Publications

The pathogenesis of pulmonary edema that occurs during interleukin-2 therapy has often been attributed to an increase in pulmonary capillary permeability. However, renal insufficiency, fluid overload, and hypotension also develop in many patients. These manifestations of systemic toxicity may contribute to the development of pulmonary edema during therapy. Understanding the cause of pulmonary edema during interleukin-2 therapy could directly affect patients' care. Therefore, we reviewed the chest radiographs and clinical course of 54 patients who received high-dose interleukin-2 therapy and lymphokine-activated killer cells for advanced carcinoma. The type, frequency, and course over time of pulmonary abnormalities were recorded and correlated with clinical measures of renal function, fluid status, and blood pressure. Focal or diffuse parenchymal lung opacities were found on radiographs in 43 (80%) of 54 patients. Findings of interstitial pulmonary edema were most common, occurring in 76% of patients. Weight gain, hypotension, and elevation of the serum creatinine level were not associated statistically with interstitial edema. Diffuse air-space disease developed in 20% of patients. Focal consolidation, which was associated with positive central venous catheter cultures (p less than .03), developed in 28% of patients. Pleural effusion occurred in 48% of patients and was associated with all types of parenchymal disease. These data suggest that the frequent development of pulmonary edema during interleukin-2 therapy is not due to renal insufficiency, fluid overload, or hypotension, but is more likely the result of an interleukin-2-related increase in pulmonary capillary permeability.

OBJECTIVE

To examine the pathogenesis of metal fume fever in humans by studying functional, cellular, and biochemical responses after exposure to zinc welding fume.

DESIGN

Clinical experimental study.

PARTICIPANTS

We studied 14 welders recruited through public advertisements.

INTERVENTIONS

Participants welded galvanized steel.

MEASUREMENTS

We measured lung volumes, airflow, diffusing capacity for carbon monoxide, and airway reactivity at baseline as well as either 6 or 20 hours after welding. We carried out bronchoalveolar lavage either 8 hours (early follow-up, 5 participants) or 22 hours (late follow-up, 9 participants) after welding, assaying the fluid for total and differential cell counts and bronchoalveolar lavage supernatant concentrations of interleukin-1 and tumor necrosis factor (TNF).

MAIN RESULTS

Changes in pulmonary function and airway reactivity were minimal. Cumulative zinc exposure and polymorphonuclear leukocyte count in bronchoalveolar lavage fluid at late (r = 0.87; P less than 0.01) and early (r = 0.93; P less than 0.05) follow-up were positively correlated. Among the late follow-up group, the mean proportion of polymorphonuclear leukocytes was 37% (range, 19% to 63%), a statistically greater proportion than the 9% (range, 2% to 21%) seen among the early follow-up group (P less than 0.05). We did not detect TNF or more than a trace amount of interleukin-1 in the bronchoalveolar lavage supernatant.

CONCLUSIONS

Zinc oxide welding fume was associated with a marked dose-dependent increase in the number of polymorphonuclear leukocytes recovered in bronchoalveolar lavage fluid 22 hours after exposure but was not associated with a clinically significant change in pulmonary function or airway reactivity. Although we did not identify increases in either interleukin-1 or TNF levels in bronchoalveolar lavage fluid, cytokines or a cytokine-like mechanism may mediate the syndrome of metal fume fever.

STUDY OBJECTIVE

To estimate the incidence of and risk factors for morbidity due to inhalation of respiratory irritants.

DESIGN

Six-month case series of inhalational exposures reported to a poison control center with follow-up, structured interviews of subjects.

SETTING

A regional poison control center providing 24-hour telephone consultation to health professionals and the public.

PATIENTS

Consecutive sample of 683 inhalation cases, with interviews of 323 subjects.

MEASUREMENTS AND MAIN RESULTS

Moderate to severe irritants accounted for 160 (50%) of the inhalational exposures in interviewed subjects. Persistent symptoms lasting 14 days or longer were reported by only 20 (6%) of the subjects. Irritant exposure was a statistically significant risk factor for acute respiratory symptoms (relative risk [RR] = 1.7; 95% confidence interval [Cl], 1.4 to 2.1) but was unrelated to persistent symptoms. Preexisting lung conditions (RR = 2.4; 95% Cl, 1.4 to 4.2) and cigarette smoking (RR = 1.7; 95% Cl, 1.3 to 2.2) were both statistically significant risk factors for persistent symptoms.

CONCLUSIONS

Symptomatic inhalational exposures due to irritants are frequent in reports from poison control centers. Residual morbidity was uncommon and did not appear to be statistically related to the degree of irritant exposure. Host-related factors may be better predictors of ongoing morbidity after inhalational exposure.

