FeNO is not a reliable predictor of asthma or COPD exacerbations overall, but may help identify patients at risk of steroid-responsive flares, a large international study suggests.

The NOVELTY study, funded by AstraZeneca and published in Thorax [link here], found that FeNO and eosinophils (EOS) had markedly different and sometimes opposite associations with exacerbation risk depending on both the disease and the exacerbation type.

The findings suggest that categorising exacerbations by treatment type, rather than treating them as a single outcome, could improve personalised management for patients with asthma and COPD, according to the study authors.

Key findings included:

• Higher baseline EOS was significantly linked with increased risk of all exacerbations in asthma (IRR 1.09, p=0.033), with a similar but non-significant trend in COPD (IRR 1.09, p=0.069).
• Higher baseline FeNO was associated with a decreased risk of all exacerbations in COPD (IRR 0.91, p=0.025), an unexpected finding the authors said made FeNO difficult to interpret in that group.
• In asthma, higher FeNO increased risk of OCS-only treated exacerbations (OR 1.16, p=0.006) but decreased risk of antibiotic-only treated exacerbations (OR 0.75, p=0.001).
• The same OCS-only pattern held in asthma+COPD overlap (OR 1.55, p<0.001), with no association for antibiotic-only exacerbations.
• Neither EOS nor FeNO was associated with exacerbation risk in COPD when exacerbations were analysed by treatment subtype.

The study’s authors said the results were the first to show that exacerbation subtype needed to be factored into biomarker assessments.

“Assessment of exacerbation subtype might improve personalised treatment management,” they wrote.

They concluded that EOS appeared to be a more useful biomarker for overall exacerbation risk than FeNO, particularly in COPD where FeNO levels were “difficult to interpret.”

The NOVELTY study enrolled more than 12,000 patients with physician-assigned or clinically suspected asthma, COPD, or asthma+COPD overlap from primary and specialist practices across 19 countries in Europe, the Americas, Asia and Australia.

The authors cautioned that the study was observational, exacerbation subtypes were defined by treatment choice without standardisation, and FeNO and EOS were measured only at baseline.