Indacaterol/glycopyrronium bromide fixed-dose combination for the treatment of COPD.

Chronic obstructive pulmonary disease (COPD) is a worldwide problem causing prolonged and progressive morbidity as well as premature mortality. Pharmacologic treatment consists primarily in the relief of symptoms and preventing or minimizing the consequences of exacerbations. Central to the pharmacologic management of COPD is the use of bronchodilator therapy. Two major classes of agents are frequently used: ß-adrenoceptor agonists and antimuscarinic agents. These drugs are used mainly in the inhalational form, primarily as rescue medication, but occasionally for maintenance in combination therapy. The availability of "ultra-long"-acting ß-adrenoceptor agonists and long-acting antimuscarinic agents opens the way for combinations of these agents to be used in maintenance therapy. Such a combination offers the potential of enhanced efficacy due to additive effects and better compliance as the result of once-daily treatment. This article reviews the rationale for current bronchodilator therapy of COPD as well as the current status of a fixed-dose combined inhaler using two novel long-acting agents: glycopyrronium bromide and indacaterol maleate.

Response to oyster mushroom (Pleurotus ostreatus) extract by sensitized and nonsensitized guinea pig trachea.

Occupational exposure to oyster mushroom (Pleurotus ostreatus) has been associated with obstructive lung disease. Previously, we studied an extract of oyster mushroom (OME) and determined that it causes dose-dependent contractions of nonsensitized guinea pig trachea (GPT). We extend these studies to the investigation of sensitized tissue. In the present study 24 animals were sensitized using ovalbumin (OA) and subsequently challenged with an aerosol of 2.5% OA. A control group of 12 nonsensitized GPs was also studied. Tracheas were removed and were divided into rings in which the epithelium was retained (EP+) or removed (EP-). Dose-related contractions of sensitized and nonsensitized GPTs were elicited with OME. In nonsensitized animals the EP+ GPTs demonstrated a significantly greater response to OME (100-1000 µl) than did the EP- GPTs (p < 0.01). By contrast, in sensitized GPTs with and without epithelium there was no difference to challenge with OME. Finally, sensitized GPTs with and without epithelium and nonsensitized GPTs with epithelium responded similarly to challenge with OME. These findings suggest that in nonsensitized animals there is an enhancement of contractile response to OME which is in part mediated by the GPT epithelium. In sensitized animals with or without epithelium, the level of bronchoconstrictor response is similar to that of the nonsensitized animals with epithelium, suggesting an enhanced constrictor response independent of epithelium in the sensitized animals.

New ß2-adrenoceptor agonists for the treatment of chronic obstructive pulmonary disease.

ß-Adrenoceptor agonists are central to the management of chronic obstructive pulmonary disease (COPD). They contribute both as rescue medications and as controller agents. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines indicate that they are useful at all stages of the disease. Current use of ß-adrenoceptor agonists emphasizes the rapidity of their onset of action and the duration of their effect. The development of newer agents seeks to improve these properties. Concern about the side effects of ß-adrenoceptor agonists-has limited their use in asthma. In view of their potential for cardiovascular effects and the prevalence of comorbidities in COPD, careful attention needs to be given when using these agents in COPD patients.

Respiratory function in wind instrument players.

BACKGROUND: The playing of wind instruments has been associated with changes in respiratory function. STUDY OBJECTIVES: To investigate the effect of playing wind instruments on lung function and respiratory symptoms. METHODS: The present study included 99 wind instrument players and a group of 41 string instrument players as a control from 3 major orchestras in Zagreb, Croatia. Data on chronic respiratory symptoms were recorded in all studied subjects. Lung function was measured in wind instrument players by recording maximum expiratory flow-volume curves. RESULTS: Wind instrument players demonstrated significantly higher prevalences of sinusitis, nasal catarrh and hoarseness compared to control musicians. One wind instrument player developed asthma associated with his work. Odds ratios for wind instrument players were significant for chronic cough, chronic phlegm and chronic bronchitis by smoking habit (p<0.05 or p<0.01) but not for length of employment. Ventilatory capacity data indicate that wind instrument players had significantly greater FEV1 (smokers and nonsmokers) as well as FEF50 (nonsmokers) (p<0.05) compared to predicted values. Regression analysis of pulmonary function tests in wind instrument players demonstrate a significant link between FEV1 and FEF50 and length of employment. Those wind instrument players with longer employment had the greatest increases in lung function. CONCLUSIONS: Our data suggest that musicians playing wind instruments may be susceptible to chronic upper airway symptoms. Interestingly wind instrument playing may be associated with higher than expected lung function parameters.

Women in medicine through the ages.

