Martin Rosewich1, Ulrich M Zissler2, Tanja Kheiri3, Sandra Voss3, Olaf Eickmeier3, Johannes Schulze3, Eva Herrmann4, Ruth Pia Dücker3, Ralf Schubert3, Stefan Zielen3. 1. Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Electronic address: Martin.Rosewich@kgu.de. 2. Center of Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Germany. 3. Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. 4. Institute of Biostatistics and Mathematical Modelling, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Abstract
BACKGROUND: Airway inflammation plays a major role in the progression of chronic lung diseases. The features of airway inflammation are not well defined among patients with cases of bronchiolitis obliterans (BO) that began in childhood. OBJECTIVES: To investigate the sputum cell and cytokine profiles of stable cases of BO regarding lung function and the involvement of small airway disease (SAD). METHODS: Twenty patients with BO (median age=14.5, range=7-23years) and 22 healthy controls (median age=16.5years, range=7-24years) were investigated. Lung function parameters and bronchial reversibility testing as well as sputum cell and cytokine profiles (IL-1β, IL-6, IL-8, TNF-α, IL-5, IFN-γ, and NFκB regulation) were analysed using quantitative RT-PCR and cytometric bead assay (CBA) in induced sputum. RESULTS: Patients with BO had significantly lower lung function values, including FVC, forced expiratory volume (FEV1), the Tiffeneau index (FEV1/VC), and MEF25, but increased functional residual capacity (RV/TLC) values. Bronchial reversibility was found in five patients (25%). Moreover, airway inflammation (as indicated by total cells, neutrophils, IL-1β, IL-6, IL-8, TNF-α, and NFκB) was significantly increased among patients with BO compared with controls. CONCLUSIONS: BO is predominantly a neutrophilic disease of the small bronchioles featuring elevated levels of pro-inflammatory cytokines leading to tissue remodelling and fibrosis of the small airways. Future therapies for patients with BO should more efficiently target the small airways.
BACKGROUND: Airway inflammation plays a major role in the progression of chronic lung diseases. The features of airway inflammation are not well defined among patients with cases of bronchiolitis obliterans (BO) that began in childhood. OBJECTIVES: To investigate the sputum cell and cytokine profiles of stable cases of BO regarding lung function and the involvement of small airway disease (SAD). METHODS: Twenty patients with BO (median age=14.5, range=7-23years) and 22 healthy controls (median age=16.5years, range=7-24years) were investigated. Lung function parameters and bronchial reversibility testing as well as sputum cell and cytokine profiles (IL-1β, IL-6, IL-8, TNF-α, IL-5, IFN-γ, and NFκB regulation) were analysed using quantitative RT-PCR and cytometric bead assay (CBA) in induced sputum. RESULTS:Patients with BO had significantly lower lung function values, including FVC, forced expiratory volume (FEV1), the Tiffeneau index (FEV1/VC), and MEF25, but increased functional residual capacity (RV/TLC) values. Bronchial reversibility was found in five patients (25%). Moreover, airway inflammation (as indicated by total cells, neutrophils, IL-1β, IL-6, IL-8, TNF-α, and NFκB) was significantly increased among patients with BO compared with controls. CONCLUSIONS: BO is predominantly a neutrophilic disease of the small bronchioles featuring elevated levels of pro-inflammatory cytokines leading to tissue remodelling and fibrosis of the small airways. Future therapies for patients with BO should more efficiently target the small airways.
Authors: U M Zissler; A M Chaker; R Effner; M Ulrich; F Guerth; G Piontek; K Dietz; M Regn; B Knapp; F J Theis; H Heine; K Suttner; C B Schmidt-Weber Journal: Mucosal Immunol Date: 2015-11-18 Impact factor: 7.313
Authors: Martin Koppitz; Charlotte Eschenburg; Emilia Salzmann; Martin Rosewich; Ralf Schubert; Stefan Zielen Journal: PLoS One Date: 2016-06-16 Impact factor: 3.240
Authors: Olaf Eickmeier; Daniela Fussbroich; Klaus Mueller; Friederike Serve; Christina Smaczny; Stefan Zielen; Ralf Schubert Journal: PLoS One Date: 2017-02-03 Impact factor: 3.240
Authors: Dan Hameiri-Bowen; Evgeniya Sovershaeva; Trond Flaegstad; Tore Jarl Gutteberg; Lucky Gift Ngwira; Victoria Simms; Andrea M Rehman; Grace Mchugh; Tsitsi Bandason; Rashida Abbas Ferrand; Sarah Rowland-Jones; Louis-Marie Yindom Journal: AIDS Date: 2021-09-01 Impact factor: 4.632