Early Pulmonary Dysfunction in Childhood Cancer Patients

"All lung function tests are non-invasive and last about 60 minutes per child:~* Multiple Breath Washout: The nitrogen multiple-breath-washout test (N2MBW) measures ventilation inhomogeneity of the lung that occurs when smaller airways are damaged.~* Spirometry/Bodyplethysmography/DLCO: Spirometry measures dynamic air flows to quantify airway obstruction of large airways and pulmonary restriction. Plethysmography assesses static lung volumes. Diffusing capacity of the lung for carbon monoxide (DLCO) evaluates diffusion deficits."

Patients will exhale into a secondary electrospray-ionization-mass spectrometry (SESI-MS) breath analysis platform. SESI-MS allows real-time breath-printing by detection of both volatile and non-volatile trace components.

Functional MRI scan assessing regional fractional lung ventilation and relative perfusion, followed by a morphological MRI scan. This technique allows simultaneous assessment of all affected lung components, the airways, alveoli and pulmonary vasculature.

Short questions on current airway symptoms, recent colds, exercise-related respiratory symptoms, and passive smoking exposure will be assessed. The interview takes about 10 minutes.

Assessment of clinical parameters and cumulative doses to chemotherapy, radiation, surgery and hematopoietic stem cell transplantation (HSCT). Data on cumulative doses of pulmotoxic chemotherapy (carmustine, lomustine, busulfan, bleomycin, methotrexate and cyclophosphamide, fludarabine, ifosfamide, melphalan and thiotepa) and radiation therapy at the region of the chest from patient's hospital charts will be collected. Information on chest wall and lung surgery will be retrieved from the surgical reports. Information about conditioning regimens including cumulative chemotherapy doses and total body irradiation of patients undergoing HSCT will be collected. Further information on the health state of the patient and interventions (e.g. development of pneumonia, antibiotic treatment) will be collected from the hospital charts.

Germline DNA is collected (e.g. through saliva or buccal cell sampling) for later analysis on genetic risk factors for pulmonary complications.