Introduction: Over 60% of childhood asthma begins before age 3; nevertheless, infants and children have not been the focus of research. Asthma causation may be linked to the fetal and newborn environment during development of the immune system. The deleterious effect of in utero and postnatal environmental tobacco smoke (ETS) may further complicate the diagnosis and treatment of asthma. Infants of smokers have reduced lung function and increased airway responsiveness. Tobacco smoke also plays a role in whether a child's asthma becomes reversible. Hence, childhood asthma is a disease for which tobacco exposure may be directly implicated in the etiology as well as the progression of the disease. One of the greatest challenges in pediatric respiratory medicine is to identify asthmatics in early stages. Invasive studies such as bronchial biopsies and pediatric lung function tests are not easily performed in infants and children. Inflammatory markers are increasingly used in clinical practice as objectives tool to aid in the diagnosis and monitoring of asthma. Elevated serum eosinophil cationic protein (sECP) is a marker associated with asthma, and increases with tobacco smoke exposure. Urine eosinophil protein X (uEPX) significantly increases with asthma, decreasing age, and active eczema. This will be the first study to investigate the relationship between sECP, uEPX, and cotinine in asthmatic and healthy children.
Topic addressed: We hypothesize that children with asthma will have higher levels of sECP and uEPX compared to healthy children. Furthermore, infants diagnosed with asthma and exposed to in utero and/or postnatal ETS will have the highest ECP and EPX values, while healthy children unexposed to ETS will have the lowest levels of ECP and EPX.
Progress towards specific aims: We are currently conducting a prospective multi-center study in Southern California in order to recruit 200 Caucasian, African-American, Hispanic, Asian and/or Pacific Islander children (0-4 years) with newly diagnosed asthma and 200 comparison healthy children, matched on age, race, sex, clinic, and hospital site. Both groups of parents are participating in a telephone interview, and completing 2 short follow-up questionnaires and a diary of asthma symptoms. Infant sECP, uEPX, and urinary cotinine levels are being measured at baseline, and every 4 months for 1 year. Enrollment of eligible subjects is not progressing as rapidly as expected. The solutions we are immediately implementing include: 1) hiring a Spanish translator to assist with initial and follow-up visits, 2) hiring a fourth year medical student to recruit subjects, specifically at San Diego sites and an additional patient recruiter at Children's Hospital Los Angeles, and 3) enlisting several new hospital sites in the San Diego area. The sample of children who have been interviewed is incomplete, so there are no preliminary results. It is expected that 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.
Impact: The ability to identify asthmatics very early in life is important, because wheezing in early childhood carries the risk of permanent reduction in lung function. This study determine whether inflammatory markers differentiate genetically susceptible infants whose airways have been further irritated with environmental tobacco smoke, and later develop asthma. |