Editorial

Will the real inner-city allergen please stand up?

Dennis R. Ownby, MD Augusta, Ga

Key words: Inner city, urban, asthma, children, mouse, cockroach,allergen

The television game show ‘‘To Tell the Truth’’ debuted in theUnited States in 1956. A celebrity panelwould question 3 persons,each claiming to be the same notable individual. After thequestions, each panelist would have to guess which person wastelling the truth. The show host would then say, ‘‘Will the realXXXX please stand up?,’’ an idiom that has persisted in AmericanEnglish. The fun for the audience was trying to outguess thecelebrity panelists. Analogous but more serious efforts have beenmade since the early 1990s to better understand environmentalinfluences related to the high prevalence of asthma in major urbancenters across the United States.1 Many environmental exposureshave been evaluated, including differential exposures to allergens,gaseous and particulate air pollutants, emotional stressors, toxins(including endotoxin and fungal toxins), lack of exercise, and lowvitamin D levels, just to name a few. However, no single exposurehas been able to stand up to the test of time as the dominantcause.1

Although it is tempting to dismiss the search for a dominatecause as futile because of the many interacting exposures, thepublic health importance of urban asthma begs for knowledgeenabling more efficient reductions in morbidity. One of the majorarticles from the first National Institute of Allergy and Immuno-logy–sponsored inner-city asthma study was that of Rosenstreichet al2 in 1997. This study demonstrated that children sensitizedand exposed to high levels of cockroach allergen had significantlymore hospitalizations, unscheduled medical visits, days ofwheezing, missed school days, nights of lost sleep, and morefrequent changes to caregivers’ plans compared with childrensensitized and exposed to high levels of cat or dust mite allergens.The article and other supporting studies led to cockroach beingaccepted as the dominant allergen in urban housing.1,3,4 Sincethen, several studies have evaluated strategies for reducing theburden of asthma among inner-city children, and most haveincluded efforts to reduce cockroach allergen exposure.4,5

In this issue of the Journal, Ahluwalia et al6 report that mouseand not cockroach allergen is the allergen most consistently asso-ciated with asthma requiring acute care, decreased FEV1/forcedvital capacity ratio, increased fraction of exhaled nitric oxide,and bronchodilator reversibility in Baltimore, Maryland.6

Cockroach allergen was only associated with acute-care visits

From the Department of Pediatrics, Georgia Regents University.

Disclosure of potential conflict of interest: D. R. Ownby is a member of the Merck

Childhood Asthma Board and is employed by Georgia Regents University.

Received for publication June 24, 2013; accepted for publication June 25, 2013.

Available online August 24, 2013.

Corresponding author: Dennis R. Ownby, MD, Department of Pediatrics, Georgia

Regents University, 1022 15th St, Augusta, GA 30912. E-mail: downby@gru.edu.

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and bronchodilator reversibility when exposure was defined asallergen concentrations in bedroom floor dust. The implicationof this study is that public health efforts to improve asthmamanagement should focus more attention on efforts to reducemouse allergen exposure in contrast to cockroach allergenexposure. This provocative study raises important questions. Ismouse allergen exposure more strongly associated with asthmamorbidity in other urban areas beyond Baltimore? What are themost cost-effective means of reducing mouse allergen exposurein both homes and schools?Important strengths of the Ahluwalia et al6 study are the

prospective design and the repeatedmeasurement of allergen con-centrations and asthma indicators over the year of follow-up.Weaknesses are the use of a convenience sample, which mightnot represent urban children with asthma well and the inevitableincomplete data in a prospective study. Still, the strength of theresults of this study and other studies relating mouse allergenexposure to asthma symptoms suggest that more studies shouldcarefully examine the relative strengths of the relationships ofmouse and other allergens to asthma symptoms in urban residents.In urban areas of the United States, the most common indoor

mouse is the house mouse (Mus musculus), although white-footed(Peromyscus maniculatus) and deer (Peromyscus leucopus) miceare also commonly invasive. The house mouse is native tonorthern India but not North America. The house mouse arrivedwith early settlers from Europe and has become one of the mostpervasive invasive species. M musculus has also been bredextensively for research and pet keeping, suggesting that theallergens will be identical from house and laboratory mice. Themajor mouse allergen (Mus m 1) is predominantly found in urineas a complex of proteins called major urinary proteins (MUPs).Like many other animal allergens, MUPs are lipocalins thatbind and regulate the release of pheromones. There are structuralsimilarities between allergenic lipocalins from different animals,but their strong allergenic propensity has not been explained.7

