Epidemiology and costs of COPD.
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Costs and Cost Analysis↗
Biomedical subjects
J R Balmes
Publications and source records attributed to J R Balmes.
Antioxidant intake, GSTM1 polymorphism and pulmonary function in healthy young adults.
Dietary antioxidants may protect lung tissue against reactive oxygen species-induced injury, adverse respiratory effects and reduced pulmonary function. Genetic variability in antioxidant enzymes also determines response to oxidative stress in the lung. The current authors evaluated whether lung function levels are associated with dietary intake of antioxidants and the glutathione S-transferase M1 (GSTM1) polymorphism. The current study cohort consisted of healthy, nonsmoking freshmen students who were lifetime residents in the Los Angeles or the San Francisco Bay areas (CA, USA). Participants completed comprehensive residential history, health history and food frequency questionnaires. Blood for genotyping was collected and forced expiratory volume measurements were obtained. Dietary vitamin C, magnesium and daily fruit servings were associated positively with forced expiratory volume in one second in males and with maximum mid-expiratory flow, forced expiratory flow after 75% of expelled volume, and the ratio of maximum mid-expiratory flow to forced vital capacity in females. In multivariable regression, vitamin C (or fruit for male students) and magnesium showed a consistent, positive association with lung function. Among healthy female adolescents, dietary intake of vitamin C is associated with increased levels of lung function. The current study does not support a role for the glutathione S-transferase M1-null genotype as an independent risk factor for decrements in lung function.
Adolescent↗
Area-level socio-economic status and health status among adults with asthma and rhinitis.
Socio-economic status (SES) may affect health status in airway disease at the individual and area level. In a cohort of adults with asthma, rhinitis or both conditions, questionnaire-derived individual-level SES and principal components analysis (PCA) of census data for area-level SES factors were used. Regression analysis was utilised to study the associations among individual- and area-level SES for the following four health status measures: severity of asthma scores and the Short Form-12 Physical Component Scale (SF-12 PCS) (n = 404); asthma-specific quality of life (QoL) scores (n = 340); and forced expiratory volume in one second (FEV1) per cent predicted (n = 218). PCA yielded a two-factor solution for area-level SES. Factor 1 (lower area-level SES) was significantly associated with poorer SF-12 PCS and worse asthma QoL. These associations remained significant after adding individual-level SES. Factor 1 was also significantly associated with severity of asthma scores, but not after addition of the individual-level SES. Factor 2 (suburban area-level SES) was associated with lower FEV1 per cent predicted in combined area-level and individual SES models. In conclusion, area-level socio-economic status is linked to some, but not all, of the studied health status measures after taking into account individual-level socio-economic status.
Adolescent↗
The association between occupational factors and adverse health outcomes in chronic obstructive pulmonary disease.
BACKGROUND AND AIMS: Despite recognition that occupational exposures may make a substantive contribution to the aetiology of COPD, little is known about the potential role of work related factors in COPD related health outcomes. METHODS: Prospective cohort study using structured telephone interviews among a random sample of adults aged 55-75 reporting a COPD condition (emphysema, chronic bronchitis, or COPD). Using multivariate models adjusting for smoking and demographic factors, the separate and combined associations were estimated between occupational exposure to vapours, gas, dust, or fumes (VGDF) and leaving work due to lung disease (respiratory related work disability) with health outcomes and utilisation ascertained at one year follow up. RESULTS: Of 234 subjects, 128 (55%) reported exposure to VGDF on their longest held jobs, 58 (25%) reported respiratory related work disability, and 38 (16%) subjects reported both. Combined exposure to VGDF and respiratory related work disability (rather than either factor alone) was associated with the greatest risk at follow up of frequent (everyday) restricted activity days attributed to a breathing or lung condition (OR 3.8; 95% CI 1.4 to 10.1), emergency department (ED) visit (OR 3.9; 95% CI 1.4 to 10.5), and hospitalisation (OR 7.6; 95% CI 1.8 to 32). CONCLUSIONS: Among persons with COPD, past occupational exposures and work disability attributed to lung disease, particularly in combination, appear to be risk factors for adverse health related outcomes.
Aged↗
The occupational burden of chronic obstructive pulmonary disease.
Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need. A randomly selected sample of 2,061 US residents aged 55-75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis. After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (CI) 1.6-2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% CI 13-27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% CI 1.1-2.5) for high and 1.4 (95% CI 1.1-1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% CI 3-15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% CI 19-41%). Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.
Aged↗
Occupational respiratory diseases.
The respiratory tract is often the site of injury from occupational exposures because it has direct contact with the ambient environment. Inhalation of potentially toxic materials in the workplace can lead to all major lung diseases with the exception of pulmonary vascular ones. New materials are being introduced into the workplace at a rate faster than their potential toxicities can be evaluated, and some are found to cause lung disease. Therefore, the possibility of occupational lung disease should be considered whenever a working or retired person has unexplained respiratory illness.
