The NHANES 2005–2006 provided a unique opportunity to evaluate how levels of total IgE and allergen-specific IgEs relate to allergic conditions and symptoms in the US population. None of the previous NHANES studies have examined both qualitative and quantitative patterns of atopy in relation to allergy-related outcomes. Moreover, this many allergens have been examined in only a few large-scale European studies.16–18
Although several studies have investigated allergic outcomes in relation to clinical markers of atopy, limited information on quantitative relationships and sensitization patterns is available. In the NHANES 2005–2006, elevated levels of plant-, pet-, and mold-specific IgEs were most consistently associated with allergy-related outcomes. Dust mites were one of the most common sensitizers in this population, but mite-specific IgEs did not remain strongly associated with the reported symptoms. Consistent with published data,19
the majority of the allergen-specific IgEs were more prevalent among those who reported allergy-related outcomes than among asymptomatic individuals.
Allergies affect a substantial proportion of the US population; more than one-third of the NHANES 2005–2006 participants reported diagnosed allergies. Of those who reported diagnosis of any type of allergic condition, over 50% had symptoms in the past 12 months. Although the prevalence of allergic conditions appears to be similar to that reported in other national surveys,2–5
the prevalence rates may not be directly comparable. Case definitions of allergy-related outcomes tend to vary from one study to another, a fact which complicates comparisons of estimated prevalence rates.20, 21
Nonetheless, prevalence patterns across socio-demographic factors were largely similar to those reported in the literature.8
In the NHANES 2005–2006, prevalence of self-reported nasal symptoms was comparable to that reported in other national studies of rhinitis (30.2–31.5%).20, 22
Although the majority of the NHANES participants who reported current rhinitis symptoms also reported diagnosed allergies, a substantial proportion of the subjects, at least one-third, lacked any diagnosis of allergy. Several studies have shown that a large number of people who have rhinitis-related symptoms remain undiagnosed.20, 23, 24
On the other hand, it is well known that rhinitis symptoms can also be non-allergic in nature.21
Although allergic rhinitis is considered one of the most common chronic diseases in the US, the prevalence estimates have been highly variable, ranging from 9% to 42%.21, 25, 26
In the NHANES 2005–2006, more than half of the subjects with symptoms of rhinitis had detectable levels of specific IgE to at least one allergen, suggesting that approximately 18% of the US population may manifest symptoms of allergic rhinitis. Nathan and coworkers have reported similar rates (14.2%–22.0%) for allergic rhinitis, demonstrating increasing trends in the prevalence over the past decades.20, 22
A review focusing on diagnosis of allergy has recently suggested that about 50% respiratory symptoms may be allergic in origin.27
Consistent with previous NHANES findings, sensitization to grass, dust mite, and ragweed allergens was most common in the US population.1, 28
Among those who reported any allergy-related symptoms in the past 12 months, sensitization rates were variable, ranging from 24.4% to 44.2% for grass-specific allergens; from 22.3% to 24.9% for dust mite allergens; and from 23.0% to 32.8% for ragweed allergen. It was not unexpected that a larger number of specific IgEs were associated with current allergies than with current hay fever; reported allergy symptoms may relate to a variety of allergic conditions.
Hay fever symptoms were predominantly associated with the presence of plant-specific IgEs, in agreement with published data.28, 29
Although hay fever is commonly referred to as seasonal allergic rhinitis, it can also be triggered by perennial allergens. In the NHANES 2005–2006, sensitization to pets was consistently associated with current hay fever and perennial symptoms of rhinitis. This is not an unforeseen finding because dog and cat allergens are not only found in virtually all US homes, but are also most often found in elevated levels.30, 31
Pet allergens tend to accumulate on many interior materials within the home, including carpeting, upholstery, and bedding, which can serve as continuous reservoirs for those allergens. Because of the aerodynamic characteristics of cat and dog allergen carrying particles, both allergens become aerosolized easily and remain airborne for long periods of time.32, 33
While sensitization to molds has been associated with many atopic outcomes, studies suggest that sensitization is less frequent to molds than to pollen, animal or dust mite allergens.34
Nonetheless, sensitization to molds is an important risk factor for manifestations of atopy. In NHANES 2005–2006, the magnitude of the effect of sensitization on reported symptoms was comparable between molds and pets.
In contrast to previous findings,28
sensitization to dust mites did not remain significantly associated with any of the allergic outcomes in completely adjusted models. This may reflect differences in age distributions and/or analysis methods. The previous NHANES data covers a narrower age range than the NHANES 2005–2006, and because of smaller number of tested allergens, clustering effects of positive test responses have not been accounted for in the previous surveys. Moreover, the allergenic composition of the house dust extract that was used for skin prick testing in NHANES II is unknown, which complicates interpretation of the results. It is also likely that patients with allergy diagnosis, particularly those who see an allergist, have greater awareness and compliance with environmental control measures for dust mites than those who have not consulted a specialist.35
The level of total IgE is influenced by genetic and environmental factors.27
Because levels of total IgE may overlap between non-atopic and atopic individuals, as well as between different allergic diseases, the level of total IgE is generally considered less clinically relevant than specific IgE data.27, 36
In the NHANES 2005–2006, increase in total IgE appeared to have a small, but independent effect on allergy-related outcomes. After controlling for total IgE, the precision of the effect estimates in the models improved, though the patterns of the associations remained similar. In studies where accounting for clustering of sIgEs is not feasible (e.g., studies with limited number of allergens in the test panel), adjusting for total IgE may help to control confounding by other sIgEs. In fact, the effect of total IgE was less pronounced for grass- and ragweed-specific IgEs among individuals with current hay fever. Rye grass and ragweed were the most common sensitizers among mono-sensitized hay fever sufferers (data not shown), which may partially explain this finding. Furthermore, total IgE levels were significantly lower among individuals who did not report asthma than among asthmatic individuals (Figure E5), in agreement with published data.15, 37
Among those participants who reported allergy-related outcomes and who had asthma, a wide spectrum of allergen-specific IgEs were significantly elevated.
