Pulmonary function testing in pediatric allogeneic stem cell transplant recipients to monitor for Bronchiolitis obliterans syndrome: a systematic review

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BACKGROUND: Bronchiolitis obliterans syndrome (BOS) represents a significant source of morbidity and non-relapse mortality among children and young adults treated with allogeneic hematopoietic stem cell transplantation (aHSCT). Pulmonary function testing (PFT) pre- and post-aHSCT may allow for pre-symptomatic detection of BOS, and thus early intervention. Current guidelines and practices vary regarding which tests to perform and timing relative to transplant. A systematic review evaluating PFT before and after pediatric aHSCT was conducted to inform American Thoracic Society clinical practice guidelines on detection of BOS. OBJECTIVE: To determine the optimal approach to conducting PFT prior to and after pediatric aHSCT. STUDY DESIGN: We performed a systematic review of the literature to identify studies of PFT in human aHSCT recipients < 25 years of age to address two questions: (1) Should pre-transplant screening PFT be performed in pediatric patients who will undergo aHSCT? (2) At what frequency should pediatric patients who have had aHSCT undergo PFT? We searched in Medline through August 2022 for studies that enrolled patients < 25 years of age being treated with aHSCT for whom PFT data were reported before or after transplant. RESULTS: The 30 studies with pre-transplant PFT data showed a wide range of findings, with the majority demonstrating abnormalities. In studies reporting respiratory symptoms, 85-100% of patients were asymptomatic. In the 21 studies reporting post-transplant PFT, 11 used a surveillance strategy where at least one test was performed in the first year post-transplant. Median time to BOS diagnosis was 6-12 months in the regular surveillance studies, and 6-24 months in the others. Forced expiratory volume in one second at the time of BOS diagnosis was 38-84% predicted in studies with regular surveillance versus 44-57% predicted in studies with no surveillance. In the surveillance group, BOS was identified in some patients who were asymptomatic. Data quality in studies reviewed was moderate to very low. CONCLUSIONS: Abnormalities in PFT are common in children prior to aHSCT. Regular monitoring in the first 1-2 years post-aHSCT may improve early and/or pre-symptomatic identification of BOS, but significant limitations may still be seen at the time of diagnosis. Higher quality data are needed.

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