1 Section of Gynaecology, Obstetrics and Paediatrics, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet4 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
ABSTRACT BACKGROUND Elevated fraction of exhaled nitric oxide (FeNO) and bronchial hyperresponsiveness are used as surrogate markers of asthma. These traits may be continuous in the population. OBJECTIVE To investigate whether FeNO and bronchial responsiveness are associated both in children with and in children without a history of asthma symptoms. METHODS 196 six-year-old children comprising asymptomatic children, children with intermittent asthmatic symptoms and children with persistent asthma were randomly included from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) high-risk birth cohort born of mothers with asthma. Bronchial responsiveness was assessed as the relative change in specific airway resistance after cold-dry-air hyperventilation. FeNO measurements were performed prior to the hyperventilation test. The association between FeNO and bronchial responsiveness was assessed by generalized linear models. RESULTS Bronchial responsiveness and FeNO exhibited a significant and linear association in the population. A doubling of FeNO corresponded to an 8.4% increase in airway resistance after challenge testing (95% CI; 3.7-13.1; p=0.0006) and remained significant after adjustment for gender, allergic rhinitis, current asthma, inhaled corticosteroid treatment and upper respiratory tract infections prior to testing. Stratified analyses showed similar associations in children with and without asthma. CONCLUSION FeNO and bronchial responsiveness are associated traits and continuous traits in young children regardless of asthma symptoms. This suggests a continuous spectrum from sub-clinical to clinical of a process underlying asthma and cautions against the use of these surrogate markers for a dichotomized approach to asthma diagnosis.Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen; Copenhagen University Hospital, Gentofte; Copenhagen; Denmark.Correspondence: Professor Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood; Health Sciences, University of Copenhagen; & The Danish Pediatric Asthma Center; Copenhagen University Hospital, Gentofte; Copenhagen, Denmark. E-mail: firstname.lastname@example.org*Dr. Schoos and Dr. Chawes contributed equally to this manuscript.Source of funding: COPSAC is funded by private and public research funds all listed on www.copsac.com. The Lundbeck Foundation; the Pharmacy Foundation of 1991; Augustinus Foundation; the Danish Medical Research Council and The Danish Pediatric Asthma Centre provided core support for COPSAC. The funding agencies did not have any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.