PubMed Health⌕ Search

Biomedical subjects

J Balmes

Publications and source records attributed to J Balmes.

At least 19 recordsLinked to original sources
PubMed2003

Chlorine inhalation produces nasal congestion in allergic rhinitics without mast cell degranulation.

Seasonal allergic rhinitic (SAR) subjects are more sensitive to nasal irritants than nonrhinitic (NR) subjects; however, the mechanism underlying this difference is unclear. This study sought to determine whether irritant-induced nasal congestion involves mast cell degranulation. Eight SAR and eight NR subjects were exposed to both 1.0 parts per million chlorine and filtered air in separate visits; exposures were via nasal mask and lasted 15 min. Rhinomanometry was performed before, immediately after and 15 min after exposure. Following > or = 2 weeks, exposures and symptom reporting were repeated with nasal lavage, rather than rhinomanometry, pre- and postexposure. A separate substudy using rye grass antigen provided a positive control. Mast cell tryptase was measured in nasal lavage fluid from both substudies using an automated fluoroenzyme immunoassay. Chlorine provocation significantly increased nasal airway resistance in SAR but not NR subjects. Conversely, tryptase levels in nasal lavage fluid were unaffected. Nasal allergen challenge significantly increased both nasal obstruction and nasal lavage tryptase in SAR subjects. Irritant-induced nasal congestion is more pronounced among seasonal allergic rhinitic than nonrhinitic subjects. However, unlike nasal allergen challenge, the mechanism of response to chlorine does not appear to involve mast cell degranulation.

Administration, Inhalation↗
PubMed2001

Physician reports of work-related asthma in California, 1993-1996.

BACKGROUND: Work-related asthma is a leading cause of occupational respiratory illness. METHODS: Work-related asthma was studied in California over a 36-month period, from March 1, 1993 to February 29, 1996. The surveillance system identified cases from Doctor's First Reports (DFRs), a mandated physician reporting system. Structured follow-up telephone interviews of DFR asthma cases were conducted to collect work history, exposure, and medical information. Statewide employment data was used to calculate disease rates among industry groups. RESULTS: Based on 945 cases of work-related asthma, the average annual reporting rate for work-related asthma in California was 25/million workers. We estimate that the actual rate is 78/million, adjusted for likely underreporting. Janitors and cleaners (625/million) and firefighters (300/million) had the highest reporting rates of work-related asthma. Half of all work-related asthma cases were associated with agents not known to be allergens. CONCLUSIONS: A greater proportion of work-related asthma associated with irritant exposures was identified than has previously been reported. The surveillance data provide a very conservative estimate of the incidence of work-related asthma.

Adult↗
PubMed2001

The influence of sex, allergic rhinitis, and test system on nasal sensitivity to airborne irritants: a pilot study.

"Nasal irritant sensitivity" is an important construct in environmental health science; functional measures, however, lack standardization. We performed duplicate measures of nasal irritant perceptual acuity on 16 subjects (evenly divided by sex and seasonal allergy status) using two different test compounds: carbon dioxide (CO2) (detection) and n-propanol (localization). The a priori hypotheses included a) allergic rhinitics will display lower perceptual thresholds than nonrhinitics; b) females will display lower perceptual thresholds than males; and c) estimates of perceptual acuity using the two test systems will be positively correlated. We obtained CO2 detection thresholds using an ascending concentration series, presenting 3-sec pulses of CO2, paired with air in random order, by nasal cannula. We obtained localization thresholds by simultaneously presenting stimuli (ascending concentrations of n-propanol vapor in air) and blanks (saturated water vapor in air) to opposite nostrils, with laterality randomized. In terms of test-retest reliability, individual replicate measures for CO2 detection thresholds correlated more closely than did the localization thresholds of volatile organic compounds (VOC) (r = 0.65 and r = 0.60, respectively). As an intertest comparison, log-transformed individual mean CO2 and VOC measures were positively correlated with an r of 0.63 (p < 0.01). In univariate analyses, sex predicted both log-transformed CO2 and VOC thresholds (females being more "sensitive"; p < 0.05 and 0.001, respectively). Nasal allergies predicted sensory testing results only in the multivariate analysis, and then only for VOC localization (p < 0.05). The question of population variation in nasal irritant sensitivity (as well as the generalizability of results across test compounds) deserves further attention.

