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Biomedical subjects

K Kreiss

Publications and source records attributed to K Kreiss.

At least 37 records · Page 2Linked to original sources

Endemic work-related febrile respiratory illness among construction workers.

Construction workers building Denver International Airport (DIA) reported work-related respiratory and flulike symptoms of several months duration. We performed a cross-sectional interview study of 495 randomly selected DIA workers from six contractors in comparison with preplacement workers. We defined cases as workers with two work-attributed lower respiratory symptoms and one work-attributed systemic symptom. Case rates were significantly higher among DIA workers (34%) compared with those who had never worked at DIA (2%). Risk factors for illness included exposure to fireproofing (OR, 4.21; 95% CI, 1.95-9.08), work in tunnels and adjoining areas (OR, 3.07; 95% CI, 1.84-5.12), length of DIA employment (OR, 0.65; 95% CI, 0.46-0.92), and preexisting bronchitis (OR, 2.43; 95% CI, 1.17-5.05). Our industrial hygiene investigation revealed alkaline dust (pH 11) present at a worksite associated with elevated risk of illness, and we identified airborne Penicillium mold widely distributed indoors at DIA. Clinical evaluation of 26 self-identified symptomatic DIA employees, including bronchoalveolar lavage and biopsy in 10, revealed work-related asthma in three workers and histologic evidence of chronic bronchitis in four who had never smoked. We concluded that future investigations of endemic work-related febrile respiratory illness among construction workers should evaluate its association with indoor exposure to dusts from alkaline fireproofing, Penicillium mold, mycotoxins, and bacterial bioaerosols.

Adult↗

Epidemiology of beryllium sensitization and disease in nuclear workers.

We examined the epidemiology of chronic beryllium disease among a stratified, random sample (n = 895) of nuclear weapons workers using the blood beryllium lymphocyte transformation (BeLT) test and chest radiograph for case identification. Of 18 new cases of beryllium sensitization, 12 had beryllium disease, and three more developed pulmonary granulomas on lung biopsy over the succeeding 2 yr. Beryllium-sensitized cases did not differ from noncases in age, gender, race, ethnicity, smoking, most respiratory symptoms, spirometric or radiographic abnormalities, or job tenure. The six sensitized cases without initial disease differed from beryllium disease cases in having greater pack-years of smoking. Sensitization occurred among workers with inadvertent or bystander exposure, such as a secretary and security guard. However, beryllium sensitization risk was higher for machinists (4.7%) and for persons reporting measured overexposure (7.4%, odds ratio 5.1); exposure beginning before 1970 (3.6%, odds ratio 2.7); consistent beryllium exposure (3.4%); and sawing (4.7%) or band sawing (6.0%) of beryllium metal. We conclude that both individual susceptibility to sensitization and exposure circumstances are important in developing disease.

Adult↗

Building-related asthma in Denver office workers.

OBJECTIVES: Reported cases of building-related asthma and hypersensitivity pneumonitis among workers in a Denver office building prompted an epidemiologic investigation. METHODS: A cross-sectional, self-administered survey of employees in the office building of the reported cases was compared with that of employees in a comparison building. RESULTS: A significant excess of respiratory disease existed among 512 Denver workers (case building) compared with 281 office workers in a suburban agency (control building). Denver employees had a higher prevalence of respiratory symptoms, and the prevalence of physician-diagnosed asthma with onset or exacerbation since building occupancy was 4.9 times greater for Denver employees than for suburban employees. Asthma was not associated with any particular ventilation system in the building. Water incursion from a below-grade wall may have contributed to the problem, but the etiology is unknown. CONCLUSIONS: This investigation provided evidence of office building-related asthma. Individual cases may be sentinel events for other cases of work-related asthma or hypersensitivity pneumonitis and may indicate a need for public health investigation of remediable causes.

Adult↗

Beryllium disease screening in the ceramics industry. Blood lymphocyte test performance and exposure-disease relations.

We identified nine new cases of biopsy-confirmed chronic beryllium disease among 505 employees and ex-employees in a company that had manufactured beryllia ceramics from 1958 through 1975. Of tests commonly used in medical surveillance, only a confirmed blood beryllium lymphocyte transformation test had a high positive predictive value for beryllium disease (100%). However, two beryllium disease cases had either a normal or inconsistently abnormal blood test and were identified for diagnostic workup by abnormal chest radiograph. The only risk factor for beryllium disease was beryllium exposure; smoking or allergic history did not affect risk. Degree of beryllium exposure was associated with disease rates, which ranged from 2.9% to 15.8% for beryllia-exposed subgroups. One case of beryllium disease occurred in a "dust-disturber" who did not report past beryllium exposure and who began employment 8 years after commercial beryllia production had stopped. Our data support efforts to prevent beryllium disease by lowering beryllium exposures and to identify subclinical and early disease by broad-based medical surveillance using the blood beryllium lymphocyte test and chest radiograph in beryllium-using industries.

Adult↗

Nonoccupational beryllium disease masquerading as sarcoidosis: identification by blood lymphocyte proliferative response to beryllium.

