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. Author manuscript; available in PMC: 2020 Jun 10.
Published in final edited form as: Int Forum Allergy Rhinol. 2018 Feb;8(2):108–352. doi: 10.1002/alr.22073

TABLE VI.G.3.

Evidence for the hygiene hypothesis in the development of allergic rhinitis

Study Year LOE Study design Study groups Clinical endpoint Conclusion
Campbell et al.647 2015 2a SR 29 studies (1999–2014): 26 cross-sectional, 3 longitudinal. Meta-analysis: 8 studies Association of farm exposure with sensitization in childhood or adulthood Protective effect of farm exposure in infancy on allergic disease in childhood and adulthood in majority of studies. Exposure during adulthood had no consistent relationship with sensitization.
Karmaus & Botezan645 2002 2a Meta-analysis 53 studies (1986–2000). Hay fever: 17 studies (n = 253,304); Sensitization: 16 studies (n = 46,758) Association of sensitization and AR with 3 or more siblings vs no siblings Higher number of siblings was associated with less atopy. Effect was not explained by hygiene factors.
Fujimura et al.645 2016 2b Longitudinal birth cohort study 298 children followed until age 4 years Association of sensitization and asthma at age 2 years with fecal microbiota in neonates targeted at age 1 month (n = 130) or 6 months (n = 168) Reduced colonization of Bifidobacteria, Lactobacillus, Faecalibacterium, Akkermansia, and Malassezia during the neonatal period may influence the risk of multisensitization predictive for asthma.
House et al.648 2016 2b Nested case-control study Farmers and spouses: Cases: asthma (n = 1198); Controls: no asthma (n = 2031). Association of sensitization, rhinitis, eczema, and asthma with living on a farm when born and with being exposed to farm environment when mother was performing farm activities during pregnancy Early-life farm exposure associated with less atopy. No association with asthma.
Hua et al.664 2016 2b Cross-sectional study 1879 adult subjects Association of seasonal allergy with fecal microbial biodiversity Reduced fecal biodiversity and altered composition associated with more allergy. No association with asthma and eczema.
Arrieta et al.663 2015 2b Longitudinal nested case-control study 319 children followed from birth until 5 years of age Association of sensitization and wheezing at 1 year with fecal microbiota at age 3 months and 1 year Reduced colonization of Faecalibacterium, Lachnospira, Veillonella, and Rothia during the first 3 months of life may increase the risk of atopic asthma.
Strachan et al.646 2015 2b Cross-sectional study Children 6–7 years of age in 31 countries (n = 210,200); 13–14 years of age in 52 countries (n = 337,226) Association of hay fever with three or more siblings vs no siblings Protective effect of older and total number of siblings on self-reported AR. Effect was significantly stronger in affluent countries.
Valkonen et al.661 2015 2b Cross-sectional stratified population study GABRIELA study: 224 children, 6–12 years Association of sensitization with mattress bacterial diversity Exposure to more diverse bacterial flora associated with less sensitization.
Bisgaard et al.449 2011 2b Longitudinal study 253 high-asthma-risk children followed from birth to age 7 years Association of sensitization and AR with high fecal microbial biodiversity Reduced bacterial diversity associated with higher risk of sensitization and AR in childhood.
Ege et al.659 2011 2b Two cross-sectional studies PARSIFAL study: 489 rural and suburban children; GABRIELA study: 444 rural children Association of sensitization with microbes in mattress (PARSIFAL) and in airborne dust (GABRIELA) Farm-children had less asthma and atopy. Indoor microbial exposure much higher and diverse in farm homes. Microbial diversity related to asthma but not to atopy.
Tischer et al.657 2011 2b Nested case-control study 678 children at the age of 6 years from German (n = 346) and Dutch (n = 332) birth cohorts Association of rhinitis and asthma with mattress dust biological components of mold and endotoxin Inconsistent results. Microbial exposures at home had different effects on allergy in German and Dutch birth cohorts.
von Hertzen et al.660 2007 2b Cross-sectional study 563 children aged 7–16 years in Finnish and Russian Karelia Association of sensitization with microbial content in drinking water samples from school kitchens Microbial count much higher and sensitization much lower in Russia. High count of microbes associated with less atopy.
Cuello-Garcia et al.658 2015 3a Systematic review and meta-analysis 29 randomized controlled trials in infants Association of AR with probiotic supplementation to pregnant mothers, breast-feeding women, or infants No effect on allergies.
Simpson & Martinez656 2010 3a Review (2000–2007): 6 rural studies; 10 urban studies Association of sensitization with exposure to endotoxin Exposure to endotoxin protective in over 50% of studies. Endotoxin may be marker of other protective factors.
Abrahamsson et al.442 2014 3b Longitudinal case-control study 47 infants (n = 20 IgE-associated eczema; n = 27 healthy controls) followed until 7 years of age Association of sensitization, asthma and AR with fecal diversity in infancy Low microbial diversity associated with asthma later in childhood. No association with sensitization or rhinitis.

AR = allergic rhinitis; GABRIELA = GABRIEL Advanced Survey; IgE = immunoglobulin E; LOE = level of evidence; PARSIFAL = Prevention of Allergy-Risk Factors for Sensitization Related to Farming and Anthroposophic Lifestyle; SR = systematic review.

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