Airway TGF-β1 and oxidant stress in children with severe asthma: association with airflow limitation.
BACKGROUND
TGF-β1 is thought to play a role in airway remodeling in asthmatic subjects. TGF-β1 expression might be mediated by an excessive burden of reactive oxygen species and oxidant stress.


OBJECTIVE
Given the profound airway oxidant stress we have previously observed in children with severe asthma, we sought to (1) quantify TGF-β1 protein and mRNA gene expression in the airways of children with mild-to-moderate and severe atopic asthma and (2) determine the relationship of airway TGF-β1 concentrations to oxidant burden (ie, lipid peroxidation), T(H)2-mediated eosinophilic inflammation, and airflow limitation.


METHODS
Bronchoalveolar lavage fluid was collected from 68 atopic children with asthma (severe asthma, n = 28) and 12 atopic adult control subjects. Airway TGF-β1 expression and activation were assessed in relation to airway IL-13, 8-isoprostane, and malondialdehyde concentrations. The relationship of airway TGF-β1 expression to airflow limitation in children with asthma was also assessed.


RESULTS
Children with severe asthma had higher total airway concentrations of TGF-β1 that were associated with increased protein and mRNA expression of TGF-β1 in airway macrophages and an increase in concentrations of the lipid peroxidation biomarkers 8-isoprostanes and malondialdehyde. TGF-β1 activation was also greater in children with severe asthma and was associated with higher airway 8-isoprostane, malondialdehyde, and IL-13 concentrations. Total airway TGF-β1 concentrations were further associated with airflow limitation.


CONCLUSIONS
Children with severe asthma have increased airway TGF-β1 expression and activation associated with an increased airway oxidant burden. Oxidant stress might mediate the effects of TGF-β1 and promote airway remodeling in children with severe asthma.
Department of Pediatrics, Emory University, Atlanta, GA, USA.
Sheena D
SD
Brown
Katherine M
KM
Baxter
Susan T
ST
Stephenson
Annette M
AM
Esper
Lou Ann S
LA
Brown
Anne M
AM
Fitzpatrick
D000293:Adolescent; D001249:Asthma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism / Q000503:physiopathology; D018893:Bronchoalveolar Lavage; D001999:Bronchoscopy; D002648:Child; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D013147:Spirometry; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D018793:Interleukin-13; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C075750:8-epi-prostaglandin F2alpha; D008315:Malondialdehyde; D015237:Dinoprost