<i>Aspergillus</i> Infections and Progression of Structural Lung Disease in Children with Cystic Fibrosis.

Abstract

<b>Rationale:</b> Recent data show that <i>Aspergillus</i> species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown.<b>Objectives:</b> We aimed to evaluate longitudinal associations between <i>Aspergillus</i> infections and lung disease in young children with CF.<b>Methods:</b> Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between <i>Aspergillus</i> 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.<b>Measurements and Main Results:</b><i>Haemophilus influenzae</i>, <i>Staphylococcus aureus</i>, <i>Pseudomonas aeruginosa</i>, and <i>Aspergillus</i> infections were all associated with worse CT scores in the same year (<i>P</i>_overall < 0.05). Only <i>P. aeruginosa</i> and <i>Aspergillus</i> were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. <i>P. aeruginosa</i> was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; <i>P</i> = 0.003) and <i>Aspergillus</i> with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; <i>P</i> = 0.004). <i>Aspergillus</i> infections were also associated with markers of neutrophilic inflammation (<i>P</i> < 0.001) and respiratory admissions risk (<i>P</i> = 0.008).<b>Conclusions:</b> Lower respiratory <i>Aspergillus</i> infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early <i>Aspergillus</i> species infections and the feasibility, risk, and benefit of eradication regimens.