Determination of Normal Values of Nasal Nitric Oxide in Adults

Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by impaired airway mucociliary clearance leading to recurrent respiratory infections, bronchiectasis and eventually respiratory insufficiency. Diagnosis of PCD is difficult and relies on complex methods which are not widely available (1).

Nasal nitric oxide (nNO) is reduced in PCD patients as compared to normal subjects, and nNO measurement has been proposed as a non-invasive screening tool for PCD. However, nNO measurement techniques are not standardized and reference values are lacking (2, 3).

The NIOX MINO is a handheld analyzer developed for the non-invasive measurement of exhaled NO (eNO) in asthmatics. Measurement of nNO with the NIOX MINO has been reported in only few studies (4-6), which mainly compared the NIOX MINO with others NO analyzers. However, no study attempted to establish reference values with the NIOX MINO in a large number of normal subjects.

One critical issue in nNO measurement is to avoid contamination of nasal air by exhaled alveolar air during nNO sampling. This can be obtained by either breath holding, or by a breathing technique allowing soft palate closure during sampling, such as mouth breathing again resistance. However, as sampling times with the NIOX MINO are long (2 minutes at a flow of 2 ml/min, and 45 seconds at a flow of 5 ml/min), these techniques may be difficult to apply.

In this pilot study, we will determine normal nNO values in 100 healthy men and women aged 20 to 70 years using 3 different breathing techniques:

1. breath holding during 45 seconds
2. mouth breathing through a fixed resistance (a straw), to create a small positive pressure in the oropharynx during expiration only
3. mouth breathing through a continuous positive airway pressure (CPAP) apparatus, which produces continuous soft palate closure during quiet spontaneous breathing, thus allowing long sampling times for nNO measurement.

This study will allow: 1) to determine whether nNO can be reliably measured with the NIOX MINO in adult normal subjects, 2) to identify the most reproducible breathing technique, 3) to determine normal values of nNO as measured by the NIOX MINO, and 4) to explore possible differences between genders and age groups.

References:

1. J.S.A. Lucas, W.T. Walker, C.E. Kuehni and R. Lazor. Primary ciliary dyskinesia. Eur Respir Mon. 2011; 54: 201-217.
2. ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir Crit Care Med 2005; 171: 912-30.
3. Marthin JK, Nielsen KG. Choice of nasal nitric oxide technique as first-line test for primary ciliary dyskinesia. Eur Respir J 2011; 37: 559-65.
4. Marthin JK, Nielsen KG. Hand-Held Tidal Breathing Nasal Nitric Oxide Measurement - A Promising Targeted Case-Finding Tool for the Diagnosis of Primary Ciliary Dyskinesia. PLoS ONE 2013; 8: e57262.
5. Weschta M, Deutschle T, Riechelmann H. Nasal fractional exhaled nitric oxide analysis with a novel hand-held device. Rhinology 2008; 46: 23-7.
6. Maniscalco M, Laurentiis G de, Weitzberg E, Lundberg JO, Sofia M. Validation study of nasal nitric oxide measurements using a hand-held electrochemical analyser. Eur J Clin Invest 2008; 38: 197-200.