Club cells and CC16: another "smoking gun"? (With potential bullets against COPD).

Chronic obstructive pulmonary disease (COPD) remains a challenge for clinicians and scientists, as no currently available treatment can significantly change the natural history of the disease. Accelerated lung function decline and recurrent episodes of exacerbations are thought to play critical roles in precipitating patients towards comorbid conditions, long-term oxygen supplementation dependency, and finally death. Currently, the underlying paradigm counterbalances alveolar wall destruction with peribronchiolar fibrosis, the latter being hypothesised to precede the former [1]. Although small airways are now largely recognised as the critical zone of disease initiation and progression [2], very few histological and biological properties specific to this compartment in humans have been highlighted to explain this phenomenon.