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Why Is Steroid Treatment Ineffective for COPD?
COPD is a major public health
problem for both the developed
and the developing world, and
is most often caused by cigarette
COPD leads to persistent inflammation of the airways and is typically managed with corticosteroids, a class of anti-inflammatory medication. However, corticosteroids do not improve survival nor alter the progression of COPD and may reduce lung symptoms as little as 20 per cent.
COPD is a major public health problem for both the developed and the developing world, and is most often caused by cigarette smoking or exposure to pollutants from combustion. Characterised by chronic bronchitis and emphysema, COPD is the third leading cause of death in the United States and affects 24 million Americans and 210 million people worldwide.
Histone deacetylase 2 (HDAC2) is critical component in a chain of reactions that enable corticosteroids to reduce inflammation. However, HDAC2 is substantially reduced in the lung tissue of individuals with COPD. In the study, researchers found that S-nitrosylation causes HDAC2 dysfunction and leads to corticosteroid insensitivity in the alveolar macrophages of the lungs of individuals with COPD. S-nitrosylation of HDAC2 occurs from exposure to cigarette smoke, a primary cause of COPD.
“This study provides the mechanism of exaggerated inflammation observed in COPD patients during exacerbations, which has been a barrier to developing effective therapy,” said Professor Rajesh Thimmulappa, co-author of the study.
Furthermore, the research team found that treatment with sulforaphane restored HDAC2 activity and corticosteroid sensitivity. Previous studies by the research team showed sulforaphane activates the Nrf2 pathway (nuclear factor erythroid 2–related factor 2) and it is being tested in clinical trial for patients with COPD.
“Restoring corticosteroid sensitivity in patients with COPD by targeting the Nrf2 pathway holds promise for effectively treating exacerbations,” said Professor Shyam Biswal of the Johns Hopkins School of Medicine.
MEDICA.de; Source: Johns Hopkins Bloomberg School of Public Health