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

Abstract

A reduction of exhaled nitric oxide (NO) fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of the present study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux (J9aw,NO) and alveolar NO concentration (CA,NO)) and lung function tests characterising airflow limitation and pulmonary vascular bed (capillary blood volume and physiological dead space/tidal volume (VD/VT) ratio on exercise).In total, 34 patients (16 children, 18 adults) with CF, without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (carbon monoxide and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with oxygen uptake (V9O 2 ), carbon dioxide production (V9CO 2 ) and arterial blood gas evaluations.Both J9aw,NO and CA,NO correlated positively with airflow limitation. CA,NO correlated positively with capillary/alveolar volume. During exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physiological VD/VT and peak V9O 2 ). CA,NO at rest correlated positively with these parameters of wasted ventilation during exercise (physiological VD/VT, minute ventilation (V9E)/V9CO 2 at ventilatory threshold and V9E/V9CO 2 slope).Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.

Airway and alveolar nitric oxide production, lung function, and pulmonary blood flow in sickle cell disease

“…In adults with SCD, Girgis et al (11) reported a reduction in F eNO 50 ml/s but used a predominantly Caucasian control group (comprising 9 African-American, 1 Asian, and 20 Caucasian subjects) (11). Our results contrast with those from patients with cystic fibrosis and primary ciliary dyskinesia in whom airway NO is reduced compared to controls and the reduction in exhaled NO linked to more severe airway obstruction (23,24). In this study, we found no significant correlations between F eNO indices and R5 or FEV 1 :VC.…”

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.…”

Association of ex vivo vascular and bronchial dysfunctions in smokers

“…But we recently evidenced a frequent endothelial dysfunction of ex vivo pulmonary arteries of patients suffering from cystic fibrosis (that was associated with pulmonary hypertension), and we further demonstrated that criteria of mild pulmonary vascular disease were evidenced in some patients with cystic fibrosis that participated in exercise limitation [24].…”