In 1906, an Austrian physician named Clemens von Pirquet noticed that once injected with horse serum or the small pox vaccine, people often had quicker, more severe reactions to subsequent injections. The term allergy was thus forged from the Greek allos, meaning "altered state" and ergon, meaning reaction, to describe an altered body reactivity.1 Before being known as allergies, "consumption" afflictions (such as wheezing) were rare, considered non-life-threatening, and some considered them to be a sign of prestige.
Their novelty has worn off. Today, allergies are a nuisance and have crossed socio-economic barriers. In this article, we'll review our understanding about the genesis of allergies, and the role played by our environment, rural or urban, in developing them.
Allergic Prevalence
A study conducted from 1976 through 1994 in conjunction with the National Health and Nutrition Surveys with over 50,000 U.S. individuals (aged 6 through 59) found 54.3 percent to have positive skin reactions to at least one of 10 common allergens. The results are a testament to our tendency to panic over rare yet serious problems and show apathy towards the more prevalent nuisances: Dust mites, rye grass, ragweed and cockroach elicited the most responses, while peanut allergies, which receive a lot of attention, were the most infrequent.2
Allergic prevalence (both ocular and respiratory, as they are considered closely related)3 has been associated with just about anything to which the scientific community has thought to compare it—poverty,4 global warming,5 pollution,6 new airtight houses,7 obesity,8 use of antibiotics,9 race,10 intestinal flora,11 family size, daycare centers,12 intestinal parasites,13,14 etc.—and yet no single all-encompassing dogma has arisen to explain the increasing prevalence of allergies. Genetics certainly plays a role: Studies have consistently shown that the allergic tendency is heritable; that is, parents with allergies can pass the tendency to have allergies—but not the specific allergy—on to their offspring. The polygenic nature of allergies is excessively complex, and offers little hope of a quick gene fix.11,15,16 The role of the environment, however, is equally important, as it is what turns the various genetic tendencies into frustrating afflictions.3
Country vs. City
Early contact with allergens associated with farming, particularly with soil bacteria, has been repeatedly correlated with a lower incidence of allergy in children, and its effect has been suggested to last through adulthood.17 The immune response involves both Th1-mediated and Th2-mediated responses. Th1 cells activate the cellular immune system (non-specific), while Th2 cells activate the humoral immune system (specific). They need to achieve a balance with each other early on in a child's life—overactivity of the Th2 response is believed to play a role in allergic sensitization. Exposure to common allergens during childhood is thought to spur the cellular immune system into action, thereby preventing an exaggerated Th2 response. Without such exposure, the humoral immune system goes into overdrive, instigating immune responses when there is no need to. It has even been suggested that humans developed a symbiosis with certain intestinal fauna that secrete Th2-suppressing mediators. Without these bacteria, the immune system may not be able to function properly.13,14 This, in a nutshell, is the hygiene hypothesis. The helpful bacterial and allergen exposure, historically encountered in rural living, is also associated with daycare attendance and having siblings.12
However, even an "unsanitary" childhood can't protect some adults transplanted from the farm to the city.18 Indeed, allergy prevalence is generally higher in urban areas than rural, and while apartment living (a physical distance between the human and the soil bacteria) and super-insulated city homes (perfect habitats for mold and dust mites)19 have been suggested as explanations, the most glaring and likely culprit is diesel exhaust pollution. Sunlight reacts with diesel exhaust-produced hydrocarbons and nitrous oxide to produce low-level ozone, which causes oxidative stress. Research has also demonstrated that pollen grains contain oxidases that become reactive when hydrated.20 Reactive oxygen species degrade mast cell membranes and release histamine, which exacerbates the allergic reaction. Unfortunately, antioxidants and innate mechanisms for reactive oxygen species metabolism can only control the effects of oxidative stress to a limited extent.21-22 Laboratory mice start sneezing (a pathetic sight to behold) in low concentrations of diesel exhaust, but soon acclimate and symptoms disappear.23 However, sensitized mice develop symptoms of rhinoconjunctivitis when exposed to common allergenic pollens, and when exposed to diesel exhaust with pollen, the allergic symptoms are even worse.23 It turns out that diesel exhaust accumulates on pollen grains, alters their morphology, and causes them to release their protein constituents—thus, urbanites are in more contact with the allergenic properties of pollen than their rural counterparts.24 All this suggests a threshold at which genetically predisposed individuals show allergic symptoms to airborne particulates—a threshold that varies from person to person, and that is dramatically lower in the presence of pollution.25
This lowered threshold may also be a direct result of pollution. Cigarette smoke is known to be full of of free radicals, which oxidize the lipid layer of the tear film, speeding its breakdown.26 Several studies have now established that air pollution, including diesel exhaust, has similar effects on the tear-film barrier.27-29 A diminished tear film as a result of pollution can lead to dry-eye symptoms, opening the eye to the pollution-ridden pollen and allowing the allergic state to be maintained.
Treating Allergy
The battle cry of city-dwelling sufferers of allergic conjunctivitis may therefore be, "Maintain the barrier!" Humidifiers, air purifiers and pointing fans and car vents away from the face may all be helpful in minimizing symptoms. Avoiding prolonged outdoor activities in the peak pollen seasons is helpful but impractical.
The pharmaceutical industry has produced a plethora of eye lubricants, antihistamines, mast cell stabilizers and antihistamine/ mast cell stabilizer combinations. The combination products are the most effective for allergic conjunctivitis. They inhibit histamine binding to receptors in the conjunctiva as well as prevent conjunctival mast cells from releasing more histamine and other pro-inflammatory mediators, which would otherwise cause symptoms. Ironically, systemic antihistamines cause clinically significant dry-eye symptoms.30,31
Topical antihistamine/mast cell stabilizers, such as olopatadine 0.1% (Patanol, Alcon) have high H1 receptor affinity and selectivity. They therefore have no more effect on tear-film stability than do tear substitutes, and do not dry the ocular surface. (Welch D, et al. IOVS 2006;47: ARVO E-Abstract 4999) A study presented by Francis Mah, MD, at this year's meeting of the Western Society of Allergy, Asthma, and Immunology found that the recently introduced 0.2% formulation of olopatadine (Pataday, Alcon) is safe as a tear substitute in allergic conjunctivitis patients with dry eye. However, no topical allergic conjunctivitis medication builds up the tear film. It may therefore be beneficial to treat patients with eye allergies not only with antihistamine/mast cell stabilizers, but also with tear substitutes. Although dry eye is separate from allergy, it's also related to pollution.29
Although genetics plays a role in urban allergy, there's little hope for changing or avoiding our biological fate, given pollution levels. Luckily, we can manage allergies by behavior modification and the use of topical antihistamine/mast cell stabilizers, enhanced with tear substitutes.
Dr. Abelson, an associate clinical professor of ophthalmology at Harvard Medical School and senior clinical scientist at Schepens Eye Research Institute, consults in ophthalmic pharmaceuticals. Ms. Lilyestrom is a medical writer at Ophthalmic Research Associates in North Andover.
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