Aspergillus Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis

Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown.

Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF.

Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000-2018 who underwent annual chest computed tomography (CT) and bronchoalveolar lavage (BAL) were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms and admissions for exacerbations.

Results: H. influenzae, S. aureus, P. aeruginosa and Aspergillus infections were all associated with worse CT scores in the same year (poverall<0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year following an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference 0.9; 95%CI, 0.3-1.6; p=0.003) and Aspergillus with trapped-air (difference 3.2; 95%CI, 1.0-5.4; p=0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation (p<0.001) and respiratory admissions risk (p=0.008).

Conclusion: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk and benefit of eradication regimens.

Authors: Oded Breuer, Andre Schultz, Luke W Garratt, Lidija Turkovic, Tim Rosenow, Conor P Murray, Yuliya V. Karpievitch, Lauren Akesson, Samuel Dalton, Peter D Sly, Sarath Ranganathan, Stephen M Stick, Daan Caudri on behalf of AREST CF.

Published in American Journal of Respiratory and Critical Care Medicine in November 2019.