BACKGROUND: Female practitioners of the medical arts have been active since the ancient world The role of women in science, and particularly in medicine, has changed significantly over time. METHODS: We provide a chronological review of the growing knowledge in medicine related to women's activities through the ages with particular attention to occupational medicine. Throughout history hazards have been shaped by the forces that shape work itself social evolution, shifting economic powers and demographic changes. RESULTS: Mythical Greece, Egypt and ancient Rome were the cradle of ancient medicine. In the past century, women were allowed to enter the medical profession with increasing acceptance. Some of the most important women in ancient and modern medicine are recalled, such as Mother Peseshet in ancient Egypt, Artemisia of Caria and Phanostrate and Philista in the Greek period, Hildegard of Bingen, Marie Marguerite Biheron in England, Elisabeth Blackwell, Emily Jennings, Maude E. Abbott and others. Women in occupational medicine are described separately, such as Alice Hamilton, Harriet L. Hardy, Molly Newhouse and Olga Macek. CONCLUSIONS: Certainly, the first few women who iluminated the way for the generations that followed them into medicine, the women who made outstanding contributions to medicine, and the women who are currently finding success in medicine deserve our respect and admiration.

Respiratory findings in art and medical students. Effects of the art environment.

BACKGROUND: Art students are exposed to many noxious agents during their training, in contrast to medical students, who are not exposed to known environmental pollutants. OBJECTIVES: In order to investigate the potential effects of toxic agents in the art students' environment, we studied respiratory findings in a cohort of 117 art students and 128 medical students, matched for age, sex and smoking. METHODS: Acute and chronic respiratory symptoms were evaluated by modifying the British Medical Research Council questionnaire. Lung function studies were performed with a spirometer (Jaeger, Germany) measuring maximum expiratory flow-volume (MEFV) curves. On these curves we calculated the forced vital capacity (FVC), one second forced expiratory volume (FEV1) and the maximal expiratory flow at 50% and the last 25% of the FVC (FEF50, FEF25). RESULTS: Significantly higher prevalences of most of the chronic respiratory symptoms were recorded in art students compared to medical students (p < 0.05). Art students who were smokers had significantly higher prevalences of many of the chronic respiratory symptoms than nonsmoking art students. Among medical students these differences were not statistically significant (NS). High prevalences of acute symptoms related to the study environment were recorded for art students. Odds ratios in male and female art students were significant for chronic cough, chronic phlegm and chronic bronchitis for the risk factor of smoking. Significantly decreased lung function values compared to predicted values were recorded mostly for FEF50 and FEF25 in male and female art students. Smoking and non-smoking art students had similar reductions of lung function. Lung function data in medical students were within predicted values. CONCLUSIONS: Our data indicate that art students may be at risk of developing chronic respiratory symptoms and lung function changes as a result of their environmental exposure and their smoking habits.

Pharmacological study of oyster mushroom (Pleurotus ostreatus) extract on isolated guinea pig trachea smooth muscle.

Mushroom farm workers suffer from respiratory symptoms during the farming of mushrooms. The objective of this study was to analyze the effects of oyster mushroom (Pleurotus ostreatus) extract (OME) on isolated guinea pig tracheal smooth muscle in vitro. Isolated guinea pig tracheal tissue from 27 nonsensitized guinea pigs were studied. The OME was obtained from indoor mushroom growing fields and prepared as a 1:10 w/v aqueous solution. Dose-related contractions of nonsensitized guinea pig trachea were demonstrated using these extracts. The OME contained significant quantities of bacterial components (eg., endotoxin: 43,072.92 EU/mg). Parallel, pharmacological studies were performed by pre-treating the tissues with mediator-modifying agents including atropine, indomethacin, pyrilamine, BPB, acivicin, NDGA, captopril, TMB8 and capsaicin. Atropine consistently and strikingly reduced the contractile effects of this extract. These observations suggest an interaction of the OME with parasympathetic nerves or more directly with muscarinic receptors. Pretreatment with TMB8 (inhibitor of intracellular calcium mobilization) also significantly blocked the constrictor effect of OME, indicating a role of calcium mobilization in the constricting effect of OME. Inhibition of contraction by blocking of other mediators was less effective and varied depending on the drug. We conclude that OME causes a dose-related airway smooth muscle constriction by nonimmunological mechanisms involving a variety of airway mediators and possibly cholinergic receptors. This effect is not dependent on pre-sensitization of the guinea pigs.

Gender related differences of low level exposure to occupational irritants--a three-year follow-up of chemical industry workers.