1-Propanol↗
PubMed1998

Occupation, asthma, and chronic respiratory symptoms in a community sample of older women.

We evaluated the role of occupational factors on the prevalence of self-reported asthma, chronic bronchitis, and asthma-like respiratory symptoms among women >= 55 yr. Occupational history, smoking, and respiratory conditions were collected through an interviewer-administered questionnaire from 1,226 women. Lung function data from 820 subjects were used for group "validation" of the outcome variables. Significant associations were observed between the respiratory conditions and occupational groupings based on the longest occupation held. Artists, writers, decorators, and photographers (odds ratio [OR] = 3.1), and women in service occupations (OR = 2.4) had a significantly increased risk of asthma. The odds of asthma-like symptoms was significantly elevated among nurses and other nonphysician health workers (OR = 2.9), social workers (OR = 2.9), and homemakers (OR = 2.4). Exposure to dusts, gas, vapors, fumes, or sensitizers was associated with a significantly increased odds of asthma (OR = 1.8) and with a marginally significant increased odds of asthma-like symptoms (OR = 1.4). Smoking accounted for a large proportion of asthma and asthma-like conditions in this population (population attributable risk [PAR] = 40.5% and 35.0%, respectively); employment in occupations with a high probability of exposures to dusts, gas, vapors, fumes, or sensitizers also contributed significantly to the burden of asthma (PAR = 15.1 to 20.0%) and asthma-like symptoms (PAR = 7.5 to 10.2%).

Aged↗
PubMed1998

The validity of radiographic estimation of total lung capacity in patients with respiratory disease.

STUDY OBJECTIVE: To evaluate the validity of a state-of-the-art computerized planimetry technique for estimation of total lung capacity (TLC) from chest radiographs, when applied to patients with clinical lung disease receiving routine chest radiographs. DESIGN: Retrospective clinical survey. SETTING: An occupational medicine diagnostic clinic. PATIENTS: A convenience sample of 40 subjects with asbestos-related lung disease, 5 patients with nonasbestos-related restrictive defects, 15 subjects with occupational asthma, and 10 subjects with irritant tracheobronchitis. RESULTS: Estimation of TLC using state-of-the-art computerized algorithms demonstrated limited agreement with conventional measures of TLC when applied to patients with occupational lung disease receiving routine chest radiographs. The most pronounced differences occurred in patients with asbestos-related lung disease and restrictive defects, where the radiographic method of measurement significantly overestimated helium dilution TLC by 986 mL (r=0.73, p<0.001) and 1,135 mL (r=0.82, p<0.05), respectively. Good inspiratory effort was associated with significantly increased radiographic TLC relative to helium dilution TLC; however, radiographic features did not fully account for the observed differences between radiographic and helium dilution techniques. CONCLUSIONS: Our findings suggest that this planimetric technique should not be used as a substitute for conventional measures of TLC in clinic populations receiving routine radiographs. The large diagnostic group specific mean differences observed between radiographic and conventional measures of TLC also suggest that this method is of limited utility in clinical evaluation of occupational lung disease.

Adult↗
PubMed1998

Variability in the classification of radiographs using the 1980 International Labor Organization Classification for Pneumoconioses.

This study describes the extent of agreement in classification of chest radiographs using the International Labor Organization (ILO) classification among six readers from the United States and Canada. A set of 119 radiographs was created and read by three Canadian and three US readers. The two ratings of interest were profusion (scored from 0/- to 3/+) and pleural abnormalities consistent with pneumoconiosis (scored with the ILO system, then collapsed into a yes/no). We used a number of approaches to evaluate interreader agreement on profusion and pleural changes, determining concordance, observed agreement, kappa statistic, and a new measure to approximate sensitivity and specificity. This study found that five of six readers had good fair to good agreement for pleural findings and for profusion as a dichotomous variable (> or = 1/0 vs < or = 0/1) using the kappa statistic, while a sixth reader had poor agreement. We found that concordance, expressed as percent agreement, was higher for normal radiographs than for ones that showed disease, and describe the use of the kappa statistic to control for this finding. This analysis adds to the existing literature with the use of the kappa statistic, and by presenting a new measure for "underreading" and "overreading" tendencies.

