Mucus plugs associated with more severe asthma exacerbations
Patients with poorly controlled asthma and mucus plugs had significantly more airflow obstruction, type 2 inflammation and severe exacerbations, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Impaired spirometry, more frequent severe exacerbations, raised blood eosinophils, total IgE and Aspergillus fumigatus IgE increased the likelihood for mucus plugs as well, Brian Lipworth, MD, professor of allergy and pulmonology and head of the Scottish Centre for Respiratory Research at University of Dundee, and colleagues wrote.
“We were interested to know what are the phenotypic associations of mucus plugs in more severe asthma patients,” Lipworth told Healio.
The study involved 126 patients (mean age, 52 ± 14 years; 83% female) with moderate to severe asthma diagnosed by a physician. In the cohort, 25% of the patients were former smokers, 7% were current smokers and 24% had nasal polyps.
The overall median mucus plug score (MPS) — for which 0 indicated no mucus plugs, and a maximum score of 20 indicated that every one of the 20 examined lung segments had at least one mucus plug — was 1 (interquartile range, 5).
Patients with an MPS of 1 or higher had significantly lower FEV1 percentage (FEV1%), FEV1/forced vital capacity (FVC) ratios and forced expiratory flow at 25% to 75% of FVC (FEF25-75%) than patients with a 0 score.
Also, these patients had higher fractional inhaled nitric oxide, peripheral blood eosinophils, total IgE and A. fumigatus IgE titers as well as significantly more frequent prior severe exacerbations.
The researchers further found that patients with mucus plugs were receiving significantly higher doses of inhaled corticosteroids than patients who did not have any mucus plugs (mean, 1,831 µg vs. 1,633 µg; P < .01).
The likelihood that patients would have mucus plugs was significantly higher with:
- reduced FEV1/FVC ratios (adjusted OR = 3.01; 95% CI, 1.14-7.97);
- two or more exacerbations per year (aOR = 5; 95% CI, 1.55-16.11);
- raised peripheral blood eosinophils (aOR = 3.23; 95% CI, 1.16-8.96);
- higher total IgE (aOR = 3.2; 95% CI, 1.09-9.37); and
- higher A. fumigatus IgE titers (aOR = 9.37; 95% CI, 1.82-48.2).
The highest prevalence of mucus plugs occurred in the right and left lower lobes of the lungs. The researchers speculated that this may be due to the effect of gravity on mucus secretions.
Meanwhile, patients who did not have mucus plugs had preserved FEV1 (89%) and FEV1/FVC (0.73), with a 401 mL (95% CI, 91-711 mL) mean difference in FEV1 between patients with and without mucus plugs.
The researchers further called the FEF25-75% totals in patients with mucus plugs significantly impaired, with a mean difference of 0.8 L per second (95% CI, 0.44-1.17) between these patients and those who did not have mucus plugs.
“We confirmed previous observations but at the same time showed in one study that having airway obstruction, asthma exacerbations, ongoing asthmatic inflammation and presence of underlying allergy including sensitization to molds increased the likelihood of having mucus plugging,” Lipworth said.
Considering these effects that mucus plugging — detectable on high-resolution CT — had on asthma, the researchers said that physicians should include imaging as part of the routine workup of patients who have poorly controlled severe asthma to better tailor decisions about treatment with biologics.
“They should firstly do high-resolution CT chest scans on all their severe asthma patients to look not only at plugging but also for airway wall thickening and bronchiectasis,” Lipworth said.
Lipworth recommended the use of biologics such as benralizumab (Fasenra, AstraZeneca), dupilumab (Dupixent, Sanofi Genzyme/Regeneron) and tezepelumab (Tezspire; Amgen, AstraZeneca) to melt away plugs as well.
For more information:
Brian Lipworth, MD, can be reached at b.j.lipworth@dundee.ac.uk.