FeNO levels may help diagnose severe idiopathic PAH: Study

FeNO test measures how much nitric oxide a person exhales

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by Andrea Lobo |

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Levels of fractional exhaled nitric oxide (FeNO) — a measure of how much nitric oxide a person exhales — may be used as a diagnostic tool for severe disease in people with idiopathic pulmonary arterial hypertension (iPAH), a study has found.

Specifically, patients with FeNO levels lower than 23 parts per billion (ppb) are more likely to have severe PH than those with higher levels.

Also, FeNO may be associated with severe PH in patients with mixed connective tissue disease (MCTD-PH), a disease with features of two connective tissue disorders — such as lupus and systemic sclerosis.

The study, “Fractional exhaled nitric oxide in idiopathic pulmonary arterial hypertension and mixed connective tissue disease complicating pulmonary hypertension,” was published in the journal BMC Pulmonary Medicine.

PAH is caused by the narrowing of the pulmonary arteries, the blood vessels that transport blood through the lungs, causing high blood pressure and making the heart work harder to pump blood to the body. Not all cases have an identifiable cause, and these are referred to as iPAH.

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Studies indicate decrease in nitric oxide levels correlate with iPAH severity

Several studies have found a decrease in nitric oxide levels in the exhaled breaths of iPAH patients, correlating with disease severity and prognosis. In addition, its levels have been shown to increase in response to therapy.

“However, FeNO’s usefulness as a noninvasive marker remains highly controversial,” the researchers wrote.

To shed light on this knowledge gap, researchers in China collected data from 54 iPAH patients and 78 with MCTD-PH.

Both groups had a mean age slightly older than 40 years and included mainly women. FeNO levels were significantly higher in iPAH patients than in those with MCTD-PH (19 vs. 15 ppb).

Moreover, participants with iPAH had significantly better lung function, as assessed with the standard measures of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), as well as lower airway resistance, compared with MCTD-PH patients.

“These findings suggest that airway restriction and obstruction were more pronounced in MCTD-PH patients compared to those with iPAH,” the researchers wrote.

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Lower FeNO test levels linked to higher FEV1/FVC in severe iPAH

Notably, FeNO levels were inversely associated with FEV1/FVC ratio values, meaning lower FeNO levels were linked to higher FEV1/FVC, particularly in patients with severe iPAH. Lower FeNO also was associated with higher maximum expiratory flow, an indicator of airflow obstruction.

Subsequent analysis determined a cutoff FeNO value of 23 ppb for the diagnosis of severe disease in iPAH patients.

“The results of our investigation suggest that FeNO levels can indeed aid in the diagnosis of IPAH patients with severe PH, with higher FeNO levels indicating a greater degree of peripheral airway obstruction in severe IPAH,” the researchers wrote.

In those with MCTD-PH, FeNO levels were associated only with R20%, a measure of airway resistance in large airways, particularly pronounced in patients with more severe disease.

In these patients, lower FeNO levels correlated with higher respiratory exchange ratio — the ratio between the production of carbon dioxide and the uptake of oxygen — and with lower resting oxygen consumption divided by heart rate.

“This suggests a potential relationship between FeNO levels and heart function,” the researchers wrote. “As such, FeNO levels hold promise as a valuable marker for identifying severe MCTD-PH.”

Overall, “these findings provide valuable insights into the role of FeNO as an indicator of small and large airway function and its potential as a diagnostic tool for severe PH in both IPAH and MCTD-PH,” they concluded.

A Conversation With Rare Disease Advocates