Exhaled NO in cystic fibrosis: relationships with airway and lung vascular impairments

¹ Assistance Publique – Hôpitaux de Paris; Université Paris Descartes; Hôpital Cochin; Centre de Ressources et de Compétences pour la Mucoviscidose; Paris – France
² Assistance Publique – Hôpitaux de Paris; Université Paris Descartes; Hôpital Cochin; Service de Physiologie; Paris – France
³ Assistance Publique – Hôpitaux de Paris; Université Pierre et Marie Curie, Paris 6; Hôpital Armand Trousseau; Centre de Ressources et de Compétences pour la Mucoviscidose; INSERM UMR-893 Equipe 12; Paris – France
⁴ Assistance Publique – Hôpitaux de Paris; Université Paris Descartes; Hôpital européen Georges Pompidou; Unité de Recherche Clinique et d'Epidémiologie; Paris – France
⁵ Assistance Publique – Hôpitaux de Paris; Université Paris Descartes; Hôpital Necker – Enfants Malades; Centre de Ressources et de Compétences pour la Mucoviscidose; Paris – France
⁶ INSERM Unité U 841 Equipe 13; Faculté de Médecine de Créteil; Créteil – France
⁷ Assistance Publique – Hôpitaux de Paris; Université Paris Descartes; Hôpital européen Georges Pompidou; Département de Physiologie – Radio-Isotopes, Clinique de la Dyspnée; UPRES EA 4068; Paris – France

^* To whom correspondence should be addressed. E-mail: christophe.delclaux{at}egp.aphp.fr.

	Abstract

A reduction of exhaled NO fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of this study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux, J'aw_NO; alveolar NO concentration, Calv_NO) and lung function tests characterizing airflow limitation and lung vascular bed (capillary blood volume and physiological dead space/tidal volume [physVD/VT] ratio on exercise).

Thirty-four patients with CF (16 children, 18 adults), without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (CO and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with V'O₂, V'CO₂ and arterial blood gas evaluations.

Both J'aw_NO and Calv_NO correlated positively with airflow limitation. Calv_NO correlated positively with capillary volume / alveolar volume. On exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physVD/VT and peak V'O₂). Calv_NO at rest correlated positively with these parameters of wasted ventilation on exercise (physVD/VT; V'E/V'CO₂ at ventilatory threshold and V'E/V'CO₂ slope).

Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.