Defective FGFR2 Signaling in the Small Airway Basal Progenitor Cells in COPD
Early changes associated with the development of smoking-induced diseases, e.g., COPD and lung cancer (the two commonest causes of death in U.S.) are often characterized by abnormal airway epithelial differentiation. Airway basal cells (BC) are stem/progenitor cells necessary for generation of differentiated airway epithelium. Based on our preliminary observations on SAE BC cells and FGFR2 signaling, we hypothesized that suppression of FGFR2 signaling in the SAE BC stem/progenitor cells by cigarette smoking renders these cells less potent in generating and maintaining normally differentiated SAE, shifting these cells towards a COPD associated phenotype. To test this, SAE basal cells will be isolated from cultured cells obtained through bronchoscopic brushings and analyzed through in vitro assays for their stem/progenitor capacities.
• Must be capable of providing informed consent
• Males and females, age 18 or older
• Nonsmoking, matched with other groups by age, sex, ethnic/racial group
• Good overall health without history of chronic lung disease, including asthma, and without recurrent or recent (within 3 months) acute pulmonary disease
• Normal physical examination
• Normal routine laboratory evaluation, including general hematologic studies, general serologic/ immunologic studies, general biochemical analyses, and urine analysis
• Negative HIV serology
• Normal chest X-ray (PA and lateral)
• Normal electrocardiogram
• Females - not pregnant
• No history of allergies to medications to be used in the bronchoscopy procedure
• Not taking any medications relevant to lung disease or having an effect on the airway epithelium
• Willingness to participate in the study