Are Small Airways the Key to Understanding Pathophysiology and Treatment Efficacy in Chronic Obstructive Pulmonary Diseases?

This review presents updated information on small airways in the pathogenesis of chronic obstructive respiratory diseases. The lungs have a branching structure, segmentally divided from trachea down to the alveoli (generations 1 23). Airways can be divided into a conducting (generations 1 - 16) and a respiratory zone (generations 17 - 23). Conducting zone is mainly for air transportation, respiratory zone for gas exchange. Increasing attention has been directed to the role of small airways in chronic obstructive respiratory diseases. The small conducting airways <2 mm in diameter are the major site of airway inflammation and obstruction in COPD. It has been shown that the last generation of small conducting airways, the terminal bronchioles, are significantly destroyed in patients with very severe COPD. At what stage in the development of COPD the loss of small airways occurs is not exactly known. The small airways represent the most important target for deposition of inhaled therapeutic particles. Currently there is no gold standard for detecting small airway dysfunction. Techniques such as spirometry and body plethysmography can provide information on air trapping. High-resolution CT enables the diagnosis of pulmonary emphysema and diseases of the large airways. Only micro-CT imaging offers the option to describe microstructure of terminal bronchioles. Impulse oscillometry, gas washout techniques and analysis of exhaled nitric oxide are diagnostic tools which have to be validated for diagnosis and treatment response of small airway diseases.