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

Hamed Horati; Camilla Margaroli; Joshua D. Chandler; Matthew B. Kilgore; Badies Manai; Eleni Rosalina Andrinopoulou; Limin Peng; Lokesh Guglani; Harm A.M.W. Tiddens; Daan Caudri; Bob J. Scholte; Rabindra Tirouvanziam; Hettie M. Janssens

doi:10.1016/j.jcf.2024.01.002

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

Hamed Horati, Camilla Margaroli, Joshua D. Chandler, Matthew B. Kilgore, Badies Manai, Eleni Rosalina Andrinopoulou, Limin Peng, Lokesh Guglani, Harm A.M.W. Tiddens, Daan Caudri, Bob J. Scholte, Rabindra Tirouvanziam, Hettie M. Janssens^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Introduction:

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.

Methods:

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).

Results:

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).

Conclusions:

High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.

Original language	English
Pages (from-to)	450-456
Number of pages	7
Journal	Journal of Cystic Fibrosis
Volume	23
Issue number	3
DOIs	https://doi.org/10.1016/j.jcf.2024.01.002
Publication status	E-pub ahead of print - 20 Jan 2024

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© 2024

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Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CFProof, 1.2 MBLicence: CC BY

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Horati, H., Margaroli, C., Chandler, J. D., Kilgore, M. B., Manai, B., Andrinopoulou, E. R., Peng, L., Guglani, L., Tiddens, H. A. M. W., Caudri, D., Scholte, B. J., Tirouvanziam, R., & Janssens, H. M. (2024). Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF. Journal of Cystic Fibrosis, 23(3), 450-456. Advance online publication. https://doi.org/10.1016/j.jcf.2024.01.002

@article{a7de02bc77d14b2daff38718c9ad0360,

title = "Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF",

abstract = "Introduction: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. Methods: 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). Results: 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). Conclusions: High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.",

author = "Hamed Horati and Camilla Margaroli and Chandler, {Joshua D.} and Kilgore, {Matthew B.} and Badies Manai and Andrinopoulou, {Eleni Rosalina} and Limin Peng and Lokesh Guglani and Tiddens, {Harm A.M.W.} and Daan Caudri and Scholte, {Bob J.} and Rabindra Tirouvanziam and Janssens, {Hettie M.}",

note = "Publisher Copyright: {\textcopyright} 2024",

year = "2024",

month = jan,

day = "20",

doi = "10.1016/j.jcf.2024.01.002",

language = "English",

volume = "23",

pages = "450--456",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "Elsevier",

number = "3",

}

Horati, H, Margaroli, C, Chandler, JD, Kilgore, MB, Manai, B, Andrinopoulou, ER, Peng, L, Guglani, L, Tiddens, HAMW, Caudri, D, Scholte, BJ, Tirouvanziam, R & Janssens, HM 2024, 'Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF', Journal of Cystic Fibrosis, vol. 23, no. 3, pp. 450-456. https://doi.org/10.1016/j.jcf.2024.01.002

TY - JOUR

T1 - Key inflammatory markers in bronchoalveolar lavage predict bronchiectasis progression in young children with CF

AU - Horati, Hamed

AU - Margaroli, Camilla

AU - Chandler, Joshua D.

AU - Kilgore, Matthew B.

AU - Manai, Badies

AU - Andrinopoulou, Eleni Rosalina

AU - Peng, Limin

AU - Guglani, Lokesh

AU - Tiddens, Harm A.M.W.

AU - Caudri, Daan

AU - Scholte, Bob J.

AU - Tirouvanziam, Rabindra

AU - Janssens, Hettie M.

PY - 2024/1/20

Y1 - 2024/1/20

N2 - Introduction: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. Methods: 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). Results: 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). Conclusions: High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.

AB - Introduction: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. Methods: 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). Results: 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). Conclusions: High levels of IL-8, neutrophil%, ICOSGL and HGF in BALF may be good predictors for progression of bronchiectasis in young children with CF.

UR - http://www.scopus.com/inward/record.url?scp=85183016857&partnerID=8YFLogxK

U2 - 10.1016/j.jcf.2024.01.002

DO - 10.1016/j.jcf.2024.01.002

M3 - Article

C2 - 38246828

AN - SCOPUS:85183016857

SN - 1569-1993

VL - 23

SP - 450

EP - 456

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 3

ER -

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

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