Abstract
Background
Among preschool-age children in New York City neighborhoods with high asthma hospitalization rates, we analyzed the associations of total immunoglobulin E (IgE), specific IgE to common indoor allergens, and allergy symptoms with asthma.
Methods
Parents of children in New York City Head Start programs were asked to complete a questionnaire covering demographic factors, health history (including respiratory conditions), lifestyle, and home environment. Children’s serum samples were analyzed for total IgE and specific IgE antibodies to cockroach, dust mite, mouse, and cat allergens by immunoassay. Logistic regression was used to model the association between asthma and IgE, controlling for age, gender, ethnicity/national origin, BMI, parental asthma, smokers in the household, and allergy symptoms (e.g., runny nose, rash).
Results
Among 453 participating children (mean age 4.0 ± 0.5 years), 150 (33%) met our criteria for asthma. In our multivariable logistic regression models, children with asthma were more likely than other children to be sensitized to each allergen, to be sensitized to any of the four allergens (OR=1.6, 95% CI 1.0–2.6), or to be in the highest quartile of total IgE (OR=3.1, 95% CI 1.5–6.4). Allergy symptoms based on questionnaire responses were independently associated with asthma (OR=3.7, 95% CI 2.3–5.9).
Conclusions
Among preschool-aged urban children, asthma was associated with total IgE and sensitization to cat, mouse, cockroach, and dust mite allergens. However, allergy symptoms were more prevalent and more strongly associated with asthma than was any allergen-specific IgE; such symptoms may precede elevated specific IgE or represent a different pathway to asthma.
Keywords: asthma, allergy, IgE, children, Hispanic, indoor allergens
Introduction
Immunoglobulin E (IgE) is the class of antibody that is responsible for mediating hypersensitivity reactions, such as allergic asthma, by binding to high-affinity receptors on the surface of mast cells and basophils and triggering activation of these cells on contact with allergen [1]. Asthma has been associated with both respiratory allergies and total IgE measured in serum [2]. Studies have consistently shown higher IgE levels in asthmatic populations than in non-asthmatic populations [3–12]; however, the relationship between sensitization to specific indoor allergens and asthma in young children, especially those in low-income urban communities, is not well understood [13–16].
Studying asthma in preschool-aged children is challenging in part because symptoms and factors associated with asthma are heterogeneous [17–20]. Not all young children who present with wheeze have asthma later in life. However, those who present with wheeze in early childhood but are asymptomatic as adults are less likely than those who have asthma in adulthood to be sensitized to allergens [21–23]. In addition, children who have severe asthma are likely to continue to have severe asthma in adulthood [24–27]. Therefore, it seems worthwhile to try to identify modifiable factors that may contribute to asthma symptoms in children.
As markers of allergic sensitization, IgE levels may be relevant to this effort [28–31]. However, studies of the relationship between sensitization to specific indoor allergens and asthma have had conflicting results. Some studies have found an association between asthma/wheeze and an increased sum of specific IgEs to inhalant allergens, but not between asthma/wheeze and individual inhalant allergens [32–33]. Simpson et al. showed that the risk of current wheeze increased significantly with increasing IgE to dust mite, cat, and dog, as well as a sum of the three IgEs, but not with total IgE, suggesting that specific IgE may be more useful than total IgE for predicting asthma symptom development [34]. Conflicting results have also been reported regarding the association between asthma severity and sensitization to indoor allergens. Among adults with asthma in Eastern Harlem, those who were sensitized to indoor allergens did not experience significantly higher asthma morbidity than those who were not [35]. However, among children, asthma severity was associated with the level of IgE to dust mite; that finding suggested that specific IgE may be useful in identifying children who are at risk for severe asthma symptoms [5].
Although previous studies have shed some light on the relationship between asthma and sensitization to specific allergens, few have been conducted among high-risk children living in low-income urban areas. In New York City, the association between neighborhood income and asthma hospitalization rates is well established [36]. We therefore investigated the association between sensitization and asthma in a sample of children attending Head Start programs in New York City neighborhoods with high pediatric asthma hospitalization rates.
Methods
Subjects and Recruitment
Head Start is a federally funded program that provides preschool education for low-income children throughout the United States and supportive services for their families. We requested and received permission to recruit at 50 Head Start centers selected, from more than 250 in New York City, based on location in neighborhoods with high pediatric asthma hospitalization rates [36]. Overall, the 50 centers serve about 4000 children per year, and all children in their first year in the Head Start center were eligible for the study. At the centers, English- and Spanish-speaking recruiters presented the study to groups of parents. Written informed consent was obtained from interested parents for their child’s and household’s participation in the study. Monetary compensation was provided to those who participated. The study was approved by the Institutional Review Board of the Columbia University Medical Center.
Questionnaire data
Parents were asked to respond to a questionnaire that asked for a detailed history of their child’s respiratory conditions (questions covered wheezing, difficulty in breathing, and a doctor’s diagnosis of asthma), and information regarding family medical history, home environment, and demographic factors. The questionnaire also addressed parental tobacco use, educational attainment, and employment. Ethnicity was determined through questions about race, Hispanic national origin, and children’s and parents’ birthplaces. We categorized children born in the United States who had at least one parent born in a Spanish-speaking country as having that national origin. The category “other/mixed Hispanic” included children whose parents were born in a Spanish-speaking country other than the Dominican Republic, Mexico, or Puerto Rico, and children whose parents were not born in the same Spanish-speaking country. Children whose race was identified as black, African-American, or of African descent and who were not classified as having Spanish/Latino/Hispanic descent were categorized as “non-Hispanic black.” Children who were neither Hispanic nor non-Hispanic black or whose parents did not provide information about race/ethnicity were categorized as “other/unknown.”
