The methylxanthine drug theophylline could overcome steroid resistance in chronic obstructive pulmonary disease (COPD) patients, a respiratory expert has said.
Peter Barnes (National Heart & Lung Institute, Imperial College London, UK) last week told delegates at the Clinical Consensus on COPD held in London, UK, that he thinks theophylline "is the answer" to the global COPD epidemic.
Ian Adcock, also from the National Heart & Lung Institute, explains that while asthma and COPD are both characterized by chronic airway inflammation, the site and type of inflammation differ, as does the response to steroids.
"Clinically, even high doses of inhaled or oral glucocorticoids are virtually ineffective in patients with COPD compared to the marked responses seen in asthma, suggesting that the inflammation seen in COPD is essentially steroid resistant," he said.
He added that this resistance may be due to reduced expression of histone deacetylase-2 (HDAC2).
Oxidative stress, such as cigarette smoke, reduces HDAC2 activity in COPD airways and lungs, and HDAC2 expression decreases with disease severity. Theophylline – which is an activator of HDCA2 – restores steroid responsiveness in cellular models and mice exposed to smoking.
"Targeting these pathways or use of antioxidants may… restore corticosteroid responsiveness," he suggested.
In a session discussing emerging therapies, Brian O'Connor (King's College London, UK) said that Professor Barnes "made a strong case against" the role of corticosteroids for treating COPD, but added that "in some patients, there's a role."
Some evidence documents a small but effective reduction in COPD patients' decline in FEV1, and there is a rationale for using long-acting beta-agonists with inhaled corticosteroids, he explained.
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