FEF 25–75% as a spirometric variable in pulmonary function testing (PFT) is predictive for the diagnosis of obliterative bronchiolitis (OB) following myeloablative allogeneic hematopoietic stem cell transplant (HSCT)

Abstract

Introduction: Following allogeneic HSCT, a major cause of obstruction is OB (frequency, 8–33%). Diagnosis is histologic, but often presumptive, based on clinical features, radiographic and PFT changes showing obstruction, hyperinflation and gas trapping. OB is associated with chronic, but not acute graft-versus-host disease (cGVHD/aGVHD). A 5% decline in percent predicted forced expiratory volume in 1 second (FEV1), FEV1/FVC (forced vital capacity) < 0.7 or 10% fractional drop from previous best PFT was suggestive of OB in previous studies. It is yet to be defined which spirometric measurement is most suggestive for the presence of OB. Forced expiratory flow rates (FEF25–75%), with >30% decline from baseline was found to be more sensitive than FEV1 in diagnosing OB following single lung transplant [Nathan, et al, 2003 J Heart and Lung Transplantation 22(4): 427]. FEF25–75% has never been evaluated following allogeneic HSCT. Methods: We retrospectively reviewed PFT data on 48 adult patients undergoing HSCT from 1998–2003, who survived for at least 12 months and had pre and post-transplant PFT within 1-year of HSCT. Median age was 42 years (range, 20–57), and 54% were male. Forty-seven patients had malignant hematologic disorders. The conditioning regimen was TBI-based in 34 (73%) patients, and 13 received chemotherapy only. Marrow and peripheral blood stem cells were used in 22 and 26 patients respectively. Results: Incidence of aGVHD was 52%, (gradeI-II/III–IV: 88%/12%), 12% of patients had cGVHD (limited/extensive: 69%/13%). Ten patients (21%) had a diagnosis of OB (8-histologicaly, 2-based on signs and symptoms). Spirometric measurements considered as predictor variables included diffusion capacity for carbon monoxide (DLCO), FEV1, total lung capacity (TLC), FEF 25–75%. There was no significant association between diagnosis of OB and age, GVHD, stem cell source, preparatory regimen, TLC or DLCO. A backward elimination model building procedure for a logistic regression identified FEF25–75% as the sole significant explanatory variable. This model suggests that with a 40% decrease or more in FEF 25–75% compared to pre-transplant value, the estimated probability of the diagnosis of OB would be 50% or higher. Conclusion: A decrease in FEF 25–75% of ≥ of 40%, in the absence of other non-infectious pulmonary complications, was highly suggestive in allogeneic HSCT patients for the diagnosis of OB. We plan to evaluate our findings in a prospective study.