What should we tell allergic families about pets?

Abstract

The recent history of medicine includes several episodes in which apparently well-founded, sensible practices have been turned on their heads by the advent of new evidence. Recent observations on the relationship between pet ownership and the presence of asthma and allergic disease necessitate a reevaluation of previous advice that children at risk of asthma should avoid pets.1National Heart Lung and Blood Institute of National Institutes of Health Asthma management and prevention. A pocket guide for physicians and nurses. The Institute, Bethesda (MD)1998Google Scholar There is a sound basis for advice that people with pet allergy and existing asthma should avoid exposure to pets. Subjects who are allergic to cat allergen manifest airway narrowing in response to exposure to cat allergen particles in a bronchoprovocation challenge.2Sicherer SH Wood RA Eggleston PA Determinants of airway responses to cat allergen: comparison of environmental challenge to quantitative nasal and bronchial allergen challenge.J Allergy Clin Immunol. 1997; 99: 798-805Abstract Full Text PDF PubMed Scopus (34) Google Scholar In population studies in New Zealand and some parts of Australia, it has been shown that allergy to cats and, to a lesser extent, allergy to dogs are linked to the presence of airway hyperresponsiveness and asthma,3Burrows B Sears M Flannery E Herbison G Holdaway M Relations of bronchial responsiveness to allergy skin test reactivity, lung function, respiratory symptoms, and diagnoses in thirteen-year-old New Zealand children.J Allergy Clin Immunol. 1995; 95: 546-548Abstract Full Text Full Text PDF Scopus (105) Google Scholar, 4Peat J Woolcock A Sensitivity to common allergens: relation to respiratory symptoms and bronchial hyper-responsiveness in children from three different climatic areas of Australia.Clin Exp Allergy. 1991; 21: 573-581Crossref PubMed Scopus (119) Google Scholar though this is not a universal finding.4Peat J Woolcock A Sensitivity to common allergens: relation to respiratory symptoms and bronchial hyper-responsiveness in children from three different climatic areas of Australia.Clin Exp Allergy. 1991; 21: 573-581Crossref PubMed Scopus (119) Google Scholar, 5Chinn S Burney P Sunyer J Jarvis d Luczynska C on behalf of the European Community Respiratory Health Survey Sensitization to individual allergens and bronchial responsiveness in the ECRHS.Eur Respir J. 1999; 14: 876-884Crossref PubMed Scopus (68) Google Scholar Among people with asthma and specific sensitization, the level of exposure to the sensitizing allergen is related to the severity of asthma.6Plaschke P Janson C Balder B Lowhagen O Jarvholm B Adult asthmatics sensitized to cats and dogs: symptoms, severity, and bronchial hyperresponsiveness in patients with furred animals at home and patients without these animals.Allergy. 1999; 54: 843-850Crossref PubMed Scopus (38) Google Scholar, 7Tunnicliffe W Fletcher T Hammond K Roberts K Custovic A Simpson A et al.Sensitivity and exposure to indoor allergens in adults with differing asthma severity.Eur Respir J. 1999; 13: 654-659Crossref PubMed Scopus (117) Google Scholar, 8Almqvist C Wickman M Perfetti L Berglind N Renstrom A Hedren M et al.Worsening of asthma in children allergic to cats, after indirect exposure to cat at school.Am J Respir Crit Care Med. 2001; 163: 694-698Crossref PubMed Scopus (203) Google Scholar Finally, among cat-allergic subjects, a reduction in exposure to cat allergen achieved by use of a particulate air (HEPA) filter is associated with an improvement in airway hyperresponsiveness.9van der Heide S van Aalderen WM Kauffman HF Dubois AE de Monchy JG Clinical effects of air cleaners in homes of asthmatic children sensitized to pet allergens.J Allergy Clin Immunol. 1999; 104: 447-451Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar The advice that people who wish to prevent the onset of asthma should avoid pets represents an extension of the recommendation for people with existing asthma. This advice is supported by evidence that for several allergens, the onset of specific sensitization is related to the level of environmental exposure to that allergen. However, this evidence is not straightforward. Although exposure to house dust mite, cockroach,10Sporik R Squillace S Ingram J Rakes G Honsinger R Platts-Mills T Mite, cat and cockroach exposure, allergen sensitisation, and asthma in children: a case-control study of three schools.Thorax. 1999; 54: 675-680Crossref PubMed Scopus (198) Google Scholar Alternaria mold,11Peat J Mellis C Tovey E Leeder S Woolcock A Importance of house dust mite and Alternaria allergens in childhood asthma: an epidemiological study in two climatic regions of Australia.Clin Exp Allergy. 