Nitrogen single and multiple breath washout test and lung imaging to detect treatment-related pulmonary toxicity in paediatric cancer patients and survivors: a systematic review.

Background: Spirometry-based assessment of pulmonary function has limitations in detecting pulmonary toxicity following cancer treatment with chemotherapy, haematopoietic stem cell transplantation, radiotherapy or thoracic surgery. Nitrogen single and multiple breath washout tests are sensitive in assessing peripheral airway function, and lung imaging detects structural abnormalities, but little is known about their use in paediatric cancer patients and survivors. We aimed to 1) identify studies using nitrogen single or multiple breath washout tests and/or lung imaging to assess pulmonary toxicity in paediatric cancer patients and survivors, and 2) describe reported abnormalities.

Method: We systematically searched MEDLINE, Embase and the Cochrane Library for studies published in 1995‒2023. Eligible studies included paediatric cancer patients and survivors under 22 years of age receiving haematopoietic stem cell transplantation, chemotherapy, radiotherapy and/or thoracic surgery who underwent nitrogen single or multiple breath washout tests or lung imaging for detecting pulmonary toxicity. Two independent reviewers identified the studies, performed data extraction and assessed risk of bias.

Results: We included 12 of 6544 publications. Three studies used nitrogen single or multiple breath washout tests, seven conducted lung imaging using computed tomography and two used both nitrogen single or multiple breath washout tests and lung imaging. Abnormal test results for nitrogen single and multiple breath washout tests and lung imaging were mainly reported following haematopoietic stem cell transplantation (67%). All studies performing lung imaging reported structural abnormalities. Study results were heterogeneous due to varying patient and methodological characteristics.

Conclusion: We identified a limited number of studies, mainly after haematopoietic stem cell transplantation, reporting functional and structural lung abnormalities in paediatric cancer patients and survivors. Longitudinal studies with standardised assessments using nitrogen single or multiple breath washout tests and lung imaging are needed to improve our understanding of treatment-related pulmonary toxicity.