Oded Breuer1,2,3, Andre Schultz1,4,3, Luke W Garratt1, Lidija Turkovic1, Tim Rosenow1,4, Conor P Murray5, Yuliya V Karpievitch1, Lauren Akesson1,6,7, Samuel Dalton8, Peter D Sly9, Sarath Ranganathan6,8,10, Stephen M Stick1,4,3, Daan Caudri1,3,11. 1. Telethon Kids Institute and. 2. Department of Pediatrics, Pediatric Pulmonary Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 3. Department of Respiratory and Sleep Medicine and. 4. Division of Child Health, Faculty of Medicine and Dentistry, University of Western Australia, Perth, Western Australia, Australia. 5. Department of Diagnostic Imaging, Perth Children's Hospital, Perth, Western Australia, Australia. 6. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia. 7. Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Melbourne, Victoria, Australia. 8. Department of Respiratory Medicine, Royal Children's Hospital, Parkville, Victoria, Australia. 9. Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Queensland, Australia. 10. Murdoch Children's Research Institute, Parkville, Victoria, Australia; and. 11. Department of Pediatrics/Respiratory Medicine, Erasmus Medical Center-Sophia, Rotterdam, the Netherlands.
Abstract
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 and 2018 who underwent annual chest computed tomography (CT) imaging and 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.Measurements and Main Results: Haemophilus influenzae, Staphylococcus aureus, Pseudomonas 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 after 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% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 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).Conclusions: 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.
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 and 2018 who underwent annual chest computed tomography (CT) imaging and 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.Measurements and Main Results:Haemophilus influenzae, Staphylococcus aureus, Pseudomonas 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 after 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% confidence interval, 0.3-1.6; P = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 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).Conclusions: 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.
Entities:
Keywords:
Aspergillus; bronchiectasis; cystic fibrosis; lung disease progression; trapped air
Authors: Andrew D Graustein; William R Berrington; Kati J Buckingham; Felicia K Nguyen; Lara L Joudeh; Margaret Rosenfeld; Michael J Bamshad; Ronald L Gibson; Thomas R Hawn; Mary J Emond Journal: Am J Respir Cell Mol Biol Date: 2021-08 Impact factor: 6.914
Authors: Erick Forno; Steven H Abman; Jagdev Singh; Mary E Robbins; Hiran Selvadurai; Paul T Schumacker; Paul D Robinson Journal: Am J Respir Crit Care Med Date: 2021-08-01 Impact factor: 30.528