2001 Progress Report: Research Project on Asthma
EPA Grant Number: R827027C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R827027
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - Columbia University School of Public Health
Center Director: Perera, Frederica P.
Title: Research Project on Asthma
Investigators: Perera, Frederica P.
Institution: Columbia University
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through July 31, 2001 (Extended to October 31, 2004)
Project Period Covered by this Report: November 1, 2000 through October 31,2001
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects
Description:
Objective:The aims of the asthma project remain unchanged. They are to test the hypotheses that: (1) prenatal and/or postnatal exposure to home allergens (cockroach, house dust mite, and rodent) and environmental tobacco smoke (ETS), as well as postnatal exposure to PM2.5 and diesel exhaust particulate (DEP), are significant contributors to the risk of asthma, as indicated by related biomarkers and persistent wheezing; (2) risk from home allergens is increased by co-exposure to the air pollutants (ETS, PM2.5 and DEP); and (3) impaired nutritional status (inadequate levels of antioxidants) heightens susceptibility to the pollutants.
Progress Summary:Recruitment of Study Participants
To date, 372 women have met the criteria for complete enrollment into the Mothers and Newborns Study cohort (i.e., underwent prenatal monitoring, provided a prenatal questionnaire, blood sample collected at delivery from either the mother and/or her newborn).
Data Collected
Maternal and/or cord blood has been collected for 299 of the deliveries and both maternal and cord blood have been collected for 239. Questionnaire completion rates are 176/231 (76%) at 3 months; 186/190 (96%) at 6 months; and 117/126 (93%) at 12 months. For 227 cohort members, the 9-, 15-, 18-, and 21-month questionnaires have been completed. There were no significant differences in loss of respondents to follow-up by ethnic identity.
Infant Health
Preliminary analysis of data on 106 infants who have reached the age of 3 months and had a follow-up interview shows significant health complaints in the study population. During the first 3 months of life, 39 percent of the infants had at least one of the following breathing symptoms: Coughing, barking or croupy cough, difficulty breathing, and wheezing or whistling in chest. Of these infants, 24.5 percent had seen a physician, 14.8 percent had visited an Emergency Room, and 7.4 percent were hospitalized for these symptoms. These data indicate a higher rate of health care utilization for respiratory complaints in Northern Manhattan, compared to both New York City and the entire United States.
Immunoassays
Specimens from 299 mothers and their newborns have been analyzed by the Laboratory of Allergy and Inflammatory Lung Disease. Assays have been completed and statistical analyses performed from the first 167 mothers/newborns:
- Total IgE levels by radioimmunoassay (RIA) (n = 167)
- Allergen-specific IgE levels by fluorescence allergosorbent test (FAST) (n = 97 mothers, n = 76 at 24 months)
- Allergen-induced mononuclear cell proliferation assays (n = 167 mothers and newborns)
- Cytokine analysis by intracytoplasmic staining and flow cytometry (12 newborns)
- Cytokine analysis by enzyme-linked immunosorbent assay (ELISA) (62 newborns)
- Cytokine analysis by ELISPOT (10 newborns).
Tables 1 and 2 show results for allergen-induced proliferation in mothers and newborns.
The below results demonstrate a high rate of sensitization in newborns, and that for cockroach, dust mite, and tetanus, the presence of proliferation in response to allergen significantly differed between mothers and newborns.
Table 1. Frequency of Antigen-Induced Proliferation
Antigen |
Newborn |
Mother |
German Cockroach |
54% |
43% |
Dust mite (Der p 1) |
25% |
60% |
Dust mite (Der f 1) |
40% |
65% |
Mouse |
34% |
29% |
Tetanus toxoid |
3% |
41% |
McNemar Fisher Exact test was performed. Two-tailed p values are provided.
In many cases, allergen-induced proliferation occurred in cord blood in the absence of allergen-induced proliferation in maternal blood; see the negative and positive stimulation index results below.
Table 2. Comparison Between Maternal and Cord Blood SI Positivity
|
|
Cord Blood |
||
|
Maternal Blood |
Negative SI |
Positive SI |
Total |
Cockroach Extract |
Negative SI |
35 |
40 |
75 |
Positive SI |
21 |
37 |
58 |
|
Total |
56 |
77 |
133 |
|
|
p value < 0.05 |
|||
D. pteronyssinus |
Negative SI |
37 |
13 |
50 |
Positive SI |
53 |
20 |
73 |
|
Total |
90 |
33 |
123 |
|
|
p value < 0.001 |
|||
D. farinae Extract |
Negative SI |
28 |
17 |
45 |
Positive SI |
49 |
37 |
86 |
|
Total |
77 |
54 |
131 |
|
|
p value < 0.001 |
|||
Mouse Extract |
Negative SI |
63 |
30 |
93 |
Positive SI |
24 |
15 |
39 |
|
Total |
87 |
45 |
132 |
|
|
p value = NS |
|||
Tetanus Toxoid |
Negative SI |
69 |
1 |
70 |
Positive SI |
40 |
3 |
43 |
|
Total |
109 |
4 |
113 |
|
|
p value < 0.001 |
Analysis performed using Spearman’s rho calculation. P values provided are for 2-tailed significance.
These results suggest that the T cell proliferation in response to dust mite may represent an allergic immune response.
Table 3. Correlation Between Stimulation Index (SI)
and Interleukin-5 (IL-5) Level
|
N |
Correlation |
P value |
PHA |
62 |
-0.232 |
NS |
Cockroach Extract |
61 |
-0.040 |
NS |
D. pteronyssinus Extract |
57 |
0.408 |
< 0.005 |
D. farinae Extract |
61 |
0.267 |
< 0.005 |
Mouse Extract |
59 |
0.075 |
NS |
Significance
The full significance with respect to asthma is not known, but these results suggest that sensitization to indoor allergens occurs as early as in utero. In many cases, cord blood proliferation occurred in the absence of maternal blood allergen-specific proliferation and may be associated with IL-5 upregulation.
Future Activities:We plan to continue data collection over the next year in the same manner as over the past year. Evaluation of the birth cohort at age 2 is ongoing. Total and allergen-specific IgE levels at age 2 years are being compared to sensitization patterns at birth.
Supplemental Keywords:, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Biology, Risk Assessments, genetic susceptability, Health Risk Assessment, Epidemiology, Children's Health, Environmental Chemistry, exposure assessment, environmentally caused disease, acute exposure, developmental disorders, health effects, respiratory problems, assessment of exposure, prenatal exposure, childhood respiratory disease, growth and development, toxics, epidemeology, infants, sensitive populations, biological response, air pollution, airway disease, children, particulate matter, disease, growth & development, PAH, children's vulnerablity, environmental health hazard, socioeconomic status, human exposure
Relevant Websites:
http://www.mailman.hs.columbia.edu/ccceh/index.html
Progress and Final Reports:
2000 Progress Report
Original Abstract
2002 Progress Report
Main Center Abstract and Reports:
R827027 CECEHDPR - Columbia University School of Public Health
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827027C001 Community-Based Intervention: Reducing Risks of Asthma
R827027C002 Growth and Development/Evaluation of Carcinogenic Risks
R827027C003 Research Project on Asthma