Lung clearance index (LCI) assessed using the nitrogen multiple breath washout (MBW) test may be an effective diagnostic for pulmonary chronic graft-versus-host disease (p-cGVHD) in children, according to results of a study published in Transplantation and Cellular Therapy.

p-cGVHD is a highly morbid manifestation of chronic graft versus host disease (cGVHD) following hematopoietic stem cell transplantation (HSCT). The pathogenesis of p-cGVHD remains poorly understood, and among children, there is a lack of a feasible diagnostic tool.

For this cross-sectional study, 26 children who underwent HSCT were recruited at the BC Children’s Hospital in Vancouver, Canada between June 2018 and December 2019. Nitrogen MBW testing was attempted among all patients and spirometry was attempted among those aged 6 years and older. p-cGVHD incidence was related with MBW and spirometry test results.

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Patients were median age 11.1 years (IQR, 4.3), 65% were boys, patients were 26.4 months (IQR, 15.7-51.8) post-HSCT, and 76.0% had a previous cGVHD diagnosis.

A total of 6 (23%) children developed p-cGVHD, among whom only 3 met the 2014 National Institutes of Health (NIH) diagnostic criteria.

MBW was successful in all patients and spirometry testing was successful in 77%. Children who did not achieve adequate maneuvers for spirometry were aged 6.3 to 8.8 years.

Patients with p-cGVHD had significantly higher LCI compared with those who did not have cGVHD (P =.001) or who had extrapulmonary cGVHD (P =.007).

LCI was able to correctly identify p-cGVHD with an area under the receiver operating characteristic curve of 0.97. A LCI cutoff of 9.0 had a sensitivity of 100%, positive predictive value of 75%, and specificity of 90%.

This study was limited by not validating these findings among an independent sample.

The researchers concluded that MBW may be a valid tool for diagnosing p-cGVHD in children.


Rayment JH, Sandoval RA, Roden JP, Schultz KR. Multiple breath washout testing to identify pulmonary chronic graft versus host disease in children after hematopoietic stem cell transplantation. Transplant Cell Ther. Published online February 6, 2022. doi:10.1016/j.jtct.2022.02.002