Association between IgE levels and asthmaseverity among African American, Mexican,and Puerto Rican patients with asthma

Mariam Naqvi, BA,a Shweta Choudhry, PhD, MSc,a Hui-Ju Tsai, PhD,a Shannon Thyne,

MD,a Daniel Navarro, MD,a Sylvette Nazario, MD,b Jose R. Rodriguez-Santana, MD,c

Jesus Casal, MD,b Alfonso Torres, MD,b Rocio Chapela, MD,d H. Geoffrey Watson, MD,e

Kelley Meade, MD,f William Rodriguez-Cintron, MD,b Michael LeNoir, MD,g Pedro C.

Avila, MD,h and Esteban Gonzalez Burchard, MD, MPHa San Francisco and Oakland, Calif,

San Juan, Puerto Rico, Mexico City, Mexico, and Evanston, Ill

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Background: High levels of IgE are associated with asthma.

Whether higher levels of IgE are associated with more severe

asthma is still unclear.

Objective: To determine whether IgE is associated with asthma

severity among Latino and African American subjects with

asthma.

Methods: We assessed lung function and asthma severity

among African American, Mexican, and Puerto Rican

patients with asthma with high IgE levels ($100 IU/mL;

n 5 492) and compared these values to those of patients

with asthma with low IgE levels (<100 IU/mL; n 5 247).

We also examined IgE as a continuous variable among these

groups.

Results: Patients with asthma with high IgE had a lower mean

FEV1 (87.6 6 17.1, percent of predicted) than patients with

asthma with low IgE (91.5 6 17.0; P 5 .031). Regardless of race

and ethnicity, baseline FEV1, forced expiratory flow, and FEV1/

forced vital capacity were lower among subjects with high IgE

than among subjects with low IgE (P 5 .031, P < .0001, P 5

.0001, respectively). In addition, 54.7% of patients with asthma

with high IgE had been previously hospitalized, compared with

44.1% of patients with asthma with low IgE (odds ratio, 1.33;

95% CI, 1.04-1.71).

Conclusion: Higher IgE is associated with lower baseline lung

function and more severe asthma among these populations.

Clinical implications: Among patients with asthma from 3

ethnically distinct groups, total IgE levels are inversely

correlated with baseline lung function and asthma severity.

(J Allergy Clin Immunol 2007;120:137-43.)

From athe University of California, San Francisco; bthe San Juan Veterans

Affairs Medical Center, University of Puerto Rico School of Medicine;cthe Pediatric Pulmonary Program of San Juan; dInstituto Nacional de Enfer-

medades Respiratorias, Mexico City; ethe James A. Watson Wellness

Center, Oakland; fthe Children’s Hospital and Research Institute, Oakland;gBay Area Pediatrics, Oakland; and hNorthwestern University, Evanston.

Supported by the National Institutes of Health (R01 HL078885, K23

HL04464, HL07185, GM61390, American Lung Association of California,

Robert Wood Johnson Amos Medical Faculty Development Award,

National Center for Minority Health Disparities Health Disparities Scholar,

Extramural Clinical Research Loan Repayment Program for Individuals

from Disadvantaged Backgrounds, 2001-2003, to E.G.B.), (HL51823,

HL074204, 3M01RR000083-38S30488, HL56443, and HL51831 to the

Asthma Clinical Research Network), an American Thoracic Society Break-

through Opportunities in Lung Disease grant (ATS-05-078) and a Tobacco-

Related Disease Research Program New Investigator Award (15KT-0008)

to S.C., the American Lung Association of California (Research Training

Fellowship to H.-J.T.), San Francisco General Hospital General Clinical Re-

search Center M01RR00083-41, U01-HL 65899, University of California,

Key words: Asthma, IgE, African Americans, Mexicans, PuertoRicans, allergy

IgE is an antibody subclass implicated in airwayinflammation and allergic reactions. High levels of IgEare associated with asthma in both adults and children.1-5

