Cytokine. 2015 Mar 5;73(1):156-162. doi: 10.1016/j.cyto.2014.10.026.

Airway inflammation in children and adolescents with bronchiolitis obliterans.

Rosewich M¹, Zissler UM², Kheiri T³, Voss S³, Eickmeier O³, Schulze J³, Herrmann E⁴, Dücker RP³, Schubert R³, Zielen S³.

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.

Author information

• ¹Department 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.
• ²Center of Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Germany.
• ³Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children’s Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
• ⁴Institute of Biostatistics and Mathematical Modelling, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.