Grantee Research Project Results
2006 Progress Report: Environmental Tobacco Smoke, Biomarkers, and Childhood Asthma
EPA Grant Number: R830826Title: Environmental Tobacco Smoke, Biomarkers, and Childhood Asthma
Investigators: Klonoff-Cohen, Hillary , Thomas, Ronald G. , Park, Sung Min , Platzker, Arnold , Pickering, Bretten , Woo, Heide , Natarajan, Loki , Jacobs, Robert
Current Investigators: Klonoff-Cohen, Hillary
Institution: University of California - San Diego
EPA Project Officer: Aja, Hayley
Project Period: July 1, 2003 through June 30, 2009 (Extended to June 30, 2010)
Project Period Covered by this Report: July 1, 2005 through June 30, 2006
Project Amount: $750,000
RFA: Biomarkers for the Assessment of Exposure and Toxicity in Children (2002) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
Objective 1
The use of biomarkers may have important implications for the detection, prevention, and treatment of environmentally-induced diseases in children. This research will identify and evaluate two biomarkers, urine eosinophil protein X (uEPX) and serum eosinophil cationic protein (sECP), which may play a role in predicting childhood asthma. Biomarkers will be evaluated for their validity, based on predicting the presence or absence of a disease, and for their ability to quantify severity of disease; sensitivity and specificity will be determined.
Hypothesis. ECP and EPX will be useful biomarkers in predicting the presence of disease, clinical severity, and treatment efficacy in children diagnosed with asthma, and thus, provides a comprehensive health risk assessment in children.
The specific aims are to: (1) establish baseline values and distribution of sECP and uEPX in infants and young children at their initial presentation of asthma, which will be compared to those of healthy children, matched with respect to gender, age, race, hospital, and clinic to evaluate sensitivity and specificity of sECP and uEPX in predicting the presence of asthma; (2) create a time profile of sECP and uEPX levels from the initial visit through the 12 month treatment period (0, 4, 8, and 12 months); and (3) compare subjects’ sECP and uEPX levels during an asthma exacerbation with their most recent preexacerbation ECP and EPX levels.
Objective 2
Biomarkers (sECP and uEPX) will be used to predict health effects (asthma), which may occur later in life as a result of exposures early in life (i.e., in utero environmental tobacco smoke [ETS]. Infants exposed to in utero and postnatal ETS will have smaller lungs and reduced airflow, possibly predisposing them to asthma. Childhood asthma results in chronic airway inflammation with mucosal edema and chronic increased airway muscle tone in genetically predisposed children. ECP and EPX will be measured in infants to assess whether there is early lung inflammation associated with asthma, compounded by ETS exposure.
Hypothesis. In utero and postnatal ETS exposure (based on infant’s urine cotinine measurements) will result in higher levels of biomarkers (sECP and uEPX). The highest ECP and EPX values will be in asthmatic children exposed to ETS. Finally, the greater the ETS exposure and more severe the clinically related endpoints (i.e., peak expiratory flow rates [PEFR], exacerbations) the higher the ECP and EPX levels.
The specific aims are to: (1) examine the association between ETS exposure (in utero and/or postnatal) and baseline sECP and uEPX and asses the dose-response effect between numbers of cigarettes and cotinine, ECP, and EPX levels; (2) determine whether asthmatic infants exposed to ETS in utero have the highest ECP and EPX values, whether unexposed asthmatics and ETS-exposed healthy children have intermediate values, and whether healthy unexposed infants have the lowest ECP and EPX values at baseline; (3) analyze the relationship between an asthmatic infant’s lifetime ETS exposure (total number of cigarettes and cotinine levels) and clinically related endpoints, specifically pulmonary function tests (PFTs), PEFR, and occurrence of asthma exacerbations; and (4) measure ETS effects over a 12-month period (at 0, 4, 8, and 12 months) and clinical endpoints of asthma (i.e., PFTs, PEFR, and occurrence of asthma exacerbations) on ECP/EPX levels.
Progress Summary:
We anticipated recruiting approximately 132 cases and controls per year for a total of approximately 400 children. To date, we have only recruited one-third of the patients. Progress is limited because of the following problems and we are now taking the following steps to remedy this:
Work Status and Progress
Because of the lack of staff and resources required to complete the project, the progress of the research has been hindered. In the San Diego area, patient recruitment has also been held up because of lack of staff. Two new physicians at Children’s Hospital Los Angeles have temporarily agreed to recruit patients for our project. Additional funds are being sought for personnel and patient incentives, specifically, two part-time certified medical assistants for San Diego and Los Angeles counties.
Another obstacle encountered is that patients’ families commute from very long distances by public transportation to reach the hospitals. In addition, they often have children attending school and other time commitments that complicate their availability and length of time for office visits. Finally, it is difficult to convince families to participate in follow-up visits because of the expenses involved. Patients are scheduled for four visits throughout the first year. During visit 1, patients’ parents undergo a long telephone interview (1 hour for English and 1.5-2 hours for Spanish interview), complete a daily diary for 1 year, and consent for their infants to provide blood and urine samples. Furthermore, during visit 4, parents complete a final interview and infants undergo a PFT, which is stressful and time consuming for parents and children. Once again, the children also provide blood and urine samples. Therefore, we are exploring the option of providing additional compensation to reimburse patients’ families for visit 1 and visit 4. The greatest obstacles for not recruiting patients are the families’ lack of transportation and hectic time schedule. The majority of these patients’ families has no car and commutes by bus all over Los Angeles and San Diego, which puts additional strain on them. We are exploring options to provide partial taxi coupons for visits 2, 3, and 4 to encourage families to return for their follow-ups.
The last hurdle we have encountered is caused by the overestimation of persistent asthmatics attending pulmonary clinics rather than emergency rooms. It has been difficult to identify newly diagnosed asthmatics in the pulmonary clinic despite the fact that the pilot study confirmed their availability. The emergency room could be the superior setting to obtain the subjects; however, it has been extremely difficult to get their cooperation. Finally, the prevalence of newly diagnosed asthma was not optimal last year. This is because it was a relatively mild flu season; subsequently asthmatic symptoms were not triggered. Hence, in the San Diego area, patient recruitment at the three sites has been fairly slow because of the paucity of young children presenting with wheezing at the clinics.
The Head of the Emergency Department has granted permission to approach eligible cases and controls at Children’s Hospital Los Angeles. In addition, we are investigating which emergency rooms in San Diego County, Orange County, as well as in Northern California are the most viable. Then, brisk recruitment of eligible patients will begin to fulfill the desired final sample size.
Results to Date
There currently are no experimental results available because this is Year 3 of the study.
Future Activities:
During the next year, we will vigorously recruit eligible patients, obtain informed consent, conduct initial and follow-up interviews, collect urine for cotinine and EPX analyses, draw blood for sECP testing, abstract medical records, enter and clean the data, and perform preliminary statistical analyses.
Journal Articles:
No journal articles submitted with this report: View all 3 publications for this projectSupplemental Keywords:
asthma, infants, children, inflammatory markers, biomarkers, epidemiology, environmental tobacco smoke, urine EPX, serum ECP, diagnosis, prevention,Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- Final
- 2009
- 2008 Progress Report
- 2007 Progress Report
- 2005 Progress Report
- 2004 Progress Report
- Original Abstract
1 journal articles for this project