Structural alterations and markers of endothelial activation in pulmonary and bronchial arteries in fatal asthma

BACKGROUND: There is interest in better understanding vessel pathology in asthma, given the findings of loss of peripheral vasculature associated with disease severity by imaging and altered markers of endothelial activation. To date, vascular changes in asthma have been described mainly at the submucosal capillary level of the bronchial microcirculation, with sparse information available on the pathology of bronchial and pulmonary arteries. The aim of this study was to describe structural and endothelial activation markers in bronchial arteries (BAs) and pulmonary arteries (PAs) of asthma patients who died during a fatal asthma attack. METHODS: Autopsy lung tissue was obtained from 21 smoking and non-smoking patients who died of an asthma attack and nine non-smoking control patients. Verhoeff–Masson trichrome staining was used to analyse the structure of arteries. Using immuno-histochemistry and image analyses, we quantified extracellular matrix (ECM) components (collagen I, collagen III, versican, tenascin, fibronectin, elastic fibres), adhesion molecules [vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1)] and markers of vascular tone/dysfunction [endothelin-1 (ET-1) and angiotensin II type 2 receptor (AT2)] in PAs and BAs. RESULTS: There were no significant differences in ECM components, ICAM-1, ET-1 or AT2 between asthma patients and controls. Smoking asthma patients presented with decreased content of collagen III in both BA (p = 0.046) and PA (p = 0.010) walls compared to non-smoking asthma patients. Asthma patients had increased VCAM-1 content in the BA wall (p = 0.026) but not in the PA wall. CONCLUSION: Our data suggest that the mechanisms linking asthma and arterial functional abnormalities might involve systemic rather than local mediators. Loss of collagen III in the PA was observed in smoking asthma patients, and this was compatible with the degradative environment induced by cigarette smoking. Our data also reinforce the idea that the mechanisms of leukocyte efflux via adhesion molecules differ between bronchial and pulmonary circulation, which might be relevant to understanding and treating the distal lung in asthma.