(183) Chest computed tomography scan assessment to monitor cystic fibrosis structural lung disease progression in bronchiectasis over late childhood and adolescence

Background: Cystic fibrosis (CF) lung disease is characterized by progressive bronchiectasis (BE) and airway wall thickening (AWT) starting in early childhood. In the CF-FAB study, it was shown that the extent of lung disease in young children with CF (CwCF) was an important risk factor for progressive structural lung disease in adolescence using the Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF)(1). Recently, a fully automated method was developed and validated to measure airway and artery (AA) dimensions for the sensitive detection of BE and AWT. The aim of our study was to monitor progression of BE and AWT over late childhood into adolescence in a longitudinal follow-up study (CF-FAB) of the ACFBAL cohort using the AA-method and PRAGMA-CF.

Methods: CF-FAB enrolled CwCF who completed the ACFBAL study in Australia and New Zealand. Computed tomography (CT) scans were obtained at 2 time points approximately 18 months apart. CT scans were analyzed using manual PRAGMA-CF and the automated AA-method (LungQ-AA, v2.1.0, Thirona, Netherlands). PRAGMA-CF computes the volume fraction of the following structural lung components on the inspiratory CT scan: %BE, mucus plugging (%MP), %AWT, and atelectasis (%Atelec). The composite score %Disease (%Dis) is defined as the sum of %BE, %MP, and %AWT. LungQ-AA automatically segments the bronchial tree and identifies the segmental (G₀) and distal (G_1-13) airway generations. For each identified airway, the following dimensions are quantified: diameters of airway outer edge (A_out), airway lumen wall (A_lumen), artery (A), and airway wall thickness (A_wt), and AA-ratios: A_out/A, A_lumen/A, and A_wt/A. BE was defined as A_out/A > 1.1 or A_lumen/A > 0.8 and AWT as A_wt/A > 0.3. Mixed-effects models were used for analysis.

Results: In total, 120 CwCF were enrolled with a mean baseline age of 12.76 (SD 1.56) years. 115 baseline and 110 follow-up scans were obtained with a mean interval of 26 months. Coded CT scans were manually scored in random order using PRAGMA-CF. %Dis and %BE increased by 0.44% per year (p=0.03) and 0.38% per year (p=0.01), respectively. No significant progression was observed for %AWT (p=0.98).

A total of 185 CTs of 100 CwCF could be analyzed by LungQ-AA (39 excluded due to slice thickness >1.5mm, and 1 reason unknown). On baseline CT scans (n=96) 30,792 AA-pairs and on follow-up CT scans (n=89) 32,024 AA-pairs were detected from G₁ to G₁₃ and were analyzed: significant progressions were found in A_out/A and A_lumen/A (all p < 0.001), but not in A_wt/A (p=0.35). Between 64%-66% of AA-pairs were defined as BE and 59 % as AWT.

Conclusions: Progressive BE can be observed in CwCF during late childhood into adolescence. AA-analysis results agree with PRAGMA-CF results to monitor disease progression in CwCF.

Acknowledgements: On behalf of the Australasian Cystic Fibrosis Bronchoalveolar Lavage (ACFBAL) and Follow- up of the ACFBAL (CF-FAB) study groups. This study was supported by grants from the Australian National Health and Medical Research Council (9937868, 351541and 1044829). C.E. Wainwright was supported through Practitioner Fellowship through The Children’s Hospital Foundation Brisbane (RG0692016).

References: [1] Wijker NE, Vidmar S, Grimwood K, Sly PD, Byrnes CA, Carlin JB, et al. Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort. Eur Respir J. 2020;55(4).