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Biomedical subjects

H W Barkman

Publications and source records attributed to H W Barkman.

18 recordsLinked to original sources

Efficacy of oral ciprofloxacin vs. clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In this prospective, multicenter, double-blind study, the efficacy of ciprofloxacin was compared with that of clarithromycin as therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) from whom a pretherapy pathogen was isolated; the efficacy was measured by the infection-free interval. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Patients randomly received either ciprofloxacin or clarithromycin (500 mg twice a day for 14 days). Three hundred seventy-six patients with acute exacerbations of chronic bronchitis were enrolled in the study of whom 234 had an ABECB. Clinical resolution was observed in 90% (89 of 99) of ciprofloxacin recipients and 82% (75 of 91) of clarithromycin recipients for whom efficacy could be evaluated. The median infection-free interval was 142 days for ciprofloxacin recipients and 51 days for clarithromycin recipients (P = .15). Bacteriologic eradication rates were 91% (86 of 95) for ciprofloxacin recipients and 77% (67 of 87) for clarithromycin recipients (P = .01). In summary, compared with clarithromycin, treatment of ABECB with ciprofloxacin was associated with a trend toward a longer infection-free interval and a statistically significantly higher bacteriologic eradication rate.

Administration, Oral↗

Neutrophil chemotactic activity in toluene diisocyanate (TDI)-induced asthma.

We quantitated serum neutrophil chemotactic activity (NCA), which is associated with mast cell or basophil activation, to determine if mast cell or basophil mediators are released during bronchoprovocation-inhalation challenge with subirritant levels of toluene diisocyanate (TDI). Four subjects with suspected TDI-induced asthma and four mite-sensitive subjects with asthma who served as a comparison group were studied. NCA was measured in a multiwell, microchemotaxis chamber. Blood samples were collected, and FEV1 measurements were performed before challenge and at regular intervals during the subsequent 24 hours. Three of four workers clinically sensitive to TDI reacted to a subirritant TDI exposure. There was no increase in NCA during placebo challenges. NCA increased in the three TDI-sensitive workers during early and late asthmatic reactions in quantities proportional to the FEV1 decline. No increase in NCA was found during TDI exposures in the TDI-negative worker. Gel filtration analysis demonstrated the main NCA fraction eluted with macromolecules of an estimated molecular weight greater than 440,000 daltons. This characteristic is compatible with neutrophil chemotactic factor of basophil or mast cell origin. The kinetics of NCA release were similar in mite- and TDI-induced asthmatic reactions. A high correlation (r = 0.97; p = 0.0006) was obtained between the percent decrease in FEV1 during early asthmatic reactions and percent increase in NCA. These observations support the hypothesis that activation of mast cells or basophils is associated with TDI-induced early and late asthmatic reaction.

Animals↗

Reliability of cell counts and protein determinations in serial bronchoalveolar lavage procedures performed on healthy volunteers.

We measured the variability in volume, total cells, cell types, and proteins in the bronchoalveolar lavage fluid recovered from 10 volunteers (five smokers, five non-smokers) lavaged repeatedly over a three-year period. Thirty lavages were performed using a rigorously standardized approach. Differential counts on the cytospin preparations were performed by three independent readers and interobserver variability in the interpretation of these counts measured. Variability in interpreting the cellular counts was less in smokers than non-smokers and decreased as the number of cells of any particular type increased. Only one reader interpreting the mean percentage of cells recovered of one cell type (neutrophils) in only one smoking group, the nonsmokers, was significantly different from the other two. There was also considerable variability in bronchoalveolar lavage fluid total protein, albumin, IgG, and IgA. Expressing albumin and IgG as a percentage of total protein recovered and expressing IgA and albumin as a ratio in nonsmokers lessened the variability of these parameters. Mean and standard deviations of the cellular and protein concentrations showed that large differences in these parameters would be necessary in order to attribute these changes to changes in the underlying pulmonary status. Excessive variability in nearly all parameters in this group without recognized lung disease challenges the usefulness of this test in the clinical assessment of patients serially followed because of underlying lung disease.

Adult↗

Persistence of toluene diisocyanate-induced asthma despite negligible workplace exposures.

Six polyurethane foam workers were shown to have TDI-induced asthma by specific inhalation challenge testing. All remained in the workplace in jobs with minimal TDI exposures. Mean and time-weighted average exposure concentration for the asthmatic group was 0.64 +/- 0.46 ppb, less than 5 percent of the permissible exposure limit and significantly less (p less than 0.01) than the mean TWA exposures occurring in the foam line and the finishing workers. Serial evaluation of the respiratory health of these six showed all persisted with respiratory symptoms, none had improvement in bronchial hyperresponsiveness to methacholine, and three had a greater than 15 percent decline in FEV1 on one of the days of spirometric testing over the five-year period from 1982 to 1986. Although we could not have predicted the outcome of asthma had these workers left the workplace and ceased isocyanate exposure entirely, occupational asthma persisted despite negligible ongoing TDI exposures.

