The cardiovascular component associated with COPD plays a major role in prognosis of the disease, being responsible of 25% of the deaths. Experimental and initial clinical data suggest that beta-adrenergic agonists accelerate clearance of excess fluid from the alveolar airspace, with potential positive effect on cardiogenic pulmonary edema. The aim of this study was to investigate the effects of a long-acting beta-2 agonist, salmeterol, on alveolar fluid clearance in COPD patients by evaluating the diffusive and mechanical lung properties. Our experimental model to test alveolar fluid clearance was rapid saline intravenous infusion. Ten COPD and 10 healthy subjects treated with salmeterol or placebo 4 hours before the begin of the study were evaluated, in four non consecutive days, just before and after a saline infusion or a similar period without infusion. Both in COPD and healthy subjects rapid saline infusion, with placebo or salmeterol premedication, lead to a significant decrease of DLCO and FEV1. Nonetheless, salmeterol pretreatment lead to a significant reduction of the impairment of gas exchange due to saline infusion (-64% of DLCO reduction in comparison with placebo), whilst it did not affect the changes in FEV1. In the control setting, with no infusion, we did not find any significant change of both DLCO and mechanical properties of the lung. In conclusions, in COPD patients salmeterol appears to provide a protective effect against an acute alveolar fluid clereance challenge secondary to lung fluid overload providing an intriguing mechanistic explanation for the benefits observed in larger trials.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
20
50 mcg MDI (inhalatory), once on days A and C at t=0,
rapid 50-minute 750-ml 0.9% saline infusion 240 minutes after inhalatory treatment on day A and B
placebo, inhalatory (MDI) once
Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
Milan, Milan, Italy
change caused by the effect of salmeterol on lung diffusion capacity for carbon monoxide (DLCO) and its components after a challenge with rapid intravenous saline infusion
DLCO was measured twice (Sensor Medics 2200 Pulmonary Functional Test System, USA) for each oxygen mixture, with washout intervals of at least 4 minutes (the average was taken as the final result), according to the European Respiratory Society guidelines. The single-breath alveolar volume (VA) was derived by methane dilution. Alveolar-capillary membrane diffusing capacity (DM) and capillary blood volume available for gas exchange (Vc) were determined with the same equipment, according to the classic Roughton and Forster method
Time frame: 240 and 290 minutes after inhalatory treatment pulmonary function tests were performed
changes in mechanical lung properties
Mouth flow was measured by a mass flowmeter, and volume was obtained by numerical integration of the flow signal. Spirometry and flow-volume curves were obtained by manoeuvres consisting of six to eight regular tidal breaths, a forced expiration initiated from end-tidal inspiration to residual volume (partial expiratory flow-volume curve, PEFV), followed by a fast inspiration to total lung capacity and a forced expiration to residual volume (maximal expiratory flow-volume curve, MEFV).
Time frame: 240 and 290 minutes after inhalatory treatment
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