Decreased serum and bronchoalveolar lavage levels of Clara cell secretory protein (CC16) is associated with bronchiolitis obliterans syndrome and airway neutrophilia in lung transplant recipients.
BACKGROUND
The major hinderance for long-term survival after lung transplantation is chronic rejection in the form of bronchiolitis obliterans syndrome (BOS). BOS is a fibrosing process in the small airways causing irreversible airway obstruction. BOS is associated with increased oxidative burden and activation of inflammatory and growth-stimulating mediators. The Clara cell secretory protein (CCSP or CC16) is a secreted differentiation marker for the bronchiolar epithelium with both antioxidative and antiinflammatory/immmunomodulatory properties. We asked whether this molecule could have a role in the development of BOS.


METHODS
Serum and bronchoalveolar lavage (BAL) fluid samples were collected from 22 consecutive lung transplant recipients, the majority (19) was followed for 2 years. Six patients developed BOS. CCSP in serum was measured in 162 samples from 19 patients with an ELISA method, and CCSP in 191 BAL samples from 22 patients with quantitative Western blot.


RESULTS
CCSP in both serum and BAL was significantly lower in BOS compared with acute rejection or no rejection. After the first postoperative month, serum and BAL CCSP levels were consistently lower in the patients who developed BOS than in those who did not. The percentage of neutrophils in BAL correlated negatively with CCSP in BAL.


CONCLUSIONS
Levels of CCSP in serum and BAL is lowered in BOS. Serum CCSP could have a potential as an early marker for BOS. The correlation between decreased CCSP and increased neutrophils in BAL suggests a loss of local airway defense capacity in BOS.
Nord
Magnus
M
Department of Medical Nutrition, Karolinska Institute, NOVUM, Huddinge University Hospital, Stockholm, Sweden.
Schubert
Katja
K
Cassel
Tobias N
TN
Andersson
Olof
O
Riise
Gerdt C
GC
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001989:Bronchiolitis Obliterans / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival; D016041:Heart-Lung Transplantation / Q000502:physiology; D006801:Humans; D016040:Lung Transplantation / Q000502:physiology*; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D011183:Postoperative Complications / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D011506:Proteins / Q000032:analysis*; D014598:Uteroglobin
D015415:Biomarkers; D011506:Proteins; C556389:SCGB1A1 protein, human; D014598:Uteroglobin