Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkers.

Rationale: Early detection of bronchiolitis obliterans syndrome (BOS) is important because therapies are more likely to be effective if employed early in the disease process.

Objectives: To compare the performance of exhaled NO and CO (which reflect airway inflammation) and the slope of the alveolar plateau for helium (which reflects heterogeneity of ventilation distribution) for detection of BOS stages 0-p and 1.

Methods: Recipients of bilateral (n=64) and single (n=1) lung grafts were prospectively monitored for 1,249 days; the helium slope was derived from single-breath washouts and exhaled NO and CO were measured by chemiluminescence on 933 occasions.

Measurements And Main Results: At the end of follow-up, 9 patients were in stage 0-p and 16 patients were in BOS stage 1 or higher; 21 patients had at least one measurement made in BOS stage 0-p. All markers increased in BOS stage 0-p, but only the helium slope increased in BOS stage 1. The helium slope had better sensitivity for detection of stages 0-p and 1 than either exhaled NO or CO, but considering exhaled NO and CO together improved their sensitivity; the best sensitivity was found with the three markers in combination. The biomarkers had high negative predictive values, but low specificity and positive predictive values.

Conclusions: After lung transplantation, (1) the helium slope and exhaled NO, but also exhaled CO, increase in BOS stage 0-p, (2) the helium slope has better sensitivity than exhaled NO and CO for the detection of BOS stages 0-p and 1, and (3) exhaled biomarkers have high negative predictive values, but low specificity and positive predictive values.