**20. Radiological methods to predict prognosis**

Due to the complexity of CF lung disease, multiple modalities are needed to fully assess the extent of disease severity, including radiological imaging. Several imaging techniques have been employed and studied in CF; with plain radiograph, CT, and MRI all having varying abilities to predict prognosis, as well as correlate with clinical condition, and a number of scoring systems exist to qualify the extent of pulmonary involvement. High-resolution CT imaging of the lungs is currently the most sensitive method of assessing the structural changes in CF. HRCT permits airway thickness measurements and the extent of bronchiectactic changes, and these changes closely correlate with FEV1 and often adult patients with CF show more acute changes in HRCT abnormalities than decline in spirometric results [125]. The progression of bronchiectasis also correlates with CFTR genotype and levels of neutrophilic inflammation [126], while also significantly predicting exercise capacity in CF patients [127].

Newer methods to image the lungs in CF include hyperpolarised helium magnetic resonance imaging (He3-MRI) [8] and flurodeoxyglucose positron emission tomography (FDG-PET) imaging [5-7]. Both modalities correlate closely with abnormalities seen on HRCT and improve with antibiotic treatment, making them both sensitive useful tools in the acute setting. He3- MRI may identify early ventilatory changes in paediatric disease before identifiable changes on HRCT [128] and may better correlate with spirometry in assessing response after exacer‐ bation treatment [8]. These modalities are not currently in widespread use due to both cost and availability, however, He3-MRI may become more routine in the future as life expectancy increases and the risk associated with increased cumulative exposure to ionising radiation associated with CT and FDG-PET [129].

Bactericidal/permeability-increasing protein (BPI) is one of the most potent endogenously produced antibacterials secreted by neutrophils, and autoantibodies against this protein are present in up to 90% of CF patients [120]. Levels of BPI-ANCA correlate strongly with markers of lung disease and it may indicate a pathogenic role in CF [121] and a recent study has shown that the presence of BPI-ANCA correlated significantly with a poor outcome, being death or requiring a lung transplantation. Furthermore, in patients colonised with PA the outcome was

While no single biomarker of disease severity exists from either sputum or serum, there are several potential biomarkers that need further study and more robust results to support their

One biomarker that has recently re-emerged as a useful index of disease severity is the measurement of CFTR function. This may be measured by nasal potential difference (NPD) and sweat chloride concentration. It is important as a biomarker as it has been shown that CFTR and sweat chloride concentration at diagnosis predicts long term prognosis [123]. NPD is now reproducible in a more robust manor than previously, as it was difficult to accurately to so in the past [124]. The use of this biomarker has been further established in the recent clinical trials of CFTR modulators and correctors such as ivacaftor, with a change in NPD and sweat chloride seen as marker of improvement and correlating with improvements in lung function and BMI, whether this will be a long-term prognostic indictor remains to be seen [4].

Due to the complexity of CF lung disease, multiple modalities are needed to fully assess the extent of disease severity, including radiological imaging. Several imaging techniques have been employed and studied in CF; with plain radiograph, CT, and MRI all having varying abilities to predict prognosis, as well as correlate with clinical condition, and a number of scoring systems exist to qualify the extent of pulmonary involvement. High-resolution CT imaging of the lungs is currently the most sensitive method of assessing the structural changes in CF. HRCT permits airway thickness measurements and the extent of bronchiectactic changes, and these changes closely correlate with FEV1 and often adult patients with CF show more acute changes in HRCT abnormalities than decline in spirometric results [125]. The progression of bronchiectasis also correlates with CFTR genotype and levels of neutrophilic inflammation [126], while also significantly predicting exercise capacity in CF patients [127]. Newer methods to image the lungs in CF include hyperpolarised helium magnetic resonance imaging (He3-MRI) [8] and flurodeoxyglucose positron emission tomography (FDG-PET) imaging [5-7]. Both modalities correlate closely with abnormalities seen on HRCT and improve with antibiotic treatment, making them both sensitive useful tools in the acute setting. He3- MRI may identify early ventilatory changes in paediatric disease before identifiable changes on HRCT [128] and may better correlate with spirometry in assessing response after exacer‐ bation treatment [8]. These modalities are not currently in widespread use due to both cost and availability, however, He3-MRI may become more routine in the future as life expectancy

significantly worse if associated with this biomarker [122].

**20. Radiological methods to predict prognosis**

routine use in clinical practice.

18 Cystic Fibrosis in the Light of New Research

A number of different radiological scoring systems have been developed to assess disease burden in CF. Older scoring systems were based on chest radiograph changes, and these included the Brasfield [130], National Institutes of Health (NIH) chest radiograph [131], and the Royal Children's Hospital (RCH) chest radiograph score [132]. While these were somewhat useful, they correlated poorly with spirometry and with clinical condition [133]. With the continual improvement in CT imaging modalities, HRCT has become the gold standard for assessing structural abnormalities, and several robust validated scoring systems exist for CT abnormalities. These include the Brody II score [134] and the CF-CT score [135], while one of the older original scoring tools, the Bhalla score, for bronchiectasis is still widely used in modified versions [107]. The Bhalla scoring system is an objective measure incorporating all aspects of CF structural abnormalities and has been validated and correlates with spirome‐ try[136], clinical condition [127, 137], and has some correlation with health related quality of life [138], however, there is little correlation between these scores and other biomarkers of inflammation [106].

Radiological scoring systems are useful in assessing the extent of structural changes in CF, and correlate with certain aspects of the disease, however, they alone are not sufficient to predict prognosis and are likely more beneficial when used as part of composite clinical prediction tools.
