Similarly, the dysregulation of cell death is a recognised characteristic of COPD lung tissue and is linked with the development of an emphysematous phenotype, as documented in several studies.57, 58, 59, 60 The pronounced activation of HIF-1α in ACO, but not in COPD, may drive the extensive airway remodelling seen in ACO, distinguishing it from the more severe emphysema and parenchymal destruction characteristic of COPD. This evidence concerns the gene HIF1A and pulmonary emphysema.