The use of herbs has been advocated as an alternative treatment strategy for human immunodeficiency virus-related illness. To describe the use of medicinal herbs among acquired immunodeficiency syndrome clinic patients and to investigate possible toxic effects, we interviewed 114 randomly selected patients attending a university-based acquired immunodeficiency syndrome clinic and performed a structured review of the literature to identify potential adverse effects of herbal use. Twenty-five participants (22%) reported using one or more herbal products in the past 3 months. Of those taking herbs, six (24%) were unable to identify the herb that they had used. The mean number of herbal tablets taken was 4.5 tablets per day, and 12 patients (48%) reported taking herbs for longer than 90 days. The median cost to patients for their herbs was $18 per month. Of those taking herbs, five (20%) stated that their primary medical provider was unaware of their herb use, and four (16%) were involved in clinical drug trials while using herbs. Several patients reported taking herbs in doses at which potential adverse effects were identified in our literature review. These adverse effects include dermatitis, nausea, vomiting, diarrhea, thrombocytopenia, coagulopathies, altered mental status, hepatotoxicity, and electrolyte disturbances. Seven patients (28%) reported experiencing symptoms that could have been caused by one or more of the herbal products that they were taking. Physicians and clinical investigators need to inquire about patients' use of herbs. Patient care and clinical trials could be distorted because pharmacologic effects of herbs can resemble commonly occurring symptoms in human immunodeficiency virus disorders as well as side effects of prescribed or investigational medications.

Chronic granulomatous disease is characterized by recurrent infections that result from an inability of phagocytes to kill organisms effectively. We describe a patient with this disease who developed aspergillus pneumonia after shoveling moldy cedar wood chips. Despite aggressive therapy, the patient's condition deteriorated and he died. At autopsy, the lungs revealed diffuse granulomas, all of the same age, with aspergillus organisms confined to the granulomas. We propose the term "microgranulomatous aspergillosis" for this response, which does not conform to the commonly described aspergillus syndromes. We conclude that susceptible immunosuppressed patients should be advised to avoid occupational situations where high spore concentrations are generated.

We retrospectively evaluated the effect of the Loma Prieta earthquake on calls to 2 designated regional poison control centers (San Francisco and Santa Clara) in the area. In the immediate 12 hours after the earthquake, there was an initial drop (31%) in call volume, related to telephone system overload and other technical problems. Calls from Bay Area counties outside of San Francisco and Santa Clara decreased more dramatically than those from within the host counties where the poison control centers are located. In the next 2 days, each poison control center then handled a 27% increase in call volume. Requests for information regarding safety of water supplies and other environmental concerns were significantly increased. The number of cases of actual poisoning exposure decreased, particularly poison and drug ingestions in children. Most calls directly related to the earthquake included spills and leaks of hazardous materials and questions about water and food safety. Regional poison control centers play an essential role in the emergency medical response to major disasters and are critically dependent on an operational telephone system.

Pulmonary manifestations are not infrequent in the L-tryptophan-induced eosinophilia-myalgia syndrome (EMS). However, previous reports have not described the results of longitudinal pulmonary function, exercise testing, high-resolution computerized tomographic (HRCT) scanning of the chest, or detailed bronchoalveolar lavage (BAL) analysis. We report six patients with EMS who had dyspnea. The diffusing capacity for carbon monoxide was decreased in five patients tested. Exercise testing with arterial blood gas sampling in three patients was consistent with pulmonary vascular or parenchymal disease. Serial exercise testing in two of these patients demonstrated marked improvement temporally associated with corticosteroid treatment. In four patients, HRCT scanning of the chest was abnormal. One of these patients showed no abnormality on routine chest roentgenogram. Two patients undergoing BAL exhibited increased eosinophils in the lavage fluid; a third had elevated lymphocytes. Serial measurements of fibroblast proliferation-stimulating-activity in samples of BAL fluid obtained from serial examinations in two patients exhibited heightened pretreatment activity that returned to the normal range following corticosteroid therapy. In these two patients, increased proportions of T-suppressor/cytolytic (CD8+) cells were observed in the BAL fluid. Despite aggressive immunosuppressive therapy, one of the patients died of respiratory failure. Another remains markedly dyspneic with pulmonary hypertension. Of the remaining four patients, two exhibited resolution of pulmonary symptoms after systemic corticosteroid therapy, and two experienced partial improvement.

Diseases of the lung are among the work-related conditions most widely recognized among nonspecialists and the lay public. Five pulmonary conditions for which occupational or environmental exposures are not typically emphasized are reviewed here in their clinical-pathologic context. These are diffuse alveolar hemorrhage, lipoid pneumonitis, granulomatous lung disease, pulmonary alveolar proteinosis, and pulmonary vascular disease.

In order to indicate priorities for possible occupational health care planning activities, we evaluated occupational health risks, health services, and occupational research and training in Israel from the perspective of occupational medicine in the United States. We used available public information as well as data collected in a previous regional assessment of occupational health in the Negev. We estimated that each year 35% of the workforce in Israel may be exposed to high levels of noise, 4-11% to workplace toxins, and 7% to work injuries, all hazards warranting attention by health planners. Reviewing occupational health services we found that programmatic deficiencies limit the effective use of existing resources. We also evaluated the potential benefits of strengthened expert review in setting funding priorities for research and training in occupational safety and health in Israel.