Pulmonary Function Evaluation Outcomes
The main study outcome was percent predicted forced expiratory volume in one second (FEV1) as measured using spirometry. Secondary outcomes were total lung capacity (TLC), measured using body plethysmography, and diffusion capacity of the lungs for carbon monoxide (DLCO), which was adjusted for the patient’s hemoglobin level when a recent value was available (DLCOadj). Trained respiratory therapists performed and independently interpreted all PFTs for acceptability and reproducibility at the time of test completion in accordance with American Thoracic Society standards11. Pulmonary function was measured with the Vmax® Encore PFT system(Care Fusion, Yorba Linda, CA), and a modified version of the Morris et al. reference equations was used to determine percent predicted values, which were adjusted for patient age, sex and height12. All available PFTs performed from 30 days pre-diagnosis were collected retrospectively from patients’ medical records.
As per routine care practices at CHEO, all children who received pulmonary toxic therapy underwent pulmonary function testing at the end of treatment regardless of the presence of symptoms. For patients with one or more recurrences of their primary cancer, all treatment and pulmonary function data beyond the date of the relapse was censored and excluded from the analysis. This ensured that analysis was limited to lung function changes solely due to initial pulmonary toxic exposure and to avoid any confounding effects of cumulative treatment exposures due to relapse.