Outcomes
Because the children participating in the study were too young to have a definitive asthma diagnosis and were not provided with physical examinations, children were categorized as having asthma if their parents reported that they had:
A history of physician-diagnosed asthma and any wheezing or difficulty in breathing in the past year, or
Wheezing or difficulty in breathing ≥ 3 times in the past year, or
Any urgent physician, emergency department, or hospital visit because of wheezing or difficulty in breathing
Children were categorized as having allergy symptoms if their parents described them as having had food allergies; runny nose or sneezing caused by house dust, cockroaches, pollens, cats, dogs, rats, mice, or other animals; or other allergy symptoms, such as skin rashes.
Home visit data
Children were weighed on a portable Seca electronic scale and their height was assessed with a portable height board. Age- and sex-specific body mass index (BMI) percentiles were calculated for each child using formulas available from the Centers for Disease Control and Prevention (http://www.cdc.gov/healthyweight/assessing/bmi/childrens_BMI/about_childrens_BMI.html; last accessed May 28, 2009). The children were characterized as underweight or normal (below the 85th percentile), at risk for overweight (85th – 95th percentile), or overweight (above the 95th percentile).
IgE Analysis
The IgE analyses have been described elsewhere [37]. In serum samples from the children, total IgE and specific IgE antibodies against dust mite (Dermatophagoides farinae), cockroach (German cockroach whole body extract), mouse (urinary proteins), and cat (dander) were measured by the ImmunoCAP method (Phadia, Portage, Mich). Children were classified as sensitized if they had specific IgE ≥ 0.35 IU/mL to any of the four allergens tested.
Statistical Analyses
Frequency distributions of gender, presence of smokers in the child’s household (0 vs. ≥1), and body mass index categories by asthma/allergy status (categorization as having neither allergies nor asthma, allergies only, asthma only, or both allergies and asthma) were compared using chi-square tests of statistical significance. Because data (cell counts) were sparse in some categories, Fisher’s Exact Tests were used to evaluate the statistical significance of differences in distribution of national origin and parental history of asthma. An ANOVA F-test was used to compare means of age by asthma status. Logistic regression models were used to analyze the association of asthma with total IgE and specific IgE levels, controlling for age, gender, national origin, home smoking exposure, the child’s allergy status, and parental history of asthma. Total IgE was categorized as quartiles (<125, 126–249, 250–375, and >375 IU/ml). The relationship between asthma and sensitization to one or more of the four specific allergens and asthma was also assessed.
Results
Questionnaire data, anthropometric measurements, and serum samples were obtained for 453 children of mean age 4.0 (SD 0.5) years (Table 1). Boys and girls were equally represented. Almost 88% of the children were of Hispanic ethnicity; children of Mexican ethnicity were the largest single group. A total of 150 children met our criteria for asthma: 102 had a history of physician-diagnosed asthma and any wheezing or difficulty in breathing in the past year; 56 had had wheezing or difficulty in breathing ≥ 3 times in the past year; 129 had an urgent physician, emergency department, or hospital visit because of wheezing or difficulty in breathing; and 123 met more than one criterion. Of the 150 who met the study criteria for asthma, 42 (28%) were sensitized to cockroach, 33 (22%) to dust mite, 21 (14%) to cat, 28 (18.7%) to mouse, and 64 (42.7%) to one or more of the four allergens (Table 1). We found strong associations of asthma/allergy status with gender; national origin; living with smokers; parental history of asthma; total IgE; sensitization to cockroach, dust mite, cat, mouse, and one or more of the four allergens; and BMI (girls only).
Table 1.
