**9. Pulmonary function and how it predicts prognosis**

Spirometric measurement of lung function, specifically FEV1, has been the pre-eminent surrogate marker of disease staging in CF for a long time. As it is reproducible, readily available, and cheap, it provides longitudinal measurement of airflow obstruction over years. Seminal work by Kerem et al. in 1992 suggested that as an independent factor, FEV1 reliably predicts the relative risk of mortality, with a baseline FEV1 of less than 30% predicted giving a 50% two-year mortality [3, 42]. Following on from this work, further studies suggested that rate of decline of FEV1 could more accurately identify the most at risk patients [2, 43, 44]. Interestingly there is evidence that high baseline FEV1 is a risk factor for greater FEV1 decline and that this phenomenon may be explained by less aggressive prescribing patterns in patients with preserved lung function [45].

Few would argue that FEV1 is invaluable in clinical practice; however, it does fall short in identifying early lung disease where spirometry is often normal. This is especially the case in paediatric CF centres, where lung disease is often in its early stages or where technical limitations in performing reliable expiratory manoeuvres are more common. Recent interest has arisen in lung disease assessment using the Lung Clearance Index (LCI), a measurement derived from the multiple-breath inert gas washout. Whilst this technique is time consuming and less readily available, there is growing evidence that it may be more sensitive than FEV1 in diagnosing early lung disease [46, 47] and that abnormal LCI in the setting of normal FEV1 may predict future FEV1 decline [9]. Moreover, LCI correlates with high resolution compu‐ terised tomography (HRCT) findings [48] and predicts exacerbations and time to first exacer‐ bation [49]. As such LCI may prove to be an appealing tool for more sensitively detecting improvements in lung health when assessing novel therapeutic options [50] and become a useful prognostic index.
