Relation of Two Different Subtypes of Croup Before Age Three to Wheezing, Atopy, and Pulmonary Function During Childhood: A Prospective Study Jose´ A. Castro-Rodrı ´guez, MD; Catharine J. Holberg, PhD; Wayne J. Morgan, MD; Anne L. Wright, PhD; Marilyn Halonen, PhD; Lynn M. Taussig, MD; and Fernando D. Martinez, MD ABSTRACT. Objective. Some retrospective evidence suggests that children with a history of croup may be at increased risk of subsequently developing asthma, atopy, and diminished pulmonary function. The objec- tive of this study was to determine the long-term out- come of croup (as diagnosed by a physician) in early life. Methods. Lower respiratory illnesses (LRIs) in the first 3 years of life were assessed in 884 children who were enrolled in a large longitudinal study of airway diseases at birth. Pulmonary function tests, markers of atopy, and wheezing episodes were studied at different ages between birth and 13 years. Results. Ten percent of children had croup with wheeze (Croup/Wheeze), 5% had croup without wheeze (Croup/No Wheeze), 36% had another LRI (Other LRI), and 48% had no LRI. Respiratory syncytial virus was more frequently isolated in children with Croup/Wheeze and Other LRI than in those with Croup/No Wheeze. There was no association between croup in early life and markers of atopy measured during the school years. Only children with Croup/Wheeze and with Other LRI had a significant risk of subsequent persistent wheeze later in life. Significantly lower levels of indices of intrapulmo- nary airway function were observed at ages <1 (before any LRI), 6, and 11 years in children with Croup/Wheeze and Other LRI compared with children with No LRI. Conversely, inspiratory resistance before any LRI epi- sode was significantly higher in infants who later devel- oped Croup/No Wheeze than in the other 3 groups. Conclusions. We distinguish 2 manifestations of croup with and without wheezing. Children who present with croup may or may not be at increased risk of sub- sequent recurrent lower airway obstruction, depending on the initial lower airway involvement, and preillness and postillness abnormalities in lung function associated with this condition. Pediatrics 2001;170:512–518; croup, wheezing, atopy, pulmonary function, children. ABBREVIATIONS. IgE, immunoglobulin E; LRI, lower respiratory illness; RSV, respiratory syncytial virus; PFT, pulmonary function test; V9 max FRC, maximal expiratory flow at functional residual capacity; FVC, forced vital capacity; FEV 1 , forced expiratory vol- ume in 1 second; FEF 25–75 , forced expiratory flow at 25%–75% of the forced vital capacity; PEF, peak expiratory flow; SEM, stan- dard error of the mean. V iral croup (acute laryngotracheobronchitis) is a frequent childhood respiratory infection that is characterized by inspiratory stridor, hoarse voice, and barking cough. 1–4 Data from the United States indicate that croup is a common cause of medical consultation in infants, with a peak inci- dence of nearly 60 cases/1000 child-years in children between the ages of 1 and 2 years. 5 Although croup is usually a self-limited disease, there is some evi- dence to suggest that children with a history of se- vere or recurrent croup may be at increased risk of developing asthma when compared with those with mild or no croup. 1,3,4,6 In support of this contention, studies in older children show that those with a history of hospital admissions for croup have a higher prevalence of bronchial hyperresponsiveness, allergy skin test response, and increased total serum immunoglobulin E (IgE) levels than do children without such a history. 1,3,4,7,8 Diminished pulmonary function has also been reported in schoolchildren with a history of croup in infancy. 9,10 Most of these studies, however, were retrospective and were based on selected populations of children with great variability in croup severity and recur- rence. Only one published study is based on a gen- eral population sample of unselected schoolchil- dren, 11 but ascertainment of croup was retrospective and based on parental questionnaires. In this study we assessed the long-term outcome of croup in early life using data from a large longitudi- nal study of airway diseases in .1000 children who were enrolled at birth. Assessment of croup (and the concurrent presence or absence of wheeze) was made directly by a physician during early childhood. METHODS The children who were included in this study were part of a birth cohort enrolled from 1980 to 1984 in the Tucson Children’s Respiratory Study, 12 a large longitudinal study of respiratory ill- nesses during childhood. Detailed information about the study design has been published elsewhere. 12 A total of 1246 healthy newborns originally were enrolled in the study. Birth weight, level of maternal education, maternal smoking, and data on parental history of physician diagnosis of asthma and allergic rhinitis were obtained from questionnaires administered to parents shortly af- ter their child’s birth. This study was approved by the Human Subjects Committee at the University of Arizona, and informed consent was obtained from parents. Lower Respiratory Illnesses (LRIs) During the first 3 years of life, participating children were taken by their parents to consult with their pediatricians whenever they From the Respiratory Sciences Center, University of Arizona, College of Medicine, Tucson, Arizona. Dr Taussig is now at the National Jewish Medical and Research Center, Denver, Colorado. Received for publication Sep 15, 1999; accepted Jun 13, 2000. Reprint requests to (F.D.M.) 1501 N Campbell Ave, Suite 2349, Box 245030, Tucson, AZ 85724. E-mail: fernando@resp-sci.arizona.edu PEDIATRICS (ISSN 0031 4005). Copyright © 2001 by the American Acad- emy of Pediatrics. 512 PEDIATRICS Vol. 170 No. 3 March 2001