A Pilot Study of the Mechanism of Synergism Between FP and Salmeterol in Preventing COPD Exacerbations

Our objective is to examine the mechanism of the additive/synergistic properties of b2-adrenoceptor stimulation and corticosteroid receptor activation in:

• Preventing neutrophil adhesion to specific endothelial ligands, e.g. ICAM-1 and
• Undergoing activation as a consequence of this adhesion.

We hypothesize that combination therapy with salmeterol + fluticasone (FP) will:

• Augment the inhibition of adhesion of neutrophils obtained from the peripheral blood of study subjects in vitro, by blocking gIV-PLA2 translocation to the nuclear membrane as for eosinophils;
• Augment the inhibition of transendothelial migration of neutrophils into airways of subjects with chronic obstructive pulmonary disease;
• Augment the numbers and concentrations of pro-inflammatory products in the bronchoalveolar lavage fluid; and
• Decrease the number of neutrophils in the bronchial tissue of endobronchial biopsies of treated patients.

Inclusion criteria

• Males or females > 50 years of age
• Physiologic evidence of COPD defined per ATS guidelines as: cigarette smoking history >20 pack years, FEV1/FVC <70%
• Patients must have a post-bronchodilator FEV1 >50% of predicted value at enrollment
• Patient must have an O2 saturation measure by pulse oximetry >90% on RA
• Must be able to participate in the study, willing to give informed consent, and comply with the study restrictions

Exclusion criteria

• Women of child-bearing potential defined as females who are less than 5 years post menopausal unless they have had a hysterectomy or bilateral oophorectomy
• Observation of any solitary nodule in the lung requiring further medical intervention
• Patients on maintenance therapy with oral steroids
• Patients with giant bullous disease
• Significant other medical conditions, which in the opinion of the investigator, will interfere with the patient's ability to perform the study tests
• Presence of a coagulopathy as defined by a platelet count <100,000/mm3, and PT and PTT >1.2 x the upper limit of normal
• Concurrent enrollment or participation in any other clinical trials within the past 30 days
• Primary diagnosis of asthma
• History of alpha 1 antitrypsin deficiency
• Any clinically significant and active pulmonary disease that could contribute to dyspnea
• Current systemic and inhaled steroids and theophylline