The Editors' Choice

Article Outline

• Ciclesonide and allergen-induced asthmatic responses
• Wheezing in infants—associated with “stop-and-go” traffic?
• Endotoxin and the pathway to allergy
• Cholinergic urticaria patients: Sometimes allergic to their own sweat
• Sensitization to aeroallergens in the US population
• COX-2 inhibitors enhance allergic responses
• Copyright

Back to Article Outline

Ciclesonide and allergen-induced asthmatic responses 

New-generation inhaled steroids having low systemic effects are being sought for the treatment of asthma. Ciclesonide (Alvesco) is a once-daily, nonhalogenated inhaled corticosteroid (ICS) that has recently been introduced into the United Kingdom and Germany for the treatment of persistent asthma at doses of 80 μg and 160 μg. This ICS remains inactive until cleaved by esterases present in the airway, where its active metabolite, desisobutyryl-ciclesonide, then binds glucocorticoid receptors. In this issue of the Journal, Gauvreau et al (p 285) have investigated the effects of ciclesonide in a multi-center, randomized, crossover study, comparing once-daily dosing of 40 μg, 80 μg, and placebo on allergen-induced airway responses of individuals with mild asthma. This study demonstrates that ciclesonide 80 μg attenuates the allergen-induced early and late changes in FEV₁ as well as serum eosinophil cationic protein and sputum eosinophils measured at 24 hours after challenge (P < .025), whereas ciclesonide 40 μg attenuates the late asthmatic responses and sputum eosinophils measured at 24 hours after challenge (P < .025). This study provides new information regarding the minimally effective doses of inhaled ciclesonide for inhibition of allergen-induced airway responses and the apparent local anti-inflammatory effects on the airways. Further evaluation of ciclesonide will be required to address whether these low doses are clinically effective.

Back to Article Outline

Wheezing in infants—associated with “stop-and-go” traffic? 

Recent research has suggested a possible link between diesel exhaust particulates (DEP) and respiratory and allergic diseases. In this issue of the Journal, Ryan et al (p 279) describe the association between wheezing in infants less than 1 year of age and exposure to stop-and-go truck and bus traffic. The investigators observed a dramatic increase in wheezing in infants who reside less than 100 m from stop-and-go truck and bus traffic compared with infants who reside farther from all sources of DEP. In addition, African American infants had the highest prevalence of wheezing in comparison with Caucasian infants, regardless of exposure category. These findings suggest that living very close to stop-and-go traffic early in infancy is a significant risk factor for wheezing. It also suggests that even within an urban environment, an infant's risk for wheezing varies with exposure to different types and amounts of traffic. This study is the first report from the ongoing Cincinnati Childhood Allergy and Air Pollution Study, the goal of which is to elucidate the environmental and genetic contributions to the development of allergic diseases.

• 
  • View Large Image
  • Download to PowerPoint

• Prevalence of wheeze (without cold) by distance from DEP source. Moving exposure, residing within 400 m of a highway with >1000 trucks daily; Stop-and-go exposure, residing within 100 m of either a bus route or an urban state route.

Back to Article Outline

Endotoxin and the pathway to allergy 

Endotoxin, a part of the cell wall of gram-negative bacteria, is present at higher levels in households with large animals (livestock or dogs). Infant endotoxin exposure has been proposed as a factor that might protect against allergy and early childhood immune responses (eg, production of the cytokine IL-13) that increase IgE production to allergens. Cross-sectional European studies have found that elevated endotoxin levels are associated with allergy protection in children of farmers, but the immunologic pathway to explain this association is uncertain and the relevance of the finding to children in the more urban US setting is unclear. In this issue of the Journal, Abraham et al. (p 431) assessed in a cohort of US children household dust endotoxin at age 2-3 months and PBMC-proliferative and cytokine responses to cockroach, dust mite, and cat allergens and to the nonspecific mitogen phytohemagglutinin at age 2-3 years. They found that increased endotoxin levels were associated with decreased IL-13 in response to cockroach, dust mite, and cat allergen but not in response to mitogen stimulation. An inverse, though nonsignificant, association was found between endotoxin and proliferative responses. Early-life endotoxin-related reduction of IL-13 production might represent one pathway through which elevated endotoxin decreases the risk of allergic disease and allergy in later childhood.

