Inert Gas Washout: Theoretical Background and Clinical Utility in Respiratory Disease

Abstract

Inert gas washout was first described more than 60 years ago and 2 principal tests have been developed from it: the single breath and multiple breath washout (MBW) techniques. The invention of fast responding gas analysers almost 60 years ago and small computers 30 years later have facilitated breath-by-breath analysis and the development of sophisticated analysis techniques. It is now possible to detect not only the degree of pulmonary ventilation inhomogeneity, but also to gain important insight into the location of the underlying disease process. While single breath washout requires a full vital capacity effort, tidal breathing during the multiple breath test requires minimal co-operation and co-ordination, and is feasible in subjects of all ages. Available MBW normative data from parameters, such as the lung clearance index, appears to vary minimally with age, making MBW particularly useful to follow children longitudinally. Multiple breath inert gas washout has demonstrated improved sensitivity, in comparison to spirometry, in the early detection of a number of important disease processes, including cystic fibrosis. Despite this, these important techniques remain under-utilised in the clinical setting and there is a lack of commercially available devices currently available. The recent resurgence of research in this area has produced a large number of important studies and a pronounced international interest has developed in these techniques. This review article will provide an overview of the theoretical background of inert gas washout and analysis indices, review important physiological and clinical insights gained from research to date (as well as from our own experience) to illustrate its utility, and outline the challenges that lie ahead in incorporating these techniques into the mainstream clinical setting.

Is Lung Clearance Index (LCI) Affected by the Severity of Lung Disease in CF?

“…A more sophisticated analysis of the SnIII has revealed the Scond and Sacin, as indices to detect the mechanisms of ventilation inhomogeneity and the location of the different ventilated lung units. So, the Scond estimates the Convection-dependent Inhomogeneity (CDI) through the conducting airways and the Sacin estimates the Diffusion Convection Interaction Dependent Inhomogeneity (DCDI) at the mouth of the acini [38,40,47]. LCI is easily applicable in infants and preschoolers because passive cooperation is only required during measurement.…”

“…LCI seems to allow earlier detection of disease, compared to FEV 1 [36,37]. A significant advantage of LCI measurements is that it can be feasible from early age to adulthood and is not affected by age, weight, height and sex, with an exception for infants [38][39][40][41].…”

“…Two indices have been proposed [54] to assess the homogeneity of specific ventilation of partial lung units, Scond and Sacin. Scond is calculated as the linear regression of SnIII values between 1.5 and 6.0 TO (from the 6 th to the 15 th breath) and reflects the difference of gas transport through the conducting airways and Sacin, that is equal to the SnIII TO of the three first breaths minus the Scond contribution (based on the mean TO value of the three first breaths) and reflects the difference between parallel units to the acini [38,40,45].…”

Decline in Lung Volume With Duchenne Muscular Dystrophy Is Associated With Ventilation Inhomogeneity

“…8 Information about peripheral airway function can be obtained by the multiple-breath washout (MBW) lung function test, recently reintroduced into medical practice. MBW generates lung volume data (functional residual capacity [FRC]) and allows calculation of ventilation inhomogeneity markers, such as the lung clearance index (LCI), which are independent of tidal volume (V T ).…”

“…MBW generates lung volume data (functional residual capacity [FRC]) and allows calculation of ventilation inhomogeneity markers, such as the lung clearance index (LCI), which are independent of tidal volume (V T ). 8 Validated systems employing an ultrasound flow meter, as an alternative to complex and expensive measurement by mass spectrometry, have recently become available. 9 LCI elevation has been demonstrated by MBW in a variety of structural lung diseases, including cystic fibrosis, 10 asthma, 11 infant chronic lung disease, 12 and bronchiolitis obliterans.…”