COPD ground zero: small airways rather than alveoli as the initial site of injury

Chronic obstructive pulmonary disease (COPD) has long been perceived as a dichotomy—an overlapping spectrum of remodelling in the large airways (chronic bronchitis) and alveoli (emphysema). However, as our understanding of COPD grows in sophistication, the anatomical intersection between these spectra—namely, terminal bronchioles and transitional bronchioles, hereafter termed small bronchioles—is increasingly implicated as a likely so-called ground zero of COPD pathogenesis. It has long been appreciated that small bronchioles, which do not resist airflow much in the healthy state because of their abundance and parallel configuration, contribute heavily to expiratory resistance in COPD. 1 Hogg JC Macklem PT Thurlbeck WM Site and nature of airway obstruction in chronic obstructive lung disease. N Engl J Med. 1968; 278: 1355-1360 Crossref PubMed Scopus (992) Google Scholar Further evidence that these small bronchioles might be key in COPD pathogenesis has accrued slowly, with progress being hampered both by the complex anatomical and physiological interdependence of the bronchioles and alveoli as well as by technical factors related to their size and low attenuation. Previous work showed that patients with very severe COPD (Global Diagnosis of Chronic Obstructive Lung Disease [GOLD] stage 4) had a substantially reduced number of terminal bronchioles, supporting the centrality of small airways to the disease. However, the exclusion of patients with less severe disease from this analysis left unanswered the question of whether small bronchiole pruning was a feature of only advanced COPD. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional studyThese data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD. Full-Text PDF