Success and Feasibility of Multiple Breath Washout: Prospective Multi-center Results From the Transpire Study

Abstract

Rationale: Pulmonary complications, e.g., pulmonary chronic graft vs host disease and bronchiolitis obliterans, are major causes of morbidity and mortality following hematopoietic stem cell transplant. Pulmonary function testing is insensitive for detecting changes in small airways. Multiple breath nitrogen washout (MBW) is a technique used to detect ventilation heterogeneity. Primary outcome of MBW testing is lung clearance index (LCI), lung turnovers required to clear an inert gas (N2). Utilization of LCI as a marker for early disease may allow for early diagnosis. Methods: TRANSPIRE is a prospective cohort study of lung injury after pediatric HSCT. Eligible participants undergo repeated pulmonary evaluations that include PFTs, 6MWT, IOS, MBW, and 129Xe MRI. This descriptive report aims to evaluate the feasibility and success of surveillance MBW in this cohort. Subjects ≥6 years of age across 3/7 participating centers were eligible for MBW testing. Data were reviewed through Sept 14, 2023. Results: 49 participants across 3 centers were eligible for MBW. Thirty-one (63.3%) subjects attempted at least 1 MBW test completing 56 unique results. Mean age for those performing MBW was 14.01 years (6.33 - 24.8). There were more males (18/31, 58.1%). Malignancy was the most common primary diagnosis (22, 71.0%), followed by benign hematologic conditions (3), immune deficiencies (2), marrow failure (2), and genetic/metabolic causes (2). Three eligible subjects were unable to produce acceptable results due to poor technique or intolerance of testing conditions. The remainder of missing data was secondary to missed appointments, intercurrent illnesses, or refusal to participate. 22/31 (71.0%) participants with at least 1 MBW attempt have pretransplant baseline data. Eight (36.4%) of these subjects also have at least one additional post-transplant data point (Figure 1A). The mean baseline LCI2.5 was 6.50 +/-0.99 SD (range 5.35 - 9.79, ULN 7.9) (Figure 1). For pre-transplant baseline data, only one had an abnormal LCI2.5 above the upper limit of normal. Twenty-nine percent (9/31) had abnormal spirometry prior to transplant. DLCO uncorrected for hemoglobin was abnormal in 29% (6/21) at baseline and 54% (7/13) at day 100. Thirty-eight documented pulmonary events occurred in 31 participants. Two subjects registered an abnormal LCI2.5 at any timepoint. Conclusions: MBW is a feasible test that can be reliably done in patients as young as 6 years of age, regardless of primary disease or baseline pulmonary status. The relevance and applicability of outcome variables such as LCI have yet to be determined given our small sample size to date.