Feasibility of nasal NO screening in healthy newborns

Abstract

Background: Nasal nitric oxide (nNO) measurement is recommended as a first line screening test for primary ciliary dyskinesia (PCD). While reliable velum- and non-velum-closure techniques exist for preschool children and older individuals, no data are available for neonates.

Aims: To determine feasibility of nNO screening and nNO concentration in healthy newborns in the first week of life.

Methods: Nasal NO was analyzed in tidal breathing during natural sleep using a CLD-88 sp NO analyzer (chemoluminescence sensor) and a NIOX MINO (electrochemical sensor). Test success and nNO concentration were determined and compared between the two devices.

Results: Nasal NO was measured in 62 healthy neonates within the first week of life. Feasibility of nNO measurement was 100% for at least one nostril and 85.5% for both nostrils using the chemoluminescence device, but significantly lower with the electrochemical device (85.5% and 53.2%; p < .001). Median nNO concentration was 38 ppb (interquartile range, 27-55; range, 9-100) with the ECOMEDICS device and 23 (15-33, 8-59) with the NIOX MINO (p < .001), with a trend towards higher values for older subjects. None of the subjects exceeded nNO levels of 100 ppb.

Conclusion: Measurement of nNO using a chemoluminescence device is highly feasible in newborns during natural sleep. However, nNO levels are considerably lower compared to the published data for older individuals and in the range of a PCD reference group of infants between 4 and 8 weeks of age, potentially resulting in a great overlap with subjects with PCD in this age group. Therefore, screening for PCD using nasal NO might not be useful in the first week of life. Upon clinical suspicion, other diagnostic tests such as high-speed video analysis of the cilia should be applied.

Keywords: chemoluminescence; electrochemical sensor; nasal nitric oxide; newborns; primary ciliary dyskinesia; screening.

Figure 1

(A) Comparison of nNO in newborns ≤7 days of age for the chemoluminescence device and the electrochemical sensor device (p = <0.001) (Wilcoxon sign‐rank test). (B) Distribution of nNO values of the entire study sample measured with the NIOX MINO and the CLD‐88 sp NO analyzer [Color figure can be viewed at wileyonlinelibrary.com]

Figure 2

(A) Bland‐Altman plot showing the difference between nNO values measured with the CLD‐88 sp NO analyzer or the NIOX MINO device. Upper and lower limits of 95% agreement are illustrated as dashed lines. The upper and lower limits of 95% agreement between devices were 16 and −47 ppb, respectively. (B) Distribution of nNO values measured with the CLD‐88 sp NO analyzer or the NIOX MINO device. Closed blue circles show values measured with the CLD‐88 sp NO analyzer, open red circles show values measured with NIOX MINO device. Paired measurements of each study participant are connected with a line [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Nasal NO concentration during the first week of life assessed by the CLD‐88 sp NO analyzer. Median (IQR) nNO was 27 (22, 37) for day 2 (n = 22 measurements), 43 (34, 64) for day 3 (n = 26), and 47 (38, 50) for day 4 (n = 11). nNO between day 2 and 3 differed significantly (p = .001), but not between day 3 and 4 (p = .777). Tested with the Mann–Whitney test. Measurements at days 1, 5, and 6 were excluded due to low case numbers. IQR, interquartile range [Color figure can be viewed at wileyonlinelibrary.com]