Early Changes in Basement Membrane Thickness in Airway Walls Post-Lung Transplantation

Abstract

Identification of early histopathologic markers of future bronchiolitis obliterans syndrome (BOS) may enable preemptive targeted intervention, delaying and perhaps preventing the onset of BOS. This study aimed to determine if early changes in airway epithelial basement membrane thickness predisposes transplant recipients to the subsequent development of BOS. Basement membrane thickness was measured in serial endobronchial biopsies taken from 29 initially stable lung transplant recipients (sLTR) recruited 148 +/- 80 days post-transplant and followed for 3 years. A further 2 years of clinical follow-up was undertaken without biopsies to follow lung function and define ultimate BOS status. Nine healthy subjects (non-atopic, non-asthmatic) were recruited as controls. Sections of paraffinized endobronchial biopsies were stained for collagen type I immunohistochemically, and basement membrane thickness was assessed by computer image analysis. BOS developed in 21 of 29 patients in the 5 years of follow-up, 16 of which had endobronchial biopsies available for analysis before BOS developed (ever-BOS). The first endobronchial biopsies showed increased BMT in the combined sLTR and ever-BOS patients compared with the controls. This initial increase in basement membrane thickness resolved to normal levels within 300 days post-transplant, with a strong negative correlation (r2 = 0.424, p < 0.0001) of basement membrane thickness vs time. Paradoxically, the sLTR tended to have the greatest basement membrane thickness at baseline. An initial increase in basement membrane thickness is seen in the airway walls of all lung transplant recipients. This is transient and does not appear to be a risk factor for the subsequent development of BOS in lung allograft recipients.