In a real-life clinic setting study aimed at determining phenotypic associations of mucus plugging
Rory Chan, MBChB, of the University of Dundee (Scotland) and colleagues found conversely that the presence of these features was associated with an increased likelihood of mucus plugging.
Important pathophysiological characteristics of persistent asthma include mucus plugging, goblet cell hyperplasia, smooth muscle hypertrophy, and eosinophilic infiltration. Mucus plugging contributes significantly to airway obstruction and death in acute asthma, the investigators stated, noting further that the understanding of mucus plugging’s role in chronic asthma is increasing.
Their retrospective cohort study included 126 patients with respiratory physician-diagnosed moderate to severe asthma who had attended their clinic (January 2016–March 2022) and were receiving daily doses of inhaled corticosteroid (ICS) (≥ 800 mcg) and a second-line controller. All had prior high-resolution CT (HRCT) scans with mucus plugs identified by an experienced thoracic radiologist. Prior to the start of biologic therapy, a mucus plug score (MPS) signifying the number of affected lung segments (0-20) was calculated subsequently and considered along with pulmonary function testing, T2 inflammatory markers, asthma control data, and measures of peripheral blood eosinophils (PBE), as well as total IgG and IgE antibodies to Apergillus fumigatus.
The analysis showed that reduced forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) ratio (OR, 3.01; 95% confidence interval, 1.14-7.97), two or more exacerbations per year (OR, 5.00; 95% CI, 1.55-16.11), raised PBE (OR, 3.23; 95% CI, 1.16-8.96), raised total IgE (OR, 3.20; 95% CI, 1.09-9.37), and Aspergillus fumigatus IgE titers (OR, 9.37; 95% CI, 1.82-48.20) all conferred significantly higher likelihood of the presence of mucus plugging. Highest prevalence of mucus plugs was in the right and left lower lung lobes (about 26% vs. about 10% and 14% in the middle and upper lobes).
Adjusted ORs in patients with impaired FEV1/FVC, showed the likelihood of mucus plugging to be 67% higher. In those with frequent exacerbations, they were 80% higher, and in those with raised PBE and IgE, 69% higher. Patients without mucus plugging had preserved FEV1 and FEV1/FVC.
Asthma patients with mucus plugging in the study exhibited higher levels of routinely measured T2 biomarkers, including blood eosinophils, FeNO, and total IgE, with median values all exceeding traditionally accepted cut points. Although patients with mucus plugging were receiving significantly higher ICS doses, and despite the suppressive effect of ICS on FeNO, they still had higher FeNO levels. “We therefore postulate that asthma patients with the MP phenotype might potentially experience greater treatment response to biologics targeting the underlying inflammatory endotype,” the investigators stated, adding that “the presence of mucus plugging should be recognized as a treatable trait for patients with severe asthma in terms of targeting therapy with biologics.”
They wrote that, “in a real-life clinic setting, the presence of mucus plugging detected on HRCT was associated with more severe exacerbations, more severe airflow obstruction, and greater T2 inflammation. This, in turn, suggests that imaging should be part of the routine workup of patients with poorly controlled severe asthma.”
In an accompanying editorial, Jorge Cedano, MD, Jiwoong Choi, PhD, and Mario Castro, MD, MPH, of the University of Kansas, Kansas City, cited that the prevalence and contribution of mucus plugging in the pathophysiology and morbidity of uncontrolled asthma is much greater than has been appreciated. They focused particularly on the suggestion that, even after adjusting for confounders, molds such as Apergillus may play a causal role, along with blood eosinophils, fractional exhaled nitric oxide, and total IgE, in T2 inflammation.
While current biologic therapies targeting the T2 phenotype have not yet been shown to reverse the progressive loss of lung function or lung remodeling process, the editorialists referenced a recent post hoc analysis of the CASCADE study showing mucus plugging reduction with the biologic tezepelumab versus placebo correlated with lung function improvement. “At least 20% of patients with moderate to severe asthma will experience progressive decline in lung function, more exacerbations, and worse asthma control despite the use of controller therapies. If physicians could identify the MP phenotype using computed tomography, then potentially earlier treatment with biologic therapy may improve asthma control and prevent future decline in lung function,” they said.
The study limitations listed included its retrospective observational nature and the fact that the study had only one senior thoracic radiologist interpreting the lung scans.
The study authors cited numerous conflicts of interest with pharmaceutical companies and medical societies. Dr. Castro reported affiliation or involvement in multiple organizations or entities with a financial or nonfinancial interest in the subject matter or materials discussed in the article.