Study Finds Inhaled Nitric Oxide May Benefit Patients with COPD and Pulmonary Hypertension
The Centers for Disease Control and Prevention (CDC) reports that about 15.7 million people in the U.S. have been diagnosed with chronic obstructive pulmonary disease (COPD). The CDC noted in 2014 that this disease was the third leading cause of death in the U.S.
Previous research has estimated that between 30 and 70 percent of patients with COPD also have pulmonary hypertension (PH), or high blood pressure in the lungs, depending on the study type and the types of patients included in the study. Research has shown that PH-targeted medications that help by widening and relaxing the blood vessels in the lungs can help alleviate PH symptoms. However, some of these drugs have unpleasant side effects – such as low blood pressure in the rest of the body – and are not well tolerated by some patients. Since it is delivered directly to the airways – with a lower dosage than what is needed for systemic delivery – inhaled nitric oxide (iNO) could result in fewer and less severe side effects for patients who could benefit. One group of patients who were thought to potentially benefit from this type of therapy were certain patients with both COPD and PH. To test this theory, researchers at the University Hospital in Antwerp, Belgium, supported by Bellerophon Therapeutics, conducted a study and published their findings in the International Journal of COPD. For this study, all patients had relatively severe PH in addition to COPD.
The authors aimed to investigate the feasibility, safety and acute therapeutic benefit to the blood vessels of the lungs when delivering nitric oxide (NO) directly to the lungs. They looked for changes in blood volume and how the airflow was distributed when using iNO, then measured the results using functional respiratory imaging (FRI).
Three men and three women on long-term oxygen therapy took part in the study. At the start of the study, the researchers recorded the patients’ vital statistics including heart and respiratory rates, blood pressure and oxygen partial pressure. During the study, iNO was “pulsed” when the patient began to inhale, delivering a pre-set dose to the lungs. The researchers found that this delivery method had an advantage over sending a constant concentration of NO since it “…presumably delivers the drug selectively to the healthiest well-ventilated lung segments.” In other words, the drug targeted the areas of the lungs that inhaled air reaches first. At the end of the study, the authors conducted four low-dose high-resolution CT scans, which allowed them to see the results.
All the patients had significant improvement in the volume of blood vessels. In fact, the authors said in some cases blood vessel volume increased by more than 20 percent when compared to baseline. Additionally, nearly all lung lobes had substantial vasodilation (widening of blood vessels) with no decrease in oxygen saturation. More important, patients said they had a decrease in shortness of breath and could better tolerate exercise 24 hours after the 20-minute treatment with iNO.
According to the authors, only one other study has been conducted using iNO and had similar results, showing a decrease in mean pulmonary artery pressure (mPAP) and resistance in the pulmonary arteries without reducing oxygen levels. That study was also the first randomized controlled trial to determine that iNO in combination with oxygen therapy is safe for patients with COPD and PH.
While delivering NO to targeted areas has been shown to be effective, the authors of this study noted that the effect on partial pressure of oxygen in arterial blood (PaO2) might differ from one patient to the next. Specifically delivering NO might lower, increase or have no effect on PaO2. To explain these various outcomes, they surmised that perhaps different groups of patients with COPD could respond differently to the treatment; or the dosage might make a difference. The authors admitted that finding the right dosage can be challenging. Some animal studies show that a dose between 5 ppm and 80 ppm can be effective; in this study, patients received 30 ųg/kg, which is the highest dose that has safely been tested so far. Additionally, the authors suggested that the severity of PH might have an impact on the effect.
The authors reported that the use of iNO for patients with COPD and PH might also have benefits for the heart. As the blood flows more freely, delivering oxygen throughout the body, the heart is better able to function with less stress. This could account for the increased tolerance to exercise, but additional studies are needed to confirm this theory as well as the long-term effect of this type of therapy.
The positive results of treating COPD with PH led the authors to believe that iNO might also be “…a promising treatment in other lung diseases leading to PH, such as pulmonary fibrosis.”