By Debbie Bunch
August 11, 2025
Mucus Plugs Over Time Predict FEV1 Decline in COPD
Mucus plugs that persist over time pose significant problems for people with COPD, according to researchers from Brigham and Women’s Hospital and elsewhere. In a study published in The New England Journal of Medicine, researchers compared mucus plugs among 2,118 patients with COPD who underwent a baseline CT scan and a repeat scan five years later. Those who had mucus plugs on both scans had significantly lower baseline FEV1 and saw a substantially larger decrease in FEV1 at five years.
The study was based on data collected for the COPDGene study. All the participants had a ten-pack-year smoking history or more. Specific findings included:
- 44.1% of patients had no mucus plug at baseline or the five-year mark. This group was dubbed the “persistently negative group.”
- 16.1% had a mucus plug only at baseline (the “resolved group”) and 19.7% had a mucus plug only at five years (the “newly formed group”).
- A mucus plug was observed in 20.1% of cases at both baseline and five years. These patients were referred to as the “persistently positive group.”
- The highest FEV1 at baseline was 2,133 mL in the persistently negative group, followed by 1,708 in the resolved group, 1,662 mL in the newly formed group, and 1,437 mL in the persistently positive group.
- The largest average FEV1 reduction was noted among those in the persistently positive group at -60.4 mL/year, with the second largest decline, at -54.9 mL/year, found in the newly formed group. The third largest, at -39.3 mL/year, was seen in the resolved group, and the smallest, at -37.2 mL/year, in the persistently negative group.
- The difference in FEV1 decline was 23.2 mL/year in the persistently positive group compared to the persistently negative group, and 17.7 mL/year in the newly formed group compared to the persistently negative group.
- Differences in FEV1 decline were related to smoking status at baseline and five years, with an accelerated decline seen among those who resumed smoking or continued smoking throughout the study.
The fact that patients in the persistent mucus plug group experienced the most rapid decline in FEV1, despite having the lowest mean FEV1 at baseline, raises questions about other studies that have shown an inverse relationship between disease severity and FEV1 rate of decline, noted the researchers.
The authors believe that their study raises additional questions about the relationship between mucus plugs and COPD prognosis, including why plugs resolve in some individuals but not others, and whether the resolution of mucus plugs can prevent or slow lung function decline in people with COPD. Read Article Read Abstract
T2 Inflammation May Not Be the Only Culprit in Pediatric Asthma
Some children with asthma still experience asthma attacks despite treatment. Researchers publishing in JAMA Pediatrics believe they have discovered one reason why.
These children suffer from a type of asthma involving inflammatory pathways distinct from type 2 (T2) inflammation, which is triggered by cytokines that promote the production and activation of eosinophils and is the target of most asthma medications.
They reached that conclusion after analyzing data from a previous clinical trial that compared the biologic therapy mepolizumab, which targets T2 inflammation, with a placebo over 52 weeks in children with asthma from low-income urban areas in the U.S. That trial found that while the drug did significantly reduce the expression of eosinophil-associated T2 inflammation during flare-ups, asthma attacks still occurred.
The investigators used RNA sequencing of nasal samples collected during 176 episodes of acute respiratory illness to identify three additional and distinct inflammatory drivers of asthma exacerbations:
- Epithelial inflammatory pathways were increased in children receiving mepolizumab, regardless of viral infection.
- Macrophage-driven inflammation, which was explicitly linked to viral respiratory illnesses.
- Mucus hypersecretion and cellular stress responses, which were elevated in both treatment and placebo groups during flare-ups.
The authors believe that these results demonstrate the complexity of asthma and highlight the need for more personalized treatment.
“There are multiple different types of inflammatory responses that are involved in exacerbations, and they’re driving exacerbations differentially based on whether patients have a virus or are taking drugs to block different parts of the inflammatory response,” said study author Rajesh Kumar, MD, from Ann & Robert H. Lurie Children’s Hospital of Chicago. Read Press Release Read Abstract
What’s Happening When Infections Persist After Modulators in CF?
People with cystic fibrosis (CF) usually remain infected with the same bacteria that caused problems for them earlier in their disease, even when they are treated with newer drugs called CTFR modulators that treat the underlying cause of CF.
Researchers speculate areas of the lungs that are already highly damaged before treatment simply cannot clear the infections regardless of treatment.
A team from the University of Washington School of Medicine and University of Iowa decided to see what’s actually happening in the lungs of these patients in a study that involved CF patients who underwent bronchoscopy prior to beginning treatment with modulators.
The investigators sampled regions of their lungs that differed in terms of lung damage, infection, and inflammation. After a year of treatment, they repeated the test to see where infection remained, and which characteristics of the lung were related to that infection.
They speculated that infection would be most persistent in areas of the lung with the most damage, but surprisingly, the study showed that when infections had cleared, lung inflammation almost entirely cleared as well despite lingering damage. The researchers believe this suggests lung damage can be lessened in people who see their infections clear up after treatment.
Unfortunately, patients who remained infected showed signs of infection and inflammation everywhere the researchers looked in their lungs, including areas of the lung with little lung damage, leading them to conclude that lung damage alone might not be the cause of persistent infection.
How can infection persist in all the areas of the lung despite treatment with the new drugs? The investigators believe bacteria might be adapting in ways that resist clearance or perhaps may be spreading from highly damaged areas to areas with less damage.
They believe more research is needed to better understand why.
The study was published by Cell Host & Microbe. Read Article Read Full Paper
