Wheezing and Bronchial Hyper-responsiveness in Early Childhood as Predictors of Newly Diagnosed Asthma in Early Adulthood: A Longitudinal Birth-Cohort Study

Abstract

Stern DA, Morgan WJ, Halonen M, Wright AL, Martinez FD. Lancet. 2008;372(9643):1058–1064PURPOSE OF THE STUDY. To estimate the contributions of gender and early life factors to newly diagnosed and persistent asthma in young adults.STUDY POPULATION. The study evaluated 849 enrollees of the Tucson Children's Respiratory Study who had adult data at 22 years of age.METHODS. The cohort was derived from all healthy infants born in Tucson, Arizona, between 1980 and 1984. Shortly after birth, the parents completed a questionnaire on demographic data and were instructed to see a collaborating pediatrician at the first sign of lower respiratory illness. Physician-diagnosed asthma or wheezing was assessed at 2, 3, 6, 8, 11, and 16 years of age. At 6 years of age, allergy skin-prick tests were performed for all participants, and cold air bronchial challenge was performed for participants with a history of lower respiratory illness. At 22 years of age, an in-depth evaluation was performed with questionnaires on asthma symptoms, asthma medication use, and smoking history. Allergy skin-prick tests and spirometry were performed for participants still living in the Tucson area.RESULTS. Subjects with adult data at 22 years of age were more likely to have nonsmoking, nonminority parents with higher levels of education than were those without adult data. Of the 849 participants, 255 (30%) had asthma diagnosed at some time in their lives, 181 (22%) had active asthma, and 224 (26%) reported current smoking. Participants with inactive asthma had pre- and postbronchodilator spirometry results comparable to those of participants who never had asthma. Participants with newly diagnosed asthma had lower forced expiratory volume in 1 second/forced vital capacity ratios, which were not bronchodilator responsive. Factors associated with newly diagnosed asthma, chronic asthma, or shortness of breath with wheezing at 22 years of age included female gender, parental asthma, late-onset (>3 years of age) wheeze, persistent wheeze, Alternaria mold sensitivity at 6 years of age, cold air bronchial hyperresponsiveness, and reduced air flow rates at 6 years of age. Seventy percent of participants with current asthma and 63% with newly diagnosed asthma reported episodes of wheeze before 6 years of age. Male gender was a significant indicator of asthma remission by early adulthood. The combination of Alternaria sensitivity and cold air bronchial hyperresponsiveness at age 6 years and persistent wheeze at age 6 years were strong predictors of chronic asthma at age 22 years.CONCLUSIONS. Children with transient early wheezing were at much less risk for chronic asthma that persisted through childhood or reappeared more intensely in early adult life, compared with children with persistent or late-onset wheezing. Women were twice as likely to have new asthma diagnosed between 16 and 22 years of age.REVIEWER COMMENTS. This comprehensive study confirms previous longitudinal studies of the same age group. The lack of bronchodilator response of the forced expiratory volume in 1 second in newly diagnosed asthma is disconcerting but does not necessarily reflect permanent obstruction. Initial oral corticosteroid treatment has been shown to improve pulmonary function and to unmask bronchodilator responsiveness. Limitations of the study include the use of physician-diagnosed asthma in the absence of the demonstration of bronchodilator reversibility, a significant loss of participants over the course of time, with resulting skewed participant demographic characteristics, and selected assessment of responses to cold air. No risk factor alone identifies all of the possible forms of asthma.