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

https://doi.org/10.1016/j.healun.2004.11.008Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Study Population

Twenty-seven initially stable LT recipients (LTR), all BOS 01 3 to 9 months after LTx, were recruited at The Alfred Hospital between January 1997 and December 1998 (Table 1). They were followed for at least 3 years with surveillance bronchoscopic analyses that included sampling of bronchoalveolar lavage (BAL), endobronchial biopsy (EBB), and transbronchial biopsy (TBB). Nine healthy, asymptomatic, non-smoking volunteers (6 men, mean age of 31.8 years) with normal lung function were recruited as

Clinical Outcomes

Patient demographics and baseline clinical characteristics are listed in Table 1. In the Stable Group, 31 bronchoscopies were performed on 8 recipients. Eleven microorganisms were detected (6 bacterial, 4 viral, and 1 fungal), and 3 clinical infections were diagnosed from these procedures. Grade A2 rejection was diagnosed on 1 occasion.19 In the Ever BOS Group, 54 bronchoscopies were performed on 19 recipients, 17 after BOS developed (detected at a mean of 488 ± 290 days after LTx). Twenty-nine

Discussion

This study has demonstrated the presence and persistence of early increased airway vascularity in human lung allografts. This is potentially related to peri-operative events (most likely ischemia) and is probably further contributed to by subsequent airway allograft inflammation. Interestingly, increases in airway vasculature are not associated with the time after transplant or the presence of infection as indicated by both univariate and multivariable analyses.

In human lung transplantation,

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