1993; 23: 812-820Crossref PubMed Scopus (244) Google Scholar and various occupational allergens is linked to development of specific allergic sensitization, the evidence in relation to exposure to domestic pets is more complex. The situation is now clouded by an increasing array of evidence that exposure to farm animals (Table I) and cats and dogs (Table II) actually protects children against acquiring allergic disease. This evidence deserves further attention.Table IProtective effects associated with the farming environmentFindingsStudyFarm environment protects against…Farm environment has no effect on…DesignReferenceAtopy, seasonal rhinitisAsthma symptomsCross-sectionalBraun-Fahrländer et al12Braun-Fahrländer C Gassner M Grize L Neu U Sennhauser F Varonier H et al.Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community.Clin Exp Allergy. 1999; 29: 28-34Crossref PubMed Scopus (583) Google ScholarAtopy, seasonal rhinitis, asthma symptoms—Cross-sectionalRiedler et al13Riedler J Eder W Oberfeld G Schreuer M Austrian children living on a farm have less hay fever, asthma and allergic sensitization.Clin Exp Allergy. 2000; 30: 194-200Crossref PubMed Scopus (506) Google ScholarAllergic rhinitis, wheeze/asthma—Cross-sectionalKilpelainen et al14Kilpelainen M Terho EO Helenius H Koskenvuo M Farm environment in childhood prevents the development of allergies.Clin Exp Allergy. 2000; 30: 201-208Crossref PubMed Scopus (303) Google ScholarAllergic rhinitis, wheeze—Cross-sectionalVon Ehrenstein et al15Von Ehrenstein OS Von Mutius E Illi S Baumann L Bohm O von Kries R Reduced risk of hay fever and asthma among children of farmers.Clin Exp Allergy. 2000; 30: 187-193Crossref PubMed Scopus (594) Google ScholarAtopy, wheeze, airway hyperresponsiveness—Cross-sectionalErnst and Cormier 16Ernst P Cormier Y Relative scarcity of asthma and atopy among rural adolescents raised on a farm.Am J Respir Crit Care Med. 2000; 161: 1563-1566Crossref PubMed Scopus (274) Google ScholarAtopy, wheeze—Cross-sectionalDowns et al17Downs S Marks G Mitakakis T Leuppi J Car N Peat J Having lived on a farm and protection against allergic disease in Australia.Clin Exp Allergy. 2001; 31: 570-575Crossref PubMed Scopus (137) Google Scholar Open table in a new tab Table IIProtective effects associated with domestic catsFindingsStudyCat ownership protects against…Cat ownership has no effect on…DesignReference—Cat allergy,* asthma symptomsCross-sectionalIngram et al18Ingram J Sporik R Rose G Honsinger R Chapman M Platts-Mills T Quantitative assessment of exposure to dog (Can f 1) and cat (Fel d 1) allergens: relation to sensitization and asthma among children living in Los Alamos, New Mexico.J Allergy Clin Immunol. 1995; 96: 449-456Abstract Full Text Full Text PDF PubMed Scopus (285) Google ScholarCat allergy,* asthma symptoms—CohortHesselmar et al19Hesselmar B Aberg N Aberg B Eriksson B Björkstén B Does early exposure to cat or dog protect against later allergy development?.Clin Exp Allergy. 1999; 29: 611-617Crossref PubMed Scopus (469) Google ScholarCat allergy (when parents are atopic)Cat allergy (when parents are not atopic)Cross-sectionalRoost et al20Roost H-P Kunzli N Schindler C Jarvis D Chinn S Perruchoud A et al.Role of current and childhood exposure to cat and atopic sensitization.J Allergy Clin Immunol. 1999; 104: 941-947Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar—Atopy, cat allergyCross-sectionalSporik et al10Sporik R Squillace S Ingram J Rakes G Honsinger R Platts-Mills T Mite, cat and cockroach exposure, allergen sensitisation, and asthma in children: a case-control study of three schools.Thorax. 1999; 54: 675-680Crossref PubMed Scopus (198) Google ScholarAtopy† (when parents are atopic)Atopy (when parents are not atopic)Cross-sectionalSvanes et al21Svanes C Jarvis D Chinn S Burney P Childhood environment and adult atopy: results from the European Community Respiratory Health Survey.J Allergy Clin Immunol. 1999; 103: 415-420Abstract Full Text Full Text PDF PubMed Google ScholarCat allergy—Cross-sectionalPlatts-Mills et al22Platts-Mills T Vaughan J Squillace S Woodfolk J Sporik R Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study.Lancet. 2001; 357: 752-756Abstract Full Text Full Text PDF PubMed Scopus (733) Google ScholarInfantile eczema† (when parents are atopic)Infantile eczema (when parents are not atopic)CohortNafstad et al23Nafstad P Magnus P Gaarder P Jaakkola J Exposure to pets and atopy-related diseases in the first 4 years of life.Allergy. 2001; 56: 307-312Crossref PubMed Scopus (191) Google Scholar—Respiratory symptomsCohortCustovic et al24Custovic A Simpson B Simpson A Kissen P Woodcock A the NAC Manchester Asthma Allergy Study Group Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial.Lancet. 