Characteristics of participating children by asthma/allergy status
| No asthma or allergy symptoms |
Allergy symptoms only |
Asthma only |
Both Asthma and allergy symptoms |
Total | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| N | %* | N | %* | N | %* | N | %* | N | %* | P-value | |
| N | 179 | 39.5 | 124 | 27.4 | 37 | 8.0 | 113 | 24.9 | 453 | 100 | |
| Mean age in years (SD) | 4.0 | (0.5) | 3.9 | (0.6) | 4.0 | (0.5) | 3.9 | (0.5) | 4.0 | (0.5) | 0.44 |
| Sex | 0.005 | ||||||||||
| Female | 101 | 56.4 | 69 | 55.7 | 18 | 48.7 | 41 | 36.3 | 229 | 50.6 | |
| Male | 78 | 43.6 | 55 | 44.4 | 19 | 51.4 | 72 | 63.7 | 224 | 49.5 | |
| Ethnicity/National Origin | |||||||||||
| Dominican | 36 | 20.1 | 23 | 18.6 | 13 | 35.1 | 23 | 20.4 | 95 | 21.0 | 0.002 |
| Mexican | 91 | 50.8 | 45 | 36.3 | 7 | 18.9 | 22 | 19.5 | 165 | 36.4 | Referent |
| Puerto Rican | 9 | 5.0 | 18 | 14.5 | 2 | 5.4 | 26 | 23.0 | 55 | 12.1 | <0.0001 |
| Other/Mixed Hispanic | 32 | 17.9 | 22 | 17.7 | 11 | 29.7 | 17 | 15.0 | 82 | 18.1 | 0.01 |
| Non-Hispanic Black | 9 | 5.0 | 14 | 11.3 | 3 | 8.1 | 18 | 15.9 | 44 | 9.7 | <0.0001 |
| Other/Unknown | 2 | 1.1 | 2 | 1.6 | 1 | 2.7 | 7 | 6.2 | 12 | 2.7 | 0.0005 |
| Smokers in Household | 0.0008 | ||||||||||
| No | 153 | 85.5 | 90 | 72.6 | 25 | 67.6 | 75 | 66.4 | 343 | 75.7 | |
| Yes | 26 | 14.5 | 34 | 27.4 | 12 | 32.4 | 38 | 33.6 | 110 | 24.3 | |
| Parents with Asthma | |||||||||||
| Neither | 166 | 92.7 | 106 | 85.5 | 27 | 73.0 | 83 | 73.5 | 382 | 84.3 | Referent |
| Mother only | 10 | 5.6 | 11 | 8.9 | 6 | 16.2 | 16 | 14.2 | 43 | 9.5 | 0.02 |
| Father only | 2 | 1.1 | 7 | 5.7 | 3 | 8.1 | 9 | 8.0 | 21 | 4.6 | 0.01 |
| Both | 1 | 0.6 | 0 | 0.0 | 1 | 2.7 | 5 | 4.4 | 7 | 1.6 | 0.01 |
| BMI for Age by Sex- Boys | |||||||||||
| <85th percentile | 39 | 50.0 | 32 | 58.2 | 10 | 52.6 | 45 | 62.5 | 126 | 56.3 | Referent |
| 85th–95th percentile | 19 | 24.4 | 11 | 20.0 | 4 | 21.1 | 15 | 20.8 | 49 | 21.9 | 0.79 |
| >95th percentile | 20 | 25.6 | 12 | 21.8 | 5 | 26.3 | 12 | 16.7 | 49 | 21.9 | 0.46 |
| BMI for Age by Sex- Girls | |||||||||||
| <85th percentile | 64 | 63.4 | 48 | 69.6 | 7 | 38.9 | 21 | 51.2 | 140 | 61.1 | Referent |
| 85th–95th percentile | 12 | 11.9 | 12 | 17.4 | 3 | 16.7 | 10 | 24.4 | 37 | 16.2 | 0.25 0.03 |
| >95th percentile | 25 | 24.8 | 9 | 13.0 | 8 | 44.4 | 10 | 24.4 | 52 | 22.7 | |
| Total IgE (IU/ml) | |||||||||||
| <125 | 135 | 75.4 | 100 | 80.7 | 21 | 56.8 | 66 | 58.4 | 322 | 71.1 | Referent |
| 126–249 | 29 | 16.2 | 13 | 10.5 | 11 | 29.7 | 12 | 10.6 | 65 | 14.4 | 0.02 |
| 250–375 | 6 | 3.4 | 3 | 2.4 | 1 | 2.7 | 11 | 9.7 | 21 | 4.6 | 0.006 |
| >375 | 9 | 5.0 | 8 | 6.5 | 4 | 10.8 | 24 | 21.2 | 45 | 9.9 | <0.0001 |
| Sensitized to | |||||||||||
| Cockroach | 26 | 14.5 | 22 | 17.7 | 9 | 24.3 | 33 | 29.2 | 90 | 19.9 | 0.02 |
| Dust mite | 21 | 11.7 | 11 | 8.9 | 7 | 18.9 | 26 | 23.0 | 65 | 14.4 | 0.009 |
| Cat | 5 | 2.8 | 7 | 5.7 | 3 | 8.1 | 18 | 15.9 | 33 | 7.3 | 0.0004 |
| Mouse | 8 | 4.5 | 10 | 8.1 | 5 | 13.5 | 23 | 20.4 | 46 | 10.2 | 0.0001 |
| One or more of the | |||||||||||
| above | 46 | 25.7 | 36 | 29.0 | 16 | 43.2 | 48 | 42.5 | 146 | 32.2 | 0.009 |
Percents for total Ns are row percents. All others are column percents.
In logistic regression models that included gender, body mass index, national origin, living with smokers, and parental history of asthma, asthma was associated with sensitization to cockroach allergen (odds ratio (OR) = 1.8, 95% confidence interval (CI) 1.1–3.1), dust mite allergen (OR = 2.2, 95% CI 1.2–4.0), cat allergen (OR = 2.8, 95% CI 1.2–6.4), mouse allergen (OR = 2.9, 95% CI 1.4–5.8), any of the four specific allergens (OR = 1.7, 95% CI 1.1–2.6), and the highest quartile of total IgE compared to the lowest (OR = 3.2, 95% CI 1.6–6.5) (Table 2). In models that controlled for allergy symptoms, the relationships of asthma with cockroach, dust mite, cat, mouse, any allergen and total IgE remained about the same. With and without inclusion of the total and specific IgE variables, allergy symptoms were strongly associated with asthma (OR = 3.7, 95% CI 2.3–6.0). In further univariate analysis, specific and total IgE were also associated with urgent doctor visits, emergency department visits, and hospitalizations associated with asthma symptoms (Table 3). In the logistic regression models, stratification on gender produced similar point estimates but wider confidence intervals (Table 4). In the models that included allergy symptoms, the association of asthma with national origin was generally weaker (Appendix Table 1 and Table 2).
