Airway inflammation in children and adolescents with bronchiolitis obliterans

Cytokine. 2015 May;73(1):156-62. doi: 10.1016/j.cyto.2014.10.026. Epub 2015 Mar 6.


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.

Keywords: Bronchiolitis obliterans; Paediatric interstitial lung disease; Rare lung diseases; Sputum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / metabolism
  • Bronchiolitis Obliterans / complications*
  • Bronchiolitis Obliterans / physiopathology
  • Bronchodilator Agents / pharmacology
  • Case-Control Studies
  • Cell Count
  • Child
  • Cytokines / metabolism
  • Exhalation / drug effects
  • Female
  • Humans
  • Inflammation / complications*
  • Inflammation / physiopathology
  • Lung / drug effects
  • Lung / pathology*
  • Lung / physiopathology
  • Male
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Nitric Oxide / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Respiratory Function Tests
  • Sputum / cytology
  • Sputum / drug effects
  • Young Adult


  • Biomarkers
  • Bronchodilator Agents
  • Cytokines
  • RNA, Messenger
  • Nitric Oxide