2001; 358: 188-193Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar*These studies reported similar findings in relation to dog exposure and dog allergy. †In this study, dog exposure in childhood was protective against subsequent atopy, irrespective of parental allergic status. Open table in a new tab Table I, Table II list published studies reporting the relationships seen in study samples representative of the general population between exposure to a farming environment or to domestic cats in childhood and the risk of allergic disease in childhood or adult life. (In both tables, the term atopy refers to the presence of skin prick test or specific IgE responses to common inhaled allergens, and the term cat allergy refers to specific IgE directed against cat allergen.) There is consistent evidence that exposure to the farming environment confers protection against atopy and consequently against allergic diseases—rhinitis, asthma, and eczema. The protection is not limited to a specific allergen; the propensity to develop sensitization to any allergen is reduced. Detailed analyses in several of the published reports point to exposure to farm animals as the feature of the farming environment that is most strongly linked to this protection. The evidence concerning early life exposure to cat allergen is more complex. There is some—but not universal—evidence that cat exposure is associated with a reduced risk of manifesting allergy to cats in later childhood or adult life. In 3 studies, this protection was limited to children with a genetic predisposition to atopy. Some of the studies, though not all, demonstrated that this reduced risk of developing cat allergy was associated with a reduced risk of acquiring symptoms. The differences in findings did not seem to be related to the study design. In contrast, 2 cohort studies demonstrated that early exposure to cat24Custovic A Simpson B Simpson A Kissen P Woodcock A the NAC Manchester Asthma Allergy Study Group Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial.Lancet. 2001; 358: 188-193Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar or cat allergen25Wahn U Lau S Bergmann R Kulig M Forster J Bergmann K et al.Indoor allergen exposure is a risk factor for sensitization during the first three years of life.J Allergy Clin Immunol. 1997; 99: 763-769Abstract Full Text PDF PubMed Scopus (480) Google Scholar was associated with an increased risk of manifesting allergy to cat—in the first year of life in one study and during the first 3 years of life in another study. In the latter investigation, the increased risk of cat allergy was no longer evident when those in the cohort had reached 7 years of age.26Lau S Illi S Sommerfeld C Niggemann B Bergmann R von Mutius E et al.Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study.Lancet. 2000; 356: 1392-1397Abstract Full Text Full Text PDF PubMed Scopus (610) Google Scholar The effect of pet ownership in infancy on the subsequent risk of atopy and asthma has been further investigated in a cohort study reported in this issue of the JACI.27Remes S Castro-Rodriguez J CJ Martinez FD Wright AL Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy.J Allergy Clin Immunol. 2001; 108: 509-515Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar The design of this investigation, in which information on pet ownership and exposure was obtained from parents during the first year of the child's life, overcomes the problems of recall bias inherent in cross-sectional studies. Like most of the studies mentioned above, this study showed that pet ownership in infancy had no effect, either protective or adverse, on the subsequent risk of atopy to other allergens. Specific allergy to dog was not assessed, but there was no association between cat exposure in infancy and cat allergy at age 11 years. The novel finding of this study is that the incidence of asthma symptoms was reduced in those who owned a dog and probably also in those who owned a cat (though the latter effect was not statistically significant). This protective effect was independent of atopic status but was apparently limited to children without family histories of asthma. In sum, before the study of Remes et al,27Remes S Castro-Rodriguez J CJ Martinez FD Wright AL Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy.J Allergy Clin Immunol. 