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Childhood immunity: Daycare makes the immune system stronger? The hygiene hypothesis

Allergy, Asthma, Infant and Children | January 26, 2015 | Author: The Super Pharmacist

Children, allergy, Asthma

Childhood immunity: Daycare makes the immune system stronger? The hygiene hypothesis

A common belief is that exposure as a child to different viruses and bacteria (particularly in child care and schooling situations) leads to a stronger immune system. Is this true?

What doesn't kill us makes us stronger, right? That is certainly how the immune system seems to work. Once the immune system is exposed to a virus, for example, it develops a memory of and immunity against that virus. Therefore, if the virus does not initially kill us, the immune system will be able to fight it in the future. From this, one could assume that we should be exposed to any number of small insults (like viruses) early in life so that we are better prepared to face large insults in the future. Are we too clean? Should children be allowed to eat dirt (or at least get dirty)? Should we stop bathing our babies? Some experts have suggested this approach (nearly).

The origins of the hygiene hypothesis

Allergic rhinitis, commonly called hay fever or seasonal allergy, was considered uncommon before 1870s.1 However, between the 1870s and the 1950s, the number of cases of allergic rhinitis in Western countries increased dramatically. Likewise, the prevalence of asthma steadily increased since at least the 1950s. Four in 10 people in Western countries have at least one allergy.2 In fact, the prevalence of allergies is even increasing in pet dog.3  

The origins of the hygiene hypothesisWhat could be to blame for the increase in atopic immune reactions, aka type I hypersensitivity reactions or an exaggerated response to harmless antigens? During the time that the prevalence of hay fever was increasing, Western countries began separating their drinking water from sewage water. In fact, public water systems were actively chlorinated to kill pathogens. Populations were also becoming more urbanised.

Fewer people used animals for travel and farming/livestock handling was done by increasingly fewer individuals. Society as a whole became aware of the role of bacteria and viruses in human disease, which led to people to bathe and wash themselves more frequently.

In the first half of the 1900s, death from infectious disease decreased almost 90%, in large part due to these societal changes.4 During the same period, however, the number of people with atopic immune reactions increased substantially.

The “hygiene hypothesis” emerged in the late 1980s and early 1990s as a way to explain the correlation between “cleanliness” early in life (i.e. reduced exposure to antigens) and allergies/asthma.5,6 While the hygiene hypothesis has been restated several times over the years, the essential premise is that early life exposure to antigens and pathogens is associated with a decreased likelihood of developing allergy and asthma. Thus, as we improve sanitation, take more showers, and use antibacterial hand scrub, we die from infections far less frequently. Unfortunately, we are also more likely to have hay fever and asthma, presumably because we have not “primed” our immune systems early in life.

Support for the hygiene hypothesis

The hygiene hypothesis seems to explain the increase in allergy and asthma as Western cultures cleaned up their acts. Research over the past quarter-century also seems to support the hygiene hypothesis. 

One of the initial papers that prompted the formulation of the hygiene hypothesis was the observation that allergic diseases were lower among British schoolchildren who had one or more older siblings.6 Presumably, children with older siblings are exposed to more viral infections than those without older siblings.

In a separate study, American children placed in daycare during the first six months of life were 20% less likely to have asthma at age 6 and 70% less likely at age 13 than children who remained at home.7 

Other researchers have found that hay fever, asthma, and atopic sensitisation inversely correlates with endotoxin levels in dust collected from children's mattresses. 8. Moreover, cytokine levels associated with atopic immune response were lower in children with higher endotoxin levels. In other words, children who had higher exposure to endotoxin (part of the cell wall of certain bacteria) had lower rates of allergies and asthma and a decreased immune response (lower inflammatory cytokines).

The authors suggest that endotoxin exposure may help prime the immune system so that it can tolerate allergens in the environment.

Antibiotics given during first year of life for infections (other than lung infections) results in an increased incidence of asthma at age seven.9 These antibiotics kill bacteria of various types, not just these causing the initial infection. Thus, the immune system is exposed to fewer bacteria during infancy, which may increase the child's vulnerability to asthma later in life.

Finally, a dog or cat in the home during the first year of a child's life decreases the risk of developing allergic rhinitis or asthma once that child reaches school age.10 Presumably the pet provides a rich source of allergens for the child’s immune system during development.

Problems with the hygiene hypothesis

While the hygiene hypothesis seems to make sense intuitively, there are other potential explanations for the increase in allergy and asthma over the last 150 years.

