Speaker: Current biomarkers in asthma care lack stability

Key takeaways:

• Allergies, medication, obesity, smoking and other factors may influence blood eosinophil levels.
• Ethnicity, height, age, exercise, tobacco use and diet may influence fractional exhaled nitric oxide.

ANAHEIM, Calif. — Better biomarkers for diagnosis and prognosis are needed for better personalized asthma care, according to a presentation at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.

“We do need better personalized treatment for our patient population. It’s getting there, but it’s not what it should be,” Michael S. Blaiss, MD, clinical professor of pediatrics at Medical College of Georgia at Augusta University, said during his presentation.

Current biomarkers are not as accurate as they should be, Blaiss, who also is a member of the Healio Allergy/Asthma Peer Perspective Board, continued.

“Unfortunately, they don’t really tell us completely who, in fact, is going to respond to therapy,” he said.

Even phase 3 studies of the different biologics that have been approved for treating asthma in the United States do not provide true responder rates that physicians can discuss with their patients, Blaiss said.

Blaiss defined biomarkers as measurable indicators that provide information about various biologic processes, conditions and responses to therapy. Biomarkers in severe asthma include blood eosinophils, exhaled nitric oxide, serum IgE and sputum eosinophils.

“These are not stable biomarkers by any stretch of the imagination,” Blaiss said.

For example, he continued, drug allergies, allergic rhinitis, parasites, malignancies, corticosteroids, obesity, smoking and even the time of day all can affect blood eosinophil levels.

Blaiss cited a review of four double-blind, placebo-controlled studies of the use of lebrikizumab (Lilly) in asthma that drew blood and measured eosinophils each month. Considering natural variations in blood eosinophil levels, the authors used a 90% prediction interval to detect meaningful differences every 4-week period, detecting 20% variability, or approximately 50 cells/µL at a median of 250 cells/µL.

Compared with July, which the authors used as a baseline, eosinophils variations ranged from 27.9% in January to 2% in August.

The review authors also assessed characteristics that physicians often see in patients with asthma. Those that met the 20% threshold in unadjusted analyses included sinus polyps (56% variation), nasal polyps (51% variation), chronic sinusitis (26% variation), three or more past exacerbations (26% variation), theophylline usage (23% variation) and current smoking status (–25% variation).

“All of these are having effects as far as the level of blood eosinophils,” Blaiss said.

In another study, Blaiss said, researchers looked at patients with severe eosinophilic asthma who were taking mepolizumab (Nucala, GSK) and who had at least one blood eosinophil level greater than 300 cells/µL in the previous 12 months.

Patients who began treatment with a blood eosinophil level of less than 150 cells/µL had a 66% reduction in exacerbations (RR = 0.34; 95% CI, 0.26-0.44). Those who began with a level between 150 cells/µL and 300 cells/µL had a 65% reduction (RR = 0.35; 95% CI, 0.27-0.46).

The patients with 300 cells/µL to 500 cells/µL experienced a 67% (RR = 0.33; 95% CI, 0.27-0.4) reduction in exacerbations, and those with levels of 500 cells/µL or higher had a 75% (RR = 0.25; 95% CI, 0.21-0.29) reduction.

Fractional exhaled nitric oxide is another biomarker among patients with moderate to severe asthma, Blaiss said, but it is not an easy technique for patients to perform, which may impact results.

Exhalation flow rates, nasal nitric oxide contamination and even the type of nitric oxide analyzer that is used may affect results too, he continued.

Atopy is another important factor associated with elevated FeNO that is independent of asthma, Blaiss added. Ethnicity, height, age, exercise, tobacco exposure and recent dietary intake are factors as well.

“Did you eat bacon this morning?” Blaiss said. “Nitrate-rich foods, in fact, affect the level of FeNO.”

Whether FeNO is measured before or after spirometry is another variable.

“And, of course, medications like inhaled corticosteroids and leukotriene receptor antagonists also affect FeNO,” he said. “Again, it’s not a stable biomarker.”

However, Blaiss noted, age is the only factor that many guidelines suggest physicians should consider when interpreting FeNO.

Current treatments have improved care for patients with asthma, Blaiss concluded.

“There’s no doubt that asthma management is improved. We’ve got a lot of excellent treatments,” he said. “But I still think we do not have the biomarkers we need in the diagnosis and management of the condition.”

Overall, Blaiss said, physicians should consider these influences on blood eosinophils and FeNO in evaluating patients.

“One needs to be aware of the impreciseness of the present biomarkers,” he said.