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Pulsed Inhaled Nitric Oxide (iNO) Improves Exercise Tolerance in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients with Pulmonary Hypertension (PH)

B Haijan

Bharati Shivalkar

Francisca Ferreir

Cedric Van Holsbeke

Wilm Vos

Jan De Backer

Kathleen Sartoris

DQ Warren

A Hulkens

Paul Parizel


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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1054

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Authors (Continued)

Cluckers J, De Backer W


A phase 2b iNO chronic treatment study was designed to investigate the clinical relevance of previously seen acute vasodilation with respect to changes in exercise tolerance and hemodynamics.


In the previous Functional Respiratory Imaging (FRI) trial (Int J Chron Obstruct Pulmon Dis. 2016;11:1533-1541), pulsed inhaled nitric oxide (iNO) was shown to cause an acute vasodilating effect in 6 severe WHO Group 3 PH associated with COPD patients on long-term oxygen treatment (LTOT). In a follow up telephone call patients also reported improvement in their symptoms up to 24 hours after a one-time 20-minute treatment with pulsed iNO.


This study recruited 10 PH-COPD patients on long-term oxygen therapy (LTOT). Pulsed iNO was provided by the INOpulse® delivery system. For all patients, acute vasodilation under pulsed iNO, was assessed by FRI before starting a 4-week treatment with iNO (>12h/day). Exercise tolerance and hemodynamics were measured at baseline and after 4 weeks treatment with iNO (n=7).


All 10 patients experienced acute increases in blood vessel volumes following iNO treatment (+4.2%, p=0.03). There was a significant association (p<0.01) between ventilation and vasodilation during iNO therapy, suggesting that regions with better ventilation experience more vasodilation. The patients who completed 4 weeks of iNO therapy experienced reductions in pulmonary arterial pressure (-19.9%, p=0.02) and had on average a 50.4±54.4 meter increase in 6MWD (p=0.04). The therapy was well tolerated with no safety concerns.


FRI analyses demonstrated regional dilatation of blood vessels in the lungs following acute pulsed iNO treatment. Vasodilation occurs in well-ventilated areas as supported by the correlation with lobar ventilation. There were significant reductions in pulmonary artery pressures and improvements in 6MWD with four weeks of treatment with iNO. Chronic iNO therapy has the potential to significantly increase exercise tolerance in COPD patients with PH. There were no safety concerns.

Figure 1: Regional vasodynamics in a patient (right) and the changes in 6MWD after 2 and 4 weeks of treatment in all patients (left)