A Descriptive Study of Small Airway Reticular Basement Membrane Thickening in Clinically Stable Lung Transplant Recipients

Abstract

Chronic rejection functionally manifested by fixed airflow limitation, bronchiolitis obliterans syndrome (BOS), is a major problem for all lung allograft programs. The inclusion of a pre-BOS category (BOS(0 approximately p)) in the newly revised guidelines, recognizes the potential importance of early changes. We tested the hypothesis that small airway reticular basement membrane thickening exists even in clinically stable lung transplant recipients with some evidence of inflammation but who are BOS-free. A bronchoscopic study was performed on 30 clinically stable lung allograft recipients at >/=3 months post-allograft, who were BOS-free but with some evidence of airway inflammation indicated by a pathologic diagnosis of lymphocytic bronchiolitis or raised exhaled nitric oxide (NO). After baseline physiologic assessment, small airway reticular basement membrane (Rbm) thickening was quantified in transbronchial biopsy (TBB) using image analysis, with inflammation assessed by bronchoalveolar lavage (BAL) differential cell counts. Twenty-one patients had technically satisfactory measurements of Rbm thickness. We detected small airway Rbm thickening when compared with published data for control lung diseases. There was no correlation between Rbm thickening and lung function (forced expiratory volume in 1 second [FEV(1)] best post-operatively and Rbm r = -0.10, not significant). Our data suggest that airway remodeling can occur early in lung allografts and before development of airflow limitation and BOS. Longitudinal pathophysiologic studies are needed to elucidate potential relationships between airway inflammation, Rbm thickening and allograft failure. Airway biopsies would be of value in such studies.