IgE also may play a role in modulating the severity ofasthma, because previous studies have found associationsbetween high IgE levels and greater asthma severity,6-9

airway hyperresponsiveness,10 and lower baseline lungfunction.11

In 1989, Burrows et al3 demonstrated an associationbetween high total serum IgE and asthma prevalence, in-dependent of skin test reactivity to common allergens, ina study population of 2657 children and adults. Sincethen, several reports have suggested a relation betweenIgE level and asthma severity. In a study conducted byde Marco et al,12 IgE was a strong predictor of moder-ate-to-severe asthma among 856 European adult patientswith asthma. In The Epidemiology and Natural Historyof Asthma: Outcomes and Treatment Regimens (TENOR)study, higher total IgE was associated with the degree ofasthma severity among younger subjects with difficult-to-treat or severe asthma.7 In fact, therapeutic monoclonalanti-IgE antibodies have been shown to reduce exacerba-tions and steroid requirements in patients with allergy and

San Francisco-Children’s Hospital of Oakland Pediatric Clinical Research

Center (M01 RR01271), Oakland, Calif, Sandler Center for Basic Research

in Asthma, and the Sandler Family Supporting Foundation, Ernest S. Bazley

Grant to Northwestern University.

Disclosure of potential conflict of interest: M. LeNoir has consulting arrange-

ments with GlaxoSmithKline and is on the speakers’ bureau for

GlaxoSmithKline, Aventis, and Alocon. P. C. Avila has received grant sup-

port from Genentech and Novartis. The rest of the authors have declared that

they have no conflict of interest.

Received for publication September 27, 2006; revised February 10, 2007;

accepted for publication February 19, 2007.

Available online May 11, 2007.

Reprint requests: Esteban Gonzlez Burchard, MD, MPH, University of Califor-

nia, San Francisco, San Francisco, CA 94143-2911. E-mail: esteban@

sfgh.ucsf.edu.

0091-6749/$32.00

� 2007 American Academy of Allergy, Asthma & Immunology

doi:10.1016/j.jaci.2007.02.045

137

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Abbreviations usedANCOVA: Analysis of covariance

BMI: Body mass index

ETS: Environmental tobacco smoke

FEF25-75: Forced expiratory flow at 25% to 75% of forced

vital capacity

FVC: Forced vital capacity

GALA: Genetics of Asthma in Latino Americans

ICU: Intensive care unit

MFI: Median family income

OR: Odds ratio

SAGE: Study of African Americans, Asthma, Genes

and Environments

SES: Socioeconomic status

asthma;13-15 however, the underlying mechanism behindthe relation between IgE and asthma is not yet clearly un-derstood. Identifying clinical differences between subjectswith asthma with high and low IgE levels may help to clar-ify the regulatory mechanisms that account for the under-lying pathogenesis of asthma and high IgE.

IgE levels have also been shown to vary among differentethnic groups. In a study of 569 African American andEuropean American children in suburban Detroit, AfricanAmerican children had the higher IgE levels.11 Asthmaprevalence and severity vary significantly among ethnicgroups. Although asthma affects 5% to 7% of the US pop-ulation,16 a disproportionate number of those with asthmaare ethnic minorities, particularly African Americans andPuerto Ricans, who also have the highest morbidity andmortality rates from asthma in the United States.11,17-22

The role of IgE in the pathogenesis of asthma and in mod-ulating its severity still remains unknown, particularly inthose minority populations most affected by the disease.

