Environmental Tobacco Smoke, Biomarkers, and Childhood AsthmaEPA Grant Number: R830826
Title: Environmental Tobacco Smoke, Biomarkers, and Childhood Asthma
Investigators: Klonoff-Cohen, Hillary
Institution: University of California - San Diego
EPA Project Officer: Hahn, Intaek
Project Period: July 1, 2003 through June 30, 2009 (Extended to June 30, 2010)
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 , Health
Asthma is the most common condition of childhood, affecting 4.8 million newly-diagnosed children/year in the U.S. Pediatric asthma is both under-recognized and under-treated. In 1999, asthma-related costs exceeded $6.2 billion, with the greatest economic burden associated with hospital care. Children from 0-4 years have the highest hospitalization rates. Over 60% of childhood asthma begins before age 3; nevertheless, infants and children have not been the focus of research. Although little is known about the etiology of asthma, emerging research indicates that asthma causation may be linked to the fetal and newborn environment during development of the immune system. Smoking during pregnancy has been implicated as a risk factor for childhood asthma. Infants of smokers have reduced lung function and increased airway responsiveness. Furthermore, environmental tobacco smoke (ETS) exposure appears to play a role in the severity of asthma. One of the great challenges in pediatric respiratory medicine is to identify asthmatics in early stages, who presumably have early allergy-induced airway hyperactivity, during the first years of life. Inflammatory markers are increasingly used in clinical practice as an objective tool to aid in the diagnosis and monitoring of asthma. Consequently, the role of serum eosinophil cationic protein (sECP) and urine eosinophil protein X (uEPX) as biomarkers of latent effect could potentially lead to a medical breakthrough in the diagnosis of asthma in children. Elevated sECP is associated with asthma, decreases with anti-inflammatory treatment, is higher in atopic compared with non-atopic asthmatic subjects, and increases with ETS exposure. In children, uEPX increases significantly with wheeze/asthma, decreasing age, and active eczema.
Remarkably, the relationships between sECP, uEPX and ETS have never been investigated in young children. We hypothesize that in infants and children, sECP and/or uEPX may be valuable measures of eosinophil activation in asthmatics, particularly those exposed to ETS during pregnancy and postnatally (through breast milk and the environment).
A prospective study of 200 Caucasian, African-American, Hispanic, Asian and/or Pacific-Islander children (0-4 years of age), with newly diagnosed asthma at UCSD, Children's Hospital in San Diego and Los Angeles, and Mattel/UCLA Children's Hospital. A comparison group of 200 healthy children, matched on the basis of age, race, sex, clinic, and hospital site will also be recruited from general pediatrics clinics. Parents will participate in a telephone interview, and complete 2 short follow-up questionnaires and a diary on asthma symptoms. Infant sECP, uEPX, and cotinine levels will be measured at baseline, and every 4 months thereafter, for 1 year, and during 2 exacerbations throughout the remainder of the study. Serum IgE and RAST will be measured at baseline, and pediatric pulmonary function tests (PFTs) and peak expiratory flow rates (PEFRs) will be conducted in children ≥ 3 years. Longitudinal regression analyses will be performed for repeated measures, using the mixed effects model and generalized estimating equations.
Asthmatic infants exposed to ETS in utero should have the highest sECP and uEPX values, unexposed asthmatics and ETS exposed healthy children will have intermediate values, and healthy unexposed infants will have the lowest sECP and uEPX values at baseline; the latter define the low dose area of the dose-response curve.
These biomarkers are new, simple, non-invasive tests, which may have an immediate impact on childhood asthma, predicting future asthmatics who may have been exposed to tobacco smoke during and/or after pregnancy. This will have important implications for detection, prevention, and treatment of asthma as well as in improving comprehensive risk assessment in children.