Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories.

Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.

Unexplained pulmonary infiltrates in the compromised patient. An invasive investigation in a consecutive series.

A series of 51 consecutive unexplained pulmonary infiltrates were reviewed retrospectively, in a group of 48 patients in whom invasive procedures were performed. Fifty-two percent of these patients had leukemia or lymphoma and 40% had solid tumors. All patients had lung tissue obtained premortem either by transbronchial biopsy through the flexible fiberoptic bronchoscope or by open lung biopsy. There was a 27% complication rate in these invasive procedures including bleeding, pneumothorax, and ventilatory support. Infectious agents were found in only 13 cases (25%) with a mortality rate of 62%. The pathologic finding of the underlying malignant disease or organizing pneumonia portended a poor prognosis with 100% and 80% mortality, respectively. Twenty-one patients had biopsy tissue revealing only nonspecific pathologic changes and were associated with the lowest mortality (19%). It was found that 50% of the solid tumor patients with unexplained pulmonary infiltrates had nonspecific pathologic changes. The biopsy findings resulted in a change in the therapy in 29% of the cases and in 19% of the cases the subsequent change in therapy resulted in marked improvement. The lung biopsy is useful to diagnose treatable infectious disease, as well as for prognostic guidance in caring for critically ill compromised patients.