Donor clara cell secretory protein polymorphism is a risk factor for bronchiolitis obliterans syndrome after lung transplantation.
BACKGROUND
We hypothesized that a reduced potential for bronchiolar stem-cell (Clara cell)-related repair in the setting of an ever-present risk of small airway injury would increase the risk of bronchiolitis obliterans syndrome (BOS).


METHODS
CCSP A38G gene polymorphism was assessed in both lung donors and recipients in a longitudinal study cohort of 63 consecutive lung transplant recipients (LTR) with a median follow-up of 493 days (range, 26-894). Clara cell secretory protein (CCSP) and interleukin 8 levels were assessed in the bronchoalveolar lavage and plasma at 1, 3, 6, and 12 months after transplantation. CCSP-positive cells were assessed in transbronchial biopsies at 1 and 3 months.


RESULTS
Of the 63 LTR, there were 5 early deaths (≤90 days, 8% [95% confidence interval, 4%-21%]), and 20 developed BOS (32%, [95% confidence interval, 21%-45%]). Donor but not recipient CCSP A38G polymorphism was associated with more risk of BOS (relative risk, 8.6 [2.2-33.5], P<0.0001) and decreased overall survival (log-rank test, P=0.011). Bronchoalveolar lavage CCSP and CCSP/interleukin 8 levels were low and decreasing early after transplantation in LTR who developed BOS (P=0.015). CCSP+ve cells in transbronchial biopsies increased at 3 months only in LTR who remained free of BOS (P=0.003).


CONCLUSIONS
Donor CCSP A38G polymorphism is associated with decreased CCSP levels early after lung transplantation and poor long-term outcomes.
Heart and Lung Transplant Unit, Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria, Australia.
Arnaud
A
Bourdin
Nicole A
NA
Mifsud
Brice
B
Chanez
Catriona
C
McLean
Pascal
P
Chanez
Greg
G
Snell
Tom C
TC
Kotsimbos
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000097:blood / Q000235:genetics* / Q000401:mortality; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D016015:Logistic Models; D008137:Longitudinal Studies; D016040:Lung Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D014019:Tissue Donors; D016896:Treatment Outcome; D014598:Uteroglobin / Q000097:blood / Q000235:genetics*; D014739:Victoria
D015415:Biomarkers; C508606:CXCL8 protein, human; D016209:Interleukin-8; C556389:SCGB1A1 protein, human; D014598:Uteroglobin