Exhaled Carbon Monoxide as a Noninvasive Marker of Airway Neutrophilia After Lung Transplantation

Background. Neutrophilic airway inflammation and associated oxidative stress contribute to airway injury and the development of bronchiolitis obliterans syndrome after lung transplantation (LTx). Exhaled carbon monoxide (eCO) reflects heme oxygenase-1 activity in response to oxidative stress. We investigated whether airway neutrophilia and eCO levels are associated in stable LTx recipients. Methods. In this cross-sectional pilot Study, 45 stable LTx recipients were included. During routine follow-up at the outpatient clinic, pulmonary function testings together with eCO measurements before broncho-alveolar lavage (BAL) were performed. BAL cell differentials and interleukin (IL)-8 protein levels were assessed and correlated with eCO. Results. In the studied cohort, eCO levels were increased in patients with elevated (>3%) BAL neutrophilia compared with those with normal BAL neutrophilia (P=0.025). Furthermore, eCO levels significantly correlated with BAL neutrophilia and IL-8 levels in the cohort as a whole (r=0.50; P=0.0005 for total cells, r=0.43; P=0.003 for %cells and r=0.30; P=0.045 for IL-8). This was even more obvious in the LTx recipients with increased (>3%) BAL neutrophilia (r=0.70; P=0.0007 for total cells and r=0.80; P<0.0001 for %cells). For a cutoff of 4 ppm, sensitivity, specificity, positive and negative predictive value of eCO for detecting elevated BAL neutrophilia were 84.0%, 45.0%, 65.6%, and 69.2%, respectively (P=0.049). Conclusions. Elevated eCO levels in stable LTx recipients may reflect an increased BAL neutrophilia and could, therefore, be used as a noninvasive marker for airway inflammation after LTx.