Mucus Plugs Correlate with Small Airway Remodelling in Asthma: A Case-Control Study

Area of Science:

• Pulmonary Medicine
• Pathology
• Respiratory Research

Background:

• Mucus plugs in proximal airways correlate with asthma severity and airflow obstruction.
• The role of distal small airway mucus plugs (<2mm diameter) in asthma severity remains unclear due to limitations of computed tomography (CT) resolution.

Purpose of the Study:

• To determine the prevalence of distal mucus plugs in asthma.
• To investigate the association between distal mucus plugs and small airway remodeling in asthma.

Main Methods:

• Systematic random sampling of 239 lung tissue samples from 12 control, 5 non-fatal, and 11 fatal asthma lungs.
• Micro-computed tomography (micro-CT) imaging and matched histology were used to assess mucus plugs, airway wall remodeling, and mucus composition.
• Analysis focused on pre-terminal, terminal, and transitional bronchioles.

Main Results:

• Mucus plugs were prevalent in distal bronchioles of non-fatal (30-33%) and fatal (21-38%) asthma lungs, showing spatial heterogeneity.
• Mucus plugs were primarily composed of MUC5AC and MUC5B.
• Asthmatic airways with mucus plugs exhibited thickened walls, narrowed lumens, and luminal folding compared to unplugged airways, attributed to epithelial, basement membrane, and smooth muscle thickening.

Conclusions:

• Distal small airway mucus plugs are a significant and heterogeneous feature in asthma.
• These mucus plugs are associated with airway remodeling, including wall thickening and lumen narrowing.
• Targeting distal mucus plugs presents a potential strategy for improving lung ventilation and patient outcomes in asthma.