Elevated lung clearance index (LCI) as an early marker of future bronchiolitis obliterans (BOS) post lung transplant

Introduction: BOS limits survival and quality of life gains post lung transplant (LTx). BOS is defined as a persistent fall in FEV1 to ≤80% of best, after excluding reversible pathologies. However many LTx recipients have evidence of small airway disease with high LCI despite preserved FEV1. Earlier BOS detection may allow intervention before irreversible graft dysfunction; we therefore explored longitudinal outcomes post LTx to see if high LCI predicted progression to BOS. Methods: Prospective evaluation of serial FEV1 in patients previously identified with normal FEV1 but high LCI vs normal FEV1/normal LCI until International Society of Heart and Lung Transplantation (ISHLT) BOS criteria were met. Time to diagnosis of BOS and BOS stage at diagnosis were noted. Results: 24/31 patients with normal FEV1, at a median 4.7 years post op, had high LCI (mean 8.3, SD 0.8). 8 (33%) subsequently developed BOS (median FEV1 72% of baseline, range 31-80, Stage I: 5, II: 2, III: 1) after a median interval of 14 (5-27) months. There was continued decline in FEV1 in 5, of whom 3 have died. A median of 4.6 years post op, 7 patients had normal LCI (mean 6.7, SD 0.2) with normal FEV1. Only 1 met ISHLT BOS criteria, 2 months after the initial LCI reading and remains in Stage I at 22 months. All are alive at a median of 27 months post LCI. Conclusion: These exploratory data suggest that ventilation inhomogeneity due to early small airway disease in LTx recipients, detected as high LCI despite normal FEV1, may independently predict future lung function decline. This hypothesis will be tested more robustly in a 4-year prospective study using an adequately powered sample in our unit.