Here, we compare and contrast clinical characteristicsamong 739 adults and children with asthma with high IgElevels (�100 IU/mL) and low IgE levels (<100 IU/mL) ofAfrican American, Mexican, and Puerto Rican ethnicity.Mexicans and Puerto Ricans with asthma were recruited asa part of the Genetics of Asthma in Latino Americans(GALA) study, a comprehensive study initiated to under-stand better the clinical, genetic, and environmentaldifferences in asthma severity among these ethnic groups.African Americans with asthma were recruited as partof the Study of African Americans, Asthma, Genes andEnvironments (SAGE), an ongoing case-control study ofgenetic and environmental factors associated with asthmaamong African Americans, who, like Puerto Ricans, havedisproportionately high asthma prevalence, morbidity,and mortality in the United States.23,24

METHODS

Study participants

Study participants were from the following ethnic groups: Puerto

Rican, Mexican, and African American ethnicity. As part of the

GALA study, Mexican subjects with asthma were recruited from the

San Francisco Bay Area, California and Mexico City, Mexico, and

Puerto Rican subjects with asthma were recruited from New York

City and Puerto Rico.25 African Americans with asthma were re-

cruited from the San Francisco–Bay Area as part of SAGE. All

subjects with asthma were recruited from community clinics and

hospitals, and recruitment was standardized across all centers.

Eligible subjects were between the ages of 8 and 40 years, had phy-

sician-diagnosed asthma or had greater than 12% bronchodilator

responsiveness, and had experienced 2 or more episodes of asthma

symptoms (wheezing, coughing, and/or shortness of breath) in the

previous 2 years. Subjects were enrolled into the study only if both

biological parents and all biological grandparents were identified as

Puerto Rican (for the New York City and Puerto Rico sites), Mexican

(for the San Francisco and Mexico City, Mexico, sites), or African

American (for the San Francisco site). Ethnicity was self-reported

using standardized questions. Physicians who were bilingual and bi-

cultural and who specialized in asthma were present at all interviews.

Local institutional review boards approved all studies, and all sub-

jects provided written, age-appropriate informed consent or assent.

Asthma questionnaire

Trained interviewers administered a modified version of the 1978

American Thoracic Society–Division of Lung Diseases epidemiol-

ogy questionnaire,26 which gathers comprehensive information re-

lated to medical and social history, environmental exposures, and

asthma symptoms. Socioeconomic information was available for

the San Francisco site and was determined using the Federal

Financial Institutions Examination Council’s Geocoding/Mapping

System for subjects with complete street addresses. To assign socio-

economic status, we used the Federal Financial Institutions Examina-

tion Council’s Geocoding/Mapping System to classify subjects into

1 of 4 US Census 2000 tract income levels: low, moderate, middle,

and upper. These categories were based on the median family house-

hold income of the census tract for that year. Classifications are based

on the census tract’s median family income (MFI), divided by the me-

dian family income of the metropolitan area in which the tract is

located, or MFI %. If the MFI % < 50%, then the income level is

low. If the MFI %�50% and <80%, then the income level is moder-

ate. If the MFI %�80% and <120%, then the income level is middle.

If the MFI % �120%, then the income level is upper.27

The level of asthma severity was determined by a global severity

classification that used information gathered from questionnaire and

spirometry data. All subjects were classified as having either mild or

moderate-to-severe asthma on the basis of 4 criteria:

1. Use of only as-needed albuterol

2. Presence of daily asthma symptoms for 3 or more months of

the previous year, regardless of medications used

3. Presence of nocturnal asthma symptoms >1 night per week

for 3 or more months of the previous year

4. FEV1 �80% of race-corrected predicted (measured at the

study visit)

Subjects were classified as mild if they met criterion 1 and no

others and were classified as moderate-to-severe if they met any of

criteria 2, 3, or 4, regardless of whether they met criterion 1. Subjects

who did not meet any of the criteria were not included. Patients

classified as mild in this study correspond to the National Asthma

Education and Prevention Program classification of mild intermittent

asthma, and those classified as moderate-to-severe fit into the mild,

moderate, and severe-persistent classifications.

