Difficult/Therapy-Resistant Asthma: Pathogenesis and Possible Relationship with Tobacco Smoke

Author(s): Brigita Sitkauskiene, Algirda Krisiukeniene, Raimundas Sakalauskas

Journal Name: Current Respiratory Medicine Reviews

Volume 2 , Issue 1 , 2006

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In the pathogenesis of asthma, chronic inflammation within the airways plays a major role. Corticosteroids (or glucocorticosteroids) have beneficial anti-inflammatory effects and are recommended in all international guidelines for treating asthmatic inflammation. However, control remains difficult for almost 5% of asthmatics despite high doses of inhaled corticosteroids. Several classes of difficult asthma have been described: "brittle asthma", "steroid-resistant asthma", "steroid-dependent asthma", and "refractory asthma", and used interchangeably. Some hypotheses have been posed regarding the pathogenesis of difficult/therapy resistant asthma. Recent studies indicate that steroid-resistant asthma is associated with a failure of corticosteroids to inhibit T-lymphocyte proliferation and secretion or their cytokines. In cases of severe asthma, sputum and tissue eosinophilia vary from "normal" to "elevated" levels, and increased numbers of neutrophils are common. It also appears that conditional to a poor response to the treatment with corticosteroids are the abnormalities in glucocorticoid receptor (GR) number, GR binding, or corticosteroid-GR complex binding to DNA. The causes and predictors of difficult asthma are still uncertain. One predicting possibility is tobacco smoke. Smoking induces the release of interleukin-8, which is the potent neutrophil chemoattractant. Further research is required to clarify the exact mechanisms in difficult/therapy-resistant asthma, and to develop an optimal treatment approaches.

Keywords: Asthma, pathogenesis, therapy resistance, smoking

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Article Details

Year: 2006
Page: [67 - 74]
Pages: 8
DOI: 10.2174/157339806775486173

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