Table 2.
Association of asthma with allergen-specific and total IgE and allergy symptoms
| Model 1* | Model 2** | |||
|---|---|---|---|---|
| Exposure variables | OR | 95% CI | OR | 95% CI |
| Sensitized to cockroach | ||||
| No | 1.0 | Referent | 1.0 | Referent |
| Yes | 1.8 | 1.1–3.1 | 1.7 | 1.0–3.0 |
| Sensitized to dust mite | ||||
| No | 1.0 | Referent | 1.0 | Referent |
| Yes | 2.2 | 1.2–4.0 | 2.3 | 1.2–4.2 |
| Sensitized to cat | ||||
| No | 1.0 | Referent | 1.0 | Referent |
| Yes | 2.8 | 1.2–6.4 | 2.6 | 1.1–6.0 |
| Sensitized to mouse | ||||
| No | 1.0 | Referent | 1.0 | Referent |
| Yes | 2.9 | 1.4–5.8 | 2.5 | 1.2–5.1 |
| Sensitized to one or more of four | ||||
| No | 1.0 | Referent | 1.0 | Referent |
| Yes | 1.7 | 1.1–2.6 | 1.6 | 1.0–2.6 |
| Total IgE (IU/ml) | ||||
| <125 | 1.0 | Referent | 1.0 | Referent |
| 126–249 | 1.1 | 0.6–2.0 | 1.4 | 0.7–2.6 |
| 250–375 | 2.5 | 0.9–6.5 | 2.4 | 0.9–6.5 |
| >375 | 3.2 | 1.6–6.5 | 3.1 | 1.5–6.4 |
| Child has allergy symptoms | ||||
| No | 1.0 | Referent | ||
| Yes | 3.7 | 2.3–6.0 | ||
Controlling for age, sex, BMI for age by sex, national origin, number of smokers in the household, and parental asthma.
Controlling for all of the above, plus child has allergy symptoms.
Table 3.
Associations of allergen-specific and total IgE with indicators of asthma severity
| Indicator | Urgent doctor visit | Emergency department visit | Hospitalization overnight | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No | Yes | No | Yes | No | Yes | ||||||||||
| N | % | N | % | P-value | N | % | N | % | P-value | N | % | N | % | P-value | |
| 344 | 75.9 | 109 | 24.1 | 350 | 77.3 | 103 | 22.7 | 398 | 87.9 | 55 | 12.14 | ||||
| Sensitized to cockroach | 0.002 | 0.001 | 0.01 | ||||||||||||
| No | 303 | 88.1 | 76 | 69.7 | 292 | 83.4 | 71 | 68.9 | 326 | 81.9 | 37 | 67.3 | |||
| Yes | 41 | 11.9 | 33 | 30.3 | 58 | 16.6 | 32 | 31.1 | 72 | 18.1 | 18 | 32.7 | |||
| Sensitized to dust mite | 0.003 | 0.003 | 0.004 | ||||||||||||
| No | 304 | 88.4 | 84 | 77.1 | 309 | 88.3 | 79 | 76.7 | 348 | 87.4 | 40 | 72.7 | |||
| Yes | 40 | 11.6 | 25 | 22.9 | 41 | 11.7 | 24 | 23.3 | 50 | 12.6 | 15 | 27.3 | |||
| Sensitized to cat | 0.003 | <0.0001 | 0.0009 | ||||||||||||
| No | 326 | 94.8 | 94 | 86.2 | 334 | 95.4 | 86 | 83.5 | 375 | 94.2 | 45 | 81.8 | |||
| Yes | 18 | 5.2 | 15 | 13.8 | 16 | 4.6 | 17 | 16.5 | 23 | 5.8 | 10 | 18.2 | |||
| Sensitized to | |||||||||||||||
| mouse | <0.0001 | <0.0001 | <0.0001 | ||||||||||||
| No | 322 | 93.6 | 85 | 78.0 | 326 | 93.1 | 81 | 78.6 | 367 | 92.2 | 40 | 72.7 | |||
| Yes | 22 | 6.4 | 24 | 22.0 | 24 | 6.9 | 22 | 21.4 | 31 | 7.8 | 15 | 27.3 | |||
| Sensitized to any of four | 0.001 | 0.0004 | 0.002 | ||||||||||||
| No | 247 | 71.8 | 60 | 55.0 | 252 | 72.0 | 55 | 53.4 | 280 | 70.4 | 27 | 49.1 | |||
| Yes | 97 | 28.2 | 49 | 45.0 | 98 | 28.0 | 48 | 46.6 | 118 | 29.6 | 28 | 50.9 | |||
| Total IgE (IU/ml) | <0.0001 | 0.002 | 0.0006 | ||||||||||||
| <125 | 262 | 76.2 | 60 | 55.0 | 260 | 74.3 | 62 | 60.2 | 290 | 72.9 | 32 | 58.2 | |||
| 126–249 | 50 | 14.5 | 15 | 13.8 | 50 | 14.3 | 15 | 14.6 | 60 | 15.1 | 5 | 9.1 | |||
| 250–375 | 10 | 2.9 | 11 | 10.1 | 15 | 4.3 | 6 | 5.8 | 16 | 4.0 | 5 | 9.1 | |||
| >375 | 22 | 6.4 | 23 | 21.1 | 25 | 7.1 | 20 | 19.4 | 32 | 8.0 | 13 | 23.6 | |||
Table 4.
