Exhaled breath analysis in lung transplant patients diagnosed with bronchiolitis obliterans syndrome

Abstract

Background:The efficacy of lung-transplantation is limited by chronic lung allograft dysfunction (CLAD). Currently CLAD is diagnosed via spirometry using the clinical surrogate of 'bronchiolitis obliterans syndrome' (BOS). Development of an alternative non-invasive diagnostic tool may be beneficial in decreasing the disease burden of CLAD in the lung transplant (LTx) population.Aim: Determine the exhaled breath marker profile in LTx recipients as measured by potential biomarkers in the exhaled breath condensate (EBC).Methods: EBC was collected with participants breathing tidally for 10 minutes. pH and concentrations of IL-8, IL-10, IL-13, IFN-γ, NO x and H 2 O 2 were determined. LTx participants were followed for a year and progression in BOS stage was recorded.Results: EBC was collected from 55 participants (10 non-BOS, 26 BOS and 19 controls). The LTx participants had higher levels of markers of non-specific inflammation compared to controls (median ± IQ, H 2 O 2 3.03 ± 3.37 μM vs. 1.60 ± 2.06 μM, p<0.05, NO x 6.45 ± 9.16 μM vs. 0.63 ± 0.68 μM, p<0.001). Of the cytokines only IFN-γ was consistently detectable in EBC samples but no significant difference was detected between the groups. IFN-γ was higher in LTx participants with recent infection versus non-infected participants (mean ± SD:64.31 ± 77.55 pg/mL vs. 20.45 ± 32.41 pg/mL p<0.05). No marker was associated with BOS stage progression. Conclusion:Markers of non-specific inflammation were elevated in LTx recipients, therefore exhaled breath analysis may provide a useful method for detecting inflammation in those with LTx and BOS.