Diagnostic Techniques, Respiratory System↗
Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release.
Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p<0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.
Adult↗
Effect of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte subsets.
Nitrogen dioxide (NO2) is a free radical-producing oxidant gas. Inhalation of NO2 could cause airway inflammation, and decrease immune function. This experiment tested the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage (BAL); and 2) change the distribution of lymphocyte subsets and activation in BAL and peripheral blood (PB). Using a counter-balanced, repeated-measures design, 15 healthy volunteers were exposed to filtered air (FA) or 2.0 parts per million NO2 for 4 h x day(-1) (4 x 30 min of exercise), for three consecutive days. Bronchoscopy was performed 18 h following each exposure set, and PB was drawn pre-exposure and pre-bronchoscopy. Flow cytometry was used to enumerate lymphocyte subsets and activation makers in BAL and PB. In the bronchial fraction, there was an increase in the percentage of neutrophils following NO2 exposure compared to FA (median (interquartile range): 10.6 (4.8-17.2)% versus 5.3 (2.5-8.3)%; p=0.005). In the BAL, there was a decrease in the percentage of T-helper cells following NO2 exposure compared to FA (55.9 (40.8-62.7)% versus 61.6 (52.6-65.2)%; p=0.022). For PB, there were no between-condition differences in any leukocyte or lymphocyte subsets, or activation. In conclusion exposure to nitrogen dioxide results in bronchial inflammation and a minimal change in bronchoalveolar lavage T-helper cells, and no changes in peripheral blood cells.
Adult↗
Government laboratory worker with lung cancer: comparing risks from beryllium, asbestos, and tobacco smoke.
Occupational medicine physicians are frequently asked to establish cancer causation in patients with both workplace and non-workplace exposures. This is especially difficult in cases involving beryllium for which the data on human carcinogenicity are limited and controversial. In this report we present the case of a 73-year-old former technician at a government research facility who was recently diagnosed with lung cancer. The patient is a former smoker who has worked with both beryllium and asbestos. He was referred to the University of California, San Francisco, Occupational and Environmental Medicine Clinic at San Francisco General Hospital for an evaluation of whether past workplace exposures may have contributed to his current disease. The goal of this paper is to provide an example of the use of data-based risk estimates to determine causation in patients with multiple exposures. To do this, we review the current knowledge of lung cancer risks in former smokers and asbestos workers, and evaluate the controversies surrounding the epidemiologic data linking beryllium and cancer. Based on this information, we estimated that the patient's risk of lung cancer from asbestos was less than his risk from tobacco smoke, whereas his risk from beryllium was approximately equal to his risk from smoking. Based on these estimates, the patient's workplace was considered a probable contributing factor to his development of lung cancer.
Aged↗
Occupational asthma: a review.
Occupational asthma is the most common form of occupational lung disease in the developed world at the present time. In this review, the epidemiology, pathogenesis/mechanisms, clinical presentations, management, and prevention of occupational asthma are discussed. The population attributable risk of asthma due to occupational exposures is considerable. Current understanding of the mechanisms by which many agents cause occupational asthma is limited, especially for low-molecular-weight sensitizers and irritants. The diagnosis of occupational asthma is generally established on the basis of a suggestive history of a temporal association between exposure and the onset of symptoms and objective evidence that these symptoms are related to airflow limitation. Early diagnosis, elimination of exposure to the responsible agent, and early use of inhaled steroids may play important roles in the prevention of long-term persistence of asthma. Persistent occupational asthma is often associated with substantial disability and consequent impacts on income and quality of life. Prevention of new cases is the best approach to reducing the burden of asthma attributable to occupational exposures. Future research needs are identified.
Air Pollutants, Occupational↗
Subjects with seasonal allergic rhinitis and nonrhinitic subjects react differentially to nasal provocation with chlorine gas.
BACKGROUND: Nasal irritation and associated symptoms (nasal congestion, rhinorrhea, and sinus headache) are important elements of the response to indoor and outdoor air pollution. Marked interindividual variability in such symptoms has been suggested clinically and epidemiologically, but little experimental data exist on this issue. OBJECTIVE: We sought to test the hypothesis that subjects with seasonal allergic rhinitis (SAR) exhibit a more marked physiologic response (congestion) after nasal irritant provocation than do nonrhinitic subjects. METHODS: We studied eight subjects with SAR and eight nonrhinitic subjects; subjects with SAR were studied out of season. In a single-blind crossover study, subjects had their nasal airway resistance (NAR) measured in triplicate before, immediately after, and 15 minutes after a 15-minute exposure to either filtered air or 0.5 ppm chlorine in filtered air, administered through a nasal mask in a climate-controlled chamber. Log-transformed NAR values were analyzed in a repeated-measures analysis of variance model, with confirmatory testing using paired t tests. RESULTS: The net (chlorine minus air day) percent change in NAR from baseline (before exposure) to immediately after exposure was +24% in the SAR group and +3% in the nonrhinitic group (p < 0.05). The corresponding net changes from baseline to 15 minutes after exposure were +21% in the SAR group and -1% in the nonrhinitic group (p < 0.05). CONCLUSIONS: The observed augmented nasal congestive response of subjects with SAR versus nonrhinitic subjects to a controlled low-level chemical irritant provocation is consistent with epidemiologic surveys showing a higher prevalence of nasal symptoms among subjects with SAR than nonrhinitic subjects in environments involving irritant air pollutants.
