Explore This IssueMarch 2013
Allergies have been on the rise in industrialized countries for more than 50 years, according to statistics collected by the American Academy of Allergy, Asthma and Immunology. In the United States, approximately 10 percent of children suffer from hay fever and 8 percent from a food allergy of some kind. The U.S. Centers for Disease Control and Prevention documented an 18 percent increase in the number of youngsters who reported a food allergy between 1997 and 2007.
Allergies can cause a variety of ear, nose, throat and sinus issues and many otolaryngology practices offer allergy-related services, including a majority of academic otolaryngology departments in the U.S.
Allergies tend to run in families, but genetics cannot explain the rise in cases. So scientists, epidemiologists and physicians have looked to environmental influences, especially those found in first-world countries and, increasingly, in urban settings. A study published in September 2012, which surveyed U.S. households and analyzed data for 38,465 children, found higher rates of food allergy in urban areas (9.8 percent) versus rural areas (6.2 percent) (Clinical Pediatrics. 2012;51:856-861).
The “hygiene hypothesis” provides a popular framework for thinking about early environmental exposures and the development of allergic sensitization. Essentially, the hypothesis is that modern society offers a cleaner environment for kids to grow up in than did our mostly agrarian past, one free of many microbes and infections that used to go hand-in-hand with childhood and that, as the theory goes, primed the immune system to recognize true threats and ignore innocuous ones such as ragweed pollen or peanut antigens.
At the same time, present-day city life exposes children to a slew of things that were not a part of growing up just a few generations ago. To that end, researchers have started looking at environmental pollutants as possible triggers of allergic sensitization. Second-hand smoke tops the list, but recent studies have indicated that the chlorine in pools, pesticides and certain air pollutants are also associated with a greater risk for allergies (Semin Immunopathol. 2012;34:655-669.).
Here’s a closer look at some of the latest research on the role of environmental exposures and what it may mean for otolaryngologists treating allergic rhinitis and related conditions.
A study published last December analyzed data from the National Health and Nutrition Examination Survey (NHANES) and looked at 2,211 participants aged 6 years and older. The researchers concluded that excessive use of specific pesticides may be contributing to the increasing incidence of food allergies in the U.S. (Ann Allergy Asthma Immunol. 2012;109:420-425). Additionally, they found that dichlorophenol exposure was associated with sensitization to food allergens. Specifically, the study participants who were in the top 25 percent for urine levels of dichlorophenol metabolites were more likely to be sensitized to one or more food allergens. Conversely, inhalant allergies did not correlate to dichlorophenol exposure.
Dichlorophenols are present in pesticides and herbicides used on food crops and insecticides used in moth balls, said study co-author Elina Jerschow, MD, a physician and researcher in allergy and immunology at the Albert Einstein College of Medicine and Montefiore Medical Center in New York. They’re also present in trace amounts in drinking water, but Dr. Jerschow doesn’t think this is a significant exposure. “Dichlorophenols are only by-products in the water,” she said. “Their levels are strictly regulated and extensive effort is made to prevent their presence in tap water.” Further, she said, bottled water has no such requirements.
The link between pesticides and allergic rhinitis and asthma has also been noted in farmers and pesticide applicators in several countries, Dr. Jerschow said. She and her coauthors offer one possible explanation for the results that lines up with the hygiene hypothesis. Instead of taking children away from the farm and all its attendant microbial exposures, pesticides are taking the microbes away from the farm—at least those microbes important in priming the human immune system.
The strengths of the NHANES study are its large study population and its use of urinalysis to assess concrete evidence of dichlorophenol exposure. No causal link can be inferred from the association, however; that would require a prospective study, Dr. Jerschow said. Finding people who are not exposed to pesticides, treated water or swimming pools would be difficult, and following them for many years might not be feasible.
Chlorine and PAHs
Another recent report out of Belgium, published in November 2012, concluded that sensitization to dust mites in early life is associated with nasal epithelial defects, and that the nasal barrier function can be negatively modulated very early in life by environmental stressors such as pool chlorine (Sardella A, Voisin C, Dumont X, Marcucci F, Bernard A. [Published online ahead of print Nov. 20, 2012.] Pediatr Pulmonol).