Previous studies have shown that not only asthma, but also other co-morbid conditions are associated with hay fever and other forms of allergic rhinitis.7, 8, 26, 38, 39
In the NHANES 2005–2006, both asthma and sinus infections were significantly more prevalent among those who reported current hay fever or current allergies than among individuals without allergy-related outcomes.
Because sensitization is a dynamic process and affected by age,40
we examined total and specific IgEs in relation to allergy-related outcomes across different age groups. The association between total IgE and current allergies was stronger among children than among adults, perhaps reflecting a higher asthma prevalence in children. Although the specific IgE results did not suggest strong evidence for effect modification by age, the odds ratios for some of the specific IgE clusters tended to be higher among children than among adults. In particular, sensitization to pets and molds seemed to increase the odds of having allergy-related outcomes in children. Sensitization to food allergens was also more common in children than in adults, as previously shown.14
The cross-sectional nature of the NHANES 2005–2006 is an important limitation of the study. Because temporal relationships are often difficult to determine in cross-sectional studies, we primarily focused on outcomes that required the presence of symptoms in the past 12 months. We recognize that misclassification of outcomes or exposures can introduce bias. In the NHANES, outcome measures were based on questionnaire responses alone, a practice which is common in most large-scale surveys. Allergic symptoms can be difficult to distinguish from symptoms which are non-allergic in origin, because many allergic and non-allergic conditions have similar symptoms.27
Some conditions can even have both non-allergic and allergic etiologies. For example, a large proportion of rhinitis suffers may have mixed rhinitis, a combination of allergic and non-allergic rhinitis.8, 41
A considerable number of individuals with allergies may also remain undiagnosed, because many people tend to use over-the-counter products, instead of seeking medical attention.20
However, we included an allergy-related outcome that was not based on physician’s diagnosis (i.e., symptoms of current rhinitis) in our analysis. Although serological measurements provide objective evidence of atopy, the diagnosis of clinically relevant allergy also depends on symptom history. It is well known that the presence of allergen-specific antibodies does not necessarily mean that a person has clinically relevant symptoms when exposed to an allergen.19, 36
Because patterns of sensitization tend to vary with climatic and geographic factors, it is possible that the test panel may not have covered all relevant allergens. For example, a recently published list of the major clinically important outdoor aeroallergens in North America includes a number of allergens that were not included in the test panel.23
On the other hand, in national population-based studies, the test panel cannot be optimized for any specific region. Despite the limitations of the study, we believe that serious differential misclassification is unlikely; both outcomes and serum IgE levels were assessed independently, without prior knowledge of the atopic status.
One of the major strengths of the study is that the sample for the survey was selected to represent the entire US population. Indeed, the NHANES 2005–2006 provides the largest nationally representative dataset of serum IgE levels that has ever been collected on the US population. Although skin testing is often used to determine IgE-mediated sensitivity, 8
serum-specific IgE immunoassays enabled the expansion of our test panel to include a larger number of allergens. Similar sensitivities have been reported when serum-specific IgEs and skin-prick tests have been compared with respect to the presence of symptoms, although the performance characteristics of these two immunoassays are known to vary.8, 42
None of the previous population-based studies in the US have examined both qualitative and quantitative relationships between sensitization and allergy-related symptoms. The NHANES 2005–2006 was also the first study to account for clustering of specific IgEs. Studies have shown that many allergens share structural similarities and can be cross-reactive.43, 44
Because IgE-mediated allergy tends to occur to clusters of allergens,45, 46
problems of collinearity may arise during the statistical analysis. To discover patterns and relationships in the allergen-specific data, we used cluster analysis, a widely-used method to analyze correlated data. As we have previously reported in abstract form,13
the NHANES 2005–2006 specific IgE data group into seven clusters, which not only have optimal statistical properties, but also are biologically relevant.
In summary, the NHANES 2005–2006 demonstrated that a large proportion of the US population suffers from allergies. Almost half of the population is sensitized to at least one allergen and more than half of the individuals diagnosed with allergies reported active symptoms. Our findings highlight the importance of different allergens in common allergic conditions. The reported symptoms, with or without diagnosis of allergy, were most consistently associated with plant-, pet-, and mold-specific IgEs. On the contrary, sensitization to dust mites, which is highly prevalent in the population, was not strongly associated with these outcomes. Although levels of total IgE per se are diagnostically less informative than allergen-specific IgEs, measuring data on both markers of atopy can be beneficial, especially if potential clustering of sIgEs cannot be accounted for in the study. The NHANES data provides valuable information on sensitization patterns, but further studies, preferably of longitudinal design, are needed to understand the complex relationships between allergen exposures and development of allergic sensitization and disease.