• Airway Epithelium

It has long been known that first second forced expired volume (FEV₁) is insensitive both to distal airway disease and also structural lung disease as measured by high-resolution CT (HRCT).1 Furthermore, monitoring airway diseases has become harder as successful therapies have limited the rate of deterioration, making change in FEV₁ less and less useful in clinical practice and as an endpoint in randomised controlled trials. Accordingly, we have had to deploy novel measures (or in the case of multiple breath washout (MBW), rediscovered old techniques). The use of MBW to calculate lung clearance index (LCI) and calculate other, more sophisticated phase 111 analyses has taken off in the last decade or so. The most salient data have come from cystic fibrosis (CF). LCI has been shown in cross-sectional studies to be abnormal more often than spirometry or plethysmography;2 ,3 in longitudinal studies, LCI becomes abnormal before these other measures;4 it predicts future lung function5 and CF lung attacks;6 it is sensitive to interventions such as treatment of a CF lung attack with intravenous antibiotics;7 and has been used as an endpoint in randomised controlled trials,8–10 particularly in children in whom spirometry is normal or nearly normal.11 Cross-sectional comparisons with HRCT have shown that LCI is very sensitive to structural airway wall disease12 ,13 and can reduce the number of HRCT scans in the CF clinic. Furthermore, the normal values of LCI flat line throughout life, other than slight rises in the very young14 and the elderly.15 LCI clearly has limitations—there is no signal from areas of the lung that are unventilated or …