Additional research into glucocorticoid resistance will make it possible to examine how people respond to glucocorticoid before treatment and how to enhance glucocorticoid therapy

Additional research into glucocorticoid resistance will make it possible to examine how people respond to glucocorticoid before treatment and how to enhance glucocorticoid therapy. Reversal of steroid resistance is a brand new approach to deal with steroid-resistant inflammation in asthmatic patients and sufferers with COPD. There are now existing medications like, theophylline, nortriptyline, and macrolides, which are effective by aiming at the PI3Kd pathway, however long-term studies in patients with severe asthma and those with COPD is costly. Selective activation of HDAC2 can be achieved with theophylline, which restores HDAC2 activity in COPD macrophages back to normal and reverses glucocorticoid resistance. Oral theophylline is also effective in reversing glucocorticoid resistance as seen in mice exposed to cigarette smoke which developed glucocorticoid-resistant inflammation. Selective inhibition of PI3K appears to be the molecular mechanism of action of theophylline in restoring HDAC2, which is activated by oxidative stress in COPD patients. This suggests that selective PI3K inhibitors may also be effective, and these medications are presently in clinical improvement for different diseases. Because oxidative stress seems to be a key mechanism in decreasing HDAC2 and results in glucocorticoid resistance, antioxidants should likewise be effective. Regrettably, antioxidants presently available are not of very high effect, and several more powerful antioxidants are in clinical advancement. In the future novel drugs which increase HDAC2 may be developed when the molecular signalling pathways that regulate HDAC2 are better understood.

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