Study participants
Between January 2006 and December 2017, 428 children received allogeneic HSCT at Asan Medical Center. A detailed description for study participants is provided in the online supplement . In the present study, 21 children met lung function criteria modified from the National Institutes of Health consensus guidelines for diagnosis of BOS (E-figure 1) 11,20,21. No subject has concurrent pulmonary infection. In addition, all subjects underwent chest CT scans, and 13 children showed air trapping, small airway thickening, or bronchiectasis. A lung perfusion/ventilation scan was performed on eight children who showed no clear evidence of BOS according to the CT results. Of those eight, five had heterogeneous multiple matched perfusion defects. Lung biopsies were performed on nine children, and constrictive bronchiolitis was confirmed in all nine. Echocardiograms showed that all 21 patients displayed normal heart function at the time of BOS diagnosis.
The median observation period for all subjects after BOS diagnosis was 34.4 months (IQR, 11.5-62.0 months). In our current analysis, pulmonary function tests (PFTs) were gathered during 24 months after BOS diagnosis, and CT values were gathered during 12 months after diagnosis.
All subjects started treatment immediately upon diagnosis. All subjects received 6 to 17 cycles of methylprednisolone (mPD) (i.v. 20mg/kg/day for 3 days, with an interval of 1 month) except one subject who died within 6 months after BOS diagnosis. The median mPD pulse therapy period for all subjects was 12.0 months (IQR: 7.5-12.0 months) (E-table 1). A detailed description is provided in the online supplement . Diagnosis and treatment of BOS and lung function monitoring followed the Pediatric Hemato-oncology Division of Asan Medical Center protocol regarding BOS after HSCT, which was developed with the Pediatric Pulmonology Division in 2011.
We divided subjects into two groups according to BOS prognosis and compared the clinical characteristics, lung function parameters, and chest CT findings between the good and poor prognosis groups. The poor prognosis group included patients who had died or required lung TPL (hereafter labeled Group 1) and Group that had required O2 therapy after BOS diagnosis (hereafter labeled Group 3), and the good prognosis group included survivors that did not require lung TPL (hereafter labeled Group 2) or Group that did not require O2 therapy after BOS diagnosis (hereafter labeled Group 4). O2 therapy was defined as O2 therapy for more than 1 day due to dyspnea after BOS diagnosis and O2 therapy was applied when dyspnea was accompanied by less than 90% of SPO222.