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Wise et al.

Page 49

diseases, exposure to cats or dogs was protective only in children with non-allergic fathers. 534

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In a pooled analysis of 11 European birth cohorts, any furred pet ownership during the first 2 years was associated with lower risk of sensitization to aeroallergens, but not with a decreased prevalence of AR later in childhood. 552 In a recent study which investigated urban vs rural differences, the risk of AR in adulthood was 20% lower in subjects exposed to pets at birth or during childhood. However, pet keeping did not explain the protective effect of living on farm with livestock compared to urban dwelling. 643 Overall, pet allergens are ubiquitous. There is no evidence that pet avoidance in childhood prevents the development of AR or sensitization to aeroallergens later in life. Alternatively, early pet exposure may induce immune tolerance and thus reduce the chance of development of allergic disease. This protective effect seems to be strongest in non-allergic families with dog exposure in early childhood. • Aggregate Grade of Evidence: C (Level 2a: 6 studies; Level 2b: 2 studies; Table VI.G.2). VI.G.3. Hygiene (aka biodiversity or microflora) hypothesis— The inverse association of the number of siblings and the prevalence of hay fever was reported nearly 3 decades ago in British cohorts. 618 Strachan 618 proposed the term “hygiene hypothesis” and speculated that exposure to frequent infections in large families could be the protective factor. The hygiene hypothesis has evolved toward a more contemporary “biodiversity hypothesis” that looks beyond the effect of infections and single protective microbes to the potential protective effect of the colonization of mucous membranes and the skin with diverse environmental microflora. 644 Recently, the term “microbiota hypothesis” has been proposed. In addition, the term “microflora” should be substituted for the term “microbiota.” Various related potential cofactors and their relationship to the development of AR are discussed in this section. Number of siblings.: The association between number of siblings and presence of allergic diseases has been studied extensively. In a meta-analysis of 53 studies, 48 studies demonstrated that higher number of siblings was associated with decreased atopy, an effect that was more evident for AR than for sensitization and asthma 645 (Table VI.G.3). A large study based on questionnaire data for children aged 6 to 7 years from 31 countries and 13 to 14 years from 52 countries confirmed that the inverse association between the number of older siblings and prevalence of hay fever was strongest in more affluent countries. 646 Farming.: Since the first publications in 1999–2000, there is a growing interest in the “farm effect” on allergy. In a meta-analysis of 8 studies, the risk of sensitization, measured by sIgE or SPT in childhood or adulthood, was 40% lower (OR 0.60; 95% CI, 0.52 to 0.70) among subjects who had lived on a farm during the first year of life. 647 In a recent U.S. case-control study, farm exposure in utero and in early childhood protected against allergen sensitization but not asthma in adulthood. 648 The protective farm effect seems to be stronger when

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.