Researchers studied 288 kindergarteners, taking a nasal lavage to look for biomarkers of epithelial damage. Specifically, they used a ratio of the anti-inflammatory protein called Clara cell protein (CC16) and albumin as an index for epithelial integrity. Exposure to swimming pools decreased this ratio and correlated with early allergy to house dust mites.
Alfred Bernard, PhD, professor of toxicology and research director at Catholic University of Louvain in Brussels and co-author of the study, said he’d been working on developing new biomarkers with which to assess the toxic effects of chemicals in the environment. A chance discovery uncovered time spent in chlorine swimming pools as a factor in the expression of a particular surfactant-associated protein, which was indicative of epithelial damage, in the deep lung.
In the study, he and his colleagues wanted to focus on very young children, which limited the kinds of samples they could take. They devised the CC16/albumin ratio in nasal lavage fluid as a proxy of epithelial cell integrity. In addition to the negative effects of swimming pool exposure, the researchers found a positive effect of probiotic consumption and of house cleaning with bleach products, known to kill allergens such as mold and dust mites.
“Our data support the idea that this chemical [pool chlorine] promotes the expression of atopic disease,” said Dr. Bernard. Allergies to dust mites were present in kids even when the parents were not allergic. “The airway epithelia is very immature in these children,” he added, saying that there may be a specific window of sensitivity during which exposure may trigger allergic sensitization.
Like the NHANES study, the Belgian study was not able to make any claim about causality, but could only show associations between exposures, biomarkers and allergies.
A third new study, published in January, tested the interaction between polycyclic aromatic hydrocarbons (PAHs) and exposure to cockroach allergens in early childhood (Perzanowski MS, Chew GL, Divjan A, et al. [Published online ahead of print January 30, 2013.] J Allergy Clin Immunol.). Researchers studied 349 mother-child pairs in New York City, monitoring the mothers’ exposure to PAHs and cockroach allergens during pregnancy. Children were followed for up to seven years, and 31 percent tested positive for cockroach allergy. The allergy correlated with high PAH exposure.
Sources of PAHs that people commonly breathe in are car exhaust, wood smoke, cigarette smoke and industrial pollution, including coal burning and municipal trash incineration. Eating grilled or charred meats and certain processed or pickled foods can also result in PAH exposure.
Karen Calhoun, MD, an otolaryngologist at Ohio State University in Columbus, said the research is not only fascinating, but it also seems to be building. “They’re all raising the possibility of a connection between some exposure and food allergies,” she said. Dr. Calhoun noted a recent list of causes of food allergies (Semin Immunopathol. 34:655-69. doi: 10.1007/s00281-012-0323-y). Aside from genetic influences, the list included the timing and pattern of food introduction, diet and nutrition, smoking, prematurity and low birth weight, microbial exposure and race and ethnic background.
Still, it’s not clear the practitioner can apply any of these data. “There’s not a whole lot of things you can tell a parent,” she said. Doctors can advise them not to smoke, which is good for a whole lot of reasons beyond its potential to prevent allergic sensitization. But advice about when certain foods should be introduced has changed in recent years. The American Academy of Pediatrics, which used to have a list of foods to avoid in babies younger than 12 months, such as eggs, peanuts and dairy products, has since backed off that advice.
And while research links to probiotics being protective are equally intriguing, they cannot be translated into practice just yet. According to Cochrane Reviews, there is insufficient evidence to recommend probiotics as a way to prevent food allergies (Cochrane Database Syst Rev. Oct 17;(4):CD006475).
Some experimental treatments are being tested, said Dr. Calhoun, such as sublingual and oral therapies designed to desensitize patients. “I think we’ll find a way to treat food allergies soon,” she said, but there’s not enough evidence now to offer it in everyday practice. For now, the only advice for managing a food allergy is to avoid the food.
For inhalant allergy, advice is similar: Avoid when possible. While over-the-counter and prescription medications can help with symptoms of allergic rhinitis, they do not affect the underlying disease.