TABLE 3

Follow-up

Statement number	Statement	Type of statement	Strength of recommendation	Quality of evidence	Type of patient	Most relevant supporting articles
2.1	Limited data are available about the use of LUS to monitor lung status or to evaluate pulmonary exacerbation. Preliminary results show good relation between LUS and CT to assess structural changes.	Recommendation	Grade I	Low	Stable and declining	[45, 46]
2.2	Use of CR scoring systems can improve sensitivity in monitoring CF lung disease. However, their routine use in clinical practice is cumbersome, due to high inter-observer variability. Fully automated CR scoring systems based on artificial intelligence algorithms may overcome this limitation increasing the sensitivity of CR in detecting disease progression.	Recommendation	Grade C	Moderate	Stable and declining	[47–52]
2.3	There is little evidence in the literature about the optimal timing of CT monitoring. There is a need for international guidelines to schedule CT surveillance in patients with CF lung disease.	Statement of fact	NA	Low	Stable	[6, 13, 29, 53–56]
2.4	Current best clinical imaging practice in several CF centres is performing CT biennially (i.e. 1 every 2 years).	Best practice	Grade A	Moderate	Stable	[14, 15]
2.5	State-of-the-art reviews of risk related to CT radiation exposure highlight a reasonably low risk of cumulative cancer in children using biennial low dose CT. CT protocol harmonisation between CF centres should be promoted to comply with the “as low as reasonably achievable” (ALARA) concept.	Recommendation	Grade A	High	Stable	[14, 29, 35, 36, 40–44]
2.6	CT can better detect lung disease progression than standard pulmonary function tests (i.e. FEV₁) both in cooperative and uncooperative patients, irrespective of disease severity.	Recommendation	Grade B	High	Stable and declining	[5, 10, 12, 53–66]
2.7	CT is complementary to lung clearance index in the detection of disease progression or improvement by clinical intervention.	Statement of fact	NA	High	Stable and declining	[67–74]
2.8	CT provides relevant information possibly capable of modifying disease trajectory, patient management and follow-up, both in uncooperative and cooperative patients.	Statement of fact	NA	Moderate	Stable and declining	[5, 10–12, 48, 75, 76]
2.9	The use of appropriate scoring systems for CT increases its sensitivity in tracking changes in symptomatic, and asymptomatic, early lung disease. Therefore, their use is recommended to standardise interpretation of CT data according to CF centre expertise and capacity.	Recommendation	Grade A	Moderate	Stable and declining	[60, 65, 77–94]
2.10	Artificial intelligence-based scoring system and segmentation tools for CF imaging allows a fully automated volumetric quantification of CF-related abnormalities over an entire lung. These novel scoring systems, when further validated, could provide a robust disease outcome in the era of effective CFTR modulator therapy.	Statement of fact	NA	Moderate	Stable, declining and improving	[60, 65, 77–94]
2.11	CT scans performed in infants and young children with symptoms is a potential clinical trial outcome measure for novel treatments in this age group.	Statement of fact	NA	Moderate	Declining	[34, 48, 53, 60, 63, 92, 95–102]
2.12	Despite improvement in clinical, lung function, and imaging outcomes in patients undertaking CFTR modulator therapy, no deviation from the usual imaging follow-up scheme should be advised, because there is no evidence in the current literature about long-term benefit of these agents.	Statement of fact	NA	Moderate	Stable, declining and improving	[35, 36, 81, 101, 103–105]
2.13	Despite conventional MRI sequences having lower sensitivity than CT in the assessment of disease extent, state-of-the-art MRI (e.g. UTE sequence) shows comparable results to CT and provides a convenient, noninvasive, and non-ionising assessment of disease progression in cooperative patients. The beneficial absence of radiation is particularly important with respect to the need for frequent follow-up examinations and the increasing life span of CF patients.	Statement of fact	NA	High	Stable and declining	[8, 9, 106–118]
2.14	MRI provides information about ventilation, inflammation, perfusion and structure (VIPS-MRI) in a single examination that is difficult to obtain with CT.	Statement of fact	Grade B	Moderate	Stable and declining	[8, 9, 33, 119–133]
2.15	MRI is a noninvasive, radiation-free endpoint to identify potentially reversible abnormalities (e.g. mucus plugging and lung hypoperfusion) in early phase clinical trials testing novel therapeutics in symptomatic, cooperative, patients with CF.	Statement of fact	Grade B	Moderate	Stable and declining	[118, 131, 134–138]
2.16	The MRI scoring system is a promising tool to predict the loss of lung function in CF patients and can serve as a clinically relevant outcome predictor for pulmonary manifestations in CF.	Statement of fact	NA	Moderate	Stable and declining	[115, 128, 139–142]
2.17	Longitudinal studies are needed to compare the sensitivity of CT and MRI in tracking disease progression.	Statement of fact	NA	Moderate	Stable and declining	[8, 116, 143]
2.18	The use of MRI in clinical practice is hampered by its higher cost than CT; the need for state-of-the-art MR systems; the occasional need for moderate sedation/general anaesthesia in uncooperative children; nonuniformity of MR protocol; as well as substantial image variability/capability between MR brands.	Statement of fact	NA	High	Stable and declining	[7, 8, 34, 37, 144–148]

CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; CR: chest radiograph; CT: computed tomography; FEV₁: forced expiratory volume in 1 s; LUS: lung ultrasound; MR: MRI: magnetic resonance; MRI: magnetic resonance imaging; NA: not available; UTE: ultrashort echo.