IgE measurements

Total plasma IgE was measured in duplicate for all 739 subjects

with asthma by using Uni-Cap technology (Pharmacia, Kalamazoo,

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Mich). Subjects were classified as having high IgE if their total

IgE level was greater than or equal to 100 IU/mL. Subjects were

classified as having low IgE if their total IgE level was less than

100 IU/mL.

Pulmonary function tests

Spirometry was conducted on all patients according to American

Thoracic Society standards.28 Subjects with asthma were instructed

to withhold their bronchodilator medications for at least 8 hours

before pulmonary function tests. After initial spirometry, albuterol

was administered through a spacer device from a standard metered

dose inhaler: 180 mg (2 puffs) for subjects <16 years old and

360 mg (4 puffs) for subjects �16 years old. Repeat spirometry

was then performed 15 minutes after albuterol administration. Pulmo-

nary function tests are expressed as a percentage predicted by using

age- and race-adjusted prediction equations.29 Bronchodilator re-

sponsiveness (D FEV1) to albuterol is reported as percent change in

FEV1 after albuterol administration (post-FEV1 in liters minus pre-

FEV1 in liters, times 100, divided by pre-FEV1 in liters).

Statistical analysis

To investigate the relation between IgE and asthma severity, we

evaluated several indicators of asthma severity, including normalized

baseline lung function tests (FEV1, FEV1/forced vital capacity

[FVC], forced expiratory flow at 25% to 75% of forced vital capacity

[FEF25-75]); drug responsiveness (D FEV1, D FEV1/FVC, D FEF25-75);

asthma severity level (moderate-to-severe vs mild); daily symp-

toms (binary); nocturnal symptoms (binary); wheezing (binary);

chest tightness (binary); use of controller medication (single binary

variable for use of any of the following: steroids, long-acting b2-

agonists, leukotriene antagonists, theophylline, or cromolyn sodium);

steroid medication (binary); allergic reaction to pets, mold, and dust

(3 binary variables: 1 5 runny or stuffy nose, shortness of breath,

chest tightness, coughing, or wheezing after exposure, 0 5 no reac-

tion); previous hospitalization (binary); intensive care unit (ICU)

visits (binary, 1 5 has had previous visit to ICU, 0 5 has not had visit

to ICU); and previous intubation (binary). Environmental tobacco

smoke (ETS) exposure was available for subjects under age 13 years.

ETS exposure was determined to be present if 1 or both parents or any

other person in the household reported smoking during the first 2

years of the life of a child with asthma and absent if the answer

was no. Besides lung function tests and severity levels, these varia-

bles were derived from yes/no questions from the standardized

questionnaire.

For continuous variables, an ANOVA and an analysis of covari-

ance (ANCOVA) were performed to examine differences in clinical

characteristics of asthma severity between subjects with asthma with

high IgE and low IgE levels overall, within each ethnic group, and for

the subset of all subjects <18 years. IgE was entered into the model as

a binary variable (15 IgE � 100 IU/mL; 0 5 IgE < 100 IU/mL).

Covariates in these models included age, sex, race, socioeconomic

status (SES), log-transformed body mass index (BMI), and age at

disease onset. For binary variables, logistic regression was performed

including race, age, sex, BMI, and age at disease onset as covariates in

the model. For the subset of subjects under age 18, sex, race, SES,

log-transformed BMI, and age at disease onset were included as

covariates.

Last, we tested for associations between IgE and indicators of

asthma severity by entering IgE as a log-transformed continuous

variable into logistic regression models for binary outcomes and

multiple linear regression models for continuous outcomes. P values

expressed for continuous variables are from ANCOVAs unless spe-

cifically noted. STATA V.8 statistical analysis software was used

for this analysis (STATA, College Station, Tex).

RESULTS

Subject characteristics

Overall characteristics for the complete GALA andSAGE cohorts are described elsewhere (Naqvi M, et al,unpublished data, 2005).17,25 In the present analysis, weanalyzed a total of 739 patients with asthma (492 withhigh IgE and 247 with low IgE) who had complete infor-mation for IgE, asthma severity, and other variables,including BMI, age, sex, disease onset, and parental histo-ries of asthma and allergies, as described in Methods. Nosignificant differences were noted in drug response, sever-ity level, and other measures of baseline lung functionbetween subjects who were included in this analysis andthose who were excluded.

