Volume 122, Issue 3 , Pages 441-442.e1, September 2008
News beyond our pages
Article Outline
News…
Nutty pregnancies
Dutch researchers have published results from a cohort study that showed daily maternal consumption of nuts and nut products (including peanut butter) had significant association with wheeze, dyspnea, steroid use, and asthma diagnosis. Willers et al (Am J Respir Crit Care Med 2008;178:124-31) reported on maternal consumption patterns of vegetables, fruit, fish, egg, dairy, nuts, and nut products during pregnancy and the presence of asthma symptoms in the children from ages 1 through 8 years. The authors reported no association between maternal consumption of most of these foods and prevalence of asthma symptoms. However, daily but not regular (1-4 times a week) consumption of nut products did increase all asthma outcomes. Willers et al discussed the possibility that the effect of daily nut consumption may be related to an increased intake of linoleic acid, which can alter prostaglandin E2 levels that are reported to shift toward TH2 cytokine imbalance.
Maternal nut consumption during pregnancy affects asthma development
Forkhead box protein 3+ (Foxp3+) regulatory T cells in chronic inflammation
Curotto de Lafaille et al (Immunity 2008;29:114-26) have demonstrated that adaptive Foxp3+ regulatory T cells are required for the induction of mucosal tolerance and the mitigation of chronic inflammation in the airway and intestines of mice.
We asked Drs Maria Curotto de Lafaille and Juan Lafaille to comment on these findings: “We found that Foxp3+ regulatory T cells specific for an allergen develop when mice eat or inhale the allergen and are essential to establish immune tolerance. Animals in which regulatory T cells could not form due to a mutation in the Foxp3 gene became highly susceptible to develop allergy. In sensitized allergic animals, the accumulation of Foxp3+ regulatory T cells in inflamed lungs prevented severe and disseminated inflammation. Thus, therapies that enhance allergen-specific regulatory T-cell numbers or function might have beneficial effect even in established chronic inflammation.”
Maria Curotto de Lafaille
Helicobacter pylori exposure and atopic risk
The hygiene hypothesis received some added support from a recent article in The Journal of Infectious Diseases by Chen and Blaser (2008;198:553-60). The authors reported on results from cross-sectional analyses of the National Health and Nutrition Examination Survey (NHANES) data set to assess association between Helicobacter pylori seropositivity and self-reported asthma, allergic rhinitis, and dermatitis. Their findings demonstrated a strong, inverse correlation between H pylori positivity and the onset of asthma before 5 years of age, as well as allergic rhinitis in the last year.
We asked Dr Yu Chen, first author on the article, to comment on these findings: “Our observation that children colonized with Helicobacter pylori were significantly less likely to have asthma confirms and extends findings from our previous studies in adults, and provides evidence of a modifying effect of age on the association. The data suggest that H pylori colonization early in life is an independent protective risk factor for childhood asthma and allergic rhinitis. The disappearance of H pylori due to modern lifestyles may be one explanation for the sharp rise in childhood asthma. This work opens opportunities for basic and epidemiologic research of the health effects of H pylori in relation to asthma prevention.”
A strong, inverse correlation [was found] between H pylori positivity and the onset of asthma
Prodding mast cells
Mast cell activators were demonstrated to be powerful vaccine adjuvants in a recent article by McLachlan et al (Nat Med 2008;14:536-41). Using current knowledge of the role of mast cells in regulating lymphocyte migration to draining lymph nodes, the authors tested the idea that mast cell activators (cationic peptides and polymeric compounds) plus antigens would induce a persistent, adaptive immune response in mice. Mast cell activators coadministered with antigen elicited higher serum antigen-specific IgG levels than antigen alone in wild-type mice. Mucosal IgA was also elevated, indicating that the effect was both mucosal and systemic. Elevated serum IgG levels persisted for 6 months. McLachlan et al also showed that this effect occurred with administration intranasally as well as subcutaneously, suggesting a needle-free delivery system.
We asked Dr Soman Abraham, senior author on this article, to comment on these findings: “Adjuvants are compounds that are combined with vaccine antigens to boost antigen-specific immune responses. Currently, a major impediment to the development of subunit vaccines is the lack of effective and safe adjuvants. Mast cells play a powerful but largely overlooked role in initiating and amplifying immune responses to microbial infection. We have harnessed the immunomodulatory properties of mast cells to evoke protective immunity against various vaccine antigens by employing small molecule activators of mast cells as adjuvants. Mast cell activators could represent a new class of safe and highly effective adjuvants when employed judiciously and at appropriate body sites.”
