Nasal nitric oxide screening for primary ciliary dyskinesia: systematic review and meta-analysis

Abstract

Nasal nitric oxide (nNO) concentrations are low in patients with primary ciliary dyskinesia (PCD) providing a noninvasive screening test.We conducted a systematic review of the literature to examine the utility of nNO in screening for PCD, in particular 1) different respiratory manoeuvres during sampling (velum closure, tidal breathing, etc.), 2) accuracy in screening young/uncooperative children, 3) stationary versus portable analysers, and 4) nNO in ''atypical'' PCD.96 papers were assessed according to modified PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and 22 were included in this review.Meta-analysis of 11 studies comparing nNO during a velum closure breath hold gave a mean¡SD nNO of 19.4¡18.6 nL?min -1 in PCD (n5478) and 265.0¡118.9 nL?min -1 in healthy controls (n5338). Weighted mean difference for PCD versus healthy controls was 231.1 nL?min -1 (95% CI 193.3-268.9; n5338) and 114.1 nL?min -1 (95% CI 101.5-126.8; n5415) for PCD versus cystic fibrosis. Five studies of nNO measurement during tidal breathing demonstrated that this is an acceptable manoeuvre in young children where velum closure is not possible, but the discriminatory value was reduced. Four small studies of portable NO analysers suggest these are reliable tools for screening for PCD. However, nNO must be interpreted alongside clinical suspicion. Future studies should focus on standardising sampling techniques and reporting. @ERSpublications Nasal nitric oxide is a useful and increasingly versatile screening tool in primary ciliary dyskinesia at all ages http://ow.ly/AR5mqThis article has supplementary material available from erj.ersjournals.com

Diagnostic Methods in Primary Ciliary Dyskinesia

“…In the authors' centre, 77nl/min distinguished PCD positive and negative outcomes based on HSVMA and TEM in consecutive referrals with sensitivity of 0.94 and specificity of 0.83 (unpublished). Therefore, although nNO is highly specific when differentiating PCD from healthy controls [29], it is less specific when differentiating PCD from patients with upper and lower respiratory tract symptoms [32]. It should be noted that the youngest child in the North American study was 5.1 years and the mean age much higher.…”

“…Whilst the reason for reduced nNO remains elusive [27], measurement became widely established as a screening test [11,17,19,[28][29][30][31]. A recent meta-A c c e p t e d M a n u s c r i p t analysis of 11 studies comparing nNO during a velum closure breath hold reported a mean nNO output of 19 nl/min (SD 18.6) in PCD (n=478) and 265 nl/min (SD 118.9) in healthy controls (n=338) [32]. Although nNO is lower than normal in patients with CF [32] differentiation from PCD remains good.…”

“…A recent meta-A c c e p t e d M a n u s c r i p t analysis of 11 studies comparing nNO during a velum closure breath hold reported a mean nNO output of 19 nl/min (SD 18.6) in PCD (n=478) and 265 nl/min (SD 118.9) in healthy controls (n=338) [32]. Although nNO is lower than normal in patients with CF [32] differentiation from PCD remains good. nNO readings in healthy infants and young children are lower than in older children, making false positive results more likely.…”

“…The chemiluminescence analyser displays the nNO concentration in real-time allowing measurements to be taken from the peak-plateau. This method reliably differentiates patients with PCD from those with other respiratory diseases [29, M a n u s c r i p t 31,32,[34][35][36] as well as healthy controls. The limitations of this 'gold standard' method for measuring nNO are that velum closure breath hold is difficult particularly for younger children and that the chemiluminescence analysers are expensive and not easily transportable.…”

“…These electromechanical analysers are more cost effective and have excellent portability. The studies comparing portable and stationary analysers suggest that portable analysers are a reliable means of measuring nNO, [32] but the machines have some drawbacks. In particular, the lack of real-time visual display of NO does not allow the technician to assess the acceptability of the measurement.…”