Introduction 

In the COMBAT-CF study, azithromycin did clinically better than placebo in children (0–3y age) with cystic fibrosis (CF) but there was no difference in Perth-Rotterdam Annotated Grid Morphometric for CF (PRAGMA-CF) subscores. This may be attributed to its relative insensitivity as it captured low number of airways due to their small size in relation to chest computed tomography scan (CTs) resolution, low resolution for imaging the peripheral airways, and the diffuse and heterogeneous nature of lung disease in very young children. Therefore, this post-hoc study re-assessed the CTs.

Aim

To re-analyse the COMBAT-CF CTs using an automatic bronchus-artery (BA) analysis and low attenuation region (LAR) measurements in children with cystic fibrosis, treated with azithromycin as compared to placebo.

Analysis 

Method

Study Design

Endpoints

• BA-diameters: bronchial outer wall (B_out), bronchial inner wall (B_in), artery (A), and bronchial wall thickness (B_wt)
• BA-ratios were computed to measure bronchial widening (B_out/A and B_in/A) and bronchial wall thickening (B_wt/A and B_wa/B_oa, bronchial wall area/ bronchial outer area)
• LARs

Results 

• Azithromycin reduced bronchial wall thickness as associated with a lower B_wa/B_oa (mean difference 0.028, p = 0.0034) as compared to placebo
• Azithromycin was associated with a reduction in artery diameters as evident from higher B_out/A (p = 0.0088) and B_in/A (p = 0.001) and further correlated to a reduction in LAR
• The azithromycin group had lower B_wt (p = 0.0068) and lower artery diameter (p = 0.0059) relative to the placebo group
• LAR-analysis was successful in 92% at 12-months and in 81% at 36-months inspiratory and expiratory CTs
• No significant differences were seen in B_wt/A ratio, B_out diameter, B_in diameter and in LARs between the groups

Conclusion 

Azithromycin-treated infants with CF showed a reduction in bronchial wall thickness and possibly a positive effect on lung perfusion.

J Cystic Fibrosis 2024; 23: 870-873