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Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects

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Abstract

Introduction

Nasal nitric oxide (nNO) is extremely low in individuals with primary ciliary dyskinesia (PCD) and is recommended as part of early workup. We investigated whether tidal breathing sampling for a few seconds was as discriminative between PCD and healthy controls (HC) as conventional tidal breathing sampling (cTB-nNO) for 20–30 s.

Methods

We performed very rapid sampling of tidal breathing (vrTB-nNO) for 2, 4 and 6 s, respectively. Vacuum sampling with applied negative pressure (vrTB-nNOvac; negative pressure was applied by pinching the sampling tube) for < 2 s resulted in enhanced suction of nasal air during measurement. Feasibility, success rate, discriminatory capacity, repeatability and agreement were assessed for all four sampling modalities.

Results

We included 13 patients with PCD, median (IQR) age of 21.8 (12.2–27.7) years and 17 HC, 25.3 (14.5–33.4) years. Measurements were highly feasible (96.7% success rate). Measured NO values with vrTB-nNO modalities differed significantly from TB-nNO measurements (HC: p < 0.001, PCD: p < 0.05). All modalities showed excellent discrimination. The vacuum method gave remarkably high values of nNO in both groups (1865 vs. 86 ppb), but retained excellent discrimination. vrTB-nNO4sec, vrTB-nNO6sec and vrTB-nNOvac showed identical specificity to cTB-nNO (all: 1.0, 95% CI 0.77–1.0).

Conclusion

vrTB-nNO sampling requires only a few seconds of probe-in-nose time, is feasible, and provides excellent discrimination between PCD and HC. Rapid TB-nNO sampling needs standardisation and further investigations in infants, young children and patients referred for PCD workup.

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Authors and Affiliations

  1. Danish PCD & chILD Centre, CF Centre Copenhagen, Paediatric Pulmonary Service, Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Mathias G. Holgersen, June K. Marthin & Kim G. Nielsen

Authors
  1. Mathias G. Holgersen
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  2. June K. Marthin
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  3. Kim G. Nielsen
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Corresponding author

Correspondence to Kim G. Nielsen.

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Conflict of interest

KGN and JKM are members of BEAT-PCD (COST Action BM1407). KGN is partly financially supported by The Children’s Lung Foundation. MGH declares that he has no conflict of interest.

Ethical Approval

The study was approved by the Committee on Health Research Ethics in the Capital Region of Denmark in March 2017 [Journal No. H-17002138].

Informed Consent

Informed consent was obtained from all individual participants, and their parents and/or guardians when necessary, included in the study prior to enrollment.

Research Involving Human Participants

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Holgersen, M.G., Marthin, J.K. & Nielsen, K.G. Proof of Concept: Very Rapid Tidal Breathing Nasal Nitric Oxide Sampling Discriminates Primary Ciliary Dyskinesia from Healthy Subjects. Lung 197, 209–216 (2019). https://doi.org/10.1007/s00408-019-00202-x

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  • DOI: https://doi.org/10.1007/s00408-019-00202-x

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