Chronic granulomatous lung disease caused by industrial exposure to beryllium continues to occur, but no community cases have been reported in more than 30 yr. With the advent of a blood screening test that detects beryllium sensitization, physicians can discriminate chronic beryllium disease from sarcoidosis. A 56-yr-old woman in whom sarcoidosis was diagnosed had an unremarkable occupational history, but her husband was a beryllium production worker. Blood and bronchoalveolar lavage lymphocyte transformation tests, measuring the beryllium-specific cellular immune response, were abnormal, confirming a diagnosis of chronic beryllium disease. Chronic beryllium disease continues to occur in the nonoccupational setting and among bystanders in industry, masquerading as sarcoidosis. Because even transient or possibly low levels of exposure may cause disease, this case has important implications for how clinicians, industry, and government agencies define the populations at risk of chronic beryllium disease.

Berylliosis↗

Serum angiotensin converting enzyme activity in chronic beryllium disease.

Serum angiotensin converting enzyme (SACE) activity is used as a marker of sarcoidosis activity and severity, but in chronic beryllium disease (CBD) the studies of SACE give conflicting results. We examined SACE activity in 23 CBD patients, five patients with beryllium sensitization, and 25 beryllium-exposed control subjects. CBD patients underwent complete clinical evaluation, including physical examination, pulmonary function testing, exercise physiology testing, chest radiography, and bronchoscopy with bronchoalveolar lavage and biopsy. CBD SACE activity was systematically compared with these clinical markers of disease severity. Of CBD patients, 22% had elevated SACE activity. The test did not discriminate CBD patients from those in the beryllium-sensitized or beryllium-exposed groups. However, SACE activity in CBD correlated with the extent of pulmonary granulomatous inflammation as reflected by the symptom of breathlessness, the number of white cells in bronchoalveolar lavage (r = 0.44), the number of lavage lymphocytes (r = 0.58), the lavage lymphocyte percentage (r = 0.55), and the profusion of small opacities on chest radiograph (r = 0.41). The test-retest reliability of the assay was high (r = 0.84), as was the agreement between fresh and -70 degrees C frozen sera (r = 0.93). We conclude that SACE activity levels may reflect the extent of pulmonary granulomatous inflammation in CBD but that the test does not help discriminate disease from nondisease.

Adult↗

Investigation of an occupational cancer cluster using a population-based tumor registry and the National Death Index.

Occupational physicians investigate perceived cancer clusters to alleviate employee concerns and pursue etiologic hypotheses. We conducted a retrospective cohort analysis of all past and present employees of a metal fabrication plant and a comparison plant after employees recognized five cancer cases in 1987. We ascertained cases of all subjects who were employed at some time in the 8 years before 1987 through the Colorado Central Cancer Registry and determined vital status through the National Death Index. Cancer incidence at the index plant was almost identical to that of the population of the Denver metropolitan area (standardized incidence ratio [SIR] = 99, 95% confidence interval [CI] 59-165). Proportional incidence ratios revealed that no type of cancer occurred with significant excess in the index plant population during 1979 through 1986. Where population-based tumor registries exist, occupational physicians can employ this inexpensive and robust methodology to assess cancer incidence in exposed cohorts, pursue exposure-response relations, and evaluate clusters.

Adult↗

Natural killer cell tumoricidal activity in cigarette smokers and in silicotics.

Cigarette smoking and asbestos exposure have been reported to alter the tumor-killing activity of blood natural killer (NK) cells. However, NK cell function in relation to silica dust exposure has not been examined. We studied blood NK cell number, percentage, and tumoricidal activity in 120 hardrock miners, 57 of whom had radiographic evidence of silicosis, and in 33 community controls. There was a significant increase in leukocyte count and lymphocyte count in current smokers compared with former and never smokers, but these cell counts were normal in silicotics and those with silica dust exposure. No significant differences in NK cell (CD16+) number or percentage were found by flow cytometric analysis of smoking or dust exposure groups. Surprisingly, NK tumoricidal activity was significantly higher in cigarette smokers compared with former smokers and never smoker control subjects. Although tumoricidal activity was elevated in silicotics, this was accounted for by their cigarette smoking. These results suggest that cigarette smoking is associated with elevation of blood NK cell tumoricidal activity on a per cell basis, in the absence of any alteration in the absolute number of NK cells in blood.

Carcinogens↗

Reexamination of the blood lymphocyte transformation test in the diagnosis of chronic beryllium disease.

The T cell response to beryllium, measured in bronchoalveolar lavage by the lymphocyte transformation test (LTT), is a critical diagnostic test for discriminating between chronic beryllium disease (CBD) and other granulomatous diseases. We examined the sensitivity, reproducibility, and methods of a less invasive, peripheral blood LTT in 17 patients with CBD and in 18 beryllium-exposed control subjects. Ninety-four percent of CBD cases (16/17) had abnormal blood LTT results, and all 18 beryllium-exposed control subjects had normal blood LTT results. Split samples for 10 beryllium disease cases and eight control subjects demonstrated that the blood LTT was reproducible between two separate laboratories. The LTT was equally sensitive with 10% and 20% serum in the culture medium. We conclude that an abnormal blood LTT can be used to diagnose CBD in patients with compatible lung pathology.