Asthma↗

Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.

Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.

Adult↗

Spirometry: quantitative test criteria and test acceptability.

Quantitative test criteria have been developed to assess the acceptability of spirometric tracings. Most automated spirometers have been programmed with the criteria in order to assist in data collection. These instruments compare computed parameters from the collected tracings with the criteria and, after 3 acceptable FVC maneuvers have been collected, print out a statement indicating that "tests meet acceptability criteria." Technicians, nurses, and even their medical supervisors are beginning to rely on these statements as assuring overall test quality. However, a review of actual curves indicates that unacceptable results can be obtained from tests that comply with these standards. Although quantitative test criteria are a positive step toward quality assurance, they should be treated as they were developed, as "minimum" criteria. All curves should be inspected for visible defects, especially if the results are used to follow subjects longitudinally.

Forced Expiratory Volume↗

Modification of the methacholine inhalation test and its epidemiologic use in polyurethane workers.

The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.

Adult↗

Absence of hyperresponsiveness to methacholine in a worker with methylene diphenyl diisocyanate (MDI)-induced asthma.

A 29-year-old man had a persuasive history of respiratory illness following exposures to methylene diphenyl diisocyanate (MDI). He was evaluated by measuring bronchial reactivity to methacholine, both before and after controlled laboratory exposures to MDI. Despite evidence of progressive declines in FEV1 with increasing (but subirritant) doses of MDI on three consecutive days, there was no bronchial hyperresponsiveness to methacholine, before or after MDI challenge. We conclude that the absence of nonspecific bronchial hyperresponsiveness does not exclude the possibility of isocyanate asthma. In the face of a compelling history, a negative result of methacholine challenge should not deter observation or laboratory testing for specific respiratory allergy to these chemicals.

Adult↗

Gallium-67 citrate imaging in underground coal miners.

Twenty-two underground coal workers with 27 or more years of coal dust exposure were studied with gallium-67 citrate (Ga-67) imaging. Radiographic evidence of coal workers pneumoconiosis (CWP) was present in 12 subjects. The Ga-67 scan was abnormal in 11 of 12 with, and 9 of 10 without, CWP. The Ga-67 uptake index was significantly correlated with total dust exposure (p less than 0.01) and approached significant correlation with the radiographic profusion of the nodules (0.10 greater than p greater than 0.05). There was no correlation between Ga-67 uptake and spirometric function, which was normal in this group of patients; furthermore, increased lung uptake of gallium did not indicate a poor prognosis in subjects no longer exposed to coal dust. While coal dust exposure may be associated with positive Ga-67 lung scan in coal miners with many years of coal dust exposure, the scan provided no information not already available from a careful exposure history and a chest radiograph. Since Ga-67 scanning is a relatively expensive procedure we would recommend that its use in subjects with asymptomatic CWP be limited to an investigative role and not be made part of a routine evaluation.

Aged↗

Predictors of survival in subjects with chronic airflow limitation.

In a study of chronic airflow limitation, we followed 140 subjects living in Utah at altitudes of 1,300 to 1,500 meters for seven to 13 years. Twelve-year survival probabilities were determined and compared with an age- and sex-matched Utah population. The lowest 12-year survival probability was 0.40 for those patients with a forced expiratory volume in one second/forced vital capacity (FEV1/FVC) of less than or equal to 0.40, indicating that there is much variability in survival. Other indicators of a lower survival probability (and increased death risk ratio) were an FEV1 percent predicted less than or equal to 50, an FEV1 less than or equal to 1.5 liters, male gender, partial pressure of oxygen (PO2) [exercise] less than or equal to 50 mm Hg, partial pressure of carbon dioxide (PCO2) [rest] greater than 39 mm Hg, PCO2 (exercise) greater than 39 mm Hg, FVC percent predicted less than or equal to 80, PO2 (rest) less than or equal to 55 mm Hg, and a carbon monoxide diffusing capacity (DLCO) percent predicted less than or equal to 80. Current smokers had a poorer survival probability than the reference population and an increased death risk when compared with the nonsmokers in the study. Pack/years of smoking also affected survival. Other variables associated with reduced survival were a diagnosis of chronic bronchitis combined with emphysema, more rapid annual declines in the FEV1 and/or FVC, low alpha 1-antitrypsin levels, a 20 percent improvement in FEV1 following the use of a bronchodilator aerosol, and a lower socioeconomic class. Differences between these findings and those noted in other studies are in the main due to differences in the characteristics (such as age, diagnosis, and extent of disease) of the patients in the study populations. The findings have relevance in estimating a patient's prognosis and for developing guidelines for disability determination purposes.