Humans↗
PubMed1998

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part I: Variability of pulmonary function measures.

The acute and subacute effects of ambient concentrations of ozone on lung function have been studied extensively in a variety of settings. Such studies generally have focused on measures of function that reflect either lung volumes or flows that are influenced by the physiology of large and small airways (e.g., forced expiratory volume in one second [FEV1). Data from animal studies suggest that the effects of prolonged exposure to elevated ambient concentrations of ozone result in abnormalities in the centriacinar region of the lung; and dosimetry models for humans predict that long-term exposure to ozone could impact the same areas of the human lung. However, alterations in structure at this level of the lung are not well reflected by measuring FEV1 until substantial structural changes have occurred. Measures of the lung function that reflect the functional mechanics of airways smaller than 2 mm in diameter are considered to be more relevant. At least one epidemiologic study has provided evidence that small-airway functions may be relevant to effects of prolonged exposure to environments with high concentrations of oxidants. A considerable body of physiologic data has established that flow rates measured during the terminal portion of a maximum expiratory flow-volume (MEFV) curve are largely governed by airways smaller than 2 mm in diameter A similar interpretation has been given to changes in the slope of phase III (delta N2) of the single-breath nitrogen washout (SBNW) curve. Despite the attractiveness of these measures in relation to airway physiology, some data suggest that measurements of flow via the terminal portions of MEFV and SBNW curves have much greater within-subject variability than forced vital capacity (FVC and FEV1. The present study was undertaken as part of a larger feasibility study to develop methods to study the effects of prolonged exposure to elevated ambient ozone levels on lung function in adolescents. A convenience sample of 239 freshmen (ages 16-20 years) entering the University of California, Berkeley were recruited to participate in this protocol. All were lifelong residents of the San Francisco Bay Area or the Los Angeles Basin. Subjects were studied on two occasions five to seven days apart. At each test session, subjects performed up to eight forced expiratory maneuvers to produce three acceptable and reproducible MEFV curves by modified American Thoracic Society criteria. Tests of SBNW were then performed on the basis of detailed criteria for validity and reproducibility. Eight attempts to generate three curves were allowed. The delta N2 was obtained by a least-squares regression of nitrogen concentrations between the 750-mL and 1750-mL volume points. Instantaneous flow at 75% of expired volume (FEF75%), average flow between the 25% and 75% volume points (FEF25%-75%), and delta N2 were the principal outcomes. Variance components were estimated with a nested random effects model with adjustments for important covariates. The average within-subject coefficients of variation (+/-SD of distribution of means) for male subjects were: FEV1 1.2 (+/-0.8); FEF25%-75% 3.2 (+/-2.3); FEF75% 5.8 (+/-5.0); and delta N2 17.9 (+/-12.3); for female subjects they were: FEV1 1.4 (+/-0.9); FEF25%-75% 3.0 (+/-2.2); FEF75% 6.2 (+/-5.2); and delta N2 19.9 (+/-17.0). The variance attributed to test session was less than 1% for all measures. The percentages of variance due to within-subject variation for each measure (adjusted for sex, area of residence, ethnicity, and height) were: FVC 3.6%; FEV1 3.0%; FEF25%-75% 5.2%; FEF75% 8.9%; and delta N2 23.9%. Of all subjects tested, 234 (97.9%) could provide at least two acceptable MEFV curves, but only 218 (91.2%) could provide at least two acceptable SBNW curves. The results were unchanged by recent history of acute, respiratory illness.(ABSTRACT TRUNCATED)

Air Pollution↗
PubMed1998

Methods development for epidemiologic investigations of the health effects of prolonged ozone exposure. Part II. An approach to retrospective estimation of lifetime ozone exposure using a questionnaire and ambient monitoring data (California sites).