Mast cell activators were demonstrated to be powerful vaccine adjuvants
Crucial role for resolvins described
Resolvins are ω-3 fatty acid metabolites originally identified and named for their role in clearing peritoneal inflammation. In a recent Nature Immunology article (2008;9:873-9), Haworth et al described a new role for resolvin E1 (RvE1) in suppressing inflammatory responses in acute allergic airway inflammation as well actively supporting resolution mechanisms. The authors reported that RvE1 suppressed production of inflammatory cytokines IL-23, IL-6, and IL-17 and increased production of anti-inflammatory mediators IFN-γ and lipoxin A4. They noted that production of endogenous RvE1, IFN-γ, and lipoxin A4 is compromised in chronic asthma.
We asked Dr Bruce Levy, senior author on this article, to comment on these findings: “Regulation of adaptive immune responses by resolvin E1 points to important roles for IL-23 and TH17 cells in unrestrained inflammation and highlights resolvin E1 as a potential lead compound in a new therapeutic class of resolution agonists for pathologic airway responses in asthma and related diseases.”
A new role for resolvin E1 (RvE1) in suppressing inflammatory responses in acute allergic airway inflammation
Variation in the variants
Walsh et al (J Exp Med 2008;205:1285-92) characterized the modulating effect of eosinophils in airway hyperresponsiveness (AHR) elicited in a specific strain of mice (C57BL/6 ΔdblGATA mice). In contrast to other research, which suggested that eosinophils are not necessary for AHR induction in BALB/c mice, the authors' findings show that in C57BL/6 mice genetically engineered to be eosinophil deficient, T-cell recruitment to the lungs is eosinophil dependent. The eosinophil-deficient C57BL/6 mice were capable of mounting a normal immune response to allergen challenge, but because of deficiency of critical chemokines that facilitate migration, T cells did not migrate to the lungs during the response.
Translation and clinical horizons
As part of our series highlighting ongoing and future preclinical and clinical trials related to allergy, asthma, and immunodeficiency, we asked Wayne J. Morgan, MD, CM, to provide a status report on the Inner-City Anti-IgE Therapy for Asthma (ICATA) study funded by the National Institutes of Health/National Institute of Allergy and Infectious Diseases. The full text of his comments can be found in the online version of this month's News Beyond Our Pages at www.jacionline.org.
Online Repository…
As part of our series highlighting ongoing and future preclinical and clinical trials related to allergy, asthma, and immunodeficiency, we asked Wayne J. Morgan, MD, CM, to provide a status report on the Inner-City Anti-IgE Therapy for Asthma (ICATA) study funded by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID).
What is your study testing?
Funded by the NIH/NIAID, ICATA is a multicenter, randomized, double-blind, placebo-controlled, parallel-group efficacy and safety trial designed to compare 250 inner-city children and adolescents ages 6 to 20 years old with moderate-to-severe allergic asthma receiving standardized specialist care, including basic asthma education, with 250 similar children and adolescents receiving comparable standardized specialist care and treatment with anti-IgE (omalizumab). The primary endpoint is the maximum number of asthma symptom days, defined as the highest value among the following 3 variables: number of days with wheezing, tightness in the chest, or cough; number of nights with disturbed sleep as a result of asthma; and number of days on which the participant had to slow down or discontinue play/physical activities over a 2-week period, evaluated monthly. Secondary endpoints include safety, asthma related healthcare utilization and medication use, and asthma exacerbation rates. A critical ancillary study, ICATA-mechanistic, is evaluating in-depth immune and genetic predictors of response as well as basic immunologic mechanisms associated with that response.
When is ICATA likely to be completed?
Data collection will be complete by January 2010 at the latest.
If your study shows positive results, how will it affect asthma care?
Children with asthma who live in the urban environment have substantively increased morbidity and mortality from their disease. Health disparity among African American children with asthma living in the urban environment is particularly problematic. Most (95%+) of the children in the inner city who have asthma are atopic with sensitivity to aeroallergens. Further, the environment in the inner city is particularly challenging due to high-level exposure to allergens including cockroach, dust mite, and mold, among others. Thus, blocking the impact of allergen exposure on the airway in this population is an attractive strategy to improve asthma outcomes. Earlier studies of this medication indicate not only an improvement in symptoms but also reduction in steroid burden and exacerbations. Thus, it should have a significant and clinically relevant impact on asthma outcomes in this challenging group of children with asthma. However, we believe that it is critical that this study be conducted so that both groups received standardized specialist-level care for their asthma—that is, that it would be a real-world study where any result would likely be relevant for practice and generalizable. ICATA has precisely that design and should clearly delineate the role for anti-IgE therapy in urban children with asthma.
PII: S0091-6749(08)01371-7
doi:10.1016/j.jaci.2008.07.019
Volume 122, Issue 3 , Pages 441-442.e1, September 2008
