TABLE 2.

Therapeutic strategies for corticosteroid insensitivity in asthma and COPD

Therapeutic strategy	Mechanism of action		Drugs
Alternative broad-spectrum anti-inflammatory drugs	Inhibitors of calcineurin		Ciclosporin, tacrolimus
	Immunomodulators		Methotrexate
	Inhibitors of phosphodiesterase (PDE)4		Roflumilast, cilomilast
	Inhibitors of p38 mitogen-activated protein (MAP) kinase
	Inhibitors of inhibitor kappa-B kinase β (IKKβ)
Reversing steroid resistance	Inhibitors of p38 MAP kinase
	Inhibitors of c-Jun N-terminal kinase (JNK)	Decrease activator protein-1 (AP1)
	Vitamin D in steroid-resistant asthma	Increases regulatory T-cells
	Inhibitors of macrophage migration inhibitor factor (MIF)
	Inhibitors of P-glycoprotein
	Activators of histone deacetylase 2		Theophylline
		Inhibitors of phosphoinositide 3 kinase δ	Copanlisib, idelalisib, umbralisib
		Antioxidants
		Inhibitors of inducible nitric oxide synthase (iNOS)
Increase corticosteroids responsiveness	Long-acting β2-agonists	Reverse glucocorticoid receptor-α (GR-α) phosphorylation

Information from [89].