Effect of Salmeterol on Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients

Condition(s) targeted: Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients; Chronic Obstructive Pulmonary Disease; Bronchodilator Agents; Salmeterol

Intervention: Salmeterol (Drug); saline infusion (0.9 per cent sodium chloride) (Procedure); Placebo (Other)

Phase: N/A

Status: Completed

Sponsored by: University of Milan

Official(s) and/or principal investigator(s):
Stefano Centanni, MD, Study Director, Affiliation: Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital

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.

Official title: Salmeterol Improves Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients

Study design: Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Primary outcome: 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

Secondary outcome: changes in mechanical lung properties

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- COPD diagnosis (consistent with the diagnostic standards of the European Respiratory

Society, ERS, for the management of COPD)

- stable condition for ≥4 weeks and had a prebronchodilator forced expiratory volume in

one second (FEV1) of <60% of the predicted value Exclusion Criteria:

- known allergies to the study medication

- long-term oxygen therapy

- history of asthma, allergic rhinitis, atopy, or a total blood eosinophil count

greater than 400/mm3

- chronic heart failure, untreated arterial hypertension, myocardial infarction within

the last 6 months, diabetes mellitus

- increased serum potassium levels.

Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital, Milan 20142, Italy

Starting date: December 2008
Last updated: January 5, 2011