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Published ahead of print on January 18, 2007, doi:10.1164/rccm.200609-1301OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 7, April 2007, 731-736

A more recent version of this article appeared on April 1, 2007
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Submitted on September 13, 2006
Accepted on January 18, 2007

Early Detection of Chronic Pulmonary Allograft Dysfunction by Exhaled Biomarkers

Alain Van Muylem1, Christiane Knoop1, and Marc Estenne1*

1 Department of Chest Medicine, Erasme University Hospital, Universite Libre de Bruxelles, Brussels, Belgium

* To whom correspondence should be addressed. E-mail: mestenne{at}ulb.ac.be.

Rationale. Early detection of Bronchiolitis Obliterans Syndrome 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 slope of alveolar plateau for helium (which reflects heterogeneity of ventilation distribution) for detection of Bronchiolitis Obliterans Syndrome stage 0-p and 1. Methods. Recipients of bilateral (n=64) and single(n=1) lung grafts were prospectively followed during 1249 days; 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 end of follow-up, 9 patients were in stage 0-p and 16 patients in BOS≥1; 21 patients had at least one measurement made in BOS 0-p. All markers increased in BOS 0-p, but only helium slope increased in BOS 1. Helium slope had a better sensitivity for detection of stage 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 3 markers in combination. The biomarkers had high negative predictive values, but low specificity and positive predictive values. Conclusions. After lung transplantation 1) helium slope and exhaled NO, but also exhaled CO, increase in BOS 0-p; 2) helium slope has a better sensitivity than exhaled NO and CO for the detection of BOS 0-p and 1; 3) exhaled biomarkers have high negative predictive values, but low specificity and positive predictive values.


Key words: lung transplantation, graft rejection, distribution of ventilation, exhaled gases




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