Sm. Studer et al., Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection, J HEART LUN, 20(11), 2001, pp. 1158-1166
Background: Obliterative bronchiolitis (OB) remains one of the leading caus
es of death in lung transplant recipients after 2 years, and acute rejectio
n (AR) of lung allograft is a major risk factor for OB. Treatment of AR may
reduce the incidence of OB, although diagnosis of AR often requires bronch
oscopic lung biopsy. In this study, we evaluated the utility of exhaled-bre
ath biomarkers for tile non-invasive diagnosis of AR.
Methods: We obtained breath samples from 44 consecutive lung transplant rec
ipients who attended ambulatory follow-up visits for the Johns Hopkins Lung
Transplant Program. Bronchoscopy within 7 days of their breath samples sho
wed histopathology in 21of these patients, and we included them in our anal
ysis. We measured hydrocarbon markers of pro-oxidant events (ethane and 1-p
entane), isoprene, acetone, and sulfur-containing compounds (hydrogen sulfi
de and carbonyl sulfide) in exhaled breath and compared their levels to the
lung histopathology, graded as stable (non-rejection) or AR. None of the s
tudy subjects were diagnosed with OB or infection at the time of the clinic
al bronchoscopy.
Results: We found no significant difference in exhaled levels of hydrocarbo
ns, acetone, or hydrogen sulfide between the stable and AR groups. However,
we did find significant increase in exhaled carbonyl sulfide (COS) levels
in AR subjects compared with stable subjects. We also observed a trend in 7
of 8 patients who had serial sets of breath and histopathology data that s
upported a role for COS as a breath biomarker of AR.
Conclusions: This study demonstrated elevations in exhaled COS levels in su
bjects with AR compared with stable subjects, suggesting a diagnostic role
for this non-invasive Z biomarker. Further exploration of breath analysis i
n lung transplant recipients is warranted to complement fiberoptic bronchos
copy and obviate the need for this procedure in some patients.