Viral inclusion bodies in tracheobronchial epithelium of asymptomatic subjects.

During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.

Cytoplasmic inclusion bodies found in the epithelia of the urinary tract and tracheobronchial tree have been reported by several authors;1, 2, 3, 4 but whereas affected cells were found in the urinary tract of both symptomatic and asymptomatic patients, such cells have only been reported thus far in the respiratory tract of subjects with viral disease and bronchogenic carcinoma. We have been able to study the occurrence of this phenomenon because of the facility with which tracheobronchial secretions can be obtained during general endotracheal anesthesia.5, 6 Correlations have been attempted between the presence of cytoplasmic inclusions and sex, age, smoking habit, and reason for surgery of the patients concerned, as well as correlations with the time of year and other cytologic abnormalities.

PATIENTS AND METHODS

Three thousand forty-nine tracheobronchial smears randomly collected on a daily basis between April 1, 1973 and March 31, 1975 were reviewed for the presence of cytoplasmic viral inclusion bodies (Fig 1 ). The smears were obtained from consenting patients undergoing general endotracheal anesthesia for elective surgery; 5 ml of physiologic saline solution was instilled down the tracheal tube immediately after intubation and was suctioned for return within 30 seconds with a transparent catheter. The catheter was cut where it was seen to contain mucus. Secretions were retrieved with an applicator stick, smeared on slides, spray-fixed at once, and stained (Papanicolaou and PAS methods). Information obtained from all patients during a preoperative visit included age, sex, and smoking habit. In addition, all medical records were screened both before and after surgery to ascertain (1) the reason for surgery, (2) any associated unrelated pathologic findings, (3) the histopathologic findings from surgical specimens, (4) the results of other diagnostic tests, and (5) the date of surgery. Smears from patients who had suffered from known viral infections within 15 days preceding surgery and from those with prediagnosed cardiac and infective pulmonary diseases were not included in the study. All patients were screened for the first seven postoperative days; and the development of temperature elevations above 38.4°C (101.1°F), positive physical signs in the chest, and roentgenologic changes were noted. The epidemiologic approach of Goldsmith and Berglund was used. Variables among patients were listed, including age, sex, smoking habit, preoperative respiratory status, preoperative and postoperative diagnoses, and other associated diseases contributing to the physical status of the patient. The contribution of each variable to the factor studied was assessed. Significance of statistical correlations was calculated by the chi-square method, using the Yates correction factor, at values of P < 0.05, because the series was small in comparison to the total group of patients screened.

FIGURE 1

Cytoplasmic viral inclusion bodies in ciliated tracheobronchial epithelial cells (Papanicolaou stain, original magnification × 400).

RESULTS

Of the 3,049 smears screened, 35 (1.1 percent) were found to contain ciliated epithelial cells with eosinophilic cytoplasmic inclusion bodies (Papanicolaou stain). All were PAS-positive. Of these, 11 (31 percent) came from patients with extrathoracic malignant disease, one (3 percent) came from a subject with asymptomatic bronchogenic carcinoma diagnosed by routine roentgenographic study, eight (23 percent) came from subjects with benign tumors (uterus, breast, and prostate), and 15 (43 percent) came from patients suffering from a wide variety of conditions (inguinal hernia, retinal detachment, cholecystitis, fractures of the extremities, complications of pregnancy, tonsillitis, and peptic ulcer). No correlation could be found between the presence of inclusion bodies in smears and the age, sex, or smoking habit of patients. Although the incidences of malignant and benign tumors among patients with inclusion bodies appeared to be high (34 percent and 23 percent, respectively), they were not found to be significant when compared with the incidences of these tumors in the entire population screened (26 percent and 20.4 percent, respectively). No relationship was found between the presence of viral inclusion bodies and other abnormalities noted in smears; however, when the frequency of occurrence of inclusion bodies was assessed in relation to the season of the year, 60 percent (20) of all these smears (Fig 2 ) were found to have been collected during the months of January through March.

FIGURE 2

Seasonal incidence of inclusion bodies in tracheobronchial ciliated cells of asymptomatic patients.

One patient, who smoked 30 cigarettes a day, developed a temperature above 38.4°C (101.1°F) for the first three postoperative days. There were two nonsmokers who developed a temperature above 38.4°C (101.1°F) together with positive signs in the chest and roentgenologic infiltrates. One of these had an asymptomatic bronchogenic carcinoma, and the other had metastatic carcinoma of the breast and chronic lymphocytic leukemia. All signs disappeared within three days after the institution of bronchial washing and therapy with intermittent positive-pressure breathing. All other patients had uneventful postoperative courses.

DISCUSSION

Other investigators have found that the respiratory tract has the highest rate of viral isolation of all body systems. Whitehead has suggested that inapparent infection with respiratory as well as other viruses acts as a reservoir1, 3 for epidemic periods. Unlike other descriptions of patients with such inclusions, our subjects had no respiratory symptoms. Our findings are more in line with those of Ström, who found viral shedding in the urinary tract of apparently healthy individuals. The Tecumseh and other studies of respiratory infections10, 11, 12 have demonstrated an increased incidence of infection with coronavirus, respiratory syncytial virus, and rhinovirus during the winter months; and it is, therefore, probable that the majority of our patients had asymptomatic infections with these viruses.

The low postoperative respiratory complication rate noted in this series seems to indicate that the presence of viral inclusion bodies is not a precursor of respiratory disease (even under stress conditions).