Abstract
BackgroundRemodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling. The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-β signalling in COPD patients of different GOLD stages.MethodsLung tissue sections of 14 smoking controls, 16 GOLD II and 19 GOLD IV patients were included and stained for elastin and collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2.ResultsElastin was significantly decreased in COPD patients not only in alveolar, but also in small airway walls. Interestingly, both collagen and hyaluronan were increased in alveolar as well as small airway walls. The matrix changes were highly comparable between GOLD stages, with collagen content in the alveolar wall increasing further in GOLD IV. A calculated remodelling index, defined as elastin divided over collagen and hyaluronan, was decreased significantly in GOLD II and further lowered in GOLD IV patients, suggesting that matrix component alterations are involved in progressive airflow limitation. Interestingly, there was a positive correlation present between the alveolar and small airway wall stainings of the matrix components, as well as for pSMAD2. No differences in pSMAD2 staining between controls and COPD patients were found.ConclusionsIn conclusion, remodelling in the alveolar and small airway wall in COPD is markedly similar and already present in moderate COPD. Notably, alveolar collagen and a remodelling index relate to lung function.
Highlights
Remodelling in Chronic obstructive pulmonary disease (COPD) has at least two dimensions: small airway wall thickening and destruction of alveolar walls
Controls and COPD patients were matched for age, but the ratio of current to exsmokers differed significantly
Decreased elastin in alveolar and small airway walls of COPD patients Elastin is visible as dark purple strands and is notable in alveolar walls, small airway walls around the epithelium and around blood vessels
Summary
Remodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling. The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-β signalling in COPD patients of different GOLD stages. Lung remodelling in COPD is marked by several characteristics, like accumulation of mucous secretions and bronchiolar fibrosis in the proximal airways and remodelling of small airway and alveolar walls. Small airways are most important in the reduction of FEV1. Remodelling of small airways is mainly associated with excess matrix deposition, whereas the neighbouring alveoli are hallmarked by destruction.
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