Abstract
Reduced L-arginine availability for NO synthases (NOS) and increased levels of NOS inhibitor asymmetric dimethylarginine (ADMA) cause airway NO deficiency in CF patients with severe pulmonary exacerbation (PEx), but data for milder CF exacerbation or for PCD are lacking.
Methods: CF and PCD patients with PEx requiring oral AB treatment were studied. Exclusion criteria included infection with P. aeruginosa or B. cepacia. Sputum samples were obtained before (V1) and after (V2) three weeks of oral ABs. L-arginine metabolites were quantified by LC-MS/MS and NO metabolites (NOx) using Griess reagent.
Results: Eleven PCD and 16 CF patients with mean age of 10 yrs (range 7-16 yrs) were studied. Mean (±SD) FEV1 at V1 was not different between groups (63±13.8 % in PCD and 74±18.3 % predicted in CF, p=0.1). FEV1 improved to 71 (±21.2) % in PCD (p<0.05, paired t-test) and 86 (±12.3) % predicted in CF (p<0.01). NOx in PCD sputum was 184.3±35.7 µM before and increased to 444.3±82.7 µM at V2 (p=0.025, paired t test). Sputum NOx was higher in CF compared to PCD at V1 (625.5±158.1 µM, p=0.003) and did not change after treatment. There were no differences in L-arginine or ADMA levels between PCD and CF. However, the ratio of NOS substrate/NOS inhibitor (L-arginine/ADMA), was lower in PCD than CF at V1 (138.0±17.8 vs 254.4±41.8, p<0.01) but not different at V2 (320.8±66.4 vs 311.9±60.2). In addition, the L-arginine/L-ornithine ratio, an index of L-arginine availability for NOS, was lower in PCD than CF at V1 (1.0±0.1 vs 1.6±0.2, p<0.02) but not V2 (1.4±0.2 vs 1.6±0.4).
Conclusions: Children with PCD and mild pulmonary exacerbation have reduced arginine availability and airway NOx compared to CF.
- © 2014 ERS