The aim of our physiological outcomes research is to understand how outcomes derived from the Multiple Breath Washout test (MBW) may ultimately be regarded as standard of care for young children with cystic fibrosis (CF) lung disease. For the past two decades MBW has largely been a research test. Our team has worked together with collaborators from around the world to develop standard operating procedures to facilitate multi-centred clinical trials.

To optimize the test for young children, we have proposed several modifications to the standard MBW equipment set up to improve the feasibility of the test in children as young as three years old. We have collaboratively explored alternative MBW outcomes (Stanojevic, 2015) to shorten the duration test and in turn further improve the feasibility of routinely using this test in a clinical setting.

As with all other measures of lung function, correct interpretation of MBW outcomes is dependent on the collection of reliable data. During the MBW test, subjects must breathe in a resting tidal breathing pattern such that the gas mixing within the lungs can be correctly measured. Distortion of the breathing pattern during the washout may give a bias result. We have worked to determine the range of tidal breathing that is considered normal, and developed standardized quality control criteria for the test.

Through the establishment of these standards for the testing procedure and for interpretation of the test, we have studied extrinsic factors that may bias MBW results. We have demonstrated the impact of equipment dead space volume (Benseler, 2015) as well as inert gas type (Jensen, 2013) on MBW outcomes. We have investigated potential confounding influences such as the variation in MBW outcomes with growth, age (Jensen, 2014), disease severity (Oude Engberink, 2016) and the effect of tissue nitrogen (Kane, 2016), all of which may bias the interpretation of results.

This is an active area of research, with new research questions arising frequently. Many of these projects begin as summer student projects, and grow into one-year, in-depth studies for junior research staff.

• Stanojevic S, Jensen R, Sundaralingam D, Salazar JG, Yammine S. Singer F, Latzin P, Amin R, Subbarao P, Gustafsson P, Ratjen F. Alternative outcomes for the multiple breath washout in children with cystic fibrosis. J Cyst Fibros. 2015 Jul;14(4):490-6 [abstract]
• Benseler A, Stanojevic S, Jensen R, Gustafsson P, Ratjen F. The effect of equipment dead space on multiple breath washout measures. Respirology. 2015 Apr;20(3):459-66. [abstract]
• Kane, M., Stanojevic, S., Jensen, R., & Ratjen, F. (2016). Effect of tissue nitrogen excretion on multiple breath washout measurements. European Respiratory Journal, 48(Suppl 60). doi:10.1183/13993003.congress-2016.pa370 [abstract]
• Jensen, R., Stanojevic, S., Feasibility of Longitudinal Multiple Breath Washout Measurements In Preschool Children. ATS Journals [abstract]
• Jensen, R., Stanojevic, S., Gibney, K., Salazar, J. G., Gustafsson, P., Subbarao, P., & Ratjen, F. (2013). Multiple Breath Nitrogen Washout: A Feasible Alternative to Mass Spectrometry. PLoS ONE, 8(2). doi:10.1371/journal.pone.0056868 [abstract]
• Engberink, E. O., Stanojevic, S., & Ratjen, F. (2016). Clinimetric Properties of the Lung Clearance Index in Adults and Children With Cystic Fibrosis. Chest, 150(6), 1412-1413. doi:10.1016/j.chest.2016.08.1478 [abstract]