Pharmacological strategies to regain steroid sensitivity in severe asthma and COPD

•Corticosteroid resistance is a major therapeutic challenge to the treatment of severe asthma and COPD.•Cellular and molecular mechanisms underlying steroid insensitivity in severe asthma and COPD are still not fully understood.•Recent discoveries highlighted certain signaling pathways that play a role in steroid insensitivity in severe asthma and COPD.•Therapeutic strategies using biologics and small molecule inhibitors are promising approaches to reverse corticosteroid resistance.•A panel of clinically effective drugs may be successfully repositioned for clinical use in COPD and severe asthma.