Impaired Nitric Oxide Synthetase activity in Primary Ciliary Dyskinesia – data driven hypothesis

• Conditions: Q34.8; E84.0; Other specified congenital malformations of respiratory system; Cystic fibrosis with pulmonary manifestations

• Registration Number: DRKS00024201
• Lead Sponsor: St. Josef-Hospital

Brief Summary

Results In both lung diseases sputum concentrations of L-Arg (PCD 28.78 vs. CF 36.54 vs. HC 11.59 µmol/mg, p < 0.001), ADMA (PCD 0.13 vs. CF 0.18 vs. HC 0.01 µmol/mg, p < 0.001), hArg and ornithine/citrulline ratio (indirectly indicating arginase/ NO synthase activity ratio) were elevated in comparison to HC. However, nitrite and nitrate were decreased in PCD vs. HC (nitrite 5.74 vs. 9.68 µmol/mg, p < 0.001; nitrate 18.14 vs. 36.51 µmol/mg, p < 0.001), but increased in CF (nitrite 16.64 µmol/mg, nitrate 63.31 µmol/mg), indicating a PCD disease-specific effect. Metabolite concentrations in urine and plasma were similar between the groups. Conclusion Our data suggest increased sputum arginase activity and ADMA in both lung diseases with neutrophilic inflammation. In contrast, reduced NO metabolites in sputum only in pwPCD indicate an impaired NO synthesis in PCD.

Detailed Description

Not available

Study Timeline

• Study Completion: 2020-05-14
• Study Start: 2021-02-04
• Results First Posted: 2023-09-16
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 63

Inclusion Criteria

PCD patients:
- Confirmed diagnosis of PCD according to the current diagnostic standard (at least 2 pathological findings typical of PCDs in different cilia examination methods, or 3 congruent abnormal results in 1 cilia examination technique, obtained from different samples, or proving PCD molecular genetics)
- Age> = 10 years
- Consent to study participation

CF patients:
- Patients with a confirmed diagnosis of CF according to current diagnostic criteria (2x positive sweat test, positive CF molecular genetics and / or CF-typical CFTR dysfunction in CF electrophysiology (ICM or nPD))
- Age> = 10 years
- Consent to study participation

Healthy controls:
- Free from chronic respiratory diseases (such as asthma, bronchiectasis, etc.), free from acute infectious or inflammatory conditions (infections, trauma, fever), free from any chronic underlying disease with a potential inflammatory reaction / component
- Age> = 10 years
- Consent to study participation

Exclusion Criteria

- special diet in the last 2 weeks before the examination
- consumption of canned fish the day before
- for PCD and CF patients: acute pulmonary exacerbation according to modified Fuchs criteria
- for healthy controls: acute infection

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Concentration of asymmetric dimethylarginine, arginine and NO metabolites in sputum of PCD patients compared to healthy controls and CF patients

Secondary Outcome Measures

Name	Time	Method
Concentration of arginine and asymmetric dimethylarginine in plasma and urine from PCD patients compared to CF patients and healthy controls.<br>