Allergic airway diseases in a tropical urban environment are driven by dominant mono-specific sensitization against house dust mites

Abstract

Background: Southeast Asian populations are increasingly affected by allergic airway diseases. Etiology and specific causes, however, are still unknown. The aim of this study is therefore to identify allergens and risk factors for the high prevalence of allergic airway disease in the tropical urban environment.

Methods: Symptoms of allergic rhinitis (AR), asthma, and allergic dermatitis were recorded in two independent cohorts of 576 and 7373 ethnic Chinese individuals living in Singapore. Reactivity against common allergens was determined by skin prick tests (SPT); specific immunoglobulin E (sIgE) titers against 12 common allergens, as well as total serum IgE (tIgE), were measured in the smaller cohort.

Results: Immunoglobulin E sensitization was almost exclusively directed against house dust mite (HDM) allergens. More than 80% of individuals were HDM-sIgE positive. Of these, less than 30% also had sIgE for other allergens, and similarly, few of the HDM-sIgE-negative individuals reacted to other allergens. Titers for HDM-sIgE were 8-30 times higher than other non-HDM allergen titers and correlated directly with total serum tIgE levels. Migrants from nontropical countries typically arrived with low or undetectable HDM-sIgE but developed substantial titers in a time-dependent fashion. Importantly, prolonged stay in Singapore also resulted in the manifestation of AR and asthma symptoms, contributing to some of the highest national prevalence rates worldwide.

Conclusion: In a tropical urban environment, the allergic response is dominated by a single allergen class. The mono-specific IgE sensitization against HDM translates into increased prevalence of allergic airway diseases, which now impact a large proportion of the population in Singapore.

Keywords: allergens; asthma; atopy; immunoglobulin E; rhinitis.

Figure 1

Levels of specific immunoglobulin E (IgE) against the 12 common allergens tested in a cohort of 206 Chinese individuals born in Singapore. Allergens are grouped into indoor allergens (house dust mite, pet dander, and cockroach) and outdoor allergens (fungus and pollens). Specific immunoglobulin E (sIgE) titers are expressed as U/ml. The strength of IgE reactivity toward the specific allergens tested is categorized in classes from 0 to 6 according to ImmunoCAP standards. Titers < 0.35 U/ml were considered negative. The species of the allergen source is listed below together with the percentage of individuals positive for sIgE to each allergen tested. The median sIgE titer including minimum (min) and maximum (max) is calculated for reactive individuals. Dermatophagoides pteronyssinus (Der p) or Blomia tropicalis (Blo t).

Figure 2

Association of house dust mite (HDM) sensitization with ‘atopy’ and serum tIgE. Data shown are for Chinese individuals born in Singapore. (A) Percentage of HDM-specific immunoglobulin E (sIgE)-positive and immunoglobulin E (sIgE)-negative individuals. Distribution of individuals is shown based on sIgE titers specific for HDM. Color code refers to the sIgE titer class shown in Fig. 1. Individuals with sIgE titer < 0.35 U/ml were defined as HDM-sIgE negative. (B) Fraction of individuals with sIgE against non-HDM allergens among either HDM-sIgE-positive or HDM-sIgE-negative individuals. The relative fraction is shown for the two groups defined in Fig. 2A. The class of sIgE titer for non-HDM allergens is indicated by the color code. (C) Serum tIgE levels of HDM-sIgE-positive and HDM-sIgE-negative individuals in an extended cohort of 360 Singapore-born Chinese. Serum tIgE was determined by ImmunoCAP ELISA and plotted for HDM-sIgE-negative and HDM-sIgE-positive individuals (Median value indicated). Using a t-test with Welch correction, total immunoglobulin E (IgE) was found to be significantly different between the two groups (P = 6.55 × 10⁻¹⁶) (D) Correlation of tIgE levels with HDM-sIgE levels. The titers of HDM-sIgE were plotted against the serum tIgE. P and r² values for the linear regression are indicated.

Figure 3

Influence of time of exposure to tropical urban environment on house dust mite (HDM) sensitization within the discovery cohort (Table 1). (A) Percentage of HDM-specific immunoglobulin E (sIgE)-positive (titer > 0.35 U/ml) individuals among Singapore residents born in tropical and nontropical countries. (B) tIgE levels stratified by country of birth. tIgE titer for Singapore-born ethnic Chinese and Chinese migrants from China and Malaysia is shown. Median and P-values are indicated. (C) HDM-sIgE levels stratified by country of birth. (D) HDM-sIgE levels in migrants from China stratified by number of years’ residence in Singapore. (E) Distribution of HDM-sIgE levels in migrants from Malaysia stratified by number of years in Singapore.

Figure 4

Influence of time of exposure to tropical urban environment on the prevalence of allergic airway diseases in the prospective validation cohort (Table 1). (A) Percentage of house dust mite (HDM)-sensitized individuals stratified by country of birth. HDM sensitization was determined by skin prick test (SPT) on ethnic Chinese born in Singapore, or on migrants from China or Malaysia. (B) HDM sensitization, allergic rhinitis (AR), asthma, and allergic dermatitis in migrants from China stratified by number of years of residence in Singapore. The percentage of individuals from China with positive SPT or allergic symptoms is shown in reference to the duration of exposure to the tropical urban environment.