2001; 108: 509-515Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar 3 separate phenomena have been attributed to animal exposure in early life: 1.An increased risk of sensitization to cat allergen has been observed during the first 3 years of life in children who are exposed to this allergen in infancy.2.A reduced prevalence of sensitization to specific pet allergens (usually cat) has been observed in later childhood and adult life in genetically predisposed individuals who were exposed to the relevant allergen source in early life. This is almost certainly an immunologic phenomenon, and it might be explained by the development of allergen-specific IgG4 antibodies as part of a modified TH2 response, as described by Platts-Mills et al.22Platts-Mills T Vaughan J Squillace S Woodfolk J Sporik R Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study.Lancet. 2001; 357: 752-756Abstract Full Text Full Text PDF PubMed Scopus (733) Google Scholar Custovic et al24Custovic A Simpson B Simpson A Kissen P Woodcock A the NAC Manchester Asthma Allergy Study Group Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial.Lancet. 2001; 358: 188-193Abstract Full Text Full Text PDF PubMed Scopus (255) Google Scholar have suggested that the difference in effects between early and late childhood might reflect the maturation of the immune response from initial sensitization to later tolerance.3.A reduced tendency to develop sensitization to all allergens has been observed. This has been noted mainly in relation to farm animals, but it has also (in one study) been attributed to dog ownership in childhood.21Svanes C Jarvis D Chinn S Burney P Childhood environment and adult atopy: results from the European Community Respiratory Health Survey.J Allergy Clin Immunol. 1999; 103: 415-420Abstract Full Text Full Text PDF PubMed Google Scholar The presence of siblings at home28von Mutius E Martinez F Fritzsch C Nicolai T Reitmeir P Thiemann H-H Skin test reactivity and number of siblings.Br Med J. 1994; 308: 692-695Crossref PubMed Scopus (399) Google Scholar, 29Strachan D Hay fever, hygiene, and family size.Br Med J. 1989; 299: 1259-1260Crossref PubMed Scopus (3857) Google Scholar, 30Jarvis D Chinn S Luczynska C Burney P The association of family size with atopy and atopic disease.Clin Exp Allergy. 1997; 27: 240-245Crossref PubMed Scopus (127) Google Scholar, 31Matricardi P Franzinelli F Franco A Caprio G Murru F Cioffi D et al.Sibship size, birth order, and atopy in 11,371 Italian young men.J Allergy Clin Immunol. 1998; 101: 439-444Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar and child care attendance32Krämer U Heinrich J Wjst M Wichmann H-E Age of entry to day nursery and allergy in later childhood.Lancet. 1999; 353: 450-454Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar, 33Haby M Marks G Peat J Leeder S Day care attendance before the age of two protects against atopy in preschool age children.Pediatr Pulmonol. 2000; 30: 377-384Crossref PubMed Scopus (45) Google Scholar have a similar effect. The protection does not seem to be limited to those with a genetic predisposition. This nonspecific protective effect is probably not attributable to a direct immunologic mechanism. The “hygiene hypothesis”—that is, alteration of immunoregulation by the action of microbial antigens—has been invoked to explain this observation.29Strachan D Hay fever, hygiene, and family size.Br Med J. 1989; 299: 1259-1260Crossref PubMed Scopus (3857) Google Scholar The findings of Remes et al27Remes S Castro-Rodriguez J CJ Martinez FD Wright AL Dog exposure in infancy decreases the subsequent risk of frequent wheeze but not of atopy.J Allergy Clin Immunol. 2001; 108: 509-515Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar do not fit with either of these direct or indirect immunologic models. They have shown a reduction in asthma symptoms in association with early-life pet ownership independent of any effect on atopy. Furthermore, the effect was seen in those without a genetic predisposition to asthma. The implication of this finding is that something associated with dog exposure has beneficial effects on airway structure or function. The nature of and actual mechanism for this beneficial effect remains unknown. What is the status of pets in allergic families in 2001? Certainly, the news is not all bad for cats and dogs. Although people with asthma and rhinitis who are allergic to pets would be well advised to avoid exposure to them, the advice for people who wish to prevent allergies and asthma in their children is more complex. At this stage, we should probably not be advising such people to rid their homes of pets. However, we should probably also not be recommending pet ownership as prophylaxis against asthma. Further research must focus on the mechanisms underlying the observed protective effect and the path to safe, effective, and environmentally acceptable methods of achieving this reduced risk of allergic disease in the general population.