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A2844 - NIOX VERO® Nasal Measurement Mode Differentiates Individuals with PCD from Healthy Individuals with Two Breathing Methods
Author Block: M. MacDonald-Berko, K. Rickard; Circassia Pharmaceuticals, Inc., Morrisville, NC, United States.
INTRODUCTION: Diagnosis of PCD is generally made through evaluation of nasal biopsy or scraping and/or genetic testing. We performed a subset analysis of a recent study examining the use of nasal nitric oxide (nNO), measured with NIOX VERO, to differentiate healthy individuals from those with PCD. METHODS: A multi‐center, single visit, non‐randomized study with subjects >=5 years with PCD vs. age matched healthy controls (HC). Subjects with PCD were previously diagnosed based on clinical phenotype plus one of the following a) nasal biopsy or scraping showing a hallmark PCD defect, or b) genetic test positive in a known PCD-causing gene (except for RSPH1), or, in the EU, c) low nNO determined by chemiluminescent analyzer and either two occasions with hallmark changes on high speed video microscopy (HSVM) or demonstration of mis-localization of ciliary proteins by immunofluorescence microscopy (IFM). All subjects attempted measurements using tidal breathing (TB‐nNO) followed by expiration against resistance with velum closed (ER‐nNO) methods. Descriptive analyses were performed, including a Receiver Operating Characteristic (ROC) curve analysis to assess optimal cut‐off values. In this sub-analysis, subjects with PCD confirmed by genetic testing and/or nasal biopsy or scraping were analyzed. RESULTS: 149 subjects (44 PCD/105 HC) completed two measurements from one nostril with either breathing method. All 44 subjects with PCD were confirmed with nasal scraping or biopsy and/or genetic testing. For subjects with two measurements from both nostrils using the TB-nNO method, mean nNO values for the PCD cohort (n=40) was 45.6 (36.17) ppb and for the HC (n=78) was 570.0 (226.89) ppb. The optimal cut off value for the TB-nNO method of 171 ppb for TB‐nNO (AUC 100%; specificity 100%; sensitivity 100%; PPV 100%; NPV 100%). For subjects with two measurements from both nostrils using the ER-nNO method, mean nNO values for the PCD cohort (n=37) was 74.8 (65.64) ppb and for the HC (n=83) was 948.2 (387.40) ppb. The optimal cut off value for the ER-nNO method was 356 ppb for ER‐nNO (AUC 99.0%; specificity 96.3%; sensitivity 100%; PPV 92.7%; NPV 100%). CONCLUSIONS: In this population characterized by known PCD confirmed by genetic testing and/or nasal biopsy or scraping, NIOX VERO correctly differentiated subjects with PCD from healthy subjects. Both TB and ER methods can be used in the diagnostic work-up in children and adults. Nasal NO measured with NIOX VERO demonstrates good diagnostic accuracy to differentiate PCD from healthy in patients with clinical phenotype for PCD.