Pulmonary vascular effects of pulsed inhaled nitric oxide in COPD patients with pulmonary hypertension

Int J Chron Obstruct Pulmon Dis. 2016 Jul 5;11:1533-41. doi: 10.2147/COPD.S106480. eCollection 2016.


Introduction: Severe chronic obstructive pulmonary disease (COPD) is often associated with secondary pulmonary hypertension (PH), which worsens prognosis. PH can be lowered by oxygen, but also by inhaled nitric oxide (NO), which has the potential to improve the health status of these patients. NO is an important mediator in vascular reactions in the pulmonary circulation. Oral compounds can act through NO-mediated pathways, but delivering pulsed inhaled NO (iNO) directly to the airways and pulmonary vasculature could equally benefit patients. Therefore, a proof-of-concept study was performed to quantify pulmonary blood vessel caliber changes after iNO administration using computed tomography (CT)-based functional respiratory imaging (FRI).

Methods: Six patients with secondary PH due to COPD received "pulsed" iNO in combination with oxygen for 20 minutes via a nasal cannula. Patients underwent a high-resolution CT scan with contrast before and after iNO. Using FRI, changes in volumes of blood vessels and associated lobes were quantified. Oxygen saturation and blood pressure were monitored and patients were asked about their subjective feelings.

Results: Pulmonary blood vessel volume increased by 7.06%±5.37% after iNO. A strong correlation (Ω(2) 0=0.32, P=0.002) was obtained between ventilation and observed vasodilation, suggesting that using the pulsed system, iNO is directed toward the ventilated zones, which consequently experience more vasodilation. Patients did not develop oxygen desaturation, remained normotensive, and perceived an improvement in their dyspnea sensation.

Conclusion: Inhalation of pulsed NO with oxygen causes vasodilation in the pulmonary circulation of COPD patients, mainly in the well-ventilated areas. A high degree of heterogeneity was found in the level of vasodilation. Patients tend to feel better after the treatment. Chronic use trials are warranted.

Keywords: COPD; FRI; pulmonary hypertension; pulsed inhaled nitric oxide.

Publication types

  • Clinical Trial
  • Video-Audio Media

MeSH terms

  • Administration, Inhalation
  • Aged
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Arterial Pressure / drug effects
  • Computed Tomography Angiography
  • Female
  • Forced Expiratory Volume
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Lung / blood supply*
  • Lung / physiopathology
  • Male
  • Nitric Oxide / administration & dosage*
  • Nitric Oxide / adverse effects
  • Oxygen Inhalation Therapy* / adverse effects
  • Patient Satisfaction
  • Perfusion Imaging
  • Pulmonary Artery / diagnostic imaging
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiopathology
  • Pulmonary Circulation / drug effects
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Pulmonary Disease, Chronic Obstructive / therapy*
  • Pulse Therapy, Drug
  • Time Factors
  • Treatment Outcome
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / adverse effects
  • Vital Capacity


  • Antihypertensive Agents
  • Vasodilator Agents
  • Nitric Oxide