TY - JOUR
T1 - The detection of bile acids in the lungs of paediatric cystic fibrosis patients is associated with altered inflammatory patterns
AU - Caparrós-Martín, Jose A.
AU - Flynn, Stephanie
AU - Reen, F. Jerry
AU - Woods, David F.
AU - Agudelo-Romero, Patricia
AU - Ranganathan, Sarath C.
AU - Stick, Stephen M.
AU - O'Gara, Fergal
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.
AB - Background: Cystic fibrosis (CF) is a hereditary disorder in which persistent unresolved inflammation and recurrent airway infections play major roles in the initiation and progression of the disease. Little is known about triggering factors modulating the transition to chronic microbial infection and inflammation particularly in young children. Cystic fibrosis respiratory disease starts early in life, with the detection of inflammatory markers and infection evident even before respiratory symptoms arise. Thus, identifying factors that dysregulate immune responsiveness at the earliest stages of the disease will provide novel targets for early therapeutic intervention. Methods: We evaluated the clinical significance of bile acid detection in the bronchoalveolar lavage fluid of clinically stable preschool-aged children diagnosed with CF. Results: We applied an unbiased classification strategy to categorize these specimens based on bile acid profiles. We provide clear associations linking the presence of bile acids in the lungs with alterations in the expression of inflammatory markers. Using multiple regression analysis, we also demonstrate that clustering based on bile acid profiles is a meaningful predictor of the progression of structural lung disease. Conclusions: Altogether, our work has identified a clinically relevant host-derived factor that may participate in shaping early events in the aetiology of CF respiratory disease.
KW - Bile acids
KW - Cystic fibrosis
KW - Gut-lung axis
UR - http://www.scopus.com/inward/record.url?scp=85084416700&partnerID=8YFLogxK
U2 - 10.3390/diagnostics10050282
DO - 10.3390/diagnostics10050282
M3 - Article
C2 - 32384684
AN - SCOPUS:85084416700
SN - 2075-4418
VL - 10
JO - Diagnostics
JF - Diagnostics
IS - 5
M1 - 282
ER -