Value of immunohistochemical markers in preinvasive bronchial lesions in risk assessment of lung cancer.

PURPOSE: Bronchial carcinogenesis is a multistep process characterized by accumulation of genetic and molecular abnormalities, which precedes and accompanies the preinvasive lesions known as dysplasia and carcinoma in situ (CIS). We hypothesized that the level of accumulated molecular abnormalities in dysplasia assessed by immunohistochemical markers might reflect the severity of the carcinogenic process, thus allowing for risk assessment in smokers. EXPERIMENTAL DESIGN: We performed a prospective analysis of bronchial biopsies in 48 former smokers who had at least one area of metaplasia. Twenty-two of the patients had a previous history of lung cancer. Eighty bronchial lesions were recorded at baseline, including 31 metaplasia, 12 mild dysplasia, 9 moderate dysplasia, 9 severe dysplasia, and 19 CISs. Forty-one percent of the patients had multiple preinvasive lesions. Immunohistochemical analysis of P53, cyclin D1, cyclin E, Bax, and Bcl2 was performed. Aberrant expression of one of these proteins as compared with normal bronchi was recorded as one molecular alteration. RESULTS: After 18 months, 17 patients were diagnosed with lung cancer. No isolated parameter, including dysplastic grade or any isolated molecular alteration, was significantly associated with cancer occurrence at 18 months follow-up, using a logistic regression statistical analysis. In contrast, considering CIS and cancer as end point, more than two immunohistochemical abnormalities were associated with cancer or CIS occurrence (P = 0.02). CONCLUSIONS: We concluded that the cumulative index of immunohistochemical abnormalities in a random dysplasia is associated with CIS or lung cancer in the cancerization field of symptomatic smokers, independently of the histopathological grade of dysplasia. This set of histopathological biomarkers might be useful in risk assessment and provide intermediate end points for chemopreventive trials.

Cigarette smoking, preinvasive bronchial lesions, and autofluorescence bronchoscopy.

STUDY OBJECTIVES: Autofluorescence bronchoscopy (AFB), when used as an adjunct to standard white light bronchoscopy (WLB), enhances the bronchoscopist's ability to localize small neoplastic lesions, especially intraepithelial lesions. The current study was undertaken in order to define the population in which the rate of detection is higher using AFB. DESIGN AND PATIENTS: Two hundred forty-four consecutive patients, who were symptomatic smokers or patients who previously had been treated for lung cancer or head and neck cancers, underwent WLB and AFB. All patients with endoscopic abnormalities underwent biopsies. Data concerning smoking history were prospectively registered. RESULTS: We report the prevalence of high-grade or invasive lesions at the time of examination. On a lesion-by-lesion analysis, 92 low-grade lesions, 42 high-grade lesions (ie, moderate dysplasia, severe dysplasia, and carcinoma in situ), and 39 invasive carcinomas were diagnosed. There was no effect of age, gender, and age at smoking initiation on the prevalence of preinvasive or invasive lesions. The 10 patients who previously had undergone surgery for lung cancer and exhibited high-grade preinvasive lesions had a history of carcinoma of the epidermoid histologic type (p = 0.01). These 10 patients displayed multiple lesions in the bronchial tree (mean No. of lesions, 1.8 per patient). In current smokers, the prevalence of high-grade or invasive lesions were both related to the number of pack-years smoking had occurred (p = 0.01) and to the duration of smoking (p = 0.01). In contrast, the prevalence of preinvasive lesions in former smokers was related to a history of epidermoid carcinoma. CONCLUSIONS: AFB should be recommended in patients with a history of epidermoid carcinomas of the lung. Current smokers with a prolonged smoking history appear to comprise a population in which the rate of detection of preneoplastic lesions is high with AFB.

[Dyspnea and handicap in chronic obstructive pulmonary disease: interaction of their mechanisms]. / Mécanismes intégrés de la dyspnée et du handicap au cours de la bronchopneumopathie chronique obstructive.

Today, dyspnea in chronic obstructive pulmonary disease (COPD) is attributed to thoracic distention secondary to bronchial obstruction and hyperventilation. It inevitably occurs during exercise, even in patients with little obstruction, when they are capable of the elevated and prolonged power output that necessitates substantial hyperventilation. Exercise intolerance is due mainly to dyspnea, but muscle fatigue is also involved, especially in COPD patients who are malnourished. Deterioration of muscle function follows a substantial reduction in daily physical activity. In malnourished and hypoxemic subjects, however, responsibility for this is attributed to diverse aggravating biological processes related to chronic low-grade inflammation and to accentuated oxidative stress. The drastic diminution of physical activity results from ventilatory and muscle impairment and from symptoms that make movement painful. Improvement of ventilatory and muscle function, however, does not lead to recovery that allows sufficient physical activity. The spiral of disengagement, a morbid, psychodynamic process, accompanies chronic diseases and has the strongest effect in patients who were not highly physically active before becoming ill. Improvement of this handicap therefore requires a comprehensive management of patients, not confined to the prescription of physical activity under medical supervision. The aim is to offer diverse treatment propositions that can produce sustainable behavioral change.