Dataset Information

The value of nasal nitric oxide measurement in the diagnosis of primary ciliary dyskinesia.

ABSTRACT:

Importance

Nasal nitric oxide (nNO) testing is a method used in the diagnosis of primary ciliary dyskinesia (PCD). It has not been evaluated in Chinese population.

Objective

To establish a reference nNO value to assist in the diagnosis of PCD in Chinese children.

Methods

nNO values were measured in children with PCD (n = 36), cystic fibrosis (CF) (n = 20), asthma (n = 45), post-infectious bronchiolitis obliterans (BO) (n = 41) and non-PCD/non-CF bronchiectasis (n = 32). The receiver operating characteristic nNO value for the diagnosis of PCD was plotted and the area under the curve was calculated.

Results

nNO values were significantly lower in children with PCD (median 25.66 nL/min) than in children with asthma (186.26 ± 58.95 nL/ min), BO (143.47 ± 49.71 nL/min) and non-PCD/non-CF bronchiectasis (173.13 ± 63.80 nL/min), but not in children with CF (90.90 ± 43.20 nL/min). Notably however, no CF patient had an nNO value < 45 nL/min. A cut-off of 76 nL/min yielded the best sensitivity of 86.1%, and specificity of 91.4%, with an area under the curve of 0.920 (95% confidence interval 0.859-0.981) for the diagnosis of PCD. If CF was ruled out the specificity increased to nearly 100%.

Interpretation

nNO testing is able to discriminate between patients with PCD and those with CF, asthma, post-infectious BO and non-PCD/non-CF bronchiectasis. A cut-off of 76 nL/min could be further examined in patients suspected of PCD, to establish an nNO reference value for PCD screening in Chinese children.

SUBMITTER: Zhang X

PROVIDER: S-EPMC7331418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:RATIONALE:Primary ciliary dyskinesia (PCD) is a rare disorder causing chronic otosinopulmonary disease, generally diagnosed through evaluation of respiratory ciliary ultrastructure and/or genetic testing. Nasal nitric oxide (nNO) measurement is used as a PCD screening test because patients with PCD have low nNO levels, but its value as a diagnostic test remains unknown. OBJECTIVES:To perform a systematic review to assess the utility of nNO measurement (index test) as a diagnostic tool compared with the reference standard of electron microscopy (EM) evaluation of ciliary defects and/or detection of biallelic mutations in PCD genes. DATA SOURCES:Ten databases were searched for reference sources from database inception through July 29, 2016. DATA EXTRACTION:Study inclusion was limited to publications with rigorous nNO index testing, reference standard diagnostic testing with EM and/or genetics, and calculable diagnostic accuracy information for cooperative patients (generally >5 yr old) with high suspicion of PCD. SYNTHESIS:Meta-analysis provided a summary estimate for sensitivity and specificity and a hierarchical summary receiver operating characteristic curve. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess study quality, and Grading of Recommendations Assessment, Development, and Evaluation was used to assess the certainty of evidence. In 12 study populations (1,344 patients comprising 514 with PCD and 830 without PCD), using a reference standard of EM alone or EM and/or genetic testing, summary sensitivity was 97.6% (92.7-99.2) and specificity was 96.0% (87.9-98.7), with a positive likelihood ratio of 24.3 (7.6-76.9), a negative likelihood ratio of 0.03 (0.01-0.08), and a diagnostic odds ratio of 956.8 (141.2-6481.5) for nNO measurements. After studies using EM alone as the reference standard were excluded, the seven studies using an extended reference standard of EM and/or genetic testing showed a summary sensitivity of nNO measurements of 96.3% (88.7-98.9) and specificity of 96.4% (85.1-99.2), with a positive likelihood ratio of 26.5 (5.9-119.1), a negative likelihood ratio of 0.04 (0.01-0.12), and a diagnostic odds ratio of 699.3 (67.4-7256.0). Certainty of the evidence was graded as moderate. CONCLUSIONS:nNO is a sensitive and specific test for PCD in cooperative patients (generally >5 yr old) with high clinical suspicion for this disease. With a moderate level of evidence, this meta-analysis confirms that nNO testing using velum closure maneuvers has diagnostic accuracy similar to EM and/or genetic testing for PCD when cystic fibrosis is ruled out. Thus, low nNO values accompanied by an appropriate clinical phenotype could be used as a diagnostic PCD test, though EM and/or genetics will continue to provide confirmatory information.