Control of house mice involves sanitation, exclusion, andpopulation reduction.4 However, house mice have characteristicsthat make control challenging. An adult female mouse canproduce 5 to 6 young every 19 to 21 days, with 5 to 10 littersper year being typical. A mouse can live on only 3 g of foodper day, and if the food is moist, free water is not required.Mice can squeeze through openings of only a little over ¼ inch(approximately 0.6 cm) in diameter, making it challenging toseal a building well enough to prevent entry. In buildings micetypically travel in an area 3 to 9 m in diameter from their nest,meaning that traps and rodenticides must be placed in multiplelocations to be effective. Mice can develop tolerance to rodenti-cides, limiting rodenticide effectiveness.8 Although widelyadvertised, there is little evidence that ultrasonic sound devicesdrive mice from buildings.8 Thus successful control effortstypically require integrated pest management (IPM). A trial ofIPM in 18 homes in Boston showed that levels of mouse allergenwere significantly decreased in 12 homes randomized to IPM

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by 67.6%, 77.3%, and 78.8% in living rooms, bedrooms, andkitchens, respectively, compared with the 6 control homes.9

Another trial of rodent-specific intervention in a subcohort ofasthmatic children aged 5 to 11 years enrolled in the Inner-CityAsthma Study analyzed bedroom dust every 6 months for 2years.10 In this study 80% of bedrooms had detectable mouseallergen. Mouse allergen sensitization and exposure wereassociated with hospitalizations (rate ratio, 1.65; 95% CI,1.09-2.05) andwithmaximum symptom days, nights of lost sleep,and days the caretaker changed plans after controlling forcockroach sensitivity and exposure.10 Efforts at rodent allergencontrol reduced mouse allergen concentrations on the bedroomfloor by 27.3%, whereas concentrations increased by 28.0% incontrol homes.The problem of mouse allergen does not appear to be strictly

limited to urban homes. An analysis of data from 831 represen-tative homes from 75 different locations across the United States(National Survey of Lead and Allergens in Housing) showed that82% of homes had detectable MUP, and in 35% of thehomes, MUP concentrations exceeded 1.6 mg/g, a concentrationassociated with higher risk of sensitization.11 Among the 2456residents of these homes, positive associations were foundbetween MUP concentrations and both current asthma andasthma symptoms, leading the authors to conclude that mouseallergen exposure is an important risk factor for asthma morbidityacross the United States and not just in urban centers. However,not all studies have shown positive associations between mouseallergen exposure and asthma symptoms. A study of 449 PuertoRican children in Hartford, Connecticut, and 678 children inSan Juan, Puerto Rico, analyzed asthma symptoms in relationshipto dust allergen concentrations of Mus m 1, Der p 1, Bla g 2, andFel d 1. In these children higher mouse allergen concentrationswere associated with higher FEV1 and lower odds of having atleast 1 positive skin test result to at least 1 allergen.12

In summary, mouse allergens are clearly associated withoccupational asthma among animal handlers, and evidencesuggests that exposure to mouse allergen is associated withincreased risk of asthma symptoms.4 Mouse allergens aredetectable and associated with asthma in both urban and nonurbanhomes across the United States.11,13 A relatively small study hasshown that reduction of mouse allergen concentrations in homes

is associated with a reduction in asthma symptoms. These factssuggest that mouse allergen needs to be more fully investigatedas a major cause of asthma in urban homes in the hope that bettermethods of reducing mouse allergen exposure will be associatedwith less asthma morbidity, especially in urban residents.

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