Lung clearance index for early detection of pulmonary complications after allo-HSCT in children.
BACKGROUND
Pulmonary chronic graft-vs-host disease (cGvHD) after hematopoietic stem cell transplantation (HSCT) is characterized by impairment of the small airways. Assessment of lung clearance index (LCI) gained from multiple breath washout (MBW) is more sensitive than spirometry in detection of small airways disease. The aim of this study was to describe the development of LCI during the first year after pediatric HSCT and how LCI relates to other pulmonary function parameters and cGvHD.


METHODS
This prospective, longitudinal study included 28 pediatric HSCT-recipients. Spirometry, Sulfur hexafluoride MBW and diffusion capacity of the lungs were performed before and at 3, 6, 9, and 12 months after HSCT. Respiratory symptoms and signs of cGvHD were recorded at each visit.


RESULTS
Before HSCT, 47.8% had abnormal LCI and 12.5% had abnormal forced expiratory volume in 1 second (FEV1 ). Patients with persisting respiratory symptoms 12 months post-HSCT had higher median LCI (factor 5.7, P = 0.0018) and lower FEV1 z-scores (-1.5, P = 0.033) post-HSCT compared to patients free of respiratory symptoms. Overall, post-HSCT LCI values were 3.49 times higher and FEV1 was 2.31 z-scores lower in eight patients with cGvHD in any organ system compared with patients without cGvHD (P = 0.0089 and P < 0.0001). LCI values during the first 3 months were not predictive of pulmonary cGvHD.


CONCLUSION
LCI is a sensitive marker for cGvHD and high LCI values were associated with persisting respiratory symptoms after 1 year. Further evaluation of MBW in early detection of HSCT-related pulmonary complications require larger patient cohorts and closer follow-up during the first months after HSCT.
['Uhlving|Hilde H|HH|0000-0003-0389-3767', 'Skov|Linnea|L|', 'Buchvald|Frederik|F|0000-0003-4196-3893', 'Heilmann|Carsten|C|', 'Grell|Kathrine|K|', 'Ifversen|Marianne|M|', 'Green|Kent|K|', 'Müller|Klaus|K|', 'Nielsen|Kim G|KG|']
D000293:Adolescent D001944:Breath Tests D002648:Child D002675:Child, Preschool D042241:Early Diagnosis D005260:Female D006086:Graft vs Host Disease D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D008168:Lung D008297:Male D011183:Postoperative Complications D011446:Prospective Studies D012129:Respiratory Function Tests
graft-vs-host disease multiple breath washout small airways disease pediatrics allogeneic hematopoietic stem cell transplantation