An extensive body of data supports a relation between acute exposures to ambient ozone and the occurrence of various acute respiratory symptoms and changes in measures of lung function. In contrast, relatively few data are available on the human health effects that result from long-term exposure to ambient ozone, Current efforts to study long-term ozone-related health effects are limited by the methods available for ascertaining lifetime exposures to ozone. The present feasibility study was undertaken as part of the Health Effects Institute's Environmental Epidemiology Planning Project (Health Effects Institute 1994) to (1) determine whether, in the context of an epidemiologic study, reliable estimates can be obtained for lifetime exposures to ozone by combining estimates from lifetime residential histories, typical activity patterns during life, and residence-specific ambient ozone monitoring data; (2) identify the minimum data required to produce reliable estimates of lifetime exposure; and (3) analyze the relations between various estimates of lifetime ozone exposure and measures of lung function. A convenience sample of 175 first-year students at the University of California, Berkeley, who lived all of their lives in selected areas of California (the Los Angeles Basin or the San Francisco Bay Area), were studied on two occasions (test and retest or test sessions 1 and 2), five to seven days apart. Residential and lifestyle data were obtained from a questionnaire: residence-based ambient ozone exposure values were assigned by interpolation of ambient ozone monitoring data to residential locations. Estimated lifetime exposure was based on average ozone levels between 10 a.m. and 6 p.m. and hours of exposure to ozone concentrations greater than 60 parts per billion (ppb). "Effective" lifetime exposure to ozone was based on a weighted average of estimated time spent in different ambient ozone environments as determined by different combinations of activity data. Pulmonary function was evaluated with flows and volumes from maximum expiratory flow-volume curves and slope of phase III of the single-breath nitrogen washout (SBNW) curves. Although the test-retest reliability of the residential history was acceptably high only for first and second residences, most of the unreliability for other residences came from residences occupied for relatively short durations. Therefore, the test-retest reliability of estimated lifetime exposure to ozone was high, with intraclass correlations greater than 0.90 for all approaches evaluated. Multiple, linear regression analyses showed a consistently negative relation between estimates of lifetime exposure to ozone and flows that reflect the physiology of pulmonary small airways. No relation was observed between lifetime ozone exposure and forced expiratory volume or the slope of phase III, and the relation between lifetime exposure and forced expiratory volume in one second was inconsistent. The results of the flow measures were unaffected by the method used to estimate lifetime exposure and gave effect estimates that were nearly identical. The data from this study indicate that useful and reproducible estimates of lifetime ozone exposure can be obtained in epidemiologic studies by using a residential history. However, the total burden of ozone to which the subjects were exposed cannot be determined accurately from such data. Nonetheless, the estimates so obtained appear to be associated with alterations in pulmonary function that are consistent with the predicted site of maximum effect of ozone in the human lung.

Air Pollution↗
PubMed1997

The CARET asbestos-exposed cohort: baseline characteristics and comparison to other asbestos-exposed cohorts.

The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.

Asbestos↗
PubMed1997

Lobe of origin and histologic type of lung cancer associated with asbestos exposure in the Carotene and Retinol Efficacy Trial (CARET).

Lower lobe origin and histologic diagnosis of adenocarcinoma have been described as useful parameters for attributing lung cancer to prior asbestos exposure. To assess whether these characteristics differed between asbestos-exposed individuals and smokers, we evaluated lobe of origin and histologic type of tumors in 78 asbestos-exposed and 214 nonexposed heavy smokers developing lung cancer during the Carotene and Retinol Efficacy Trial (CARET), a prospective cancer chemoprevention trial. Most tumors in both cohorts, regardless of radiographic fibrosis at baseline, originated in upper lobes, representing 67% in asbestos-exposed and 80% in smokers, respectively (adjusted OR for lower lobe = 1.41; 95% CI = 0.69-2.91). Adenocarcinoma represented 32% of lung tumors in the asbestos cohort, and 30% in the smoking cohort (adjusted OR = 0.78; 95% CI = 0.40-1.55), and was inversely associated with radiographic fibrosis (adjusted OR = 0.19; 95% CI = 0.06-0.62). We conclude that neither anatomic site nor histologic cell type of tumors distinguishes effectively between smoking and asbestos as causal factors in development of lung cancer.

Adenocarcinoma↗
PubMed1997

Association between lifetime ambient ozone exposure and pulmonary function in college freshmen--results of a pilot study.

