Key Point

C-reactive protein, along with pack-years of smoking and FEV1, can accurately predict progression of lung dysplasia in high-risk smokers.

VANCOUVER, BRITISH COLUMBIA—Although 170,000 new cases of lung cancer are reported each year in the United States alone, most patients with early lung cancer are asymptomatic. In fact, symptoms often develop only after tumors become invasive or disseminated and resection is no longer feasible. Thus, researchers are seeking methods to identify persons with precancerous lesions who might benefit from therapy to prevent disease progression.

Recent data have shown that patients with non–small cell lung cancer have significantly higher levels of inflammatory markers such as C-reactive protein (CRP) and interleukin-6 and that these markers correlate with prognosis. In light of these findings, a group of Canadian researchers set out to determine whether inflammatory markers measured at baseline could predict the progression of bronchial dysplasia over a six-month period.¹

The investigators used data taken from a chemoprevention trial of individuals at high risk of developing lung cancer. Fluorescence bronchoscopy was performed and samples were taken from abnormal areas larger than 1.2 mm. Six months later, patients underwent a second bronchoscopy, and biopsies were obtained from the same sites as the baseline biopsies plus any new sites of suspicious dysplasia. Biopsy samples were systematically reviewed by two pathologists.

Progressive disease was defined as worsening of the dysplastic lesion by two or more grades or development of new lesions that were defined as mild dysplasia or worse. All other dysplasias were classified as stable. Levels of cytokines and CRP were measured in plasma samples using standard enzyme-linked immunosorbent assay. The primary end point was the relationship between baseline CRP levels and the progression of airway dysplasia.

CRP LEVELS AND PROGRESSION

Sixty-five of the 105 patients in the original study had plasma samples available for analysis. The mean age of this group was 57; 75% of patients were men, and 74% were active smokers with an average of 52 pack-years of smoking. Thirty-two patients had progressive dysplastic lesions after six months, and 33 had stable lesions or lesions that had regressed. At baseline, those who would later develop progressive lesions were more likely to be current smokers with lower FEV₁ than were those whose lesions did not progress.

Of the cytokines examined, only baseline CRP differed between those who did and did not develop progressive lesions. CRP levels were, on average, 64% higher in those with progressive disease. Only one of eight individuals with CRP levels below 0.5 mg/L developed progressive disease, compared with 31 of 57 who had CRP levels greater than 0.5 mg/L. The odds of developing progressive disease were 9.6-fold higher in those with higher CRP levels. At CRP levels greater than 1.0 mg/L the relationship was weaker—possibly because of the small sample size, the authors noted. They also added that age, current smoking status,and sex were not significantly predictive of disease progression. Conversely, baseline CRP, pack-years of smoking, and percent predicted FEV1 together had "excellent predictive power in estimating progression of disease."

Among those with progressive disease, 17 had worsening of dysplastic lesions by two or more grades, and 15 had new dysplastic lesions at follow-up. The authors pointed out that over the six-month period, patients’ CRP levels were stable, making a one-time measurement a reasonably good marker for their CRP burdens.

"However," they continued, "before CRP levels can be routinely advocated for clinical settings, additional studies are needed to confirm these early findings and to better define the exact thresholds at which CRP levels can optimally risk-stratify patients."

—Gale Jurasek

Reference
1. Sin DD, Man SFP, McWilliams A, Lam S. Progression of airway dysplasia and C-reactive protein in smokers at high risk of lung cancer. Am J Respir Crit Care Med. 2006;173:535-539.

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