Odds ratios for the associations of allergen-specific and total IgE with asthma, by gender
| Model 1 | Model 2 | |||
|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | |
| Boys | ||||
| Sensitized to cockroach | 1.5 | 0.7–3.0 | 1.5 | 0.8–3.0 |
| Sensitized to dust mite | 3.6 | 1.5–8.7 | 3.0 | 1.3–6.9 |
| Sensitized to cat | 2.0 | 0.6–6.2 | 2.0 | 0.7–5.9 |
| sensitized to mouse | 2.4 | 0.9–6.1 | 2.5 | 1.0–6.1 |
| Sensitized to one or more of four | 1.9 | 1.0–3.8 | 1.8 | 0.9–3.3 |
| Total IgE (IU/ml) | ||||
| <125 | 1.0 | Referent | 1.0 | Referent |
| 126–249 | 1.1 | 0.5–2.7 | 0.7 | 0.3–1.7 |
| 250–375 | 2.7 | 0.8–9.2 | 2.9 | 0.9–9.4 |
| >375 | 2.8 | 1.0–7.9 | 2.3 | 0.9–6.0 |
| Child has allergy symptoms | 4.1 | 2.1–8.0 | ||
| Girls | ||||
| Sensitized to cockroach | 1.9 | 0.8–4.7 | 2.3 | 1.0–5.4 |
| Sensitized to dust mite | 1.5 | 0.5–3.9 | 1.7 | 0.7–4.4 |
| Sensitized to cat | 2.9 | 0.8–10.6 | 4.2 | 1.2–14.9 |
| sensitized to mouse | 2.7 | 0.8–8.9 | 4.1 | 1.3–12.8 |
| Sensitized to one or more of four | 1.2 | 0.6–2.6 | 1.5 | 0.8–3.2 |
| Total IgE (IU/ml) | ||||
| <125 | 1.0 | Referent | 1.0 | Referent |
| 126–249 | 2.5 | 0.9–7.1 | 2.3 | 0.9–6.3 |
| 250–375 | 1.1 | 0.1–9.5 | 1.0 | 0.1–7.3 |
| >375 | 3.3 | 1.0–10.6 | 5.1 | 1.7–15.9 |
| Child has allergy symptoms | 4.1 | 1.9–8.6 | ||
Controlling for age, sex, BMI for age by sex, national origin, number of smokers in the household, and parental asthma.
Controlling for all of the above, plus child has allergy symptoms.
Appendix Table 1.
Odds ratios (with 95% confidence intervals) for all the variables included in Model 1 (Table 2)
| Exposure variables | Cockroach | Dust mite | Cat | Mouse | Any of Four | Total IgE quartiles | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | |||
| Age in months | 1.0 | 0.9–1.0 | 1.0 | 0.9–1.0 | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 | 1.0 | 0.9–1.0 | 1.0 | 0.9–1.0 | ||
| Sex | ||||||||||||||
| Male | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | ||
| Female | 0.5 | 0.3–0.8 | 0.5 | 0.3–0.8 | 0.5 | 0.3–0.8 | 0.5 | 0.3–0.8 | 0.5 | 0.3–0.8 | 0.5 | 0.3–0.8 | ||
| BMI for age by sex | ||||||||||||||
| <85th percentile | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | ||
| 85th–95th percentile | 1.2 | 0.9–1.6 | 1.2 | 0.9–1.6 | 1.1 | 0.8–1.5 | 1.1 | 0.9–1.5 | 1.2 | 0.9–1.5 | 1.1 | 0.9–1.5 | ||
| >95th percentile | 1.1 | 0.9–1.3 | 1.1 | 0.9–1.3 | 1.1 | 0.9–1.3 | 1.1 | 0.9–1.3 | 1.1 | 0.9–1.3 | 1.1 | 0.9–1.3 | ||
| National Origin | ||||||||||||||
| Mexican | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | ||
| Dominican | 2.8 | 1.5–5.1 | 2.8 | 1.5–5.0 | 2.7 | 1.5–4.9 | 2.7 | 1.5–5.0 | 2.7 | 1.5–4.9 | 2.6 | 1.4–4.9 | ||
| Puerto Rican | 3.3 | 1.5–7.0 | 3.2 | 1.5–6.9 | 2.6 | 1.2–5.7 | 3.5 | 1.6–7.4 | 3.1 | 1.4–6.7 | 3.2 | 1.5–6.9 | ||
| Other/Mixed Hispanic | 2.5 | 1.3–4.6 | 2.4 | 1.3–4.5 | 2.4 | 1.3–4.5 | 2.3 | 1.2–4.4 | 2.3 | 1.2–4.4 | 2.5 | 1.3–4.7 | ||
| Non-Hispanic Black | 3.7 | 1.8–7.9 | 3.5 | 1.7–7.5 | 3.2 | 1.5–6.9 | 3.4 | 1.6–7.2 | 3.6 | 1.7–7.7 | 3.1 | 1.4–6.7 | ||
| Other/Unknown | 9.7 | 2.6–36.1 | 8.8 | 2.3–32.9 | 8.1 | 2.1–30.8 | 8.7 | 2.3–33.1 | 9.2 | 2.4–34.3 | 8.8 | 2.3–33.7 | ||
| Smokers in household | ||||||||||||||
| No | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | ||
| Yes | 1.6 | 1.0–2.6 | 1.6 | 1.0–2.6 | 1.6 | 1.0–2.6 | 1.5 | 0.9–2.5 | 1.6 | 1.0–2.6 | 1.6 | 1.0–2.7 | ||
| Parents with Asthma | ||||||||||||||
| Neither | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | ||