Human health effects due to chronic exposure to ozone (O3) have not been established due to problems with exposure assignment and the use of measures of lung function which may not reflect the site of O3 toxicity in the lung. We investigated the feasibility of retrospective assessment of O3 exposure-relevant covariates and derived lifetime "effective exposure" to ozone. Mid- and end-expiratory flows (FEF25-75%, FEF75%) were regressed against effective exposure and ecological lifetime exposure. A convenience sample of 130 UC Berkeley freshmen, ages 17-21, participated twice in the same tests (residential history, questionnaire, pulmonary function), 5-7 days apart. Students had to be lifelong residents of Northern (SF) or Southern (LA) California. Monthly ambient O3 concentrations (OZ) were assigned based on the lifetime residential history. An "effective time" (T) spent in OZ environments was derived for each residence and age stratum (0-2, 3-5, 6-11, 12+) with the use of questions about "total time spent outdoors" and time spent in "moderate" and/or "heavy" activity. Effective exposure was calculated over the lifetime (OZ x T) of each subject. Ozone metrics used were 8-hr averages (10 AM-6 PM) and "hours above 60 ppb." FEF25-75% and FEF75% decreased with both effective exposure and ecologic assignment of O3 exposure. For a 20 ppb increase (interquartile range) in 8-hr O3, FEF75% decreased 334 ml/sec (95%Cl:11-657 ml/sec), which corresponds to 14% (1.0-28.3%) of the population mean FEF75%. The corresponding effect on FEF25-75% was -420 ml/sec (95%Cl: +46 to -886, P = 0.08) or 7.2% of the mean. Use of time-activity data to define exposure had no impact on estimates. Negative confounding factors were region (SF vs LA), gender, and ethnicity. Lifetime 8-hr average O3 concentrations ranged from 16 to 74 ppb with little overlap between regions. There was no evidence for different O3 effects across regions. Effects were independent of lifetime mean PM10, NO2, temperature, or humidity. Effects on FEV1 tended to be negative whereas those for FVC, although negative in some models, where inconsistent and small. The strong relationship of lifetime ambient O3 on mid- and end-expiratory flows of college freshmen and the lack of association with FEV1 and FVC are consistent with biologic models of chronic effects of O3 in the small airways. Since the present study was designed as a pilot study, these findings have to be confirmed in a larger sample that is representative of the target population.

Adolescent↗
PubMed1997

Reproducibility of retrospective assessment of outdoor time-activity patterns as an individual determinant of long-term ambient ozone exposure.

BACKGROUND: Long-term effects of ambient ozone pollution are not clearly established to date. Epidemiological assessment of these effects might benefit from improved exposure measures. Tools to retrospectively assess long-term time-activity patterns as a potentially important co-predictor of true exposure have not yet been developed. METHODS: Three self-completed questionnaires for the retrospective assessment of outdoor time-activity patterns were tested in 168 lifelong residents (ages 17-21) of California. A test-retest design (within 5-7 days) was employed. (1) Based on a set of questions (AQUES) on outdoor 'heavy' and 'moderate' activity, h/day engaged in activity were derived. Definition of activity levels was based on published data regarding energy expenditure of physical activities. (2) A table format (ATAB) asked quantitative questions for each activity engaged in. (3) A 24-hour-log (A24H) had to be completed to indicate time spent outdoors in four levels of activity (heavy, moderate, light, at rest) on a 'typical day' (n = 44). Test-retest reliability was assessed. Comparison across approaches was restricted to the subgroup of 44 students that completed all three approaches. RESULTS: All approaches yielded reasonably reliable results (between-test variance 13-39% of total variance, Spearman rank correlations: 0.68-0.86 for time spent in outdoor activities). Population mean values differed across approaches, ranging from 1.0 (ATAB) to an unrealistically high estimate of 3.5 (A24H) h/day. The ATAB mean values were close to expectations when compared to published data. CONCLUSIONS: The structure of ATAB has major advantages and mean results were the most valid estimates compared to California population data. The AQUES is a less transparent 'black box' measure of exposure. For long-term retrospective time-activity assessment, we propose to use ATAB. For shorter recall periods the easier AQUES may be a reasonable alternative, yielding similar results as ATAB. The A24H was of limited value.

Adolescent↗
PubMed1997

Tuberculosis in health care settings and the estimated benefits of engineering controls and respiratory protection.

