Mucus plugging may persist in severe asthma despite biologic treatment
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Key takeaways:
- Mucus scores included 6 for the nonbiologic group and 3 for the biologic group.
- Mucus scores also included 5 for patients on anti-IL5 monoclonal antibodies and 1 for patients on IL-4R antagonists.
SAN DIEGO — Patients with severe asthma often experience residual mucus plugging even with biologic treatment, according to a presentation at the American Thoracic Society International Conference.
However, their disease burden is significantly lower compared with patients who have not been treated with biologics, Parameswaran Krishna Nair, MD, PhD, Frederick E. Hargreave Teva Innovation Chair in Airway Diseases, division of respirology, McMaster University, and colleagues wrote.
“Mucus has long been recognized to contribute to asthma severity,” Nair told Healio. “However, until recently, it was not assessed in clinical practice. A mucus score in a CT scan of the airways is a reliable method to identify it.”
Monoclonal antibodies are new treatments for airway inflammation in patients with severe asthma, Nair said. But although they largely clear the airways of eosinophils, he continued, their effects on airway mucus are less well known.
“We had observed that not all patients with severe asthma get better when treated with biologicals,” Nair said. “We wanted to examine if ongoing symptoms in patients treated with biologics might be due to persisting mucus in the airways and the mechanisms contributing to the persistence of mucus.”
The retrospective analysis included 71 adults with severe asthma (35 women; median age, 54 years) with a median daily inhaled corticosteroid dose of 1,000 µg. Also, 32% were using systemic steroids.
The 36 patients who were using biologics included 16 on dupilumab (Dupixent; Regeneron, Sanofi), 13 on benralizumab (Fasenra, AstraZeneca), two on mepolizumab (Nucala, GSK), two on reslizumab (Cinqair, Teva Pharmaceutical) and three on dual biologic therapy, comprising dupilumab and anti-IL-5 treatment.
Patients also had inspiratory chest CT scans acquired at total lung capacity after 3 months or more of treatment and reviewed using VIDA|vision software (VIDA Diagnostics Inc.).
Defined by a mucus score of greater than 3, 69% of the patients who were not on biologics and 44% of the patients who were on biologics had residual mucus plugging (P = .04). Also, the group that had not used biologics had a mucus score of 6, and the group that had used biologics had a mucus score of 3 (P = .02).
Mucus scores in the biologics group included 5 for those patients receiving anti-IL-5 monoclonal antibodies and 1 for those receiving IL-4R antagonists (P = .005).
Also, among the biologics group, the researchers said there was an association between higher mucus scores and worse asthma control based on 5-question Asthma Control Questionnaire scores (r2 = 0.13; P = .03) and more severe airflow obstruction (r2 = 0.2; P = .006).
However, the patients in the biologics group did not have any associations between higher mucus scores and blood eosinophils, sputum cell counts or fractional exhaled nitric oxide levels.
The researchers also measured cytokines in the sputum of the patients with residual mucus and observed that measurements might predict responses to treatment, Nair said.
“It also gave us insight that mucus might not always be due to cytokines and that therapies other than biologics might be necessary in some patients,” he said.
Based on these findings, the researchers concluded that patients with severe asthma who have been treated with anti-IL-5 or anti-IL-4R monoclonal antibodies can still experience residual mucus plugs, with worse asthma control and pulmonary function, but with less disease burden than those patients who have not been treated with these biologics.
“The study encourages physicians to assess mucus using CT scans and to judiciously use the correct biologic that could be guided by sputum cell counts and cytokine measurements in sputum,” Nair said.
Research should continue in this area, he added.
“The nature of mucus is being assessed with more advanced magnetic resonance and CT imaging as well as the consequence of the mucus with xenon ventilation MRI,” Nair said. “This would lead to better treatment strategies for mucus that is not responding to biologics.”