2000 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: September 1, 1999 through August 31,2000
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

As described in the previous report, we presently have a total of 218 women actively enrolled in the study. Reasons for loss of respondents after enrollment include: respondent was unavailable or refused (36%), miscarriage or death of infant (22%), failed to notify of delivery (19%), delivered before monitoring (17%), and other (6%). There were no significant differences in loss of respondents to follow-up by ethnic identity (χ2 = 1.01, p = 0.3).

Data Collected

As of August 5, 1999, environmental exposure monitoring has been completed on 168 (77%) of the subjects currently enrolled in the study, and 142 (66%) of the subjects have delivered.

Table 1. Disposition of Follow-Up Interviews for Babies Delivered as of August 17, 1999 (N = 142)

Baby’s Age
as of August 5, 1999

Babies Reached Age
n (% of delivered)

Follow-Up Interview Completed
n (% of eligible)

3 months

108 (76%)

81 (75%)*

6 months

70 (49%)

67 (96%)

9 months

41 (29%)

38 (93%)

12 months

21 (15%)

20 (95%)

*15 infants in the parent Growth and Development study were not administered this questionnaire as they had reached 3 months before the instrument was completed.

Infant Health

Preliminary analysis of data on 58 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, 27 (47%) 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, 18 (67%) had seen a physician, 13 (48%) had visited an e mergency r oom, and 4 (15%) were hospitalized for these symptoms. Two additional infants were hospitalized for other symptoms (e.g., ear infection, sore throat). Of all 58 infants, 14 (24%) received a physician diagnosis of pneumonia, bronchiolit is, bronchitis, sinus disease, or other illnesses.

Immunoassays

The following assays have been performed by the Laboratory of Allergy and Inflammatory Lung Disease on blood from the 58 mothers and/or newborns mentioned above:

  • Total IgE levels by radioimmunoassay (RIA) (n = 54 mothers; n = 58 newborns)
  • Allergen-specific IgE levels by fluorescence allergosorbent test (FAST) (n = 54 mothers)
  • Mitogen or allergen-induced proliferation assays (n = 37 mothers; n = 57 newborns)
  • Cytokine analysis by intracytoplasmic staining and flow cytometry (12 newborns)
  • Cytokine analysis by enzyme-linked immunoso rbent assay (ELISA) (12 newborns)

At present, the database is nearly established and statistical analysis is about to begin. Some of the findings are summarized in Table 2 :

Table 2. Frequency of Allergen-Induced Proliferation

Newborns

Mothers

German cockroach 22/57 = 38.6%

German cockroach 9/37 = 24.3%

Dust mite (Der p 1) 15/50 = 30.0%

Dust mite (Der p 1) 21/36 = 58.3%

Dust mite (Der f 1) 20/55 = 36.4%

Dust mite (Der f 1) 22/37 = 59.5%

Mouse 14/55 = 25.5%

Mouse 2/37 = 5.4%

Mountain cedar 1/13 = 7.7%

Mountain cedar 0/13 = 0%

Tetanus toxoid 2/29 = 6.9%

Tetanus toxoid 15/28 = 53.6%

Mumps 0/10 = 0%

Mumps 3/13 = 23.1%

Thymidine incorporation of cord blood mononuclear cells is measured after 5 days in culture and upon exposure to PHA (positive control), cockroach (CR), Der p 1, Der f 1, mouse or mountain cedar allergen (unrelated allergen) or tetanus toxoid (negative control) and after pulsing with H3. The r atio of thymidine uptake is expressed as a ratio of counts per minute in response to allergen divided by counts per minute background. A ratio above 2 is considered positive. These results suggest that in utero sensitization to indoor allergens can occur.

Similarly, thymidine incorporation of maternal blood monoculear cells is measured after 5 days in culture and upon exposure to PHA (positive control), cockroach (CR), Der p 1, Der f 1, mouse or mountain cedar allergen (unrelated allergen) or tetanus toxoid (negative control) and after pulsing with H3. The ratio of thymidine uptake is expressed as a ratio of counts per minute in response to allergen divided by counts per minute background. A ratio above 2 is considered positive.

Table 3. Comparison of Presence of Proliferation (Yes/No) Between Newborns and Mothers per Allergen Mother

 Text Box: Newborn

 

Cockroach

Der P 1

Der F 1

Mouse

Tetanus

 

Yes

No

Yes

No

Yes

No

Yes

No

Yes

No

Yes

7

11

10

4

11

5

0

11

2

0

No

2

17

10

10

10

10

2

25

13

12

Finally, we found an association between allergen-specific IgE levels and allergen-induced proliferation (data not shown). Statistical analyses of these data, as well as measured cytokine levels in response to in vitro stimulation with allergen, are underway.

Significance

These results demonstrate that, in many cases, cord blood proliferation occurs in the absence of maternal blood allergen-specific proliferation. In addition, the data suggest that sensitization to indoor allergens occurs as early as in utero.

Future Activities:

We plan to continue data collection over the next year in the same manner that has occurred over the past year.

Supplemental Keywords:

prenatal exposure, PAH, PM, particulate matter, ETS, nutritional status., 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
  • 2001 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