Doppler echocardiographic assessment of the effects of inhaled long-acting beta2-agonists on pulmonary artery pressure in COPD patients

Abstract

Increase in pulmonary artery pressure (PAP), which is common in severe chronic obstructive pulmonary disease (COPD), is a predictor of mortality independent of airflow limitation. beta-agonists might slightly attenuate this increase because they exert a vasodilating effect on pulmonary circulation when systematically administered. We have investigated the acute effects of salmeterol and formoterol on echocardiographic systolic pulmonary artery pressure (sPAP) in 20 patients with COPD and a sPAP greater than 20mmHg at rest. Acute haemodynamic responses to inhaled formoterol or salmeterol were assessed in all patients, in a randomized, double-blind double-dummy fashion. On two consecutive days, patients received, in a randomized order, formoterol 12microg via Turbuhaler plus placebo via Diskus or salmeterol 50microg via Diskus plus placebo via Turbuhaler. Transthoracic Doppler echocardiography measurements of sPAP were made before and 15, 30, 60 and 180min after bronchodilator inhalation. Lung function, pulse oximetry and heart rate were also monitored at the same times. Mean sPAP significantly (p<0.05) decreased in comparison with baseline at 15, 30, and 60min post inhalation but returned towards control levels at 180min after both salmeterol and formoterol. There was no correlation between the maximum increase in FEV(1) and maximum decrease in sPAP either after inhalation of salmeterol (r(2)=0.071) or after that of formoterol (r(2)=0.0006). The increases in FEV(1) in comparison with baseline were always significant (p<0.05) from 15 to 180min post inhalation after either salmeterol or formoterol. Neither pulse oximetry nor heart rate changed in a significant manner (p>0.05). This study demonstrated that salmeterol and formoterol were equally beneficial for pulmonary haemodynamics in patients with COPD. A direct vasodilatation due to the activation of beta-adrenoceptors that are present in pulmonary vessels is a likely mechanism of their action in inducing the decrease in sPAP.