Problems with the hygiene hypothesisPerhaps the most important change that occurred over this time is the indoor home environment. Homes now have insulation and many homes have wall-to-wall carpeting (a trend that started in the 1930s). Both of these substances increase indoor allergen concentrations11, especially dust mites12, which strongly sensitise children to asthma.13 Indeed, homes are warmer and moister than they used to be, which fosters the growth of pathogens.

We also spend more time indoors than we used to, further increasing our allergen exposure. With more time spent indoors and changes in diet, obesity is a major problem in Western cultures. Obesity increases the severity of asthma.14

The verdict

There is likely a complex association between early life allergen/pathogen exposures and atopic immune reactions later in life. There is some merit to the hygiene hypothesis, though a considerable amount of confusion exists (both for parents and doctors). It seems clear that having a dog in the home during the first year of a child's life is protective. Likewise, placing a child in daycare during that time, or at least exposing the child to children who are presumably carriers of bacteria and viruses, is also protective. Excessive use of antibiotics early in life may predispose children to developing asthma. Modest antigen exposure, such as allowing mild illnesses to take their course, getting recommended vaccination/immunisations, and exposing infants to other people and the environment early in life can aid in immune system priming.15 Thus, using hand sanitisers before touching children and taking excessive precautions to separate children from possible sources of infection is unwarranted. On the other hand, parents should not abandon cleanliness and hygiene altogether. Large doses of pathogens can still cause serious diseases. Parents should practice good hand, food, and personal hygiene without being obsessive.

Exposure to antigens during the first year of life, within reason, is important for immune system development. It is important that the child is not placed in serious risk of harm from that exposure, however.

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References

1. Platts‐Mills TA, Woodfolk JA. Allergens and their role in the allergic immune response. Immunological reviews. 2011;242(1):51-68.

2. Bloomfield S, Stanwell‐Smith R, Crevel R, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clinical & Experimental Allergy. 2006;36(4):402-425.

3. Hillier A, Griffin CE. The ACVD task force on canine atopic dermatitis (I): incidence and prevalence. Veterinary immunology and immunopathology. 2001;81(3):147-151.

4. Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA. Jan 6 1999;281(1):61-66.

5. Martinez FD. Role of viral infections in the inception of asthma and allergies during childhood: could they be protective? Thorax. Dec 1994;49(12):1189-1191.

6. Strachan DP. Hay fever, hygiene, and household size. BMJ. Nov 18 1989;299(6710):1259-1260.

7. Ball TM, Castro-Rodriguez JA, Griffith KA, Holberg CJ, Martinez FD, Wright AL. Siblings, day-care attendance, and the risk of asthma and wheezing during childhood. N Engl J Med. Aug 24 2000;343(8):538-543. doi:10.1056/nejm200008243430803

8. Braun-Fahrländer C, Riedler J, Herz U, et al. Environmental exposure to endotoxin and its relation to asthma in school-age children. New England Journal of Medicine. 2002;347(12):869-877.

9. Kozyrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. Chest. Jun 2007;131(6):1753-1759. doi:10.1378/chest.06-3008

10. Hesselmar B, Aberg N, Aberg B, Eriksson B, Bjorksten B. Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy. May 1999;29(5):611-617.

11. Platts-Mills TA. How environment affects patients with allergic disease: indoor allergens and asthma. Ann Allergy. Apr 1994;72(4):381-384.

12. Tovey ER, Chapman MD, Wells CW, Platts-Mills TA. The distribution of dust mite allergen in the houses of patients with asthma. Am Rev Respir Dis. Nov 1981;124(5):630-635.

13. Sporik R, Holgate ST, Platts-Mills TA, Cogswell JJ. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. A prospective study. N Engl J Med. Aug 23 1990;323(8):502-507. doi:10.1056/nejm199008233230802

14. Boulet LP. Asthma and obesity. Clin Exp Allergy. Jan 2013;43(1):8-21. doi:10.1111/j.1365-2222.2012.04040.x

15. Kramer A, Bekeschus S, Broker BM, Schleibinger H, Razavi B, Assadian O. Maintaining health by balancing microbial exposure and prevention of infection: the hygiene hypothesis versus the hypothesis of early immune challenge. J Hosp Infect. Feb 2013;83 Suppl 1:S29-34. doi:10.1016/s0195-6701(13)60007-9

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