Why are many COPD patients less responsive to corticosteroids compared to asthma patients?

Many COPD patients demonstrate a reduced response to corticosteroids primarily due to a reduction in histone deacetylase (HDAC) expression. HDACs are enzymes that play a crucial role in regulating gene expression related to inflammatory responses. When HDAC activity decreases, it leads to an increase in pro-inflammatory cytokines and a reduction in the efficacy of corticosteroids, which normally work to suppress these inflammatory pathways.

In asthma, patients typically have more significant and better-targeted responses to corticosteroids, as their inflammatory processes are often more directly linked to allergic reactions and airway hyperresponsiveness. The differences between the underlying mechanisms in asthma and COPD, particularly the lower levels of HDAC in COPD, account for the poorer response to corticosteroids noted in these patients.

Other factors mentioned do not primarily explain the corticosteroid response disparity. For instance, although leukotrienes are involved in inflammation, their elevated levels alone do not sufficiently account for the lack of corticosteroid response in COPD. Similarly, IgE levels and allergen exposure are primarily related to allergic processes seen in asthma rather than the chronic inflammatory processes typical of COPD. Thus, the reduction in HDAC expression is the most accurate reason for the diminished corticosteroid responsiveness observed in COPD patients.