Gas mixing efficiency from birth to adulthood measured by multiple-breath washout

Abstract

Efficient mixing of inspired gas with the resident gas of the lung is an essential requirement of effective respiration. This review focuses on one method for quantifying ventilation inhomogeneity: the multiple-breath inert gas washout (MBW).

MBW has been employed as a research tool in adults and school age children for more than 50 years. Modifications allowing data collection in infants and preschoolers have been described recently. Indices of overall ventilation inhomogeneity, such as the lung clearance index and moment ratios, are raised in many infants with lung disease of prematurity, and in young children with cystic fibrosis. These indices may be more sensitive than other lung function measures for the early detection of airway disease. We describe, for the first time, a development of the MBW analysis that allows calculation of acinar and conductive zone inhomogeneity indices in spontaneously breathing children.

Although methodological and analytical issues remain, the future clinical and research applications of MBW justify accelerated research in this field.

Introduction

Mixing of inspired gas with the resident gas of the lung is an essential requirement of effective respiration. If gas mixing is inefficient or inhomogeneous, then an increase in minute ventilation is required to deliver inspired gas to the alveoli and to effect adequate gas exchange. The efficiency of gas mixing is dependent upon the architecture of the lung, particularly of the peripheral airways; and upon relative time constants of parallel lung units, which in turn are determined by heterogeneity of airway resistance and lung compliance (Engel, 1983). Instruments that measure the efficiency of gas mixing in childhood have enormous potential application, most obviously for the early detection of lung disease, but also to record the growth and development of the lungs.

Such instruments may now exist. Recent reports have described the use of electrical impedance tomography (Frerichs, 2000), aerosol deposition studies (Darquenne and Prisk, 2004) and single-breath inert gas washout (Ljungberg and Gustafsson, 2003) for the quantification of ventilation inhomogeneity. However, none of these techniques have been extensively employed in unsedated children to date. This review will therefore focus on a fourth method: the multiple-breath inert gas washout (MBW).

Although initially described many years ago, MBW has only been used intermittently to assess gas mixing efficiency or ventilation inhomogeneity in infants and young children (Wall, 1985), possibly reflecting the complexity of data analysis and the lack of commercially available equipment and software. During recent years, technological advances combined with increasing awareness that conventional measures of airway function may not detect early changes in peripheral airway function until lung disease is well established have led to a resurgence of interest in this field (Gustafsson et al., 2003). The MBW is applicable to subjects of all ages, including unsedated infants (Hjalmarson and Sandberg, 2002), as measurements are performed during spontaneous tidal breathing. A variety of indices have been reported from MBW. Some of these describe overall ventilation inhomogeneity, but others may describe specific mechanisms by which inhomogeneity is generated, and thereby provide detailed indirect information on lung development and pathology. Specific adaptations to data collection methods are required for young children (Aurora et al., 2005, Hjalmarson and Sandberg, 2002), and a number of challenges remain, particularly with regard to data analysis. The aim of this review is to describe these methods, summarise published data from studies in children and discuss priorities for future research. Prior to exploring this theme, it is necessary to briefly consider both structural and functional aspects of lung development. Such knowledge is fundamental not only for lung modelling during early life but for the measurement, analysis and interpretation of the efficiency of gas mixing throughout childhood.