Back to Article Outline

Cholinergic urticaria patients: Sometimes allergic to their own sweat 

Cholinergic urticaria (CU) presents a characteristic picture of pinpoint-sized, highly pruritic wheals with surrounding erythema that occurs after sweating during physical exercise, bathing, or emotional stress. The pathogenesis of CU is not well defined. However, it has been reported that these patients have positive intradermal skin tests to their own sweat. In this issue of the Journal, Dr Fukunaga and colleagues (p 397) report on this sensitization in 18 subjects with CU and 10 controls. They performed intradermal skin testing and basophil histamine release with autologous sweat and serum. Eleven of 17 patients with CU had positive skin test results, and 10 of 17 had basophil histamine release with autologous sweat, with a significant correlation between the 2 responses. Nine of 16 of the patients with CU had a positive intradermal skin test result with autologous serum. The authors proposed that there are 2 distinct subtypes of patients with CU: (a) those who have strong reactions to autologous sweat and negative reactions to autologous serum whose wheals are not associated with hair follicles and (b) those characterized by weak reactions to autologous sweat and positive reactions to autologous serum whose wheals are associated with hair follicles.

Back to Article Outline

Sensitization to aeroallergens in the US population 

The National Health and Nutrition Examination Survey (NHANES) is a population-based survey undertaken periodically by the National Center for Health Statistics to determine the health and nutritional status of the US population. Prick/puncture skin testing (PPST) was performed in a subset of subjects to 8 aeroallergens in NHANES II (1976-80) and to 9 aeroallergens and peanuts in NHANES III (1988-94). The results of the skin testing in NHANES III are reported by Dr Arbes and colleagues in this issue of the Journal (p 377). Of 10,508 skin-tested subjects aged 6 to 59 years, more than half had at least 1 positive PPST result to the 9 aeroallergens. Those skin tests most commonly positive were to dust mite (positive in 27.5% of subjects), rye grass (in 26.9%), short ragweed (in 26.2%), and German cockroach (in 26.1%). The remainder—Bermuda grass, Russian thistle, white oak, cat, and Alternaria alternata—were positive in 10% to 20% of subjects. The least commonly positive skin test was to peanut (8.6%). The 3 most significant independent predictors of a positive PPST result to aeroallergens were age (maximal for the 20- to 29-years age group), male sex, and minority ethnicity, especially non-Hispanic black. Comparison of these results with the results of the skin testing performed in NHANES II was difficult because of numerous methodologic differences between the 2 studies. However, for the 6 aeroallergens tested in both surveys, a positive PPST result was 2.1 to 5.5 times more common in NHANES III than in NHANES II. Although the authors could not definitely conclude that these differences represent an increased sensitivity in the US population, they point out that such an increase would be consistent with reports from other countries.

• 
  • View Large Image
  • Download to PowerPoint

• Distribution of positive skin tests to 9 aeroallergens and peanuts in the US population, age 6 to 59 years.

Back to Article Outline

COX-2 inhibitors enhance allergic responses 

Mechanical injury to the skin by scratching is an important feature of atopic dermatitis (AD). In this issue of the Journal, Laouini et al (p 390) show that mechanical injury to mouse skin inflicted by tape stripping results in rapid induction of cyclooxygenase-2 (COX-2) mRNA and protein and in accumulation of the COX-2 product prostaglandin E₂ (PGE₂). The role of COX-2 was examined in a mouse model of AD elicited by repeated epicutaneous (EC) sensitization with ovalbumin (OVA) and characterized by eosinophil skin infiltration and a systemic T_H2 response to antigen. Administration of the COX-2 selective inhibitor NS-398 during EC sensitization resulted in enhanced skin infiltration by eosinophils and expression of IL-4 mRNA, enhanced OVA-specific IgE and IgG1 antibody responses, and increased IL-4 secretion by splenocytes following OVA stimulation. COX-2–deficient mice also exhibited an enhanced systemic T_H2 response to EC sensitization. These results demonstrate that COX-2 products limit allergic skin inflammation, and they are consistent with the recent finding that engagement of the EP3 receptor by PGE₂ inhibits allergic reactions (Nat Immunol 2005;6:524-31). More importantly, the work of Laouini et al suggests that COX-2 inhibitors might worsen allergic skin inflammation and should be avoided in patients with AD.