Bronchiolitis obliterans (BO) is a major problem that decreases the long-term survival of lung transplant recipients. The early diagnosis of BO is very difficult and requires invasive diagnostic tests such as a lung biopsy. The term Bronchiolitis Obliterans Syndrome (BOS) was adopted due to the poor sensitivity of biopsy for diagnosing early BO. Patients are diagnosed with BOS when they have a sustained drop in FEV1 of at least 20% from their post-transplant baseline. By the time the diagnosis is made, most patients have significant and irreversible loss of lung function. There is a need for a simple and accurate diagnostic test for BO in lung transplant recipients. KL-6 is a protein expressed on the surface of pulmonary epithelial cells and has been reported to be elevated in the sera of patients with interstitial lung diseases. We hypothesized that serum levels of KL-6 would be elevated in patients who develop BOS after lung transplantation.
We collected single serum samples from 26 lung transplant recipients and 20 healthy controls. The BOS status of the lung transplant recipients was determined based upon routinely collected lung function testing. Of the 26 lung transplant recipients, 8 met the criteria for BOS and 18 did not. The serum KL-6 levels were determined using a sandwich ELISA technique.
Mean serum KL-6 concentration ± standard deviation in lung transplant recipients with BOS, without BOS and controls were 688.7 ± 225.8, 321.3 ± 163.9 and 235.2 ± 141.5 U/ml, respectively (p<0.01, for patients with BOS vs. patients without BOS and patients with BOS vs. controls). There was a significant correlation between the decrease in FEV1 from the post-transplant baseline and the serum KL-6 levels (R=0.44, p<0.05).
Serum KL-6 levels were significantly elevated in lung transplant recipients with BOS when compared with lung transplant recipients without BOS.
Our results indicate that serum KL-6 measurement has the potential to serve as a non-invasive diagnostic test for the detection of BO in lung transplant recipients.
Joseph Walter, None.