This Article Full Text Full Text (PDF) All Versions of this Article: 200907-1079OCv1 181/4/324    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Olin, A.-C. Articles by Torén, K. PubMed PubMed Citation Articles by Olin, A.-C. Articles by Torén, K.

Increased Fraction of Exhaled Nitric Oxide Predicts New-Onset Wheeze in a General Population

¹ Occupational and Environmental Medicine, ² Cardiovascular Disease, and ³ Community Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden; and ⁴ Department of Biostatistics, Faculty of Medicine, University of Oslo, Norway

Correspondence and requests for reprints should be addressed to Anna-Carin Olin, M.D., Occupational and Environmental Medicine, Sahlgrenska University Hospital, Box 414, SE 405 30 Göteborg, Sweden. E-mail: Anna-Carin.Olin{at}amm.gu.se

Rationale: Fraction of exhaled nitric oxide (FE_NO) is regarded as a marker of airway inflammation. It is unknown whether increased FE_NO in respiratorily healthy subjects increases the risk of developing wheeze.

Objectives: To examine if increased levels of FE_NO predicts later onset of wheeze.

Methods: We followed up 2,200 men and women from a general population–based study. At baseline, the subjects were investigated with questionnaires, blood samples, pulmonary function tests, and FE_NO. At follow-up 4 years later, all subjects were mailed a respiratory questionnaire. The association between incident wheeze and baseline levels of FE_NO over the 90th percentile were evaluated calculating hazard ratios using Cox regression models adjusted for smoking habits, age, height, sex, and atopy.

Measurements and Main Results: The follow-up questionnaire was completed by 1,896 subjects (86.2%). All subjects reporting wheeze, asthma, or asthma symptoms at baseline were excluded resulting in a study population of 1,506 subjects. Of these, 49 subjects reported new-onset wheeze. The median concentration of FE_NO at baseline was significantly higher among those with new-onset wheeze (18.8 ppb vs. 15.8 ppb, P = 0.03). In a Cox regression model including all subjects, FE_NO over the 90th percentile predicted onset of wheeze (hazard ratio 2.7; 95% confidence interval, 1.4–5.4). In stratified models, this was most apparent among never-smokers and in atopic subjects, for whom the odds ratios were higher.

Conclusions: Our results indicate that increased FE_NO is associated with an increased risk of developing wheeze. The results also support the hypothesis that increased level of FE_NO among subjects without respiratory symptoms is a sign of subclinical airways inflammation.

Key Words: exhaled nitric oxide • new-onset wheeze • airways inflammation • epidemiology • longitudinal

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject There is a lack of knowledge whether increased levels of fraction of exhaled nitric oxide (FENO) predict subsequent asthma symptoms among adults in a general population. What This Study Adds to the Field Increased levels of FENO are associated with an increased risk of developing wheeze, supporting the hypothesis that increased level of FENO among subjects without respiratory symptoms is a sign of subclinical airways inflammation.