FeNO indicates airway inflammation with longitudinal fidelity in severe asthma
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Key takeaways:
- Patients with predominantly high fractional exhaled nitric oxide levels had high baseline blood eosinophil and exacerbation totals.
- IL-4, IL-5 and IL-13 mRNA expression was high at baseline as well.
WASHINGTON — Fractional exhaled nitric oxide represents a noninvasive marker of airway inflammation with good longitudinal fidelity among patients with severe asthma, according to data presented here.
Repeated high levels during multiple visits may indicate patients who would benefit from early escalation of therapy, Elizabeth A. Townsend, MD, PhD, Anna K. Arndt Professor, University of Wisconsin-Madison, and colleagues wrote.
Townsend attributed the need to investigate FeNO as a biomarker to the American Thoracic Society 2021 Clinical Practice Guideline, which she said does not address its utility in monitoring asthma.
Also, Townsend said, she and her colleagues had been tracking the study’s cohort for a prolonged period.
“Most data look at FeNO as a single measurement, either in response to a therapy change or to the initial classification,” Townsend told Healio. “We’re really classifying it over a long period of time to see how it predicts our severe asthma population.”
The multicenter, longitudinal and comprehensive Severe Asthma Research Program-3 (SARP3) characterization study comprises 714 adults and children with severe asthma across the United States who have been followed for more than 6 years.
Participants were assessed at least three times, including for asthma symptom and medication history, spirometry, FeNO and other biomarkers.
The current analysis, findings of which were presented at the American Thoracic Society International Conference, involved 457 adults who were aged 18 years and older at their first of their FeNO measurements. Also, 269 (58.8%) of these patients had severe asthma.
With 25 ± 5 ppb used as a cutoff, patients were categorized with predominantly low (n = 168), variable (n = 123) or predominantly high (n = 166) longitudinal FeNO.
Patients received intramuscular triamcinolone acetonide (TA) injections at baseline with repeat characterization 2 to 4 weeks later as well.
Baseline blood eosinophil counts included 366.5 ± 25.3 cells/µL for the predominantly high group and 206.2 ± 2 cells/µL for the predominantly low group (P < .001).
Baseline percent sputum eosinophil totals included 7.11% ± 0.84% for the predominantly high group and 1.53% ± 0.81% for the predominantly low group (P < .001).
Baseline exacerbation totals during follow-up included 8.9 for the predominantly high group and 6.2 for the predominantly low group (P < .05).
When the researchers compared sputum at baseline, IL-4 mRNA expression was 15.2% ± 0.28% for the high group and 13.25% ± 0.27% for the low group (P < .001).
Additionally, IL-5 mRNA expression was 19.02% ± 0.31% for the high group and 16.37% ± 0.3% for the low group (P < .001). IL-13 mRNA expression was 20.44% ± 0.24% for the high group and 18.14% ± 0.23% for the low group (P < .001).
Based on these findings, Townsend said that FeNO had good longitudinal fidelity as a noninvasive marker of airway inflammation among patients with severe asthma.
Systemic and airway T2 inflammatory markers predicted predominantly high FeNO, Townsend continued, but BMI, inhaled corticosteroid use and baseline spirometry did not.
This overall stability was surprising, as was the lack of change in exhaled nitric oxide among these patients during the follow-up period, Townsend said, particularly in response to oral corticosteroids or the intramuscular TA injection as the researchers did not identify any change in FeNO after TA when normalized to pre-TA FeNO.
“Those systemic corticosteroids didn’t really impact the grouping of exhaled nitric oxide,” Townsend said.
Levels of asthma severity were equally represented in all three groups as well, she continued. Baseline measures of severity, Asthma Control Questionnaire scores, BMI, or FEV1 percent predicted ± bronchodilator response did not predict FeNO category.
“We were anticipating that more severe asthmatics would be in the high exhaled nitric oxide group, but we really found that they were equally distributed amongst all of our groups,” Townsend said.
The predominantly high FeNO group, however, had significantly decreased ratios of bronchodilator FEV1 to forced vital capacity percentage predicted, indicating greater airflow limitation.
Considering the association between more frequent asthma exacerbations and the predominantly high FeNO phenotype, Townsend said, doctors should continue to measure it in patients with asthma.
“Even though it isn’t necessarily a good marker in severe asthmatics of response to therapy, we do think that continuing to measure it and possibly start using it as a predictive biomarker of who would benefit from either changes in therapy or escalation of therapy, or maybe the addition of a biologic would be helpful,” she said.
Townsend said that she and her colleagues are excited to continue their work. For example, she said, they would like to determine how biologics may help patients who continue to have elevated exhaled nitric oxide despite the ongoing use of anti-inflammatories and steroids.
“There have been a few studies whose primary endpoint was not looking at exhaled nitric oxide and biologics, but what they found was patients with higher exhaled nitric oxide were more responsive to biologics once they were added,” she said. “We think that’s a really great potential opportunity for this.”
For more information:
Elizabeth A. Townsend, MD, PhD, can be reached at eatownsend@wisc.edu.