2001 Progress Report: Research Project on Asthma

EPA Grant Number: R827027C003
Subproject: 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 in the City of New York
EPA Project Officer: Callan, Richard
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) RFA Text |  Recipients Lists
Research Category: Children's Health , Health Effects , Health

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
Extract

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:

 , RFA, Health, Scientific Discipline, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, health effects, particulate matter, sensitive populations, infants, prenatal exposure, airway disease, respiratory problems, biological response, socioeconomic status, air pollution, children, Human Health Risk Assessment, PAH, human exposure, children's vulnerablity, assessment of exposure, childhood respiratory disease, growth and development, epidemeology, environmentally caused disease, environmental health hazard, growth & development, acute exposure, developmental disorders, disease, exposure assessment

Relevant Websites:

http://www.mailman.hs.columbia.edu/ccceh/index.html Exit

Progress and Final Reports:

Original Abstract
  • 1999
  • 2000 Progress Report
  • 2002 Progress Report
  • 2003
  • 2004
  • Final

  • 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