Table I describes characteristic of patients with asthmawith high (�100 IU/mL) and low (<100 IU/mL) IgElevels. Through univariate regression, African Americanswere more prevalent in the group with low IgE (P < .001)than in the group with high IgE. Earlier age at onset wasassociated with high IgE (P 5 .013). As expected, hay fe-ver was associated with high IgE (P < .0001). Sex, age,and BMI were not independently associated with highIgE. Parental histories of asthma, eczema, and hay feverwere not significantly associated with high IgE.

After adjustment for age, sex, BMI, and age at asthmaonset, African Americans had significantly lower IgElevels (mean, 285.9 IU/mL) than did Mexicans and PuertoRicans (mean, 472.9 IU/mL and 460.2 IU/mL, respec-tively; P < .0001). Adjusted logistic regression analysisshowed that Puerto Ricans and Mexicans were more likelyto have high IgE levels than were African Americans(odds ratio [OR], 2.46; 95% CI, 1.6-3.7; and OR, 2.68;95% CI, 1.82-3.94, respectively). Table E1 (see this arti-cle’s Online Repository at www.jacionline.org) summa-rizes IgE levels and subject characteristics stratified byrace.

Among study participants for whom SES data wereavailable (Mexicans and African Americans in the conti-nental United States), no association was found betweenSES and IgE by univariate logistic regression (P > .05),nor did SES vary significantly between Mexican andAfrican American populations (P > .05). Because of thesefindings and the unavailability of comparable SES dataamong Puerto Ricans, SES was not used as a covariatein our models.

Comparison of asthma severity and clinicaloutcomes among subjects high and low IgE

Mean values for lung function and drug responsivenessamong subjects with asthma with high and low IgE levelsare shown in Table II. Mean lung function tests for indi-vidual ethnic groups are shown in Table E2 (see this arti-cle’s Online Repository at www.jacionline.org). Afteradjusting for ethnic background, age, sex, BMI, and ageof disease onset, participants with high IgE had signifi-cantly lower lung function than did those with low IgE.Participants with high IgE had lower baseline values ofFEV1, FEF25-75, and FEV1/FVC, percent of predicted,

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TABLE I. Characteristics of subjects with asthma with high and low IgE levels

Subjects with IgE $100 IU/mL

(n 5 492)

Subjects with IgE <100 IU/mL

(n 5 247) P value*

(% or mean 6 SD)

Race/ethnicity

Mexican 40.2 29.2 <.001

Puerto Rican 32.9 22.7 <.001

African American 26.8 48.2 —

Subject characteristics

Age (y) 16.3 6 8.0 17.3 6 9.5 .129

Male sex 52.8 45.7 .069

BMI 24.3 6 6.9 25.2 6 7.5 .148

SES 2.01 6 .8 2.11 6 .85 .237

Breast-fed 56.1 54.9 .834

ETS exposure 30 26.7 .529

Age at asthma onset 5.8 6 7.6 7.4 6 8.6 .013

Eczema 35.2 32.8 .510

Hay fever 84.9 71.7 <.001

Maternal history

Asthma 34.4 29.8 .217

Eczema 10.1 6.3 .095

Hay fever 27.8 32.8 .171

Paternal history

Asthma 23.4 24.1 .845

Eczema 7.5 8.4 .697

Hay fever 24.7 22.6 .556

*Univariate regression.

