Potential mechanisms to explain how LABAs and PDE4 inhibitors enhance the clinical efficacy of glucocorticoids in inflammatory lung diseases

F1000prime Reports
Mark A Giembycz, Robert Newton

Abstract

Inhaled glucocorticoids acting via the glucocorticoid receptor are a mainstay treatment option for individuals with asthma. There is a consensus that the remedial actions of inhaled glucocorticoids are due to their ability to suppress inflammation by modulating gene expression. While inhaled glucocorticoids are generally effective in asthma, there are subjects with moderate-to-severe disease in whom inhaled glucocorticoids fail to provide adequate control. For these individuals, asthma guidelines recommend that a long-acting β2-adrenoceptor agonist (LABA) be administered concurrently with an inhaled glucocorticoid. This so-called "combination therapy" is often effective and clinically superior to the inhaled glucocorticoid alone, irrespective of dose. LABAs, and another class of drug known as phosphodiesterase 4 (PDE4) inhibitors, may also enhance the efficacy of inhaled glucocorticoids in chronic obstructive pulmonary disease (COPD). In both conditions, these drugs are believed to work by elevating the concentration of cyclic adenosine-3',5'-monophosphate (cAMP) in target cells and tissues. Despite the success of inhaled glucocorticoid/LABA combination therapy, it remains unclear how an increase in cAMP enhances the clinical e...Continue Reading

Citations

Apr 26, 2016·European Journal of Pharmacology·Nowshin N Rumzhum, Alaina J Ammit
Apr 27, 2016·Pharmacology & Therapeutics·Tonio Pera, Raymond B Penn
Jun 12, 2016·Pharmacology & Therapeutics·Janet P HapgoodJohnson M Moliki
Dec 21, 2016·American Journal of Respiratory Cell and Molecular Biology·Brijeshkumar S PatelAlaina J Ammit
Aug 12, 2017·Respiratory Research·Seyed M MoosaviAlaina J Ammit
Jan 17, 2016·Respiratory Research·Rabih HalwaniSaleh Al-Muhsen
Dec 19, 2019·Pharmacological Reviews·M G MateraM Cazzola
Sep 11, 2020·Pharmacology & Therapeutics·Mengyuan Kan, Blanca E Himes
Nov 8, 2020·The Journal of Pharmacology and Experimental Therapeutics·Radhika JoshiMark A Giembycz
Feb 3, 2021·The International Journal of Biochemistry & Cell Biology·Jenny P NguyenJeremy A Hirota
Aug 27, 2021·Frontiers in Pharmacology·Theerasuk Kawamatawong

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