Flow-independent Nitric Oxide Exchange Parameters in Cystic Fibrosis

Abstract

Exhaled nitric oxide (NO) remains a promising noninvasive index for monitoring inflammatory lung diseases; however, the plateau concentration (C NO,plat ) is nonspecific and requires a constant exhalation flow rate. We utilized a new technique that employs a variable flow rate to estimate key flow-independent parameters characteristic of NO exchange in a group (n ϭ 9) of 10 to 14 yr-old healthy children and children with cystic fibrosis (CF): maximum flux of NO from the airways (J NO,max , pl s

Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments

“…Along this line, NO fraction has been found to be decreased in upper (nasal) airways in CF patients, whereas exhaled NO fraction (FeNO) had a nil to moderate decrease from infancy to adulthood [3][4][5][6][7]. This variable decrease in exhaled NO has been related to a defective expression of type 2 inducible NO synthase, which may participate to the susceptibility to Pseudomonas aeruginosa infection (bactericidal function) [8].…”

Probing the impact of axial diffusion on nitric oxide exchange dynamics with heliox

“…The characteristics of NO gas exchange are unique compared with other endogenous gases because exhaled NO is thought to have a significant alveolar and airway source (6,8,15,22). A two-compartment model is commonly used to characterize NO exchange dynamics for healthy and diseased lungs (9,11,13,20,21,23,24,27,29), by partitioning exhaled NO into airway and alveolar contributions using three flow-independent NO exchange parameters: maximum flux of NO from the airways (JЈaw NO ), the diffusing capacity of NO in the airways (Daw NO ), and the steady-state alveolar concentration (CA NO ). However, the two-compartment model considers only convection of NO in the airways as a transport mechanism and has neglected axial diffusion of NO in the gas phase to preserve mathematical simplicity.…”

Endogenous and nitrovasodilator-induced release of NO in the airways of end-stage cystic fibrosis patients

“…Despite the chronic inflammatory nature of the disease, exhaled NO has been reported unchanged or low depending on severity of the disease [2,[4][5][6][7]. Our study investigating exhaled NO in ventilated patients undergoing lung transplantation clearly demonstrates a profound reduction in endogenous gas-phase NO in the isolated lower airways of patients with end-stage CF.…”

“…However, there remains controversy regarding the anatomical localisation and mechanisms of NO deficiency, and its relationship with CF disease progression. By using extended exhaled NO analysis at different expiratory flow rates, indirect studies have attempted to distinguish NO production into bronchial and alveolar compartments based on basic models [4][5][6][7]. However, the fate of NO delivered directly to the alveoli has not been demonstrated in these patients.…”

“…Recent studies utilising extended NO exchange analysis resulted in contradictory findings showing no alterations, increased or decreased bronchial fluxes and/or alveolar NO concentrations in CF children and adults [4][5][6][7]. The emerging consensus suggests that the main mechanism of NO deficiency in adult CF may relate to increased bronchial inflammation and associated defective NO synthase expression, activity and NO production or increased degradation of produced NO [2,3,6,9].…”