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Article Outline

• What factors are associated with increased parental comfort with EpiPen use?
• Proasthmatic effects of dust mite allergen in airway smooth muscle
• High fevers early in life might reduce allergy and asthma risk
• Genes modulate the response to childhood cat exposure
• Effect of immunotherapy on IL-9 and c-Kit+ mast cells in allergic rhinitis
• Seven-year results from a multifaceted intervention study
• Copyright

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What factors are associated with increased parental comfort with EpiPen use? 

EpiPen is underused in food-allergic children experiencing anaphylaxis. Previous studies have revealed deficiencies in parental knowledge surrounding indications for EpiPen use as well as the methodological aspects of its administration. Furthermore, quality of life has been shown to be diminished in this population, implying a psychological burden of disease. In this issue of the Journal, Kim et al (p 164) explore the factors that contribute to parental discomfort with EpiPen administration. A written survey was mailed to parents of children with food allergy. Perceived comfort with administering EpiPen, knowledge of EpiPen use and anaphylaxis, and parental empowerment (as a psychological resource) were assessed. Inclusion criteria were met by 165 completed surveys (46% response rate). Anaphylaxis was reported in 42% of children (n=70); 8% of parents (n=14) had administered EpiPen to their children. Factors correlating with comfort included prior administration of EpiPen (P=.009), EpiPen training (P=.005), and empowerment (P < .0005). Surprisingly, neither a history of anaphylaxis nor knowledge correlated with an increased level of comfort with administration. The authors assert that EpiPen training can improve parental comfort with administration. This is the first study to investigate the psychological factors that influence EpiPen administration by parents to their food-allergic children.

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Proasthmatic effects of dust mite allergen in airway smooth muscle 

Aeroallergens that possess intrinsic protease activities, including the dust mite allergen, Der p 1, can disrupt the airway epithelial barrier and thereby facilitate initiation of local airway immune responses. In this issue of the Journal, Grunstein et al (p 94) report that direct exposure of rabbit airway smooth muscle (ASM) tissues to Der p 1 produces proasthmatic-like changes in ASM constrictor and relaxation responsiveness. These effects of Der p 1 were attributed to its intrinsic cysteine protease activity, which elicits coactivation of the mitogen-activated protein kinase (MAPK) signaling pathways, ERK1/2 and p38 MAPK, in the Der p 1–exposed ASM. Interestingly, blockade of ERK1/2 signaling was found to prevent the effects of Der p 1 on ASM responsiveness, whereas inhibition of p38 MAPK was found to enhance the action of Der p 1 due to augmented activation of ERK1/2. Thus, this study provided new evidence demonstrating that Der p 1 exposure elicits proasthmatic-like changes in ASM responsiveness secondary to activation of ERK1/2, while co-activation of p38 MAPK serves to homeostatically limit the magnitude of Der p 1–induced changes in ASM responsiveness by downregulating ERK1/2 signaling. Collectively, these findings support the novel concept that ASM might play an important innate role in the acquisition of dust mite allergen–induced airway sensitization and asthma.

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• Der p 1–induced impaired airway smooth muscle relaxation is prevented by the cysteine protease inhibitor, E-64.

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High fevers early in life might reduce allergy and asthma risk 

Consistent with the hygiene hypothesis, previous studies have shown that fevers early in life might reduce the risk of allergies and asthma. In this issue of the Journal, Williams et al of Henry Ford Hospital (p 102) expand their previous work by examining whether the timing and intensity of fevers in the first 2 years of life are important factors related to the development of allergic sensitization and asthma. A total of 447 children from the Childhood Allergy Study of southeast Michigan were evaluated from birth to an average age of 6.7 years. When the first 2 years of life were considered in 6-month intervals, only fevers occurring between 7 and 12 months of age were significantly related to a lower risk of allergic sensitization and asthma at 6-7 years of age. Similarly, higher temperatures during this period were also associated with significant reductions in these outcomes. The authors conclude that both the age of the child at the time of the fever and the magnitude of the fever are important factors related to the risk of allergies and asthma later in childhood.