| Mother only | 2.2 | 1.1–4.3 | 2.2 | 1.1–4.4 | 2.3 | 1.1–4.6 | 2.1 | 1.0–4.2 | 2.1 | 1.1–4.3 | 2.0 | 1.0–4.0 | ||
| Father only | 2.4 | 0.9–6.3 | 2.5 | 1.0–6.5 | 2.9 | 1.1–7.7 | 2.6 | 1.0–6.7 | 2.5 | 0.9–6.5 | 2.5 | 0.9–6.6 | ||
| Both | 7.2 | 0.8–65.6 | 7.7 | 0.8–71.2 | 8.3 | 0.9–76.8 | 5.4 | 0.6–50.0 | 6.7 | 0.7–61.1 | 4.2 | 0.5–39.8 | ||
| Sensitized to cockroach | ||||||||||||||
| No | 1.0 | Referent | ||||||||||||
| Yes | 1.8 | 1.1–3.1 | ||||||||||||
| Sensitized to dust mite | ||||||||||||||
| No | 1.0 | Referent | ||||||||||||
| Yes | 2.2 | 1.2–4.0 | ||||||||||||
| Sensitized to cat | ||||||||||||||
| No | 1.0 | Referent | ||||||||||||
| Yes | 2.8 | 1.2–6.4 | ||||||||||||
| Sensitized to mouse | ||||||||||||||
| No | 1.0 | Referent | ||||||||||||
| Yes | 2.9 | 1.4–5.8 | ||||||||||||
| Sensitized to any of four | ||||||||||||||
| No | 1.0 | Referent | ||||||||||||
| Yes | 1.7 | 1.1–2.6 | ||||||||||||
| Total IgE (IU/ml) | ||||||||||||||
| <125 | 1.0 | Referent | ||||||||||||
| 126–249 | 1.1 | 0.6–2.0 | ||||||||||||
| 250–375 | 2.5 | 0.9–6.5 | ||||||||||||
| >375 | 3.2 | 1.6–6.5 | ||||||||||||
Appendix Table 2.
Odds ratios (with 95% confidence intervals) for all the variables included in Model 2 (Table 2)
| Exposure variables | Cockroach | Dust mite | Cat | Mouse | ||||
|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | OR | 95% CI | OR | 95% CI | |
| Age in months | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 |
| Sex | ||||||||
| Male | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Female | 0.6 | 0.4–0.9 | 0.5 | 0.3–0.9 | 0.5 | 0.3–0.8 | 0.5 | 1.0–1.0 |
| BMI for age by sex | ||||||||
| <85th percentile | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| 85th–95th percentile | 1.2 | 0.9–1.6 | 1.2 | 0.9–1.6 | 1.1 | 0.8–1.5 | 1.1 | 0.8–1.5 |
| >95th percentile | 1.1 | 0.9–1.4 | 1.1 | 0.9–1.4 | 1.1 | 0.9–1.4 | 1.1 | 1.0–1.4 |
| National Origin | ||||||||
| Mexican | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Dominican | 2.8 | 1.5–5.2 | 2.8 | 1.5–5.2 | 2.7 | 1.4–5.0 | 2.7 | 1.5–5.1 |
| Puerto Rican | 2.2 | 1.0–4.9 | 2.2 | 1.0–4.9 | 1.9 | 0.8–4.1 | 2.4 | 1.1–5.2 |
| Other/Mixed Hispanic | 2.4 | 1.2–4.6 | 2.4 | 1.2–4.6 | 2.3 | 1.2–4.5 | 2.3 | 1.2–4.4 |
| Non-Hispanic Black | 2.9 | 1.3–6.2 | 2.7 | 1.2–5.8 | 2.5 | 1.1–5.5 | 2.6 | 1.2–5.7 |
| Other/Unknown | 7.9 | 2.0–31.7 | 7.1 | 1.8–28.1 | 6.8 | 1.6–27.7 | 7.2 | 1.8–29.2 |
| Smokers in household | ||||||||
| No | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Yes | 1.5 | 0.9–2.5 | 1.5 | 0.9–2.5 | 1.5 | 0.9–2.5 | 1.5 | 0.9–2.4 |
| Parents with Asthma | ||||||||
| Neither | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Mother only | 2.1 | 1.0–4.2 | 2.1 | 1.0–4.3 | 2.2 | 1.1–4.5 | 2.0 | 1.0–4.1 |
| Father only | 2.0 | 0.7–5.5 | 2.1 | 0.8–5.7 | 2.5 | 0.9–6.7 | 2.2 | 0.8–5.9 |
| Both | 9.1 | 0.9–90.9 | 10.5 | 1.0–107.9 | 11.1 | 1.1–113.5 | 7.2 | 0.7–70.7 |
| Child has allergy symptoms | ||||||||
| No | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Yes | 3.6 | 2.2–5.9 | 3.8 | 2.3–6.1 | 3.6 | 2.2–5.8 | 3.5 | 2.2–5.7 |
| Sensitized to cockroach | ||||||||
| No | 1.0 | Referent | ||||||
| Yes | 1.7 | 1.0–3.0 | ||||||
| Sensitized to dust mite | ||||||||
| No | 1.0 | Referent | ||||||
| Yes | 2.3 | 1.2–4.2 | ||||||
| Sensitized to cat | ||||||||
| No | 1.0 | Referent | ||||||
| Yes | 2.6 | 1.1–6.0 | ||||||
| Sensitized to mouse | ||||||||
| No | 1.0 | Referent | ||||||
| Yes | 2.5 | 1.2–5.1 | ||||||
| Sensitized to any of four | ||||||||
| No | ||||||||
| Yes | ||||||||
