Exhaustion of Airway Basal Progenitor Cells in Early and Established Chronic Obstructive Pulmonary Disease.
RATIONALE
Up to 40% of smokers develop chronic obstructive pulmonary disease (COPD) over a period that spans decades. Despite the importance of COPD, much remains to be learned about susceptibility and pathogenesis, especially during early, prediagnostic stages of disease. Airway basal progenitor cells are crucial for lung health and resilience because of their ability to repair injured airways. In COPD, the normal airway epithelium is replaced with increased basal and secretory (mucous) cells and decreased ciliated cells, suggesting that progenitors are impaired.


OBJECTIVES
To examine airway basal progenitor cells and lung function in smokers with and without COPD.


METHODS
Bronchial biopsies taken from smokers at risk for COPD and lung cancer were used to acquire airway basal progenitor cells. They were evaluated for count, self-renewal, and multipotentiality (ability to differentiate to basal, mucous, and ciliated cells), and progenitor count was examined for its relationship with lung function.


MEASUREMENTS AND MAIN RESULTS
Basal progenitor count, self-renewal, and multipotentiality were all reduced in COPD versus non-COPD. COPD progenitors produced an epithelium with increased basal and mucous cells and decreased ciliated cells, replicating the COPD phenotype. Progenitor depletion correlated with lung function and identified a subset of subjects without COPD with lung function that was midway between non-COPD with high progenitor counts and those with COPD.


CONCLUSIONS
Basal progenitor dysfunction relates to the histologic and physiologic manifestations of COPD and identifies a subset that may represent an early, prediagnostic stage of COPD, indicating that progenitor exhaustion is involved in COPD pathogenesis.
['Ghosh|Moumita|M|', 'Miller|York E|YE|', 'Nakachi|Ichiro|I|', 'Kwon|Jennifer B|JB|', 'Barón|Anna E|AE|', 'Brantley|Alexandra E|AE|', 'Merrick|Daniel T|DT|', 'Franklin|Wilbur A|WA|', 'Keith|Robert L|RL|', 'Vandivier|R William|RW|']
D001706:Biopsy D003430:Cross-Sectional Studies D018450:Disease Progression D004848:Epithelium D005260:Female D006801:Humans D008168:Lung D008297:Male D008875:Middle Aged D029424:Pulmonary Disease, Chronic Obstructive D012720:Severity of Illness Index D000074285:Smokers D012907:Smoking D013234:Stem Cells D013995:Time
multipotentiality cell self-renewal disease susceptibility early diagnosis stem cells