Lung clearance index for early detection of pulmonary complications after allo‐HSCT in children

Abstract

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 (FEV 1 ) . Patients with persisting respiratory symptoms 12 months post-HSCT had higher median LCI (factor 5.7, P = 0.0018) and lower FEV 1 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 FEV 1 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.

Pulmonary Dysfunction after Treatment for Childhood Cancer. Comparing Multiple-Breath Washout with Spirometry

“…In the only study that assessed N 2 MBW in pediatric HSCT recipients who were still under active cancer treatment (14), 28 children underwent pulmonary function assessment before and after HSCT. Again, LCI was a sensitive marker for cGvHD and was associated with persisting pulmonary symptoms, but LCI measured at HSCT was not predictive for the development of pulmonary cGvHD within one year after HSCT (14).…”

“…N 2 MBW has to date been investigated only in pediatric cancer patients undergoing HSCT (14). This is the first study that shows results of N 2 MBW tests in long-term survivors of childhood cancer.…”

“…Its main outcome indices are the lung clearance index (LCI), a marker for global ventilation inhomogeneity, and the acinar ventilation inhomogeneity index (S ACIN ), which measures global and acinar ventilation inhomogeneity. N 2 MBW is more sensitive than spirometry for the detection of early pulmonary disease in children with cystic fibrosis (12,13), in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) (14) and lung transplantation (15), and in adults after HSCT (14,16). It has not yet been used with childhood cancer survivors.…”

Pediatric pulmonology year in review 2019: Physiology

“…Spirometry is not a sensitive test for detection of early small airway obstruction. Uhlving et al 28 studied the potential role of LCI in identifying or predicting pulmonary complications of cGVHD in a cohort of 30 children who received HSCT. Post‐HSCT LCI was significantly higher in children who developed cGVHD, but LCI measured before and 3 months post‐HSCT was not superior to spirometry in predicting BOS.…”

Pediatric pulmonology 2019 year in review: rare and diffuse lung disease

“…Typically, HSCT recipients are monitored using spirometry, but other modalities such as multiple breath washout (MBW) may have advantages for detecting small airway dysfunction. In a prospective longitudinal study of 28 pediatric HSCT recipients, Uhlving et al 53 found that lung clearance index (LCI) using MBW was sensitive for identifying pulmonary GvHD. Although more data are needed, the measurement of LCI offers another potential tool to aid in the early detection of an insidious pulmonary complication of cancer therapy.…”