Intervention trials and ventilation distribution in mild cystic fibrosis lung disease: will it all come out in the wash?

Abstract

The identification of clinically relevant end-points for use in clinical trials of new treatments in cystic fibrosis (CF) lung disease is an ongoing problem for physicians and researchers working in the field of CF care. Lung disease almost certainly starts in early infancy 1–6 and is progressive, leading to significant structural lung disease in the preschool years 7. Despite this, the majority of young children with CF tend to have spirometry within the normal range at early school age 1, 8, 9. It is well recognised that relying on spirometry alone to identify children at risk of progressive lung disease has significant limitations. This has led to renewed emphasis on the assessment of physiological outcomes in infancy and the preschool years, as well as increased focus on lung function tests that are more sensitive to early lung dysfunction than spirometry 10–13. One such outcome is the assessment of ventilation inhomogeneity obtained from the multiple breath inert gas washout test (MBW), the most commonly reported outcome being the lung clearance index (LCI). A significant advantage of this technique is that it can be applied from infancy through to adulthood, with only minor changes in equipment and methodology, particularly from the preschool years onwards 14–16. The LCI has been shown to be abnormal in the presence of normal spirometry in both preschool children 7 and older children with CF 9, 17–22, suggesting that it is a more sensitive marker of early lung disease in such …