Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report

Padmaja Subbarao, Carlos Milla, Paul Aurora, Jane C Davies, Stephanie D Davis, Graham L Hall, Sonya Heltshe, Philipp Latzin, Anders Lindblad, Jessica E Pittman, Paul D Robinson, Margaret Rosenfeld, Florian Singer, Tim D Starner, Felix Ratjen, Wayne Morgan, Padmaja Subbarao, Carlos Milla, Paul Aurora, Jane C Davies, Stephanie D Davis, Graham L Hall, Sonya Heltshe, Philipp Latzin, Anders Lindblad, Jessica E Pittman, Paul D Robinson, Margaret Rosenfeld, Florian Singer, Tim D Starner, Felix Ratjen, Wayne Morgan

Abstract

The lung clearance index (LCI) is a lung function parameter derived from the multiple-breath washout (MBW) test. Although first developed 60 years ago, the technique was not widely used for many years. Recent technological advances in equipment design have produced gains in popularity for this test among cystic fibrosis (CF) researchers and clinicians, particularly for testing preschool-aged children. LCI has been shown to be feasible and sensitive to early CF lung disease in patients of all ages from infancy to adulthood. A workshop was convened in January 2014 by the North American Cystic Fibrosis Foundation to determine the readiness of the LCI for use in multicenter clinical trials as well as clinical care. The workshop concluded that the MBW text is a valuable potential outcome measure for CF clinical trials in preschool-aged patients and in older patients with FEV1 in the normal range. However, gaps in knowledge about the choice of device, gas, and standardization across systems are key issues precluding its use as a clinical trial end point in infants. Based on the current evidence, there are insufficient data to support the use of LCI or MBW parameters in the routine clinical management of patients with CF.

Keywords: cystic fibrosis; lung clearance index; multiple-breath washout; pulmonary function tests.

Figures

Figure 1.
Figure 1.
Schematic representation of two washout phase tests using the two techniques. (A) N2-based setup. During the N2 washout, 100% oxygen is delivered using a bias flow. The blue tracing shows the decay in the N2 signal during expiration. (B) Extrinsic gas, SF6-based setup. The green tracing shows the decay in the SF6 concentration during the washout-phase. R/A = room air.

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