Correspondence

Cats and dogs: An attractive remedy versusatopy?

To the Editor:Because I am very keen on cats and dogs, I read with interest

both the article by Mandhane et al1 and the related editorial.2 Thefirst article provides evidence that living with cats and dogs isassociated with a lower risk of atopy during childhood and youngadulthood.

As stated in the editorial,2 it is not possible to evaluate whetherthe protective effect is associated with cat allergens, dog aller-gens, or both or with other exposures, such as endotoxin and othermicrobial products that have been linked to the presence of ani-mals. A ��healthy worker’� effect has been invoked as a possibleexplanation for the lower prevalence of atopy among childrenraised on farms.3

I think that the presence of both dogs and cats can be related tothe presence of a garden in the house of these pets owners,therefore they surely have been indirectly in contact with mud andits bacterial population.

Even if no garden is present, it can be assumed that dogs need tobe taken for a walk at least twice a day, whereas cats are mostlypresent at home, and this may influence the results reported byMandhane et al.1 How many times do owners take care to washdeeply and disinfect the legs of their favorite pets?

Furthermore, it has been reported4 that cat ownership in Europeis highly variable and not exceptionally high, but pet ownership isnot an absolute criterion to be referred to. According to Eurispes,5

in 2006 about 6.5 million dogs and 8.5 million cats were thoughtto live in Italy, of which half a million and 2.5 million, respec-tively, were strays. How many times have babies been licked inthe face by a puppy or had an arm or hand scratched by a kitten?By the way, I have never owned dogs or cats, but I practicallyalways stop to pet my friends’ pets and most of the stray pets Iencounter.

Together, these facts could act as a powerful means to induceatopy, along with the minor daily wounds that my generationnormally reported during our rough but happy childhood.6

Oreste V. Brenna, PhD

From the Dipartimento di Scienze e Tecnologie Alimentari e Microbiologiche,

Universita degli Studi di Milano, Italy. E-mail: oreste.brenna@unimi.it.

Disclosure of potential conflict of interest: The author has declared that he has no conflict

of interest.

REFERENCES

1. Mandhane PJ, Sears MR, Poulton R, Greene JM, Lou WYW, Taylor DR, et al. Cats

and dogs and the risk of atopy in childhood and adulthood. J Allergy Clin Immunol

2009;124:745-50.

2. Salo PM, Zeldin DC. Does exposure to cats and dogs decrease the risk of allergic

sensitization and disease? J Allergy Clin Immunol 2009;124:751-2.

3. Braback L. Does farming provide protection from asthma and allergies? Acta

Paediatr 2002;91:1147-9.

4. Heinrich J, Bedada GB, Zock JP, Chinn S, Norback D, Olivieri M, et al. Cat allergen

level: its determinants and relationship to specific IgE to cat across European

centers. J Allergy Clin Immunol 2006;118:674-81.

5. Eurispes business annual reports, 2009, p.125. http://www.eurispes.it/index.php/

Rapporto-Italia/rapporto-italia-2009.html. Accessed December 24, 2009.

6. Brenna OV. In pride of a rough-and-tumble life. Trends Immunol 2008;29:1-2.

Available online February 8, 2010.

doi:10.1016/j.jaci.2009.11.013

Reply

To the Editor:We thank Dr Brenna1 for his comments on our article.2 We do

not know what aspect of cat and dog ownership might reduce therisk of allergy. As we acknowledge in the article, the apparentprotective effect could be a result of exposure to allergens,endotoxins, or perhaps some other exposure associated with petownership, as Dr Brenna suggests. However, we do not thinkthat a ‘‘healthy worker’’ effect can account for our findingsbecause neither a family history of allergies nor a personal historyof atopy influenced pet ownership.2

Quantifying the exposure to animals over the course of alifetime is problematic. Even direct sampling of allergens andendotoxin in the home will not be representative of all ages in aperson’s life and will miss exposures outside the home. With thevery high rates of pet ownership that we observed in the Dunedincohort, it is probable that all participants had some contact withthese animals. Nevertheless, ownership of a pet is likely toindicate a higher exposure to the animal than casual contactoutside the home, and our findings suggest that it is this high levelof exposure to both cats and dogs that may confer a protectiveeffect. Misclassification of exposure would be most likely toreduce the strength of the observed associations rather thanproduce the associations that we observed.

