Pulmonary dysfunction after treatment for childhood cancer – Comparing multiple-breath washout with spirometry

Abstract

Rationale: Childhood cancer survivors are at risk of long-term pulmonary dysfunction, but we lack sensitive outcome measures to detect early pulmonary damage.

Objective: To assess the ability of nitrogen multiple-breath washout (N₂MBW) to detect pulmonary damage compared to spirometry in childhood cancer survivors.

Methods: Cross-sectional analysis from long-term (≥5-year) childhood cancer survivors. We categorized subjects by risk group: i) high risk: pulmotoxic chemotherapy, chest radiation, thoracic surgery, hematopoietic stem cell transplantation ii) standard risk: other cancer therapies. Primary outcomes were lung clearance index (LCI), acinar ventilation inhomogeneity index (S_ACIN), FEV1 and FVC. We calculated z scores and compared pulmonary dysfunction between risk groups.

Results: We studied 46 survivors, median age at diagnosis 10 years, 30 years at study. 37% were in the high, 63% in the standard risk group. LCI and S_ACIN were higher in the high risk vs the standard risk group (mean LCI 2.09, standard deviation [SD] 2.39 vs 0.95, SD 2.81; mean S_ACIN 2.45, SD 3.29 vs 0.65, SD 2.79). FEV1 and FVC were lower in the high risk vs the standard risk group (mean FEV1 -0.94, SD 1.39 vs -0.10, SD 1.07; mean FVC -1.14, SD 1.23 vs 0.15, SD 1.61). LCI, S_ACIN, FEV1, and FVC were abnormal in 60%, 53%, 33%, and 33% in the high risk compared to 23%, 21%, 0%, and 4% in standard risk group.

Conclusion: N₂MBW identified more cases of pulmonary damage in long-term childhood cancer survivors than spirometry, even in patients with cancer therapy not known as pulmotoxic. N2MBW could be an effective screening tool for early pulmonary damage after childhood cancer treatment.