A Single-Cell Atlas of Small Airway Disease in Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study
Abstract
RATIONALE
Emerging data demonstrate that the smallest conducting airways, terminal bronchioles (TBs), are reduced by 41% by the time someone is diagnosed with mild (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage1) COPD.
OBJECTIVES
To understand the structural, cellular and extracellular matrix alterations underlying TB loss in COPD and how they might be targeted for therapeutic intervention.
METHODS
This cross-sectional study of 34 ex-smokers with normal lung function (n=10), GOLD1 (n=10), GOLD2 (n=8), and GOLD4 (n=6) COPD used micro-computed tomography, and non-linear optical microscopy imaging to assess the morphology and extracellular matrix of TBs in 262 lung samples. A subset of 57 TBs across all groups was assessed using imaging mass spectrometry to generate a single-cell atlas of TB pathology.
MEASUREMENTS AND MAIN RESULTS
Compared to ex-smokers the TB airway wall in all GOLD stages was homogenously thickened, but the TB lumen was progressively narrowed with disease severity(p<0.05). Progressive loss of radial tethering due to reduced numbers of alveolar attachments/TB perimeter(p<0.05), was associated with degradation and fragmentation of radial elastic fibers and accumulation of disorganized fibrilar collagen(p<0.05). Single-cell imaging identified adaptive immune cells within the TB wall and M1-like macrophage aggregates and neutrophils in alveolar attachments. TB pathology was associated with the upregulation of genes involved in innate and…
How strong is the evidence?
Evidence Hub reads this as a cross-sectional. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 10 participants or records.
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