Intra-institutional spread of tuberculosis (Tb) has re-emerged as a substantial public and occupational health threat. To characterize the person-hours and lifetime risks of Tb-related morbidity and mortality, we performed a risk assessment for health care workers (HCWs) developing Tb-related morbidity and mortality at varying levels of exposure, engineering controls, and respiratory protection. Under average conditions of exposure, one Tb skin-test conversion is estimated to occur for every 2650 person-hours of work by unprotected workers. With higher exposures, a skin-test conversion for an unprotected worker may occur in as few as 3 person-hours. Use of respiratory protection is estimated to reduce risks by the following proportions: surgical mask, 2.4-fold; disposable dust, fume, mist, or disposable high-efficiency particulate air filtering (HEPA) mask, 17.5-fold; elastomeric HEPA cartridge respirator, 45.5-fold; or powered air-purifying respirator (PAPR), 238-fold. Assuming a lifetime exposure of 250 hours, the risk of a skin-test conversion is estimated to be 9%. We conclude that HCWs are at substantial risk for Tb-related morbidity and mortality, and that administrative controls, engineering controls, and respirators offer substantial benefits in risk reduction.

Humans↗
PubMed1996

Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

Anticarcinogenic Agents↗
PubMed1996

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Aged↗
PubMed1996

Differential regulation of airway epithelial integrins by growth factors.

The pattern of integrin expression on human airway epithelium changes significantly in injury or inflammation. In particular, two integrins, the fibronectin receptor, alpha 5 beta 1 and the fibronectin/tenascin receptor alpha v beta 6, are expressed at low or undetectable levels in normal airways in vivo but are induced in response to airway epithelial injury. We investigated the effects of various growth factors known to be present in the airways on the expression of constitutively expressed and inducible airway epithelial integrins using flow cytometry. In primary cultures of human airway epithelial cells, transforming growth factor-beta 1 (TGF beta 1) dramatically increased expression of alpha v beta 6 and essentially did not affect the expression of any other integrin, including alpha 5 beta 1. In contrast, epidermal growth factor (EGF) upregulated surface levels of both alpha v beta 6 and alpha 5 beta 1. Together, TGF beta 1 and EGF had an additive effect on alpha v beta 6 and alpha 5 beta 1 expression while increasing levels of alpha 2 beta 1 and decreasing expression of alpha 3 beta 1- and alpha 6-containing integrins. In contrast, the transformed airway epithelial cell line, BEAS-2B, expressed a markedly different repertoire of integrins. Integrin expression on BEAS-2B cells was not affected by any of the growth factors tested in this study. These results demonstrate that, in primary cultures of human airway epithelial cells, the pattern of integrin expression can be dramatically altered by growth factors. The inducible integrins, alpha v beta 6, and alpha 5 beta 1 are most subject to regulation by growth factors and expression of each of these can be differentially regulated. The differential regulation of the two principal fibronectin receptors on airway epithelial cells suggests that they may mediate different cellular responses to fibronectin.

Antibodies, Monoclonal↗
PubMed1996

Longitudinal pattern of reported respiratory symptoms and accelerated ventilatory loss in asbestos-exposed workers.

Studies investigating the relation between respiratory symptoms and change in ventilatory function have been limited by use of reported symptoms at a single point in time. To assess the relation between the longitudinal pattern of reported cough, phlegm, wheeze, and dyspnea and ventilatory loss, we prospectively investigated changes in FVC and FEV1 associated with development, resolution, or persistence of these symptoms over a 3- to 5-year period in 446 asbestos-exposed workers. Longitudinally reported symptoms changed frequently, with 52 to 61% of subjects reporting a specific symptom noting resolution or development of that symptom during follow-up. Initially reported symptoms were not predictive of accelerated loss of FVC or FEV1. In contrast, development of any new respiratory symptom, and to a lesser extent persistence of symptoms during follow-up, were associated with significantly greater ventilatory losses compared with asymptomatic individuals, ranging from 28 mL/yr in FEV1 for newly developed dyspnea, to 67 mL/yr in FVC for developed wheeze (p < 0.01). We conclude that development or persistence of respiratory symptoms over time, rather than the presence of symptoms per se, is predictive of future ventilatory loss. Recognition of interval changes in symptom reporting during surveillance of asbestos-exposed workers may effectively identify groups at risk for progressive ventilatory impairment.

Aged↗