title: Effects of inhaled nitric oxide at rest and during exercise in idiopathic pulmonary fibrosis.
abstract: Patients with idiopathic pulmonary fibrosis (IPF) usually develop hypoxemia and pulmonary hypertension when exercising. To what extent endothelium-derived vasodilating agents modify these changes is unknown. The study was aimed to investigate in patients with IPF whether exercise induces changes in plasma levels of endothelium-derived signaling mediators, and to assess the acute effects of inhaled nitric oxide (NO) on pulmonary hemodynamics and gas exchange, at rest and during exercise. We evaluated seven patients with IPF (6 men/1 woman; 57 ± 11 yr; forced vital capacity, 60 ± 13% predicted; carbon monoxide diffusing capacity, 52 ± 10% predicted). Levels of endothelin, 6-keto-prostaglandin-F(1α), thromboxane B(2), and nitrates were measured at rest and during submaximal exercise. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion relationships, were assessed breathing ambient air and 40 ppm NO, both at rest and during submaximal exercise. The concentration of thromboxane B(2) increased during exercise (P = 0.046), whereas levels of other mediators did not change. The change in 6-keto-prostaglandin-F(1α) correlated with that of mean pulmonary arterial pressure (r = 0.94; P < 0.005). Inhaled NO reduced mean pulmonary arterial pressure at rest (-4.6 ± 2.1 mmHg) and during exercise (-11.7 ± 7.1 mmHg) (P = 0.001 and P = 0.004, respectively), without altering arterial oxygenation or ventilation-perfusion distributions in any of the study conditions. Alveolar-to-capillary oxygen diffusion limitation, which accounted for the decrease of arterial Po(2) during exercise, was not modified by NO administration. We conclude that, in IPF, some endothelium-derived signaling molecules may modulate the development of pulmonary hypertension during exercise, and that the administration of inhaled NO reduces pulmonary vascular resistance without disturbing gas exchange.
authors.affiliation: Department of Pulmonary Medicine, Institut Clínic del Tórax, Hospital Clínic-Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blanco
authors.forename: Jesús
authors.initials: J
authors.lastname: Ribas
authors.forename: Antoni
authors.initials: A
authors.lastname: Xaubet
authors.forename: Federico P
authors.initials: FP
authors.lastname: Gómez
authors.forename: Josep
authors.initials: J
authors.lastname: Roca
authors.forename: Robert
authors.initials: R
authors.lastname: Rodriguez-Roisin
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D005080:Exercise Test; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D005082:Physical Exertion / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D014665:Vasodilator Agents; D009569:Nitric Oxide