Adult↗

Screening blood test identifies subclinical beryllium disease.

We evaluated the beryllium-specific lymphocyte transformation test as a workplace screening tool for early beryllium disease. Fifty-one of 58 workers with current beryllium exposure completed questionnaires and gave blood specimens for the lymphocyte transformation test. Six workers (11.8%) had elevated test results ranging from 5.7-fold to 16.7-fold stimulation. Of five who underwent clinical evaluation, four had beryllium disease, demonstrated by granulomata on transbronchial lung biopsy and elevated lymphocyte transformation tests by bronchoalveolar lavage cells (ranging from 18.6-fold to 44.3-fold stimulation). Our data show that (1) minimally symptomatic cases of beryllium disease can be identified by this peripheral blood test, (2) not all individuals with a positive peripheral blood lymphocyte transformation test have beryllium disease at the time of their initial evaluation, and (3) lymphocyte transformation test reproducibility is good, justifying further evaluation of this test for screening. We conclude that the peripheral blood lymphocyte transformation test may prove useful in preventing clinical chronic beryllium disease by early diagnosis in a subclinical phase.

Adult↗

Histocompatibility antigens in a population based silicosis series.

Individual susceptibility to silicosis is suggested by the lack of a uniform dose response relation and by the presence of immunological epiphenomena, such as increased antibody levels and associated diseases that reflect altered immune regulation. Human leucocyte antigens (HLA) are linked with immune response capability and might indicate a possible genetic susceptibility to silicosis. Forty nine silicotic subjects were identified from chest radiographs in a population based study in Leadville, Colorado. They were interviewed for symptoms and occupational history and gave a blood specimen for HLA-A, -B, -DR, and -DQ typing and for antinuclear antibody, immune complexes, immunoglobulins, and rheumatoid factor. Silicotic subjects had twice the prevalence of B44 (45%) of the reference population and had triple the prevalence of A29 (20%), both of which were statistically significant when corrected for the number of comparisons made. No perturbations in D-region antigen frequencies were detected. B44-positive subjects were older at diagnosis and had less dyspnoea than other subjects. A29-positive subjects were more likely to have abnormal levels of IgA and had higher levels of immune complexes. This study is the first to find significant HLA antigen excesses among a series of silicotic cases and extends earlier reported hypotheses that were based on groups of antigens of which B44 and A29 are components.

Adult↗

Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history.

Beryllium lung disease is a chronic granulomatous disorder in which a beryllium-specific immune response plays a central role. By using a measure of cellular immune response to beryllium salts, bronchoalveolar lavage (BAL), and lung biopsy, we have identified 12 new cases of beryllium disease. Each of these individuals had pathologic changes on biopsy, lymphocytic alveolitis on BAL, and positive BAL lymphocyte transformation tests (LTT) in response to beryllium sulfate. This group of patients was remarkable for its paucity of clinical findings. At initial evaluation, seven had no respiratory symptoms, and four had normal physical examinations. Five had no increase in interstitial markings on chest radiograph. In eight cases, flow rates and lung volumes were normal. Diffusing capacity for carbon monoxide was low in only one case, and oxygen exchange during exercise was normal in six of nine subjects studied. In addition to the 12 cases, we evaluated eight beryllium-exposed workers who had other (nonberyllium) lung diseases; two of these eight demonstrated beryllium sensitization based on BAL LTT. We conclude that use of fiberoptic bronchoscopy with transbronchial biopsy and BAL facilitates diagnosis of beryllium workers who have histopathologic and immunologic alterations consistent with chronic beryllium disease. These findings may precede frank clinical illness and physiologic impairment, having important implications for our understanding of the natural history of beryllium disease.

Adult↗

Hard-rock mining exposures affect smokers and nonsmokers differently. Results of a community prevalence study.

The physiologic consequences of occupational dust exposure, their relation to smoking, and their reversibility with cessation of exposure remain controversial. To address these questions, we studied a random sample of male residents of Leadville, Colorado when the major employer, a hard-rock mine, had been closed for 5 to 11 months. Subjects were interviewed for respiratory symptoms and occupational history, underwent plethysmographic measurements of lung volume and airflow, and performed a single breath diffusing capacity procedure. Dyspnea was the only respiratory symptom exacerbated by mining exposures. Cumulative dust exposure, estimated with historic respirable dust measurements for mining job titles and weighted by time at the job, was associated with decreases in maximal expiratory flow rates when controlled for smoking, age, and height. However, determinations of plethysmographic lung volume that allowed calculation of flow rates at equivalent absolute lung volume indicated that dust effects differed in never-smokers and smokers. In never-smokers, dust exposure was associated with decreased lung volume, increased flow rates, and increased DLCO/VA. In smokers, dust exposure was associated with increased lung volume, lower flow rates, and lower DLCO/VA than that accounted for by smoking. We suggest that hard-rock mining exposures result in irreversible pulmonary function changes of airflow limitation in smokers and of a restrictive nature in never-smokers.

Adult↗