An international survey on nasal nitric oxide measurement practices for the diagnosis of primary ciliary dyskinesia

Abstract

Nasal nitric oxide (nNO) measurements are routinely used in the assessment of patients suspected to have primary ciliary dyskinesia (PCD), but recommendations for performing such measurements have not focused on children and do not include all current practices. To guide the development of a European Respiratory Society-supported technical standard for nNO measurements in children, an international online survey was conducted to better understand current practices for measuring nNO among providers involved in PCD diagnostics.Seventy-eight professionals responded, representing 65 centres across 18 countries, mainly located in Europe and North America. Nearly all centres measured nNO in children and more than half of them performed measurements before 5-years of age. The test was often postponed in children with signs of acute airway infection. In Europe, the electrochemical technique was more frequently used than chemiluminescence. A similar proportion of centres performed measurements during exhalation against a resistance (49/65) or during tidal breathing (50/65) with 15 centres using only exhalation against a resistance and 15 centres using only tidal breathing. The cut-off values used to discriminate PCD was consistent across centres using chemiluminescence analyzers and these centres reported results as an output (nL.min−1). However, cut-off values were highly variable across centres using electrochemical devices, and nNO concentrations were typically reported as ppb.This survey represents the first to determine real-world use of nNO measurements worldwide and revealed remarkable variability in methodology, equipment, and interpretation. These findings will be useful to standardise methods and training.

Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard

“…Ideally, nNO should be measured in a clinic or hospital space that has low ambient NO levels to avoid potentially artefactual results [30,31], but a recent survey showed that not all users measure ambient levels [20]. Environmental NO levels <20 ppb are generally considered acceptable to allow testing to proceed.…”

“…While children requiring PCD diagnostic testing typically have chronic upper and lower airway symptoms, these data strongly indicate that nNO measurements should not be measured during infective exacerbations. Many centres delay testing for 2-4 weeks following infection [20], but there is no evidence concerning the appropriate duration. In the absence of clear evidence, we suggest testing should be delayed 2-4 weeks after exacerbation symptoms have resolved and if doubt exists concerning a low nNO measurement the test should be repeated on a separate day.…”

“…While American Thoracic Society (ATS)/ERS guidelines recommend that nNO measurements are performed using chemiluminescence analysers [6,7,19], a recent worldwide survey reported that electrochemical devices are more frequently used, particularly outside North America [20]. Chemiluminescence analysers produce a real-time display of the NO signal, which is important for quality assurance, and there are standardised, validated methods using these analysers.…”

“…Internationally, clinicians and researchers are using different equipment, breathing manoeuvres, diagnostic cut-off values and reporting standards. The PCD community has identified the need for standardised and validated methods for nNO measurements as a priority [20].…”

Nasal nitric oxide measurement variability to establish a standard for reliable results

“…<1 ppb with 1% linearity from 0.1 to 5000 ppb for CLD 88 (Eco Medics, Duernten, Switzerland)) than for widely used electrochemical devices ( e.g. ±5 ppb for values <50 ppb and 10% for values >50 ppb for Niox Vero (Circassia, Oxford, UK)) [ 2 ], little is known on the biological variability of nNO measurements, except for increased nNO output variability in adults with rhinitis compared with healthy subjects and the positive effect of training on the level of nNO taken during expiration against a resistance (nNO-ER) in children [ 3 , 4 ]. The PCD Foundation Clinical Center Network and Genetic Disorders of Mucociliary Clearance Consortium recommend sampling both nostrils for nNO-ER and to perform at least two measurements per nostril with the aim of obtaining a 10% repeatability [ 4 ].…”