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

Rationale: Childhood cancer survivors are at risk of long-term pulmonary dysfunction, but we lack sensitive outcome measures to detect early pulmonary damage.Objectives: To assess the ability of nitrogen multiple-breath washout (N₂MBW) for detecting pulmonary dysfunction compared with spirometry in long-term survivors of childhood cancer.Methods: We analyzed cross-sectional data from long-term (≥5-yr) survivors of childhood cancer, aged ≤16 years at cancer diagnosis, ≥16 years at study (assessment period 2015-2019). We categorized survivors by risk: high risk for those having had pulmotoxic chemotherapy, chest radiation, thoracic surgery, and/or hematopoietic stem cell transplantation, and standard risk for other cancer therapies. Primary outcomes were the global lung clearance index (LCI) and acinar ventilation inhomogeneity index (S_ACIN) from N₂MBW, and forced expiratory volume in 1 second (FEV₁) and functional vital capacity (FVC) from spirometry. We calculated z-scores for N₂MBW and spirometry parameters and compared pulmonary dysfunction between risk groups. Pulmonary dysfunction was defined as z-score +1.64 for N₂MBW and -1.64 for spirometry.Results: We studied 46 survivors, median age at diagnosis 10 years (interquartile range, 4-14), median age at study 30 years (interquartile range, 25-40). Thirty-seven percent were at high risk and 63% at standard risk for pulmonary dysfunction. LCI and S_ACIN were higher in the high-risk group compared with the standard-risk group (mean LCI z-scores 2.09, standard deviation [SD] 2.39 vs. 0.95, SD 2.81; mean S_ACINz-scores 2.45, SD 3.29 vs. 0.65, SD 2.79). FEV₁ and FVC were lower in the high-risk compared with the standard-risk group (mean FEV₁z-scores -0.94, SD 1.39 vs. -0.10, SD 1.07; mean FVC z-scores -1.14, SD 1.23 vs. 0.15, SD 1.61). Overall, LCI, S_ACIN, FEV₁, and FVC were abnormal in 60%, 53%, 33%, and 33% of high-risk patients compared with 23%, 21%, 0%, and 4% of standard-risk patients.Conclusions: N₂MBW identified more cases of pulmonary dysfunction in long-term survivors of childhood cancer than spirometry, even in patients who had cancer therapy not specifically known as being pulmotoxic. N₂MBW could be a complementary screening tool for early pulmonary damage after treatment for childhood cancer.Clinical trial registered with www.clinicaltrials.gov (NCT02730767).