TABLE II. Comparison of lung function between subjects with asthma with high and low IgE levels

Subjects with IgE $100 IU/mL

(n 5 492)

Subjects with IgE <100 IU/mL

(n 5 247)

P,

ANOVA

P,*y

ANCOVA

(% or mean 6 SD)

FEV1 87.6 6 17.1 91.5 6 17.0 .0058 .031

FEF25-75 68 6 26.3 78.8 6 27.3 <.0001 <.0001

FEV1/FVC 89.2 6 11.4 93.5 6 10.7 <.0001 .0001

FEV1 < 80% 32.3 21.9 .011 .023

D FEV1 9.2 6 12.8 7.8 6 9.4 .041 .066

D FEF25-75 31.1 6 53.7 22.6 6 38.4 .024 .038

D FEV1/FVC 6 6 14.6 4.2 6 9.1 .05 .130

*Covariates in ANCOVA included age, sex, BMI (log-transformed values), ethnicity, and age at asthma onset.

�ANCOVA analyzing variance in D FEV1, D FEF25-75, and D FEV1/FVC in addition included baseline FEV1, baseline FEF25-75, and baseline FEV1/FVC,

respectively, as covariates.

than did those with low IgE (P 5 .031, P < .0001, P 5

.0001, respectively). In addition, a greater proportion ofsubjects with high IgE had baseline FEV1 < 80% of pre-dicted than did those with low IgE (P 5 .021). With regardto IgE levels, the same trends in FEV1, FEF25-75, andFEV1/FVC and higher proportion of participants withbaseline FEV1 < 80% of predicted regarding IgE levelswere seen in each ethnic group. Multiple linear regressionconfirmed that baseline FEV1, FEF25-75, and FEV1/FVC,percent of predicted, were all associated with higher IgE(continuous and log-transformed) both before and afteradjustment for covariates (P 5 .007, P < .001, P 5

.001, respectively). Bronchodilator drug responsivenesswas not associated with IgE levels in our study population.

Clinical characteristics and outcomes of participants,stratified by IgE levels, are shown in Table III. Clinical

characteristics for individual ethnic groups are shown inTable E3 (see this article’s Online Repository at www.jacionline.org). Presented ORs are from logistic regressionanalysis, using the binary severity indicator as the out-come variable. Subjects were classified as having mildasthma or moderate-to-severe asthma, as described inMethods, with 72.2% of those with high IgE having mod-erate-to-severe asthma compared with 65.6% of those withlow IgE. Logistic regression using IgE as a continuouslog-transformed variable showed that IgE was associatedwith moderate-to-severe asthma before and after adjustingfor race and ethnicity, age, sex, BMI, and age at diseaseonset (OR, 1.39; 95% CI, 1.08-1.8). In addition, 54.7%of subjects with asthma with high IgE had been previouslyhospitalized, compared with 44.1% of those with low IgE(OR, 1.33; 95% CI, 1.04-1.71). Intubations and ICU visits

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TABLE III. Clinical characteristics and outcomes among subjects with asthma with high and low IgE

Outcome variable

Subjects with IgE $100 IU/mL

(n 5 492)

Subjects with IgE <100 IU/mL

(n 5 247) Adjusted OR* 95% CI P value

(Percent)

Asthma severity

Moderate-to-severe asthma 72.2 65.6 1.39 1.08 1.80 .011

Diurnal asthma symptoms 54.8 51.5 1.18 0.93 1.50 .172

Nocturnal asthma 47 51.5 1.05 0.82 1.35 .681

Symptoms and medication

Wheezing 83.1 92.3 1.05 0.77 1.44 .750

Chest tightness 83.1 93.4 0.98 0.71 1.34 .890

Controller medication 64.2 59.1 1.21 0.96 1.55 .108

Steroid medication 57.3 54.2 1.21 0.95 1.53 .119

Allergic reactions

Pets 59.4 40.8 1.90 1.48 2.43 <.0001

Mold 75 76.1 1.02 0.78 1.33 .898

Dust 91.1 87.4 1.38 0.95 2.01 .095

Hospitalization

Hospitalization 54.7 44.1 1.33 1.04 1.71 .023

Intubation 3.7 7.3 0.71 0.41 1.20 .200

ICU 11.7 11 1.37 0.92 2.03 .120

*Covariates in regression included age, sex, BMI (log-transformed values), ethnicity, and age of asthma onset. IgE was entered into the model as a continuous,

log-transformed variable.

