Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: a meta-analysis

Abstract

BackgroundTo date, diagnosis of Primary Ciliary Dyskinesia (PCD) remains difficult and challenging. We systematically evaluated the diagnostic performance of nasal Nitric Oxide (nNO) measurement for the detection of PCD, using either velum-closure (VC) or non-velum-closure (non-VC) techniques.MethodsAll major electronic databases were searched from inception until March 2015 using appropriate terms. The sensitivity and specificity of nNO measurement was calculated in PCD patients diagnosed by transmission electron microscopy, high speed video-microscopy or genetic testing. Summary receiver operating characteristic (HSROC) curves were drawn using the parameters of the fitted models.ResultsTwelve studies provided data for 13 different populations, including nine case–control (n = 793) and four prospective cohorts (n = 392). The overall sensitivity of nNO measured by VC techniques was 0.95 (95 % CI 0.91–0.97), while specificity was 0.94 (95 % CI 0.88–0.97). The positive likelihood ratio (LR+) of the test was 15.8 (95 % CI 8.1–30.6), whereas the negative likelihood ratio (LR-) was 0.06 (95 % CI 0.04–0.09). For non-VC techniques, the overall sensitivity of nNO measurement was 0.93 (95 % CI 0.89–0.96) whereas specificity was 0.95 (95 % CI 0.82–0.99). The LR+ of the test was 18.5 (95 % CI 4.6–73.8) whereas the LR- was 0.07 (95 % CI 0.04–0.12).ConclusionsDiagnostic accuracy of nNO measurement both with VC and non-VC maneuvers is high and can be effectively employed in the clinical setting to detect PCD even in young children, thus potentiating early diagnosis. Measurement of nNO merits to be part of a revised diagnostic algorithm with the most efficacious combination of tests to achieve PCD diagnosis.

Primary Ciliary Dyskinesia

“…Exhaled air from the lower airways has a much lower concentration of NO than the nose; thus, maneuvers must be instituted to close the soft palate to limit contamination of nasal air by air from the lower airways (48). This approach has been validated in adults and children over 5 years of age (13, 49), but is less feasible in younger children. For infants and young children, one study measured nNO during tidal breathing (50); however, it should be noted that nNO values during tidal breathing are ~40% lower in healthy subjects than values obtained at plateau during palate closure.…”

“…Findings include subsegmental atelectasis, mucus plugging, air trapping, ground-glass opacity, and peribronchial thickening. Bronchiectasis can occur during infancy, and ~50–75% of older pediatric patients and nearly all adults with PCD have bronchiectasis with worse disease in the middle lobe and lingula, as well as basilar regions (25-27, 49, 58). Chest CT is more sensitive for detecting early lung disease in PCD, compared to lung function testing by spirometry (60).…”

Prevalence of primary ciliary dyskinesia in consecutive referrals of suspect cases and the transmission electron microscopy detection rate: a systematic review and meta-analysis

“…The other routinely used PCD diagnostic tests, the measurement of nNO and HSVM, have both been reported to perform better than TEM. More specifically, a recent meta-analysis of nNO measurements in PCD patients has demonstrated a pooled sensitivity of 93 to 95% depending on vellum closure status during testing (42) while a number of studies have reported high sensitivity values for HSVM ranging from 89 (43) to 100% (29). Although our findings suggest that PCD diagnosis should not rely only on TEM, performance of this test may still be beneficial since determination of an ultrastructural defect or confirmation of its absence may guide genetic testing wherever this is available.…”

Primary ciliary dyskinesia (PCD): A genetic disorder of motile cilia

“…Nitric oxide (NO) is a small diffusible gas molecule that is involved in multiple functions throughout the body. Multiple studies have demonstrated that nitric oxide within the nasal cavity (particularly within the sinuses) is high in healthy individuals and much lower (<10% of normal values) in PCD, suggesting that nasal NO (nNO) measurement may be a useful test for PCD [29,84,88,135]. Nasal NO is measured by a non-invasive approach using a small nasal probe to aspirate nasal gas at a rate of approximately 5 ml/second for measurement of nitric oxide content [10,14].…”