| Total IgE (IU/ml) | ||||||||
| <125 | ||||||||
| 126–249 | ||||||||
| 250–375 | ||||||||
| >375 | ||||||||
| Any of four | Total IgE Quartiles | None | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | OR | 95% CI | OR | 95% CI | |
| Age in months | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 | 1.0 | 1.0–1.0 |
| Sex | ||||||
| Male | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Female | 0.6 | 0.4–0.9 | 0.6 | 0.4–0.9 | 0.5 | 0.3–0.8 |
| BMI for age by sex | ||||||
| <85th percentile | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| 85th–95th percentile | 1.1 | 0.9–1.5 | 1.1 | 0.8–1.5 | 1.2 | 0.9–1.6 |
| >95th percentile | 1.1 | 0.9–1.4 | 1.2 | 1.0–1.4 | 1.1 | 1.0–1.4 |
| National Origin | ||||||
| Mexican | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Dominican | 2.7 | 1.5–5.1 | 2.6 | 1.4–4.9 | 2.7 | 1.4–5.0 |
| Puerto Rican | 2.2 | 1.0–4.7 | 2.2 | 1.0–4.9 | 2.1 | 1.0–4.5 |
| Other/Mixed Hispanic | 2.3 | 1.2–4.4 | 2.4 | 1.2–4.6 | 2.4 | 1.2–4.5 |
| Non-Hispanic Black | 2.8 | 1.3–6.0 | 2.4 | 1.1–5.3 | 2.7 | 1.3–5.9 |
| Other/Unknown | 7.5 | 1.9–29.8 | 6.9 | 1.7–28.5 | 7.0 | 1.8–28.1 |
| Smokers in household | ||||||
| No | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Yes | 1.5 | 0.9–2.5 | 1.5 | 0.9–2.5 | 1.5 | 0.9–2.6 |
| Parents with Asthma | ||||||
| Neither | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Mother only | 2.0 | 1.0–4.2 | 1.9 | 0.9–3.9 | 2.1 | 1.0–4.3 |
| Father only | 2.1 | 0.8–5.7 | 2.1 | 0.8–5.7 | 2.3 | 0.9–6.4 |
| Both | 8.1 | 0.8–78.9 | 5.8 | 0.6–59.5 | 10.4 | 1.1–102.7 |
| Child has allergy symptoms | ||||||
| No | 1.0 | Referent | 1.0 | Referent | 1.0 | Referent |
| Yes | 3.7 | 2.3–5.9 | 3.7 | 2.2–6.0 | 3.7 | 2.3–6.0 |
| Sensitized to cockroach | ||||||
| No | ||||||
| Yes | ||||||
| Sensitized to dust mite | ||||||
| No | ||||||
| Yes | ||||||
| Sensitized to cat | ||||||
| No | ||||||
| Yes | ||||||
| Sensitized to mouse | ||||||
| No | ||||||
| Yes | ||||||
| Sensitized to any of four | ||||||
| No | 1.0 | Referent | ||||
| Yes | 1.6 | 1.0–2.6 | ||||
| Total IgE (IU/ml) | ||||||
| <125 | 1.0 | Referent | ||||
| 126–249 | 1.4 | 0.7–2.6 | ||||
| 250–375 | 2.4 | 0.9–6.5 | ||||
| >375 | 3.1 | 1.5–6.4 | ||||
Discussion
Among study participants living in New York City neighborhoods with high asthma hospitalization rates, we found that children specifically sensitized to cockroach, dust mite, cat, or mouse allergens were more likely to have asthma symptoms and to require medical care for those symptoms than children who were not sensitized. Consistent with previous research [3–12], children in the highest quartile of total IgE were three times as likely to have asthma as children in the lowest quartile. Like other studies, ours found that children with asthma were more likely than those without asthma to live with smokers and to have parents with asthma [38–39]. Our study also showed that allergy symptoms were significantly associated with asthma, even in models that included IgE. These findings suggest that serum IgE may not have accounted for all the factors that triggered the allergy symptoms [40, 41]. Because IgE levels usually peak between the ages of 8 and 12 years, the children may have been too young at the time of measurement for IgE to be a marker of all of the sensitizations that they would develop [3, 10]. Or perhaps their symptoms were triggered by irritants or infectious agents as well as allergens. In any case, IgE and allergy symptoms were independently associated with asthma.