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did not differ between subjects with high IgE and low IgE,although we had little power to detect such associationsgiven the low proportions of each. Other indicators ofseverity, however, including medication use, nocturnalsymptoms, daily symptoms, wheezing, and chest tight-ness, did not vary significantly between subjects withhigh and low IgE. Finally, as expected, subjects withasthma with high IgE were more likely to have had an al-lergic reaction to pets than those with low IgE (59.4% and40.8%, respectively; OR, 1.90; 95% CI, 1.48-2.43).

To address the possible confounding effects of differ-ences between childhood and adult allergic asthma, werepeated the analysis on the subset of children with asthmaunder age 18 years (n 5 526). Among this group, childrenwith IgE � 100 IU/mL (n 5 354) still had lower lungfunction than did children with IgE < 100 IU/mL (n 5

172) after adjustment for the covariates listed in Methods.Specifically, the children with high IgE had lower meanbaseline FEV1, FEF25-75, and FEV1/FVC (89.2 6 15.7,69.5 6 25.7, 89.2 6 10.9, respectively) than did childrenwith low IgE (93.1 6 16.9, 78.6 6 28.0, 93.0 6 11.3,respectively). These differences were significant afteradjustment for confounders by ANCOVA (P 5 .032, P 5

.002, P 5 .004, respectively). Among children withasthma and high IgE levels, a significantly higher propor-tion of subjects reported an allergic reaction to pets thanamong those with asthma and low IgE levels (58.2%and 38.2%, respectively; OR, 2.20; 95% CI, 1.49-3.25).ETS information was available for children <13 years ofage. Incorporating ETS into this group, we found that sub-jects with low IgE levels had significantly higher levels ofFEF25-75 and FEV1/FVC (P 5 .011 and P 5 .044, respec-tively.) As in adults, no association was found betweenIgE levels and bronchodilator drug responsiveness.

DISCUSSION

The results of our analysis demonstrate an associationbetween high IgE levels and asthma severity amongMexican, Puerto Rican, and African American patientswith asthma. These findings remain significant afteraccounting for differences in race/ethnicity, age, sex,BMI, and age of asthma onset, and also after stratificationof patients with asthma into children and adults. Althoughasthma has already been shown to be associated withserum IgE levels,1-3 our results expand on previous find-ings by demonstrating that higher IgE levels are correlatedwith lower lung function and more severe asthma. In addi-tion, these findings are notable among Mexican, PuertoRican, and African American subjects with asthma, high-risk populations that are often understudied. To our knowl-edge, this is the first and largest investigation of IgE andasthma severity (defined by questionnaire and spirometry)conducted specifically among 3 US minority populations.

Previous studies examining IgE, asthma characteristics,and lung function have shown an association betweenseverity and IgE in adults and children7; however, one ofthe limitations of these evaluations is the lack of standard-ization of asthma classification. Our study used formallung function studies (in addition to physician assessmentand symptom scores) in all patients and, as such, offersobjective and reproducible severity classification, asdemonstrated in multiple previous studies.30-32

Our study found an association between lower baselinelung function and IgE levels among subjects with asthmain 3 minority populations, as well as associations withmoderate-to-severe asthma and hospitalizations forasthma. In conjunction with the established relationshipbetween IgE and asthma phenotype, these findings

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suggest a relationship between IgE and severity level thatis related to asthma pathology. We are aware of only1 previous study that has attempted to examine thisrelationship. An epidemiologic longitudinal study per-formed by Annesi et al8 specifically examined FEV1 andmethacholine reactivity in a cohort of 310 French adultmen in a 5-year period. They found a decline in FEV1

was associated with IgE in nonsmokers (P 5 .03) and inexsmokers (P 5 .06). Although this study does demon-strate a relationship between IgE and lung function, theirpopulation included both subjects with and withoutasthma. In addition, this study did not assess such a rela-tionship in children with asthma.

