Tim Rosenow1, L Clara Mok2, Lidija Turkovic2, Luke J Berry2, Peter D Sly3, Sarath Ranganathan4,5, Harm A W M Tiddens6, Stephen M Stick2,7,8. 1. Telethon Kids Institute, Centre for Child Health Research, University of Western Australia, Subiaco, Australia tim.Rosenow@telethonkids.org.au. 2. Telethon Kids Institute, Centre for Child Health Research, University of Western Australia, Subiaco, Australia. 3. Children's Health and Environment Program, Child Health Research Centre, The University of Queensland, Brisbane, Australia. 4. Depts of Paediatrics and Respiratory Medicine, Royal Children's Hospital, Melbourne, Australia. 5. Infection and Immunity Theme, Murdoch Children's Research Institute, Melbourne, Australia. 6. Dept of Pulmonology, Sophia Children's Hospital, Erasmus MC, Rotterdam, The Netherlands. 7. Dept of Respiratory and Sleep Medicine, Perth Children's Hospital, Nedlands, Australia. 8. Telethon Kids Respiratory Research Centre, Nedlands, Australia.
Abstract
INTRODUCTION: Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. METHODS: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. RESULTS: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09-0.54; p=0.007) but not infection (0.23, 95% CI -0.01-0.47; p=0.060) detections. Reference equations were determined. CONCLUSIONS: Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.
INTRODUCTION:Pulmonary inflammation and infection are important clinical and prognostic markers of lung disease in cystic fibrosis (CF). However, whether in young children they are transient findings or have cumulative, long-term impacts on respiratory health is largely unknown. We aimed to determine whether their repeated detection has a deleterious effect on structural lung disease. METHODS: All patients aged <6 years with annual computed tomography (CT) and bronchoalveolar lavage (BAL) were included. Structural lung disease on CT (%Disease) was determined using the PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) method. The number of times free neutrophil elastase (NE) and infection were detected in BAL were counted, to determine cumulative BAL history. Linear mixed model analysis, accounting for repeat visits and adjusted for age, was used to determine associations. RESULTS: 265 children (683 scans) were included for analysis, with BAL history comprising 1161 visits. %Disease was significantly associated with the number of prior NE (0.31, 95% CI 0.09-0.54; p=0.007) but not infection (0.23, 95% CI -0.01-0.47; p=0.060) detections. Reference equations were determined. CONCLUSIONS:Pulmonary inflammation in surveillance BAL has a cumulative effect on structural lung disease extent, more so than infection. This provides a strong rationale for therapies aimed at reducing inflammation in young children.
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