The small airways in chronic obstructive pulmonary disease: pathology and effects on disease progression and survival

Chronic obstructive pulmonary disease (COPD) is caused by a mixture of small airway disease (obstructive bronchitis) and parenchymal lung tissue destruction (emphysema). The relative contributions of these two pathologic states vary from person to person. Having the ability to phenotype patients into predominately small airways disease or emphysema may affect the clinical management.

Pathologic studies have shown that the progression of COPD from Global Initiative for Chronic Obstructive Lung Disease stages 0 to 4 is most strongly associated with small airway wall thickening as a result of lung repair or remodeling. The narrowing and loss of small airways occurs prior to emphysematous destruction. There is an increase in the amount of neutrophils and CD8⁺ T lymphocytes (cells that induce apoptosis and necrosis) in the small airways in COPD. Small airways disease can be identified on pulmonary function testing, using multiple nitrogen breath washout testing, indirectly through high-resolution chest computed tomography (CT) imaging or MRI, or directly by using microCT of resected lung tissue. There may be increased mortality in advanced COPD and concomitant small airway disease. There are newer methods to deliver respiratory therapies to reach the small airways.

The current techniques utilized to assess patients for small airway disease need to be improved, so clinicians can more effectively phenotype patients with COPD and small airways disease. This will allow new therapies that target the small airways to be developed and tested, and positively impact on the natural progression of COPD.