Chlorine↗
Ozone-induced inflammation is attenuated with multiday exposure.
It is well known that ozone (O3) causes acute lung inflammation. What is not known is whether there is progression of the inflammatory response in humans with repeated short-term exposures. Our study was designed to test the hypothesis that repeated exposures to a high-ambient concentration of O3 (0.2 ppm) over several days would cause more inflammation than a single exposure. Fifteen healthy volunteers were exposed in random fashion to 0.2 ppm ozone for 4 h on a single day and to 0.2 ppm O3 for 4 h on 4 consecutive days while exercising moderately for 30 min of each hour. Pulmonary function tests were obtained immediately before and after each 4-h exposure. Bronchoscopy was performed 20 h after the completion of each exposure arm to obtain bronchoalveolar lavage (BAL) for measurement of markers of inflammation. Our results show initial progression followed by attenuation of the acute physiologic response to O3 with repeated daily exposures. We found a significant difference in percent change in FEV1, FVC, and specific airway resistance (SRaw) across the single-day exposure when compared with the change across Day 4 of the 4-d exposure. Bronchial fraction (the first 15 ml of BAL return) and BAL were analyzed for the following end points: total and differential cell counts, total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-6 (IL-6), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In the bronchial fraction the number of polymorphonuclear cells (PMN)s and fibronectin concentration were significantly decreased after 4-d exposure compared with single-day exposure. In BAL, significant decreases in the number of PMNs, fibronectin, and IL-6 were found after 4-d exposure versus single-day exposure. These results suggest that there is attenuation of the O3-induced inflammatory response in both proximal airways and distal lung with repeated daily exposures.
Adult↗
The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort.
The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.
Aged↗
Effects of ozone on normal and potentially sensitive human subjects. Part I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects.
We report here the results of a multiphase project to assess the significance of airway responsiveness and airway injury in ozone (O3)* sensitivity. In Phase I, we measured the preexposure methacholine responsiveness of 66 normal subjects and then exposed these subjects to 0.2 ppm O3 for 4 hours with moderate exercise. Preexposure methacholine responsiveness was weakly correlated with O3-induced increases in specific airway resistance (sRaw) but not O3-induced declines in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). In addition, O3-induced lower respiratory symptoms were not well correlated with O3-induced changes in lung function. In Phase II, we exposed 23 normal subjects to O3, following an identical protocol to that of Phase I, and then performed bronchoscopy with proximal airway lavage (PAL), bronchoalveolar lavage (BAL), and bronchial biopsy at 18 hours after exposure. Ozone-induced increases in percentage of neutrophils and total protein concentration were observed in both bronchial fraction and BAL fluids; increased percentage of neutrophils also was observed in PAL fluid. These increases were correlated with O3-induced increases in sRaw, but not with O3-induced declines in FEV1 or FVC. Ozone also appeared to increase expression of intercellular adhesion molecule-1, an important mediator of neutrophil recruitment, in bronchial mucosa. In Phase III, we exposed a group of 19 asthmatic subjects to O3, following a protocol identical to that of Phase II. We then compared the lower respiratory symptom and lung function responses of the asthmatic subjects to those of the 81 normal subjects who participated in Phase I, Phase II, or both. The changes in the PAL and BAL fluids of the asthmatic subjects were compared with those of the normal subjects who participated in Phase II. Although both the asthmatic and nonasthmatic subjects showed significant O3-induced changes in lower respiratory symptoms, FEV1, FVC, and sRaw, no significant differences were found between the groups. For sRaw, however, a nonsignificant trend toward a greater O3-induced increase was noted for the asthmatic subjects. In contrast, the O3-induced increases in percentage of neutrophils and total protein concentration in BAL fluid were significantly greater for the asthmatic subjects than for the nonasthmatic subjects. These data suggest that although the lower respiratory symptom and lung function responses to O3 are not markedly greater in asthmatic subjects than in healthy subjects, the inflammatory response of the asthmatic lung may be more intense.