It remains to be seen what aspect of animal exposure mayprotect against allergy and whether this can be manipulated toreduce the burden of allergies in the population.

Robert J. Hancox, MDa

Piush J. Mandhane, MDb

Malcolm R. Sears, MBc

From athe Department of Preventive and Social Medicine, University of Otago, Dune-

din, New Zealand; bthe Department of Pediatrics, University of Alberta, Edmonton;

and cthe Department of Medicine, McMaster University, and Firestone Institute for

Respiratory Health, St Joseph’s Healthcare, Hamilton, Ontario, Canada. E-mail:

bob.hancox@otago.ac.nz.

The Dunedin Multidisciplinary Health and Development Research Unit is supported by

the Health Research Council of New Zealand. P.J.M. was a CIHR Strategic Training

Fellow in the Canadian Child Health Clinician Scientist Program. M.R.S. holds the

AstraZeneca Chair in Respiratory Epidemiology, McMaster University.

Disclosure of potential conflict of interest: R. J. Hancox has received research support

from the Health Research Council of New Zealand and Waikato Medical Research

Foundation and is Medical Director of the Asthma and Respiratory Foundation of New

Zealand. The rest of the authors have declared that they have no conflict of interest.

REFERENCES

1. Brenna OV. Cats and dogs: An attractive remedy versus atopy? J Allergy Clin Im-

munol 2010;125:765.

2. Mandhane PJ, Sears MR, Poulton R, Greene JM, Lou WYW, Taylor DR, et al. Cats

and dogs and the risk of atopy in childhood and adulthood. J Allergy Clin Immunol

2009;124:745-50.

Available online February 8, 2010.

doi:10.1016/j.jaci.2009.11.011

Reply

To the Editor:Dr Brenna1 raises several important issues in his commen-

tary. In epidemiologic studies, selection bias and lack of

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J ALLERGY CLIN IMMUNOL

MARCH 2010

766 CORRESPONDENCE

generalizability are not uncommon concerns. Study findingscan be influenced by self-selection (ie, the healthy workereffect), especially in cross-sectional occupational studies.Studies of farming populations, however, have provided aunique opportunity to study the role of environmental factorsin the development of atopic disorders. In the study by Man-dhane et al,2 the longitudinal data were derived from a large,unselected, population-based cohort, which is one of the majorstrengths of the work. Indeed, the authors found no signs ofselection bias in their study.

We acknowledge that pet ownership is not a very good surrogatefor pet allergen exposures. In particular, personal allergen expo-sure can be highly variable, both spatially and temporally, becauseexposure levels are influenced by several factors, including theproximity of the source, reservoir concentration of allergen,nature of the source, and behavioral factors (eg, activity levels).3

Although homes may be the primary sites of exposure, exposureto cat and dog allergens is not limited to residential environments;both allergens are passively transported from one environment toanother.4 However, the presence of indoor pets, cats and/or dogs,has been shown to be the strongest predictor of high pet allergenlevels in homes.5

The hygiene hypothesis that was proposed as a potentialexplanation for time trends in allergic disease has remained asubject of intense debate over recent decades.6 Although thehypothesis has stimulated a substantial amount of research, theunderlying etiologic mechanisms that confer protection againstdeveloping atopy are not completely understood. Nonetheless,there is increasing evidence to support that exposure to microbialinfections in early life, as well as exposure to noninfectious mi-croorganisms and microbial components, can influence innateand adaptive immune responses.7 Not only are cats and dogs sour-ces of allergens, but also their presence has also been associatedwith other potential immunomodulatory agents, including endo-toxin and other bacterial products.8,9 It is therefore not surprisingthat exposure to cats and dogs in the home might modify immunesystem development. Exposure to pet allergens and microbialstimuli may have independent effects, or they may operate in aninteractive manner. For example, studies have shown that cat-induced tolerance (modified TH2 response) is allergen-specificand cannot be explained by increased exposure to endotoxin.9 Itis likely that gene-environment interactions also play an impor-tant role in the pathogenesis of allergic disorders. Emergingresearch suggests that an individual’s response to microbial orother environmental exposures depends on genetic polymor-phisms that alter immune responses to environmental stimuli.7

Although the findings reported by Mandhane et al2 are intrigu-ing, further research is needed to elucidate the complex relation-ships between atopy and environmental exposures, includingexposures to cats and dogs.

