Tolerance & resistance to ß2-agonist bronchodilators.

For the past half-century, ß2-agonists have been the mainstay of treatment of the bronchoconstriction associated with asthma. Although their usefulness in reversing acute bronchospasm remains undiminished, there is increasing evidence that chronic use may lead to development of tolerance and thus, potentially increasing morbidity and even mortality. In addition, genetic studies have shown that certain individuals carrying specific mutations may be prone to developing resistance to ß2-agonists regardless of the duration of treatment. This article reviews the current evidence regarding the underlying mechanisms that cause or contribute to the development of the resistance, as well as the strategies for the evaluation and management of patients who are at risk for or have developed tolerance to ß2-agonists.

Steroid-resistant asthma.

Steroid-resistant asthma (SRA) refers to patients with symptoms consistent with asthma who show very poor or no response at all to high doses of inhaled or even of systemic corticosteroids. The current article reviews the SRA related literature focusing on the problems associated with the definition of SRA (especially its association with difficult to control, or severe asthma), its various phenotypes, its molecular basis, and the potential treatment options. The article also discusses the limitations of some of the key criteria used for the determination of SRA and proposes a modified set of criteria that are more applicable to children.