Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
COPD, Chronic Obstructive, Pulmonary Disease, Inhaled Corticosteroids, Airway Inflammation, Bronchoscopy
Brief summary
The purpose of this study is to evaluate the blood and airway of subjects with mild to moderate COPD while undergoing standard treatment.
Detailed description
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.
Interventions
DRUGfluticasone and salmeterol
1. will start with fluticasone 220 mcg BID first and then crossover to combination therapy with salmeterol 50 mcg BID 2. will start with salmeterol 50 mcg BID first and then crossover to combination therapy with fluticasone 220 mcg BID.
Sponsors
GlaxoSmithKline
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate blood and airway neutrophil population in COPD patients by examining adhesion and migration in patients with mild to moderate COPD | 12 weeks |
Countries
United States
Outcome results
None listed