Airway inflammation in children and adolescents with bronchiolitis obliterans.
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.


OBJECTIVE
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.
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.
Martin
M
Rosewich
Center of Allergy and Environment (ZAUM), Technical University and Helmholtz Center Munich, Germany.
Ulrich M
UM
Zissler
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Tanja
T
Kheiri
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Sandra
S
Voss
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Olaf
O
Eickmeier
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Johannes
J
Schulze
Institute of Biostatistics and Mathematical Modelling, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Eva
E
Herrmann
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Ruth Pia
RP
Dücker
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Ralf
R
Schubert
Department of Paediatric Pulmonology, Allergy and Cystic Fibrosis, Children's Hospital, Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Stefan
S
Zielen
D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000150:complications* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000494:pharmacology; D016022:Case-Control Studies; D002452:Cell Count; D002648:Child; D016207:Cytokines / Q000378:metabolism; D045853:Exhalation / Q000187:drug effects; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D013183:Sputum / Q000166:cytology / Q000187:drug effects; D055815:Young Adult
D015415:Biomarkers; D001993:Bronchodilator Agents; D016207:Cytokines; D012333:RNA, Messenger; D009569:Nitric Oxide
Bronchiolitis obliterans; Paediatric interstitial lung disease; Rare lung diseases; Sputum