In our study, African American subjects were older thansubjects in the other 2 groups. Although our models wereadjusted for age, this age difference may account for theskewed proportion of African American asthmatics withlow IgE. To further adjust for age differences, we stratifiedsubjects into adults (�18 years) and children (<18 years).We found that subjects with asthma with high IgE still hadsignificantly lower lung function than those with low IgE,as shown by 3 separate indexes, regardless of age group.Although our findings thereby lost significance, the sametrends regarding lower lung function and IgE remainedwhen ethnic groups were examined individually.

In addition to asthma severity, we also comparedasthma-related characteristics among racial/ethnic groups.We found that African American patients with asthma hadsignificantly lower IgE levels and were less likely to havehigh IgE levels compared with both Puerto Rican andMexican patients with asthma, even after adjustment forrace, age, sex, BMI, and age at asthma onset. Althoughthere have been few studies that directly compare IgElevels and asthma-related traits across racial/ethnicgroups, Joseph et al11 demonstrated that, among childrenin suburban Detroit, African Americans without asthmahad significantly higher IgE levels and higher airway re-sponsiveness than European American children. However,among subjects with asthma, they found no significant dif-ferences in IgE across racial groups. Overall, the mean IgElevels in all of our populations were higher than the meanIgE levels of subjects participating in the study by Josephet al.11 The difference in IgE levels between the differentstudy populations likely reflects differences in ascertain-ment and exposure characteristics of their populations.

Although the major strengths of our study are theobjective nature of the measurements (IgE levels andspirometry), the large sample size, and 3 separate popu-lations, it has several important limitations that must beconsidered when interpreting our results. This was not apopulation-based study. Therefore, it is possible that wemay have introduced bias. However, in these analyses,we have taken steps to adjust for potential confoundingfactors. In addition, there are no published pulmonaryfunction reference values for Puerto Ricans. This limita-tion highlights the need for more research in minoritypopulations. We used the predictive equations of Hankin-son et al,29 the most extensive data set of normal spiromet-ric values for Latinos of all ages. These reference values,

however, do not distinguish among the different Latinoethnicities. It has been shown that African Americanshave smaller lungs than white subjects.33-36 As such, theremay be differences in lung size between Puerto Ricans,Mexicans, and African Americans that are not accountedfor in our analysis. However, we found that FEV1,FEF25-75, and FEV1/FVC ratio, the last of which is an indexof airway obstruction adjusted for individual vital capac-ity, was lower among subjects with high IgE levels acrossall 3 ethnic groups. This consistency reinforces the valid-ity of our results.

By evaluating a large sample of subjects with asthma,including a large number of children, the current studymay improve the clinician’s ability to predict long-termoutcomes for children with asthma symptoms. We foundthat among the overall subject population, and in thesubset of children under age 18 years, higher IgE levels areassociated with an increase in symptom-based and pul-monary function–based asthma severity. This suggeststhat, among subjects with asthma with high IgE levels, theprogression to more severe asthma may begin early in life.Although these results will need to be confirmed throughadditional investigation, we conclude that aggressivetreatment of allergic patients with asthma may help pre-vent further decline in lung function over the lifetime ofa subject with asthma. If validated, these results couldhave an important effect on the clinical management ofindividuals with and without allergy with asthma.

We acknowledge the families and the patients for their participa-

tion. We also thank the numerous health care providers and commu-

nity clinics for their support and participation in the GALA and

SAGE studies. We thank especially Jeffrey M. Drazen, MD, Scott

Weiss, MD, Ed Silverman, MD, PhD, Homer A. Boushey, MD, and

Jean G. Ford, MD, for all of their effort towards the creation of the

GALA study. Finally, we thank the Sandler Family Supporting

Foundation, the primary sponsor of this investigation.

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