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.

Lipid profiles in pediatric thoracic transplant recipients are determined by their immunosuppressive regimens.

BACKGROUND: Controversy exists over the pattern of lipidemic effects from calcineurin inhibitors and prednisone. We report an extensive longitudinal study of lipid profiles in pediatric thoracic transplant recipients. METHODS: Serial fasting lipids of subjects from a single pediatric center, along with their immunosuppressive regimens, were examined. Groups were analyzed according to cyclosporine- or tacrolimus-based immunosuppression in addition to whether prednisone was used as adjunctive therapy. RESULTS: Of a total of 119 subjects, 85 were and remained on tacrolimus (TAC), 13 remained on cyclosporine (CSA), 4 switched from TAC to CSA, and 17 switched from CSA to TAC. The median age at transplant was 100 months, and the latest follow-up was 48 months. The CSA Group had higher lipid levels than the TAC Group, and levels changed minimally over time. At 1 year, TAC vs CSA total cholesterol was 153 vs 186 mg/dl (p = 0.002), low-density lipoprotein (LDL) cholesterol was 92 vs 117 (p = 0.09), and high-density lipoprotein (HDL) cholesterol was 42 vs 48 (p = NS), respectively. At the latest follow-up, the TAC vs CSA cholesterol was 143 vs 180 mg/dl (p = 0.001), LDL was 84 vs 115 (p = 0.001), and HDL was 42 vs 41 (p = NS). Profiles of subjects that switched agents reflected the agent used (e.g., higher total cholesterol, LDL, and HDL while on cyclosporine). Sub-group analysis showed prednisone augmented the hyperlipidemic effects. CONCLUSION: Hyperlipidemia is common in pediatric thoracic transplant patients and persists over time. It is more pronounced in cyclosporine subjects and is further elevated with prednisone. These findings indicate the need for close monitoring, and consideration for intervention, especially in high-risk sub-groups.

Spectrum of clinical manifestations of West Nile virus infection in children.

Reports of clinical manifestations of West Nile virus (WNV) infections in children have been relatively rare. Four cases of WNV infection in children are described: the first report of prolonged encephalitis and fulminant hepatitis caused by WNV, and 3 other presentations of WNV, including the first report of ocular involvement in a child.