Blood Test for Emphysema

Endothelial microparticles (EMPs) in plasma may be an early marker for emphysema, according to a study published online March 11 in the American Journal of Respiratory and Critical Care Medicine.

Alveoli enable gas exchange between air and blood through the alveolar epithelium, interstitial connective tissue, and capillary endothelium. The stress of chronic smoking can destroy alveoli, resulting in emphysema. Increasing evidence suggests that apoptosis in alveolar endothelial cells is a key element in the pathogenesis of lung damage.

EMPs are small vesicles that are released from activated or apoptotic endothelial cells, and plasma levels are elevated in vascular disorders. The researchers hypothesized that in smokers, EMP levels in plasma could be used as a marker for emphysema.

Cynthia Gordon, PhD, from the Department of Genetic Medicine, and Ronald C. Crystal, MD, senior author and chief, Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York City, and colleagues assessed lung health using pulmonary function tests, including total lung capacity (DLCO) and normal spirometry, as well as chest X-ray. Smoking status was determined by urine nicotine and cotinine. The researchers classified EMP levels (CD42b−CD31+ microparticles) as activated or apoptotic.

The study included an initial cohort of 92 healthy nonsmokers (defined by pulmonary function test), healthy smokers, and smokers with early signs of lung destruction (normal spirometry, low DLCO). The researchers then tested 2 prospective cohorts: One group was similar to the first, and another was HIV1-positive.

Compared with healthy nonsmokers, there was a slight increase in EMP levels in healthy smokers with normal spirometry and normal DLCO, as well as symptomatic smokers (P < 10−4 for both comparisons). The researchers found no differences between healthy smokers and symptomatic smokers (P > .4).

However, EMP levels were significantly higher in healthy smokers with normal spirometry but low DLCO (P < 10−4 compared with healthy nonsmokers; P < 10−3 compared with healthy smokers). EMP levels in healthy nonsmokers were between 0 and 500 EMP/μL. In 50% of healthy smokers, EMP levels were above the normal range seen in healthy nonsmokers. EMP levels were above the range of healthy smokers in 95% of healthy smokers with normal spirometry and low DLCO: 52% were distributed between 500 and 1250 EMP/μL, and 43% had levels higher than1250 EMP/μL.

Ratios of CD62+/CD31+ were reduced (P < 10−4), and CD42b−CD31+ annexin V+ EMPs were elevated (P < 10−4). These results suggest involvement of endothelial apoptosis.

Most elevated EMPs were positive for angiotensin converting enzyme, a sign that they might originate from pulmonary capillaries. The data from the initial cohort were confirmed in both prospective cohorts.

The results suggest that EMP levels could be a useful means of screening for early stages of emphysema without resorting to radiation exposure that is associated with chest high-resolution computed tomography.

"Interestingly, the smokers with the highest plasma EMP levels are healthy smokers with normal spirometry and isolated low DLCO. This suggests that the vascular-based contributions to the pathogenesis of emphysema may contribute to the early development of emphysema, and may identify a point in time where intervention with smoking cessation therapy may prevent the irreversible lung destruction associated with the development of (chronic obstructive pulmonary disease)," the authors write.

The study was supported in part by grant funding from the National Institutes of Health. The authors have disclosed no relevant financial relationships.