|
|
 |
JACI Clinical Highlights - May 2008
The following summaries highlight several of the clinically relevant articles featured in the May 2008 issue of The Journal of Allergy and Clinical Immunology (JACI). These articles have been selected by the Editors for their novel findings, outstanding study design, and potential usefulness to practicing clinicians.
Novel Mechanism of Corticosteroids as Inhibitors of Cysteinyl Leukotriene Action
Oral or inhaled corticosteroids are considered first-line treatments for allergic diseases, including asthma and allergic rhinitis (hay fever). However, these drugs do not influence secretion of cysteinyl leukotrienes, lipids that are considered among the most potent mediators of these diseases. Borish et al speculated that corticosteroids might reduce expression of the 2 cysteinyl leukotrienes receptors and thereby render these mediators less harmful. While not influencing basal or stimulated expression of the type 1 cysteinyl leukotriene receptor, corticosteroids inhibited type 2 receptor expression on many inflammatory cell types. This lack of effect on type 1 receptor expression is consistent with their lack of influence on bronchospasm, which is mediated through this receptor. Type 2 receptors have previously been shown to be important in mediating inflammation, fibrosis, and irreversible obstruction in models of airways disease. The authors’ results suggest a novel mechanism by which corticosteroids could attenuate inflammatory and remodeling pathways mediated through the type 2 cysteinyl leukotriene receptor.
"Corticosteroids as Inhibitors of Cysteinyl Leukotriene Metabolic and Signaling Pathways" by Negri et al
(JACI May 2008 Volume 121 No. 5)
Is an Early Treatment Intervention of Benefit in Mild Asthma?
Although asthma guidelines recommend inhaled corticosteroids (ICS) for mild persistent asthma, the benefit of this approach remains under debate. As reported by Busse et al, START (The Inhaled Steroid Treatment As Regular Therapy in Early Asthma) was a 5-year, worldwide study of more than 7000 patients with mild, persistent asthma. The first three years of study were a double-blind, placebo controlled protocol in which patients with recent-onset asthma were treated with budesonide (200 mcg daily for children <11 years old) or 400 mcg daily in older subjects versus placebo. Three years later, the patients entered an open-label trial in which placebo-treated patients were given budesonide along with their usual medications; the budesonide-treated individuals were continued on this treatment. At the end of the 2-year add-on open-label trial, subjects initially given budesonide (versus placebo) had a significantly lower risk (OR = 0.61; P < .001) for a severe asthma-related event. Moreover, the early-treated budesonide group required less additional asthma medications to maintain asthma control. Although early ICS intervention did not affect lung function, this approach led to improved asthma control with less additional medication needed in mild persistent asthma.
"START study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma" by Busse al
(JACI May 2008 Volume 121 No. 5)
How Common are Plant Food Allergies?
Patients and their families, health professionals, policymakers, and those in the food industry are uncertain about the prevalence of food allergies, particularly allergies to plant food. Zuidmeer et al searched for reports on the prevalence of fruits, vegetables, nuts, seeds, soy, wheat, and other edible plants. Thirty-six population-based studies were included in this systematic review; the data were from more than 250,000 subjects. Only six studies used food challenge tests, the diagnostic "gold standard," to confirm diagnosis; however, these studies reported prevalence generally under 2%. Most studies, based on self- or parental perception, arrived at much higher prevalence estimates—e.g., for fruit in preschool children up to 11.5% and in adults up to 6.6%. Some reactions to plants—e.g., tomatoes and citrus fruits in young children—are often erroneously interpreted as allergic. The authors emphasize caution in placing too much reliance on published prevalence estimates. Suspected allergic reactions to food should be confirmed whenever possible by double-blind, placebo-controlled food challenge tests in clinical settings. Further progress on the prevalence of plant food allergy should be based on population studies using standardized methods, as currently being conducted in the pan-European EuroPrevall study.
"The prevalence of plant food allergies: a systematic review" by Zuidmeer et al
(JACI May 2008 Volume 121 No. 5)
Filaggrin Mutations Confer Substantial Risk for Eczema and Atopy in Children
Weidinger et al report the first large-scale cross-sectional study on the effect of mutations in the skin barrier protein filaggrin (FLG) on allergic diseases at the population level. They investigated the 2 common FLG mutations, R501X and 2282del4, as well as 3 rare variants, in 3099 German children. FLG mutations were greatly overrepresented in children with eczema (carrier frequency, 16% [in contrast to 5.5% in healthy controls]). In the total population, FLG mutations were present in 7.4% of children. FLG variants increased the risk for eczema more than 3-fold. In addition, independently from eczema, FLG mutations conferred a substantial risk for allergic sensitization and hay fever. The population-attributable risk, which indicates the proportion of disease cases in the population attributable to mutant FLG alleles, was 13.5% for eczema, 10.8% for hay fever, and 20.1% for hay fever in combination with eczema. While FLG mutations were not associated with asthma per se, there was a strong association with the combined phenotype "eczema plus asthma," indicating that patients with filaggrin-related eczema are at increased risk to additionally develop asthma.
"Filaggrin mutations, atopic eczema, hay fever and asthma in children" by Weidinger et al
(JACI May 2008 Volume 121 No. 5)
<back>
|
