Measuring Exhaled NO Levels May Help Diagnose PH in COPD Patients

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Levels of fractional exhaled nitric oxide (FeNO) — a measure of how much nitric oxide a person exhales — may help diagnose pulmonary hypertension in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), a Chinese study suggests.

Nitric oxide, called NO, is a vasodilator that helps open the airways, and high levels in the breath can indicate inflammation.

“FeNO level at admission can act as an indicator for PH diagnosis in AECOPD patients,” the researchers wrote.

The study, “Clinical Value of FeNO for Pulmonary Hypertension Diagnosis in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease,” was published in the journal Emergency Medicine International.

In COPD, the airways become blocked due to chronic inflammation, resulting in lung damage and impaired breathing. Pulmonary hypertension (PH) is a major complication of COPD that increases the risk of right heart failure.

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Several studies have reported that delaying or preventing PH progression can significantly improve the outcomes of COPD patients, in particular those with acute exacerbations (AE), periods characterized by rapid disease worsening. These are known as AECOPD.

Given the poorer outcomes of AECOPD patients with PH (AECOPD-PH), early diagnosis and treatment are key to reducing the risk of disease progression.

The American Thoracic Society recommends the use of the fractional exhaled nitric oxide (FeNO) test as a noninvasive way to assess inflammation in the airways and to guide treatment for AECOPD.

Prior studies have shown that FeNO levels are significantly increased in these patients, while the opposite is true for those with PH only.

However, it remains unknown if measuring FeNO may help diagnose AECOPD-PH.

To answer this question, a group of researchers in China performed a retrospective analysis of medical records of 83 AECOPD patients, with and without PH, admitted to the Harrison International Peace Hospital between January 2017 and May 2018.

Specifically, they reviewed data from 56 AECOPD patients and 27 AECOPD participants also with PH. Those with AECOPD had a mean age of 67.9 and 60.7% were men, while the patients with AECOPD-PH were on average 68.1 years old and were 55.5% male. FeNO levels were measured after the patients’ admittance to the ER and before any treatment for symptoms.

Compared with patients with AECOPD, those with AECOPD-PH had significantly higher levels of BNP (brain natriuretic peptide), an established marker of heart failure, and C-reactive protein, a sign of inflammation. The patients with PH also had longer hospital stays and a greater need for invasive mechanical ventilation.

The mean levels of FeNO were significantly lower in the AECOPD-PH (18.78 parts per billion, ppb) compared with the AECOPD group (33.14 ppb).

The researchers then assessed FeNO levels within the AECOPD-PH group, with patients being further divided according to PH severity — nine patients in the mild subgroup, 14 in the moderate subgroup, and four participants in the severe subgroup.

Mean FeNO levels were reduced as PH severity increased, with those in the mild group showing significantly higher FeNO levels (mean 25.22 ppb) compared with those in the moderate group (16.64 ppb) and severe group (11.75 ppb).

Pulmonary artery systolic pressure (PASP) — the blood pressure in the pulmonary artery during a heartbeat — followed the opposite trend, with patients with mild disease showing significantly lower levels (mean 44 mmHg), compared with the moderate group (52.50 mmHg) and the severe group (69.75 mmHg).

FeNO levels showed a positive correlation — meaning the greater is one, the greater is the other — with C-reactive protein levels in AECOPD patients but not among those with AECOPD-PH. In this group, FeNO levels showed a negative correlation with BNP, with one decreasing when the other one increases.

The optimal cutoff diagnostic value of FeNO for AECOPD-PH was 24.5 ppb, with this value being able to diagnose AECOPD-PH  with a sensitivity of 69.6% and specificity of 85.2%. Of note, a test’s sensitivity is its ability to correctly identify those with a given disease, while specificity refers to accurately identifying those without it.

Overall, these results show that “FeNO can be used to diagnose AECOPD patients with PH,” the researchers wrote.

“This study further promotes understanding of airway inflammatory diseases and the diagnosis and treatment of AECOPD patients,” the team concluded.