Airway Vascular Changes After Lung Transplant: Potential Contribution to the Pathophysiology of Bronchiolitis Obliterans Syndrome

Bronchiolitis obliterans syndrome (BOS) remains the primary factor limiting successful lung transplantation. In asthma and lung transplantation BOS-increased sub-mucosal vascularity has been shown to contribute to airflow limitation. Vascularity has 2 components: sprouting angiogenesis (more vessels) and microvascular enlargement (larger vessels). We hypothesized that the lack of a reanastomosed bronchial arterial blood supply at the time of transplant might stimulate angiogenesis and be a risk factor for subsequent BOS. Twenty-seven initially stable lung transplant recipients (BOS 0) were recruited at 148 ± 80 days post-transplant and underwent clinical and bronchoscopic longitudinal follow-up for at least 3 years. Eight remained stable and BOS developed in 19. Nine normal controls were also recruited. Airway vasculature was examined immunohistochemically in endobronchial biopsy (EBB) specimens with collagen IV antibody, quantified by computer image analysis, and expressed as average vessel size, vessel number, and overall vascularity. The effects of demographic, clinical, bronchoalveolar lavage (BAL), and EBB variables on airway vasculature were analyzed in a multivariate model. No significant differences in airway vascularity were found between stable and BOS lung transplant recipients cross-sectionally or longitudinally. However, both lung transplant groups at baseline showed significantly greater airway vascularity compared with normal controls ( p < .05). Multivariate analysis suggested that the percentage of BAL CD3 + cells and acute rejection are the most influential variables on airway vasculature. This study suggests early and persistent airway vasculature changes occur in lung transplant recipients, mainly manifested as microvascular enlargement. Potentially this baseline change contributes to airway obstruction and also puts all lung transplant recipients at risk for further exponential loss of airway caliber with any subsequent airway inflammatory insult.