Adolescent↗
Effects of ozone on normal and potentially sensitive human subjects. Part III: Mediators of inflammation in bronchoalveolar lavage fluid from nonsmokers, smokers, and asthmatic subjects exposed to ozone: a collaborative study.
To provide bases of comparison between the studies described in Parts I and II of this Research Report, concentrations of interleukin 6 (IL-6)*, interleukin 8 (IL-8), and alpha 2-macroglobulin (a2M) were measured in airway lavage fluids obtained in the Balmes study (Part I) and compared with the same measurements in the Frampton study (Part II). For healthy subjects in the Balmes study, IL-6 and a2M, but not IL-8, increased in association with ozone exposure. Statistical analyses suggested that effects of ozone on IL-8 levels observed in the first exposure and bronchoscopy may have carried over to the second exposure and bronchoscopy, which may have obscured an effect of ozone on IL-8 after the second exposure. For asthmatic subjects in the Balmes study, IL-6 and IL-8 increased in both bronchial and alveolar lavage fluid, but not in proximal airway lavage fluid. The mean interval between exposures was longer for asthmatic subjects than for healthy subjects, and no carryover effects were seen. When the Balmes and Frampton data were analyzed together, subject groups in the two studies (nonsmokers, smokers, and subjects without and with asthma) did not differ significantly in the response of cytokines to ozone exposure. The finding of possible carryover effects in one group suggests that subtle effects of ozone exposure, or bronchoscopy including proximal airway lavage and biopsy, or both, may persist for three weeks in some subjects.
Adolescent↗
Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.
In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.
Adult↗
Greater ozone-induced inflammatory responses in subjects with asthma.
In order to test the hypothesis that ozone (O3)-induced changes in lung function and respiratory tract injury/inflammation are greater in subjects with asthma than in normal subjects, we exposed 18 asthmatic subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and specific airway resistance [SRaw]) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with proximal airway lavage (PAL) of the isolated left main bronchus and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following endpoints: total and differential cell counts; total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), myeloperoxidase (MPO), and transforming growth factor-beta (TGF beta 2) concentrations. We found a significant O3 effect on FEV1, FVC, SRaw (p < 0.04) and lower respiratory symptoms (p < 0.001) for the asthmatic subjects. Ozone exposure also significantly increased the percent neutrophils in PAL (p < 0.01); percent neutrophils, total protein, and IL-8 in the bronchial fraction (p < 0.001, p < 0.05, and p < 0.01, respectively); and the percent neutrophils, total protein, LDH, fibronectin, IL-8, GM-CSF, and MPO in BAL (p < 0.001, p < 0.01, p < 0.01, p < 0.001, p < 0.05, p < 0.01, and p < 0.001, respectively) for the asthmatic subjects. There were no significant differences in the lung function responses of the asthmatic subjects in comparison with a group of normal subjects (n = 81) previously studied using an identical protocol, although there was a trend toward a greater O3-induced increase in SRaw in the asthmatic subjects (p < 0.13). In contrast, the asthmatic subjects showed significantly greater (p < 0.05) O3-induced increases in several inflammatory endpoints (percent neutrophils and total protein concentration) in BAL as compared with normal subjects who underwent bronchoscopy (n = 20). Our results indicate that asthmatic persons may be at risk of developing more severe O3-induced respiratory tract injury/inflammation than normal persons, and may help explain the increased asthma morbidity associated with O3 pollution episodes observed in epidemiologic studies.
Adolescent↗
Respiratory effects of occupational exposure to aerosolized pentamidine.
To determine the respiratory effects on health care workers of occupational exposure to aerosolized pentamidine (AP) used for the prophylaxis of Pneumocystis carinii pneumonia, we designed a clinical prospective study using subjects as their own controls. Sixteen health care workers whose job duties included administration of AP at one or more of nine San Francisco Bay Area medical centers participated in the study. Pentamidine concentrations ranged in breathing zone samples from < 0.03 to 62.2 micrograms/m3. Pentamidine was not detected in the urine of any of the subjects. There were no significant increases in symptoms on days when AP was administered. Cross-workshift spirometry on days when AP was administered showed a statistically significant mean decrease (0.14 liter) in forced expiratory volume in 1 second. There was no statistically significant difference in mean diurnal variation of peak expiratory flow rate on days when AP was administered. Methacholine inhalation challenge testing did not show a statistically significant mean change in airway responsiveness across the workweek. The ambient concentrations of pentamidine that we measured document that detectable occupational exposure to AP can occur in poorly ventilated treatment rooms. The cross-workshift decrement in forced expiratory volume in 1 second that we observed in association with AP administration supports the respiratory tract irritant potential of inhaled pentamidine. We recommend that steps be taken to minimize health care worker exposure to AP.
AIDS-Related Opportunistic Infections↗