Children with some types of cancer or blood disorders may need to undergo a bone marrow transplant. This life-saving treatment works by wiping out a patient’s immune system, and replacing it with donor cells. However, a potential side effect is that this new immune system may later recognize the patient’s organs as foreign and attack them. When this occurs in the lungs, it is known as pulmonary chronic graft-versus-host disease (cGvHD). To provide children who have signs of this complication with proper diagnosis and treatment, the 2014 National Institutes of Health (NIH) guidelines recommend that clinicians obtain a lung biopsy or a breathing test called spirometry, which measures how much and how fast kids can breathe in and out of their lungs.
“When done properly, spirometry is the gold standard test, but it requires a big forced breathing manoeuvre that is often hard for children, especially if they’re feeling weak,” says Dr. Jonathan Rayment, investigator at BC Children’s Hospital Research Institute and clinical associate professor in the Department of Pediatrics at the University of British Columbia. “We don’t even ask kids under six years old to do it, so a lot of the time we're flying blind when monitoring their lung health.”
Pediatric cGvHD can happen anywhere in the body, but one of the worst places for it to occur is in the lungs and not all risk factors are known, so researching ways to monitor this complication is key. One of the alternatives is using the multiple breath washout (MBW), a test that measures how well gases mix in the lungs. “This option only requires patients to sit down and breathe quietly, so it’s easier to do,” Dr. Rayment says.
In a study on lung cGvHD in 2022, Dr. Rayment investigated the utility of MBW, and addressed some of the limitations in the NIH guidelines. While MBW was successful for all the children in the study who tried it — including three-year-olds — only two-thirds of the children who attempted spirometry — all at the age of six or older — were able to perform an acceptable test.
“There’s evidence that MBW is feasible, sensitive, and specific for the diagnosis of cGvHD in younger children, and this test is especially useful for kids who can’t perform spirometry,” he says.
When lung complications first arise, doing the MBW test could help clinicians detect the presence of cGvHD earlier. In the 2022 study, children without lung cGvHD had MBW levels consistently normal, but the results coming from spirometry were inconsistent. “We showed that MBW picked up all the cases of pediatric cGvHD without giving false positives,” says Dr. Rayment.
“The findings from our ongoing research monitoring patients over two years led to discussions with international experts in the field, and played a part in integrating MBW into recent recommendations to screen for lung cGvHD,” Dr. Rayment says. He co-authored a recent paper published in the Journal of Transplantation and Cellular Therapy that discusses the limitations of the NIH criteria, and authored the MBW section in the American Thoracic Society (ATS) Clinical Practice Guideline, published in the American Journal of Respiratory and Critical Care Medicine.
The recommendation to use MBW has just been integrated into ATS’s guidelines, but BC Children’s Hospital changed its local practice two years ago. “It’s been part of our routine lung function for monitoring kids after bone marrow transplants,” says Dr. Rayment. There are operational challenges to implementing MBW in clinical practice, however. While MBW is an easier test for children, it requires dedicated expertise. Unlike spirometry, MBW is not a standard breathing tool in lung function laboratories in North America and, to a great extent, is still confined to the research world.
“For facilities that have MBW and clinicians trained to use it, we recommend it as a baseline and adjunct measure to monitor children with suspicion of lung cGvHD.”
When clinicians are monitoring a child’s health, if they see that the spirometry numbers dropped, the child isn’t acting like someone who has cGvHD, and the MBW test is normal, they need to find out why spirometry values dropped. That would include considering if the child might have another disease and if spirometry has been done properly. “MBW is an extra tool in the toolkit that may allow us to more precisely identify lung disease in kids,” the researcher says.
Dr. Rayment remains engaged with international partners to continue research on lung cGvHD in pediatric patients post-transplant and to discuss how to implement the MBW test broadly and effectively. “In many situations, there was no tool offering pulmonary diagnostic testing for younger kids and now there is,” he says. “I believe that broad implementation of MBW, especially for younger children, will help with earlier diagnosis of lung complications, allowing for earlier treatments and better outcomes.”
