Mild to moderate asthma may include high FeNO, eosinophil counts

Key takeaways:

• High FeNO levels indicate exacerbation and lung function risks.
• Most patients with high FeNO levels also had high eosinophil levels.
• ICS doses had similar distributions across groups based on FeNO levels.

Patients with mild to moderate asthma and self-reported asthma control may have elevated levels of fractional exhaled nitric oxide and eosinophils, according to a poster presented at the European Respiratory Society International Congress.

This subgroup of patients may be at high risk for exacerbations and accelerated loss of lung function, Benjamin T. Suratt, MD, global project head and clinical lead, early development, immunity and inflammation, Sanofi, and colleagues wrote.

The role of FeNO

“Increased levels of FeNO, as well as high peripheral blood eosinophil count, put adults with asthma at high risk for future asthma exacerbations and developing a fixed airflow limitation,” Suratt told Healio.

Approximately half of patients with severe asthma have elevated FeNO, he continued.

Benjamin T. Suratt

“However, in patients with asthma that is not characterized as severe, the prevalence of elevated FeNO and its relationship to disease outcomes have not been as well characterized,” Suratt said.

The researchers aimed to evaluate the prevalence of FeNO in adults with mild to moderate asthma with self-reported controlled asthma, he said.

“By evaluating the FeNO concentration, we can detect eosinophilic airway inflammation and predict the likelihood of inhaled corticosteroid (ICS) responsiveness in adults with asthma,” Suratt said.

Previous research has described biomarkers of type 2 inflammation among patients with severe asthma, but the role of these biomarkers among patients with milder asthma is less understood, Suratt said.

“High FeNO levels and elevated eosinophils in those with nonsevere asthma may identify a population at increased risk for future asthma exacerbations,” he said.

The study also evaluated the efficacy of lunsekimig, an IL-13/thymic stromal lymphopoietin (TSLP) nanobody compound, in this high-risk asthma population, he added. Previously, the researchers found that a single dose of lunsekimig strongly suppressed FeNO and type 2 inflammation in mild to moderate, controlled asthma.

“The data suggest that a dual-targeting approach to TSLP and IL-13 inhibition may potentially result in synergistic function and support the use of lunsekimig in human asthma clinical trials,” Suratt said.

Study design, results

Study participants were aged 18 to 60 years and had a diagnosis of mild to moderate and self-reported controlled asthma based on Global Initiative for Asthma guidelines. They also used as-needed reliever therapy with short-acting beta agonists as well as no or low to medium doses of ICS with additional controllers allowed.

The prescreening stage included 769 patients (52% women; median age, 31 years) with a median FeNO of 20 ppb (range, 4-301) and 58% with levels under 25 ppb, which the researchers classified as normal. Among the 42% with FeNO of 25 ppb or higher, 29% had FeNO of 35 ppb or higher, and 19% had FeNO of 50 ppb or higher.

Also, prescreening indicated ICS controller medication use among 332 (43%) participants, with levels of use evenly distributed across subgroups of patients with high FeNO levels. Overall, 46% to 49% of these patients were ICS naïve, 3% to 4% had used ICS as needed, 38% to 40% were using low doses of ICS and 9% to 10% were using medium doses of ICS.

“Results showed ICS controller medication use and dose was similar regardless of the FeNO cutoff used,” Suratt said.

Specifically, 40% of those patients with FeNO of 25 ppb and over, 38% of those with FeNO of 35 ppb and over, and 40% of those with FeNO of 50 ppb and over had used low doses of ICS.

The screening stage included 62 patients (44% women; median age, 32 years; age range, 18-58 years) whose FeNO levels were elevated during the prescreening. Assessments found a median FeNO of 43 ppb (range, 9-300). Specific levels included less than 25 ppb for 16%, 25 ppb or higher for 84%, 35 ppb or higher for 63% and 50 ppb or higher for 35%.

This group also had a mean eosinophil level of 250 cells/µL (range, 50-1,680).

Also, 87% of the 52 patients in this group who had FeNO of 25 ppb or higher had eosinophil levels of 150 cells/µL, which the researchers called elevated. The researchers further said there was an association between highly elevated FeNO levels of 500 ppb and higher and elevated eosinophil levels of 300 cells/µL and higher.

Conclusions, next steps

These findings indicate that nearly half of patients with mild to moderate asthma and self-reported asthma control had elevated FeNO levels and that most of these patients also had high eosinophil levels, suggesting that they are at high risk.

“These findings suggest that elevated airway inflammation may be prevalent in even symptomatically controlled asthmatics,” Suratt said.

Other studies have indicated that such inflammation puts patients at risk for poor outcomes, he continued.

“It should prompt an evaluation of the patient’s treatment regimen with an eye to escalating it, particularly if the patient has had an asthma exacerbation in the past year,” Suratt said.

Also, Suratt said, the findings demonstrate that a sizable portion of mild to moderate asthmatics appear to have poorly controlled type 2 airway inflammation even though they have adequate symptom control.

“Future efforts should be devoted to adapting our treatment approach to proactively identify and treat such asthmatics early in their disease course,” he said.