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• Birth by cesarean delivery and atopy in children with parental history of allergies
• Bacillus licheniformis spores mediate allergy protection but provoke inflammation
• Childhood eczema “continues to march” into adult life
• Heme oxygenase 1: Therapeutic promise for atopic dermatitis
• Central mechanism in allergy elucidated by use of recombinant IgE antibodies
• Specialist allergy care is the gold standard for nut allergy
• Copyright

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Birth by cesarean delivery and atopy in children with parental history of allergies 

Previous studies of the relation between mode of delivery and atopy have included subjects not selected on the basis of familial history. As reported in this issue of the Journal, Pistiner et al (p 274) examined the relation between birth by cesarean delivery and atopy and allergic diseases in 432 children with parental history of asthma or allergies. Participating children were followed from birth until age 9 years. Stepwise logistic regression was used to study the relation between cesarean delivery and asthma, allergic rhinitis, and atopy (defined as at least 1 positive skin test result or an elevated IgE to common allergens). Children born by cesarean section had 2-fold higher odds of atopy than those born by vaginal delivery (adjusted odds ratio [OR], 2.1; 95% CI, 1.1-3.9; see Table). In multivariate analyses, birth by cesarean section was associated with increased odds of allergic rhinitis (adjusted OR, 1.8; 95% CI, 1.0-3.1) but not with asthma. These findings suggest that cesarean delivery leads to an increased risk of allergic rhinitis and atopy among children with parental history of asthma or allergies. This is the first study of cesarean delivery and allergy and allergic diseases among schoolchildren at high risk for atopy.

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Bacillus licheniformis spores mediate allergy protection but provoke inflammation 

Farm life in early childhood is associated with an allergy-protective effect in numerous epidemiologic studies. Recent publications provide evidence for the importance of microbial exposure in this context. On the basis of investigations of stable dust, Vogel et al (p 307) analyzed the microbial flora of farm dusts and identified the spore-forming species Bacillus licheniformis as the most prominent microorganism. Considering the possibility of spore germination and outgrowth in the lower airways of newborns, they examined the spore specificity of innate immune stimulation and prevention of OVA-induced asthma in mice. Spores induced a specific expression of T_H1 cytokines in vitro. This specificity was not confirmed on the level of intranasal treatment during allergen sensitization and provocation in mice. B licheniformis spore application prevented eosinophilia and goblet cell hyperplasia in a comparable manner to the vegetative form of the bacterium, but both forms also induced the formation of multinucleated giant cells (see Figure). However, different mechanisms were involved in the downregulation of eosinophilia by spores and vegetative bacteria inducing macrophage and neutrophil recruitment, respectively. Of clinical relevance is the contribution of B licheniformis spores to allergy protection of farm life, providing insight into prospective allergy-preventive applications in comparison with other investigated bacteria.

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• Periodic acid-Schiff staining of mice airways after OVA allergen sensitization.

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Childhood eczema “continues to march” into adult life 

Using data gathered over 37 years from the Tasmanian Longitudinal Health Study, one of the world's largest and longest-running studies of respiratory disease, Burgess and colleagues (p 280) examined the relationship between childhood eczema and childhood asthma and between childhood eczema and the development of asthma over time. The researchers found that among children who were asthma free by the age of 7 years, those with a history of childhood eczema were at greater risk of developing asthma in later life than those children with no eczema history. The risk was nearly twice as great across the time span from the age of 8 to 44 years and was consistently increased in each period of preadolescence, adolescence, and adult life. Burgess and colleagues also found that childhood eczema was linked to childhood asthma, as has been shown in earlier studies, but that the risk of childhood asthma was further increased if the child with eczema also had a serious lung infection or impaired lung function. Relating these findings to clinical practice, the authors suggest that clinicians who are prepared to adopt more vigorous treatment of eczema in children might lessen the burden of asthma in later life.

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Heme oxygenase 1: Therapeutic promise for atopic dermatitis 

Oxidative stress has been implicated in the exacerbation of atopic dermatitis (AD). Kirino et al (p 290) describe the pathophysiologic roles of heme oxygenase 1 (HO-1), an inducible heme-degrading enzyme with antioxidative properties, in the development of AD. The authors found increased HO-1 expressions in sera and inflamed skin of patients with AD (see Figure). Interestingly, serum HO-1 levels correlated with the severity of skin manifestations and humoral parameters such as serum IgE, lactate dehydrogenase, IL-18, and thymus and activation-regulated chemokine levels in patients with AD. They then employed AD model DS-Nh mice to explore the localization and function of HO-1. AD-like skin lesions showed marked HO-1 expression in macrophages and dendritic cells. Treatment with hemin, a potent HO-1 inducer, led to accumulation of HO-1–positive macrophages in the dermis and attenuated the development of AD-like skin lesions. The therapeutic effect was associated with reduced serum IL-18 levels. The authors conclude that enhancement of HO-1 serves as a promising therapeutic strategy for AD.

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• HO-1–positive cells stained in brown accumulated in the skin lesions of a patient with AD.

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Central mechanism in allergy elucidated by use of recombinant IgE antibodies 

The immediate allergic reaction experienced by allergic patients on exposure to allergen relies on IgE-mediated degranulation of effector cells—ie, mast cells and basophils. Significant variations in the levels of total- and allergen-specific IgE occur among allergic patients, and the levels of allergen-specific IgE are often used in in vitro testing as a measure for the severity of sensitization. Having used a large panel of humanized recombinant IgE antibodies specific for the major house dust mite allergen, Der p 2, Christensen et al (p 298) describe in detail the contribution and interrelatedness of IgE concentration, IgE antibody affinity, and clonality on allergen-mediated degranulation of human basophils. These data demonstrate that in addition to IgE concentration, the composition of a given IgE repertoire has a marked impact on effector cell degranulation (see Figure) and indicates that sera with the same IgE titers might exhibit different effector cell degranulation potentials. Most notably, the finding that even a low-affinity IgE is able to mediate an effective cellular degranulation response when a high-affinity IgE is present in the IgE repertoire indicates a role for low-affinity IgEs in allergy (in particular, cross-allergy) and suggests that future diagnostic assays should address the composition of IgE repertoires rather than just antibody titers.

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• Factors affecting effector cell degranulation investigated by use of recombinant IgE antibodies.

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Specialist allergy care is the gold standard for nut allergy 

Peanut and nut allergy is the most frequent cause of fatal food allergic reactions. There is no cure, the disease is persistent, and the diagnosis causes anxiety. Few studies provide data on the outcome of children who receive a management package under the care of an allergy center. Clark and Ewan (p 286) followed 785 peanut/nut-allergic children over a median of 4 years comparing their worst-ever reaction before enrollment in a management plan, with accidental reactions occurring afterwards. They found a low incidence of accidental reactions (3% per year) compared to 14-55% in other studies. No child went from a mild to a severe reaction. Epinephrine was required in only 1 child for a severe reaction. Most reactions were mild, needing little or no medication. Preschool children had the lowest incidence of accidental reactions, and none was severe. In contrast to other studies, school-age children rarely had accidental reactions in school, and most occurred at home or other community sites. New nut allergies appeared, justifying the avoidance of all nuts. These findings suggest that children who receive an allergist's management package are relatively well protected, reactions being uncommon and usually mild. Self-treatment was successful, and a second injection of epinephrine was never needed.