PWA was performed until there was no further drop in AIx. After AIx returned to baseline, salbutamol was administered via the alternative route and measurements were repeated. The primary outcome was the intraclass correlation coefficient of agreement (ICC) between maximum change in AIx following inhaled and nebulized salbutamol. The ICC was 0.32 (95% CI -0.07 to 0.64) and 0.39 (95% CI -0.04 to 0.70) with and without correction for heart rate. The median maximum decrease in AIx after inhaler was 4.8% (IQR 1.8-7.1), and after nebulizer was 8.5% (IQR 7.5-11.4) (p = <.001). When corrected for heart rate, the median maximum fall in AIx after inhaler was 4.0% (IQR 2.0-7.9) and after nebulized salbutamol was 5.0% (IQR 3.8-9.6) (p = 0.24). Although inhaled and nebulized salbutamol produced similar median reductions in AIx, the correlation between the two methods of salbutamol delivery was weak. Further research is required to validate the fall in AIx after nebulized salbutamol as a measure of endothelial dysfunction.