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Genes modulate the response to childhood cat exposure 

Data are accumulating that exposure to cats, and perhaps dogs, in early childhood is protective against IgE-mediated sensitization to these animals, likely through a shift in the specific immune response toward IgG₄. The protective effect of early pet exposure and its possible relation to IL-1 and IL-10 genotypes are explored in this issue of the Journal by Karjalainen and colleagues from Finland (p 223). They examined skin test responses to cat and dog in a population-based sample of 245 adults with asthma and 405 nonasthmatic controls. They found that the number of positive reactions to cat allergen was markedly lower in asthmatic individuals with daily cat exposure in early childhood. This effect was increased in asthmatic individuals with a family background of asthma or allergy. No association was found between dog exposure in childhood and sensitization to dog. The protective effect of cat exposure was observed only in subjects who exhibited an IL1A (+4845) allele G homozygosity (odds ratio [OR], 0.27) and in subjects with high IL-10 producer haplotypes (OR, 0.39). The strongest cat exposure–related protective effect against cat sensitization was found in the combined groups of asthmatic individuals and controls with a history of parental asthma or allergy. In this group the prevalence of a positive reaction to cat allergen was 14.5% in cat-exposed and 40.4% in cat-nonexposed subjects. When the IL1A and IL10 polymorphisms were included in the analyses, the risk was further reduced to an OR of 0.09 in IL1A (+4845) allele G homozygotes and an OR of 0.17 in IL10 high producers. The authors conclude that the development of exposure-related tolerance to cat allergen is substantially mediated by the IL1A and IL10 genes.

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Effect of immunotherapy on IL-9 and c-Kit⁺ mast cells in allergic rhinitis 

Allergen-specific immunotherapy is the only currently available treatment that favorably influences the long-term natural history of allergic disease. In this issue of the Journal, a study by Nouri-Aria et al (p 73) examines the effect of 2 years of grass pollen injection immunotherapy on mast cell numbers and IL-9 expression in the nasal mucosa in patients with seasonal rhinitis with/without seasonal asthma. In placebo-treated patients, the numbers of mast cells expressing c-Kit (the receptor for stem cell factor) and the mast cell cytokine IL-9 were increased during the pollen season. IL-9 expression correlated with tissue infiltration of eosinophils and IL-5 expression. All of these cellular events were markedly inhibited in patients receiving immunotherapy. Whether these biological effects of allergen immunotherapy are either surrogate or predictive of clinical efficacy in individual patients remains to be determined. There might be therapeutic implications. Whereas the targeting of IL-5 only has thus far been unsuccessful, these results raise the question of whether combined antagonism of both IL-5 and IL-9 might be a more effective option in allergic disease.

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• IL-9 protein-positive cells (left) and IL-9 mRNA-positive cells (right) in the human nasal mucosa.

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Seven-year results from a multifaceted intervention study 

The recent increase in the prevalence of allergy and asthma has emphasized the importance of environmental factors in these conditions. However, interventions aimed at reducing exposure to individual risk factors have generally not been successful in preventing the development of asthma. A multifaceted intervention program for primary prevention of asthma was initiated in 545 high-risk infants. Interventions included avoidance of house dust mites, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid food. In this issue of the Journal, Chan-Yeung and associates (p 49) report the 7-year outcome in these children, 380 of whom returned for assessment. The prevalence of pediatric allergist–diagnosed asthma was significantly lower in the intervention group (14.9%) than in the control group (23.0%); in addition, asthma, defined as wheezing in the last 12 months together with bronchial hyperresponsiveness, was lower in the intervention group (12.9%) than in the control group (25.0%). Other outcomes, including the prevalence of allergic rhinitis, atopic dermatitis, positive skin test reactions, and bronchial hyperresponsiveness, did not differ between the 2 groups. The authors conclude that the multifaceted intervention program applied before birth and during the first year of life was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.