Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF

• Published in: Journal of cystic fibrosis 2024-05, Vol.23 (3), p.450-456
• Main Authors: Horati, Hamed, Margaroli, Camilla, Chandler, Joshua D., Kilgore, Matthew B., Manai, Badies, Andrinopoulou, Eleni-Rosalina, Peng, Limin, Guglani, Lokesh, Tiddens, Harm A.M.W., Caudri, Daan, Scholte, Bob J., Tirouvanziam, Rabindra, Janssens, Hettie M.
• Format: Article
• Language: English
• Subjects: Bronchiectasis; Bronchoalveolar lavage; Children; Cystic fibrosis; Inflammatory markers
• ISSN: 1569-1993; 1873-5010; 1873-5010
• DOI: 10.1016/j.jcf.2024.01.002

•Aim of the IBALL study is to identify inflammation markers in young children with CF.•MPO, IL-8, ICOSLG, HGF and Percentage neutrophils are associated with increase in Bronchiectasis.•IL-8, ICOSLG, HGF and Percentage neutrophils could predict a more than average increase in bronchiectasis over two years. Inflammation appears early in cystic fibrosis (CF) pathogenesis, with specific elevated inflammatory markers in bronchoalveolar lavage fluid (BALF) correlating with structural lung disease. Our aim was to identify markers of airway inflammation able to predict bronchiectasis progression over two years with high sensitivity and specificity. Children with CF with two chest computed tomography (CT) scans and bronchoscopies at a two-year interval were included (n= 10 at 1 and 3 years and n= 27 at 3 and 5 years). Chest CTs were scored for increase in bronchiectasis (Δ%Bx), using the PRAGMA-CF score. BALF collected with the first CT scan were analyzed for neutrophil% (n= 36), myeloperoxidase (MPO) (n= 25), neutrophil elastase (NE) (n= 26), and with a protein array for inflammatory and fibrotic markers (n= 26). MPO, neutrophil%, and inducible T-cell costimulator ligand (ICOSLG), but not clinical characteristics, correlated significantly with Δ%Bx. Evaluation of neutrophil%, NE, MPO, interleukin-8 (IL-8), ICOSLG, and hepatocyte growth factor (HGF), for predicting an increase of > 0.5% of Δ%Bx in two years, showed that IL-8 had the best sensitivity (82%) and specificity (73%). Neutrophil%, ICOSLG and HGF had sensitivities of 85, 82, and 82% and specificities of 59, 67 and 60%, respectively. The odds ratio for risk of >0.5% Δ%Bx was higher for IL-8 (12.4) than for neutrophil%, ICOSLG, and HGF (5.9, 5.3, and 6.7, respectively). Sensitivity and specificity were lower for NE and MPO). High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.