Effects of Smoking and Secondhand Smoke (SHS) on Response to Corticosteroids
| Effects | References |
|---|---|
| It is unknown if there is a synergistic effect of smoking and asthma on airway mucosal permeability; however, this could contribute to increased clearance of inhaled corticosteroids from the airways of asthmatic smokers | 91 |
| Chronic hypersecretion of mucus is caused by cigarette smoking in patients with asthma, and this could impede the ability of inhaled corticosteroids to bind to GRs in the airways | 92 |
| S2-agonists increase the nuclear localization of GRs, which may potentiate the effects of corticosteroids | 93 |
| Cigarette smoke leads to increased numbers of neutrophils and CD8+ lymphocytes and decreased numbers of eosinophils in the airways, which may contribute to corticosteroid resistance | 91 |
| Nitric oxide in cigarette smoke has been shown to decrease the binding affinity of glucocorticoid receptors (GR) in vitro; it remains to be seen whether or not nitric oxide shows the same effect in vivo 94 | 94 |
| Other proposed mechanisms include overexpression of proinflammatory transcription factors such as NF-κβ, activator protein-1, and signal transduction-activated factor | 95, 96 |
| HDAC activity is necessary for corticosteroids to fully suppress cytokine production, and smokers have decreased HDAC activity in alveolar macrophages, which could lead to corticosteroid resistance | 97 |
| The p38 mitogen-activated protein kinase signaling pathway may be activated in asthmatic smokers which phosphorylates GRs and decreases corticosteroid affinity | 98 |
GR, glucocorticoid receptor; HDAC, histone deacetylase.