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. 2022 Sep 26;90(5):399-406.
doi: 10.3390/arm90050050.

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico

Wilfredo De Jesús-Rojas  1   2 , Francisco Alvarado-Huerta  1 , Jesús M Meléndez-Montañez  2 , José Muñiz-Hernández  3 , Arnaldo Santos-López  2 , Ricardo A Mosquera  4
Affiliations

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico

Wilfredo De Jesús-Rojas et al. Adv Respir Med. .

Abstract

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the island. The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD. The acquisition of state-of-the-art diagnostic tools such as nNO positively impacted and expanded our current PCD diagnostic capabilities in Puerto Rico for our founder genetic mutation. The addition of nNO technology promotes earlier disease screening and recognition for patients with PCD on the island. The access to nNO helped us to properly characterize the PCD diagnosis for patients with the RSPH4A (c.921+3_921+6del (intronic)). As a result, our findings will allow us to be part of the national PCD foundation registry and represent Puerto Rican Hispanics in future PCD multicentric clinical trials.

Keywords: Primary Ciliary Dyskinesia; Puerto Rico; RSPH4A; cilia; founder mutation; genotype; nasal Nitric Oxide; phenotype.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Methodology approach: Stratification of subjects by cohorts for nNO levels measurement analysis.
Figure 2
Figure 2
Nasal Nitric Oxide (nNO) Levels in PCD subjects with the RSPH4A founder (c.921+3_921+6del (intronic)) pathogenic variant compared with gender–age-matched controls. Cutoff value: 77 nL/min. Subjects in cohorts 2 and 3 compared to cohort 4 were not statistically significantly different. ** Kruskal–Wallis Test, * Wilcoxon Signed-Rank Test. A subject with an nNO value below the cutoff point (red triangle) was identified in cohort 3 with an nNO level of 36.2 nL/min.
See this image and copyright information in PMC

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