The children in our study were predominantly of Hispanic origin, and the relationship between asthma/allergy status and non-Mexican national origin was highly significant. Mexican families that participated in our study are part of a recent wave of immigration to New York City [42]. Genetic research has suggested that some of the variability in the association of Hispanic ethnicity with asthma is due to differences in ancestry [43]. However, we accounted for family history of asthma in all our models, and other studies have shown that asthma prevalence is higher among Mexicans living in the United States than among Mexicans living in Mexico [44–45]. Those observations seem consistent with the findings of the ISAAC Phase II Study Group, regarding the associations of asthma and atopy with economic development at the population level [46]. In that study of 8–12-year-old children, the association between current wheeze and skin test reactivity, country by country, was directly correlated with gross national income. Taken together, the studies implicate some aspect of the environment associated with modernization, rather than genetics, as playing a role in the relationship between sensitization and asthma.
Including allergy symptoms in the models weakened the association of asthma with national origin, although, with one exception, it remained statistically significant. Including allergy symptoms also weakened the association of asthma with parental asthma, except among the (seven) children who had two affected parents. The associations of asthma with national origin and with having one affected parent may have been mediated by allergy symptoms independent of IgE. Temporally, nationality and the asthma status of parents must precede the development of both allergy symptoms and asthma in the child, and allergy symptoms may be on the causal pathway between family background and asthma.
Although both cockroach and dust mite sensitization were more prevalent than cat or mouse sensitization, they were less strongly associated with asthma in both the univariate analyses and the logistic regression models. Similarly, Simpson et al found that both dog and cat IgEs were more strongly related to wheeze than dust mite IgE [34]. Mammalian allergens or the antibody response they stimulate may differ from insect allergens or IgE against insect allergens in propensity to cause symptoms in the lung.
One of the limitations of our study is that we categorized children’s asthma status on the basis of questionnaire data alone. It is difficult to confirm an asthma diagnosis in preschool-aged children because many children stop wheezing as they grow older, and because relatively few can perform spirometric maneuvers consistently before the age of 6 years. In the absence of a gold standard for diagnosis, questionnaire data are generally accepted for the purpose of distinguishing children at high risk for asthma from others in population studies [39]. The criteria we used for baseline categorization of asthma are commonly used for preschool-aged children and therefore seemed reasonable for studying factors associated with asthma in this population. Moreover, the conditions that met our criteria represent a significant burden on the children who experience them and their families, whether or not they are considered asthma. The associations of specific and total IgE with urgent doctor visits, emergency department visits, and hospitalization that we observed suggest that IgE is relevant to asthma as a public health issue.
Another limitation is that we based our serologic assessment of atopic potential on a one-time measurement of total and specific IgE at mean age 4 years. We hope to analyze changes in those markers over time in a subset of the study participants.
Another limitation of the study is possible selection bias. We recruited parents in Head Start centers and offered them monetary incentives for participation. Parents who consented may also have been more likely than other Head Start parents to have a child with asthma. However, selection factors are unlikely to have influenced our results because the participants were enrolled independent of exposure status, and the same inclusion criteria were used for all participants. We recruited families of children enrolled in the Head Start program in the hope of overcoming the barriers associated with studying asthma in preschool-aged children without introducing bias. A study of non-inner city Head Start children noted that outside the Head Start population, preschool-aged children from low-income families are difficult to study; because few attend school and many lack access to care, they cannot be recruited through school or health care databases [47].
Our findings in our Head Start sample may not be generalizable to all preschool-age children, or to low-income children who are not enrolled in preschool, but given the high prevalence of asthma that we observed, we believe that our sample may be representative of the children in the communities most burdened by asthma.
Some [5, 34], but not all [32, 35] previous studies in industrialized countries have found that specific IgE was associated with asthma symptoms. For example, a Finnish study found no significant association between asthma and specific IgEs; however, sensitization to individual inhalant allergens was very rare and the sample size was very small [32]. Our findings are consistent with those of Simpson et al. [34], but we analyzed sensitization to specific allergen as a categorical rather than a continuous variable, and we tested for cockroach allergen instead of dog allergen because cockroach exposure is more common among low-income urban children and very few of the children in our study had lived with a dog [15].
Overall, we found that among preschool-aged children in low-income urban communities in New York City, those with high levels of total IgE or those with elevated IgE to cockroach, dust mite, cat, or mouse were more likely to have asthma as we defined it than other children. We also found a strong association of allergy symptoms with asthma. These findings are consistent with those of other studies. However, more than 25% of children not identified as having either asthma or allergies had detectable IgE to at least one of the four allergens, and most of the children with asthma were sensitized to none of them.
Experts warn that IgE responses should be evaluated in the context of symptoms [48]. However, the pathways to asthma need to be better understood. Prospective studies are needed to explore those pathways. If such studies find that sensitization precedes symptom development, we may derive insight from them about how to identify children who might develop asthma symptoms, and thus reduce asthma morbidity and mortality through IgE analysis. If our findings are confirmed by further research, children who are at an increased risk of developing asthma can be identified through testing as candidates for new treatments, perhaps including IgE-directed treatments or allergen avoidance, as primary prevention of asthma [49]. In any case, a better understanding of how IgE and allergy symptoms relate to asthma can help us reduce the burden of asthma among children in the United States.
Acknowledgments
We thank the field team for their hard work in collecting the data for this study. This study was supported by grants from the NHLBI (HL068236) and NIEHS P30 ES 009.
Footnotes
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