Abstract
Fractional exhaled nitric oxide (FeNO) is a non-invasive marker for eosinophilic airway inflammation and has been used for monitoring asthma. Here, we assess the characteristics of FeNO from preschool to school age, in parallel with asthma activity. A total of 167 asthmatic children and 66 healthy, age-matched controls were included in the 2-year prospective PreDicta study evaluating wheeze/asthma persistence in preschool-aged children. Information on asthma/rhinitis activity, infections and atopy was recorded at baseline. Follow-up visits were performed at 6-month intervals, as well as upon exacerbation/cold and 4–6 weeks later in the asthmatic group. We obtained 539 FeNO measurements from asthmatics and 42 from controls. At baseline, FeNO values did not differ between the two groups (median: 3.0 ppb vs. 2.0 ppb, respectively). FeNO values at 6, 12, 18 and 24 months (4.0, CI: 0.0–8.6; 6.0, CI: 2.8–12.0; 8.0, CI: 4.0–14.0; 8.5, CI: 4.4–14.5 ppb, respectively) increased with age (correlation p ≤ 0.001) and atopy (p = 0.03). FeNO was non-significantly increased from baseline to the symptomatic visit, while it decreased after convalescence (p = 0.007). Markers of disease activity, such as wheezing episodes and days with asthma were associated with increased FeNO values during the study (p < 0.05 for all). Age, atopy and disease activity were found to be important FeNO determinants in preschool children. Longitudinal and individualized FeNO assessment may be valuable in monitoring asthmatic children with recurrent wheezing or mild asthma.
Highlights
The use of objective measurements, including the measurement of lung function and airway inflammation by means of fractional exhaled nitric oxide (FeNO) is currently becoming reinforced in most official recommendations for children with asthma, even though there are not always clear correlations between the two
A limited number of cross-sectional studies have shown that preschool children with increased wheezing morbidity, as assessed by symptom frequency and persistence, present higher levels of FeNO, which suggests that FeNO levels might correlate with current and/or subsequent asthma diagnosis [7,8]
Days with symptoms in the last 3 months 1/week but 2 times/month, n (%) >1/week, n (%) daily, n (%) Cough, wheeze or difficulty in breathing during or after exercise in the last 12 months, n (%) Limitation of activities limited by asthma symptoms, n (%) Child completely well between symptomatic periods, n (%) Number of episodes of wheezing/asthma/cough in the last 3 months, median (25–75 percentiles) Number of episodes of wheezing/asthma/cough in the last 12 months, median (CIs) Inhaled corticosteroids as prophylactic treatment, n (%)
Summary
The use of objective measurements, including the measurement of lung function and airway inflammation by means of fractional exhaled nitric oxide (FeNO) is currently becoming reinforced in most official recommendations for children with asthma, even though there are not always clear correlations between the two. Associations between disease activity and airway inflammation are frequently inconclusive or negative, probably because they have mostly been assessed cross-sectionally or for limited time periods [1,2]. A limited number of cross-sectional studies have shown that preschool children with increased wheezing morbidity, as assessed by symptom frequency and persistence, present higher levels of FeNO, which suggests that FeNO levels might correlate with current and/or subsequent asthma diagnosis [7,8]. Fluctuations in airway inflammation have not been extensively studied in young children with asthma-associated symptoms, either due to difficulties in obtaining acceptable and repeatable maneuvers or to the potential impact of viral respiratory infections, use of inhaled corticosteroids and atopy per se [9]
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