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. 2025 Sep 24.
doi: 10.1097/TP.0000000000005515. Online ahead of print.

Characterization of Spirometric Response to Standard-of-care Treatment in Lung Allograft Recipients With Bronchiolitis Obliterans and the Utility of Spirometric Criteria for Rescue Therapy: Implications for the Design of Risk-stratified Clinical Trials

Derek E Byers  1 , Ramsey Hachem  2 , Chadi A Hage  3 , Rajat Walia  4 , Hilary Goldberg  5 , Mrunal Patel  6 , John Reynolds  7 , Julia Klesney-Tait  8 , Selim Arcasoy  9 , Chetan Naik  10 , Nicoe De Simone  11 , Amena Usmani  12 , Reda Girgis  13 , Francis Cordova  14 , Brian Keller  15 , David Nunley  16 , Jagadish Patil  17 , Matthew Morrell  2 , Elizabeth Lendermon  18 , Howard Huang  19 , Andres Pelaez  20 , Amir Emtazoo  21 , Keith Wille  22 , Kevin Chan  23 , Gordon Yung  24 , Maher Baz  25 , Shambhu Aryal  26 , Suresh Vedantham  27 , Mary Clare Derfler  27 , Paul Commean  28 , Keith Berman  29 , Andrew Atkinson  30 , Jeff Atkinson  31 , Alexey Prokudin  32 , John McCarthy  33 , George J Despotis  32   34 ; on the behalf of the EPI Study Group
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Characterization of Spirometric Response to Standard-of-care Treatment in Lung Allograft Recipients With Bronchiolitis Obliterans and the Utility of Spirometric Criteria for Rescue Therapy: Implications for the Design of Risk-stratified Clinical Trials

Derek E Byers et al. Transplantation. .

Abstract

Background: The spirometric response to standard-of-care (SOC) immunosuppressive therapy for the management of bronchiolitis obliterans syndrome (BOS) has been sparsely reported in the literature. Data from a Medicare-approved Registry were analyzed to characterize the effectiveness/durability of a wide range of SOC interventions to manage the decline of lung function and to validate the study spirometric criteria for initiation of rescue therapy.

Methods: Lung transplant recipients with refractory BOS at 21 US collaborating centers were enrolled in the Registry. Data included both nonspirometric (eg, demographic, Immunosuppressive Regimens for management of BOS) and spirometric parameters (ie, FEV1 measurements and derived indices). The utility of study forced expiratory volume in 1 s (FEV1) criteria for treatment (ie, statistically significant rate of FEV1 decline >30 mL/mo) was evaluated by comparing the spirometric course between participants who met or did not meet this criterion.

Results: Only 21% of participants treated with SOC therapy had >50% decrease (76 ± 25% decrease) in the rate of FEV1 decline. Although 51% of participants had a partial response (rate of FEV1 decline decreased on average 71%), 49% of participants had a substantial increase (mean increase 224%). The FEV1 criterion for treatment was able to identify 19% of participants (48/258) who achieved durable stabilization (ie, nonsignificant rate of FEV1 <30 mL/mo) with SOC therapy.

Conclusions: Patients with BOS have a widely variable response to SOC therapy. Our findings support the use of FEV1 rate of decline to assess response to SOC therapy and to assure appropriate assignment of participants with refractory BOS to rescue therapy treatment cohorts.

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Conflict of interest statement

R.H. received grant from Mallinckrodt. S.Arcasoy received grants from Sanofi, Renovion, Zambon, Caredx, and Natera. B.K. is a consultant/Scientific Advisory Board of CareDx and Zambon. S.V., C.D., P.C., A.A., A.Prokudin, and G.D. are team members of the study team from Washington University involved with research management of the Investigator Initiated ECP trial funded by a research grant from Therakos. The other authors declare no conflicts of interest.

References

    1. Verleden GM, Glanville AR, Lease ED, et al. Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment—a consensus report from the Pulmonary Council of the ISHLT. J Heart Lung Transplant. 2019;38:493–503.
    1. Yusen RD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: thirty-second official adult lung and heart-lung transplantation report—2015; focus theme: early graft failure. J Heart Lung Transplant. 2015;34:1264–1277.
    1. Verleden SE, Vasilescu DM, McDonough JE, et al. Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure. Eur Respir J. 2015;46:1430–1439.
    1. Heng D, Sharples LD, McNeil K, et al. Bronchiolitis obliterans syndrome: incidence, natural history, prognosis, and risk factors. J Heart Lung Transplant. 1998;17:1255–1263.
    1. Finlen Copeland CA, Snyder LD, Zaas DW, et al. Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients. Am J Respir Crit Care Med. 2010;182:784–789.

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