Clinical trial NCT01271556: Effect of Salmeterol on Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients
Official title: Salmeterol Improves Fluid Clearance From Alveolar-Capillary Membrane in COPD Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Salmeterol Effect Against an Acute Alveolar Fluid Clearance Challenge Secondary to Lung Fluid Overload in COPD Patients
Chronic Obstructive Pulmonary Disease
Bronchodilator Agents
Salmeterol
Keywords: COPD
LABA
salmeterol
Lead sponsor: University of Milan
Sponsor class: OTHER
First posted: 2011-01-06
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 240 and 290 minutes after inhalatory treatment pulmonary function tests were performed
Secondary outcomes:
measure: changes in mechanical lung properties
timeFrame: 240 and 290 minutes after inhalatory treatment
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
Study officials:
affiliation: Respiratory Medicine Section, Dipartimento Toraco-Polmonare e Cardiocircolatorio, Università degli Studi di Milano, San Paolo Hospital
name: Stefano Centanni, MD
role: STUDY_DIRECTOR
References: