ORIGINAL PAPER Tidal off-line exhaled nitric oxide measurements in a pre-school population Received: 25 November 2002 / Revised: 25 February 2003 / Accepted: 27 February 2003 / Published online: 9 May 2003 Ó Springer-Verlag 2003 Abstract Exhaled nitric oxide (ENO) is used as a non- invasive marker of airway inflammation. The aim of this study was to measure ENO in a pre-school population using a relatively novel method, the off-line tidal breathing method, and to investigate differences in ENO between subjects with different presentations of wheez- ing. ENO was measured in 129 children (median age 4.4 years, quartiles 4.0–4.8 years) through a mouth mask attached to a two-way valve with an expiratory resis- tance of 5 cm H 2 O. Mean tidal ENO concentration (tENO) was calculated from triplicate measurements. Mean ± SEM tENO for 89 control subjects was 13±0.4 ppb (95%CI 11.8–13.7 ppb); this level was sig- nificantly different from tENO in 15 children with a history of recurrent wheezing (18.6±1.9 ppb; 95%CI 14.5–22.7 ppb; t-test P <0.0001). Mean tENO in 16 children with a single wheezing episode was 11.4±1.0 ppb (95%CI 9.2–13.6 ppb) and thus significantly different from the recurrent wheezing group (t-test P =0.0024). Conclusion: The off-line tidal breathing method is a feasible and appealing method for measuring exhaled nitric oxide in pre-school children. With this method, higher tidal exhaled nitric oxide levels were found in children with recurrent wheezing. Keywords Asthma Æ Exhaled nitric oxide Æ Paediatrics Æ Wheezing Abbreviations ENO exhaled nitric oxide Æ tENO tidal exhaled nitric oxide Introduction Nearly 30% of children in the western world are affected by asthma, with indications that the prevalence is increasing [31]. In recent years, airway inflammation has been studied intensively as the central pathogenic mechanism, leading to irreversible tissue destruction and concomitant impaired lung function, a process known as remodeling [9, 13]. Data from autopsy studies and in- duced sputum studies suggest that this airway inflam- mation and remodeling have their onset in early childhood [12, 25]. In infants and toddlers, however, it is unlikely that all forms of acute and recurrent airway obstruction repre- sent asthmatic inflammation. On the contrary, wheez- ing-associated respiratory illnesses in early childhood seem to comprise a heterogeneous group of conditions [30]. For instance, small airways are believed to predis- pose infants and toddlers to wheezing in association with viral upper respiratory tract infections [23]. It is tempt- ing to speculate that in this latter group of children there is little evidence of airway inflammation as opposed to those children with true asthma. This is in agreement with the findings from induced sputum studies [25]. The Global Initiative on Asthma (GINA) encourages the development and use of non-invasive tests to assess asthmatic airway inflammation. The need for methods to detect early asthma in young children is emphasised [26]. Moreover, the diagnosis of asthma is hampered by the lack of objective measures as children younger than 6 years are usually unable to perform reproducible spirometry measurements. Therefore, a simple and non- invasive and thus safe evaluation of airway inflamma- tion would be helpful in detecting asthma in these children. Exhaled nitric oxide (ENO) is being studied as a non- invasive marker of airway inflammation [16]. ENO levels Eur J Pediatr (2003) 162: 506–510 DOI 10.1007/s00431-003-1215-x Isabelle Meyts Æ Marijke Proesmans Veerle Van Gerven Æ Karel Hoppenbrouwers Kris De Boeck I. Meyts Æ M. Proesmans Æ K. De Boeck (&) Paediatric Pulmonology Department, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium E-mail: Christiane.DeBoeck@uz.kuleuven.ac.be Tel.: +32-16-343830 Fax: +32-16-343832 V. V. Gerven Æ K. Hoppenbrouwers Youth Health Care Centre, Centre for Preventive Medicine, Leuven, Belgium