Adult↗

Immunologic aberrations in asbestos cement workers: dissociation from asbestosis.

Immunoregulatory disorders have been implicated in the pathogenesis of asbestosis. We therefore compared the immunologic status of a well-characterized group of 31 current and former asbestos-cement workers with that of a group of 52 healthy controls, after adjustments had been made for the possible confounding effects of age, race, and smoking. The asbestos workers had significantly decreased percentages and numbers of both B and T lymphocytes in peripheral blood and a paradoxical IgG hypergammaglobulinemia. Analysis of T-lymphocyte subpopulations revealed that total T-cell numbers (OKT3+), helper-inducer T-cell numbers (OKT4+), and suppressor-cytotoxic T cell numbers (OKT8+) were decreased by similar proportions. These decreases were negatively correlated with time elapsing since the end of exposure to asbestos. In both workers and controls, lymphocyte proliferative responses to phytohemagglutinin (PHA) were correlated positively with the number of OKT4+ cells and negatively with age and serum IgG levels. When adjustments had been made for these confounding variables, no differences in PHA responses were noted between workers and controls. No relationship was detected in the workers between any of the immunologic aberrations noted and (1) radiographic category of pneumoconiosis, (2) estimates of cumulative asbestos exposure, or (3) abnormalities of pulmonary function. These data suggest that the immunologic perturbations we have noted in asbestos-exposed individuals are epiphenomena, unrelated to the pathogenesis of asbestosis itself.

Adult↗

Immunopathogenesis of asbestosis, silicosis, and coal workers' pneumoconiosis.

From these discussions, it is apparent that immunologic aberrations occur in several inorganic dust diseases. Although the role of these immunologic mechanisms in disease pathogenesis remains speculative, recent studies demonstrating the regulation of fibroblast proliferation by macrophage and asbestos or silica interaction support a role for this cell type in the immunopathogenesis of disease. Future cellular and humoral investigations of the bronchoalveolar lavage in workers with pneumoconiosis may clarify the immunologic contributions in the development of fibrosis observed in these diseases.

Antibodies, Antinuclear↗

Lidocaine effects on immunocompetent cells. Implications for studies of cells obtained by bronchoalveolar lavage.

Immunologic data obtained from bronchoalveolar lavage (BAL) is useful for both clinical and investigative purposes. Although lidocaine, used for local anesthesia, is present in BAL in up to 12 mmol concentration, its effects on immunologic tests are unclear. The results of our study show that lidocaine has profound effects on the results of functional studies of immuno-competent cells. Care should be taken to quantify, standardize, and limit the exposure of alveolar cells to lidocaine during bronchoscopy if such studies are to be performed. However, exposure of cells for 25 minutes or less to lidocaine solutions up to 12mmol in concentration does not affect a variety of immunologic tests of interest. At the same time, carefully controlled use of lidocaine in lavage solutions significantly increases the number of cells obtained for study.

B-Lymphocytes↗

A portable volume/flow calibrating syringe.

Two samples of a manual 3 L calibrating syringe which displays an electronically calculated FEF25-75% were evaluated to determine its suitability as a flow calibrator were evaluated. Room air was discharged into a manual spirometer system known to be accurate. The calibrator-determined values correlated very closely with the spirometer values over an FEF25-75% range of 0.4 to 9 L/sec. The differences between calibrator and spirometer FEF25-75% values were small (mean +/- 1 percent, greatest 3.7 percent) and of little importance clinically. This portable, simple to operate calibrating syringe provides accurate FEF25-75% and volume values. By adding flow calibrating capability to a recommended standard volume calibrating syringe, it will facilitate the routine calibration of spirometers in the laboratory and in the field. Since it uses displaced air, it can be used at altitude and with flow measuring instruments without the correction required for calibrators using CO2 cartridges.

Calibration↗

Respiratory disease in Utah coal miners.

Two hundred forty-two Utah underground coal miners volunteered to participate in a respiratory disease study. They were an older group (mean, 56 years of age) and had spent a mean of 29 years in the coal-mining industry. The prevalence of chronic bronchitis was 57%, and that of coal worker's pneumoconiosis, 25%; only one worker had progressive massive fibrosis. Significant impairment of pulmonary function was found among those with a history of cigarette smoking. Chronic bronchitis or coal worker's penumoconiosis among nonsmokers did not impair pulmonary function. There was a significant association among the nonsmokers between increasing exposure to coal dust and coal worker's pneumoconiosis, but not for changes in pulmonary function. Coal mine dust had a significant influence in causing the symptom complex of chronic cough and sputum production, and coal worker's pneumoconiosis.

Bronchitis↗