Local and systemic alterations of the L-arginine/nitric oxide pathway in sputum, blood, and urine of pediatric cystic fibrosis patients and effects of antibiotic treatment

  • Alterations in the L-arginine (Arg)/nitric oxide (NO) pathway have been reported in cystic fibrosis (CF; OMIM 219700) as the result of various factors including systemic and local inflammatory activity in the airways. The aim of the present study was to evaluate the Arg/NO metabolism in pediatric CF patients with special emphasis on lung impairment and antibiotic treatment. Seventy CF patients and 78 healthy controls were included in the study. CF patients (43% male, median age 11.8 years) showed moderately impaired lung functions (FEV1 90.5 \(\pm\) 19.1% (mean \(\pm\) SD); 21 (30%) had a chronic \(\textit {Pseudomonas aeruginosa}\) (PSA) infection, and 24 (33%) had an acute exacerbation). Plasma, urinary, and sputum concentrations of the main Arg/NO metabolites, nitrate, nitrite, Arg, homoarginine (hArg), and asymmetric dimethylarginine (ADMA) were determined in pediatric CF patients and in healthy age-matched controls. Clinical parameters in CF patients included lung function and infection with PSA. Additionally, the Arg/NO pathway in sputum samples of five CF patients was analyzed before and after routine antibiotic therapy. CF patients with low fractionally exhaled NO (FENO) showed lower plasma Arg and nitrate concentrations. During acute exacerbation, sputum Arg and hArg levels were high and dropped after antibiotic treatment: Arg: pre-antibiotics: 4.14 nmol/25 mg sputum vs. post-antibiotics: 2.33 nmol/25 mg sputum, \(\it p\) = 0.008; hArg: pre-antibiotics: 0.042 nmol/25 mg sputum vs. post-antibiotics: 0.029 nmol/25 mg sputum, \(\it p\) = 0.035. The activated Arg/NO metabolism in stable CF patients may be a result of chronic inflammation. PSA infection did not play a major role regarding these differences. Exacerbation increased and antibiotic therapy decreased sputum Arg concentrations.

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Author:Beatrice HanuschGND, Folke BrinkmannORCiDGND, Sebene MayorandanGND, Kristine Chobanyan-JürgensGND, Anna WiemersGND, Kathrin JansenGND, Manfred BallmannORCiDGND, Anjona Schmidt-ChoudhuryGND, Alexander BollenbachGND, Nico DerichsGND, Dimitrios TsikasORCiDGND, Thomas LückeGND
URN:urn:nbn:de:hbz:294-77779
DOI:https://doi.org/10.3390/jcm9123802
Parent Title (English):Journal of clinical medicine
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2021/01/15
Date of first Publication:2020/11/24
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Pseudomonas aeruginosa; antibiotics; cystic fibrosis; inflammation; nitric oxide
Volume:9
Issue:12, Article 3802
First Page:3802-1
Last Page:3802-19
Institutes/Facilities:St. Josef-Hospital Bochum, Klinik für Kinder- und Jugendmedizin
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International