Overcoming steroid insensitivity in smoking asthmatics.
Asthma is successfully treated in most patients through the use of conventional corticosteroid therapy. The majority (90 to 95%) of patients respond effectively to moderate doses of inhaled corticosteroids with minimal side effects. Nevertheless, there is a small population of asthmatic patients, including present and ex-cigarette smokers, who fail to respond adequately to corticosteroid treatment even at high doses or with the addition of supplementary therapy. These patients account for a disproportionate amount of healthcare costs because they exacerbate more frequently and are more likely to be admitted to hospital due to their asthma. Cigarette smoking is an important factor associated with corticosteroid resistance in asthmatics, and there is scope for the development of novel therapies to target this subgroup of asthmatics. This review summarizes the various hypotheses underlying corticosteroid insensitivity in smoking asthmatics and discusses the development of potential novel therapies based on these concepts.
Ahmad
Tehireem
T
Imperial College London, National Heart and Lung Institute, Airways Disease Section, Dovehouse Street, London, SW3 6LY, UK.
Barnes
Peter J
PJ
Adcock
Ian M
IM
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors; D004351:Drug Resistance; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D058988:Phosphodiesterase 4 Inhibitors; D021381:Protein Transport; D011965:Receptors, Glucocorticoid / Q000502:physiology; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D058988:Phosphodiesterase 4 Inhibitors; D011965:Receptors, Glucocorticoid