Paivi M. Salo, PhD

Darryl C. Zeldin, MD

From the National Institute of Environmental Health Sciences, National Institutes

of Health, Research Triangle Park, NC. E-mail: zeldin@niehs.nih.gov.

Supported by the Intramural Research Program of the NIH, National Institute of

Environmental Health Sciences (Z01 ES025041).

Disclosure of potential conflict of interest: The authors have declared that they have no

conflict of interest.

REFERENCES

1. Brenna OV. Cats and dogs: An attractive remedy versus atopy? J Allergy Clin Im-

munol 2010;125:765.

2. Mandhane PJ, Sears MR, Poulton R, Greene JM, Lou WYW, Taylor DR, et al. Cats

and dogs and the risk of atopy in childhood and adulthood. J Allergy Clin Immunol

2009;124:745-50.

3. O’Meara T, Tovey E. Monitoring personal allergen exposure. Clin Rev Allergy

Immunol 2000;18:341-95.

4. Salo PM, Sever ML, Zeldin DC. Indoor allergens in school and day care environ-

ments. J Allergy Clin Immunol 2009;124:185-92.

5. Arbes SJ Jr, Cohn RD, Yin M, Muilenberg ML, Friedman W, Zeldin DC. Dog aller-

gen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Sur-

vey of Lead and Allergens in Housing. J Allergy Clin Immunol 2004;114:111-7.

6. Strachan DP. Family size, infection and atopy: the first decade of the ‘‘hygiene

hypothesis.’’ Thorax 2000;55(suppl 1):S2-10.

7. von Mutius E. Allergies, infections and the hygiene hypothesis—the epidemiologi-

cal evidence. Immunobiology 2007;212:433-9.

8. Bufford JD, Reardon CL, Li Z, Roberg KA, DaSilva D, Eggleston PA, et al. Effects

of dog ownership in early childhood on immune development and atopic diseases.

Clin Exp Allergy 2008;38:1635-43.

9. Platts-Mills JA, Custis NJ, Woodfolk JA, Platts-Mills TA. Airborne endotoxin in

homes with domestic animals: implications for cat-specific tolerance. J Allergy

Clin Immunol 2005;116:384-9.

Available online February 8, 2010.

doi:10.1016/j.jaci.2009.11.012

Trichuris suis might be effective in treatingallergic rhinitis

To the Editor:We compliment Bager et al1 for performing the first random-

ized, double-blind controlled trial of Trichuris suis ova in thetreatment of allergic rhinitis. They concluded that the agent hadno therapeutic effect on grass pollen–induced disease. Our studiesdemonstrated that T suis exposure reduced disease activity in pa-tients with immune-mediated ulcerative colitis and Crohn dis-ease.2,3 Mechanistic studies in animals demonstrated thathelminth exposure reduced hyperactive airway disease throughinduction of regulatory T cells.4,5 In the study by Bager et al,1

T suis ova treatment produced definite biologic effects, includingincreased eosinophil counts and T suis–specific IgE, IgG4, andIgA levels. These observations established that T suis had a signif-icant effect on the human immune system. However, several fea-tures of the study design and conduct possibly caused theinvestigators to miss a treatment benefit.

The most important problem with the study was late admin-istration of T suis ova with respect to the tree allergy season be-cause it takes time for the helminths to induce clinicallysignificant disease modulation. Subjects were enrolled fromMarch 10 through May 15, and the allergic rhinitis season wasfrom May 28 through July 27, with the peak beginning June 9.Distribution of enrollment dates is not described in detail with re-spect to the allergy season, but by season peak, some subjects hadreceived only 2 treatments administered 21 days apart, and 23%of subjects were treated for only 3 to 5 weeks. Thus many subjectswere treated too late for therapeutically apparent effects by seasonpeak. In our studies clinical effects were not apparent until 6weeks.2 Post hoc analysis of those patients treated for 6 to 15weeks increases type 2 error.

Subject characteristics were similar except that severity ofallergic rhinitis was greater in the T suis ova–treated group (mod-erate-severe, 94%; mild, 6%) than in the placebo-treated group(moderate-severe, 82%; mild, 18%). Differences in severitymight have skewed the results against the T suis ova–treated sub-jects, particularly when combined with incomplete T suis expo-sure at peak season.