Unveiling four sensitization patterns among sensitized U.S. participants: Associations with allergic disease outcomes

Background: Cosensitization to multiple allergens may play an important role in the development and clinical expression of allergic diseases. This study aimed to characterize multidimensional patterns of allergen sensitization and their cross-sectional associations with allergic diseases among participants who were sensitized in the U.S. National Health and Nutrition Examination Survey (NHANES) by using allergen-specific immunoglobulin E (IgE) data from NHANES 2005-2006. Methods: In this cross-sectional analysis of participants with at least one positive allergen-specific IgE test, exploratory factor analysis and partitioning around medoids clustering were used to identify latent allergen factors and classify individuals into distinct sensitization patterns. Logistic regression, adjusted for sex, age, race/ethnicity, questionnaire-defined overweight, and household income, evaluated associations between clusters and self-reported allergic diseases. Results: Among 3512 participants who were sensitized, seven allergen factors were identified, and four clusters were defined: limited-sensitization (cluster 1), pollen-enriched (cluster 2), mite-enriched (cluster 3), and fungus-enriched (cluster 4). Notable differences in demographics and in the prevalence of allergic diseases were observed across clusters. Relative to cluster 1, cluster 2 had the highest odds of allergic rhinitis (odds ratio [OR] 2.04 [95% confidence interval {CI}, 1.69-2.48]), whereas cluster 3 had the highest odds of chronic rash (OR 1.58 [95% CI, 1.17-2.09]) and cluster 4 showed the greatest odds of asthma (OR 3.44 [95% CI, 2.68-4.40]). For eczema, clusters 3 and 4 showed comparable elevated odds (OR 1.63 [95% CI, 1.19-2.21] and OR 1.64 [95% CI, 1.14-2.32], respectively). After adjustment for confounders, associations for rhinitis, asthma, and chronic rash were essentially unchanged, whereas the eczema association persisted for cluster 3 (adjusted OR 1.61 [95% CI, 1.16-2.21]) but attenuated for cluster 4 (adjusted OR 1.39 [95% CI, 1.10-2.00]). Conclusion: The participants who were sensitized could be grouped into four distinct sensitization patterns differentially associated with asthma, rhinitis, eczema, and chronic rash. These patterns may help generate hypotheses for future clinical stratification and more tailored management research.