title: Lung function decline in asthma patients with elevated bronchial CD8, CD4 and CD3 cells.
abstract: Which inflammatory markers in the bronchial mucosa of asthma patients are associated with decline of lung function during 14 years of prospective follow-up?To address this question, 19 mild-to-moderate, atopic asthmatic patients underwent spirometry and bronchoscopy at baseline and after 14 years of follow-up (t=14). Baseline bronchial biopsies were analysed for reticular layer thickness, eosinophil cationic protein (EG2), mast cell tryptase (AA1), CD3, CD4 and CD8. Follow-up biopsies were stained for EG2, AA1, neutrophil elastase, CD3, CD4, CD8, CD20, granzyme B, CD68, DC-SIGN, Ki67 and mucins.Decline in forced expiratory volume in 1 s (FEV1) % predicted was highest in patients with high CD8 (p=0.01, both pre- and post-bronchodilator) or high CD4 counts at baseline (p=0.04 pre-bronchodilator, p=0.03 post-bronchodilator). Patients with high CD8, CD3 or granzyme B counts at t=14 also exhibited faster decline in FEV1 (p=0.00 CD8 pre-bronchodilator, p=0.04 CD8 post-bronchodilator, p=0.01 granzyme B pre-bronchodilator, and p<0.01 CD3 pre-bronchodilator).Long-term lung function decline in asthma is associated with elevation of bronchial CD8 and CD4 at baseline, and CD8, CD3 and granzyme B at follow-up. This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes.
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands I.den_Otter@lumc.nl.
authors.forename: Irene
authors.initials: I
authors.lastname: den Otter
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Luuk N A
authors.initials: LN
authors.lastname: Willems
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: van Schadewijk
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Simone
authors.initials: S
authors.lastname: van Wijngaarden
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Janssen
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: de Jeu
authors.affiliation: Dept of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands Dept of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Dept of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology* / Q000628:therapy; D001706:Biopsy; D001980:Bronchi / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007249:Inflammation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D012129:Respiratory Function Tests; D013147:Spirometry
chemical_list: D001993:Bronchodilator Agents; D017252:CD3 Complex; D053804:Granzymes