The authors followed changes in the ventilatory function in a group of 102 chemical workers over a three year period to evaluate gender related differences on respiratory effects of low concentrations of occupational irritants. Measurements were performed annually and the results of ventilatory test were compared to predicted normal values. Lung function was measured by recording maximum expiratory flow-volume (MEFV) curves. Baseline data show ventilatory function impairments of the obstructive-restrictive type, as measured by the Tiffeneau index and FEV1. After one and two years of exposure, impairment in flow rates at low lung volumes became prominent. Analysis of lung function in three years of the study suggests obstructive impairments mostly in the larger airways accompanied by a restrictive component. The ventilatory flow at low lung volumes was characterized by obstruction, but not by restrictive findings. Women appear to be more sensitive than men to the irritant effects of these exposures as measured by flow rates at low lung volumes--the smaller airways (FEF50% = 82.7 +/- 23.6 in women and FEF50% = 92.1 +/- 32.1 in men; p = 0.017), while men experienced greater changes than women to irritant effects on their ventilatory capacity--the large airways (FVC = 99.6 +/- 10.6 in men and FVC = 106.74 +/- 9.8 in women; p = 0.001). The additive effect of smoking to environmental irritation is demonstrated by the proportionately lower lung capacity in smokers. Overall, the effect of these pollutants in women is more synergistic than additive.

Respiratory findings in farmworkers.

This investigation was designed to study respiratory problems in farmworkers. To better define the consequences of this work environment on respiratory health, 814 farmworkers (738 male and 76 female) were studied. The mean age of the men in this study was 38 years, and the mean duration of their employment was 15 years. For women, the mean age was 44 years and the mean duration of their employment was 10 years. Of the men, 56.5% were regular smokers, and 23.7% of the women were regular smokers. A group of 635 control workers without significant exposure to air pollutants were matched by sex, age, employment, and smoking habit. The prevalence of chronic symptoms among male farmworkers was greater (P < 0.01) than among male control subjects for chronic cough (24.8% vs 11.4%), chronic phlegm (22.8% vs 9.1%), and chronic bronchitis (20.1% vs 7.4%). Among women farmworkers, a significant difference was noted with controls for chest tightness (farmworkers, 21.1%; control subjects, 0%; P < 0.001). There was a high prevalence of acute symptoms among male and female farmworkers. In particular, farmworkers complained of more frequent cough, eye irritation, dyspnea, and throat irritation than did control subjects. For respiratory symptoms in male and female farmworkers, odds ratios were generally significant for smoking, age, and duration of employment. Ventilatory capacity tests were significantly reduced for farmworkers compared with predicted values. Regression analysis of ventilatory capacity tests in male farmworkers as a percentage of predicted values demonstrated significant coefficients for employment and smoking. Our data suggest that farmworkers are exposed to noxious agents that cause respiratory symptoms and ventilatory capacity impairment.

Occupational airway diseases.

In this review we describe characteristics of occupational airway diseases, as well as physical and chemical characteristics of agents inducing airway disease. Occupational airway diseases include industrial bronchitis, reactive airway dysfunction syndrome, bronchiolitis obliterans, and occupational asthma. High- and low-molecular weight substances associated with occupational airway disease are listed. The importance of host factors is stressed. Diagnostic approaches, particularly indicators for specific challenge testing with occupational materials, are described. Preventive and control measures are presented.

Respiratory function in active firefighters.

BACKGROUND: Exposure to environmental pollution during firefighting may results in the development of respiratory disorders in firefighters. METHODS: The health effects of firefighting on respiratory function was investigated in a group of 128 active firefighters by recording respiratory symptoms and measuring lung function. In addition, 88 control workers, not exposed to known pollutants were studied for the prevalence of acute and chronic respiratory symptoms. RESULTS: Significantly higher prevalences of dyspnea, nasal catarrh, sinusitis, and hoarseness were recorded in firefighters compared to control workers (P < 0.01). One subject developed asthma symptoms following two intense firefighting episodes. A high prevalence of acute symptoms experienced during and after fire extinguishing was also documented among these firefighters. Eye and throat irritation as well as headache were prominent. A logistic regression analysis of chronic respiratory symptoms demonstrated that odds ratios were significant for both duration of work exposure and for smoking. Lung function testing demonstrated a decrease in FEF75 in relation to predicted suggesting obstructive changes in the smaller airways. A regression analysis of ventilatory capacity tests indicated a positive relationship of forced vital capacity with length of employment, 1 s forced expiratory volume as well as FEF50 were related to smoking, and FEF75 was related to both smoking and length of employment. CONCLUSIONS: Our data suggest that firefighters are at risk for developing acute and chronic respiratory symptoms as well as obstructive airway changes.

Respiratory findings in livestock farmworkers.

In this cross-sectional study, the prevalence of acute and chronic respiratory symptoms and lung function were investigated in 236 (169 male and 67 female) livestock farmworkers raising domestic animals, including cattle and horses. The prevalence of acute and chronic respiratory symptoms was recorded by administering a modified version of the British Medical Research Council questionnaire on respiratory symptoms. Lung function was measured by recording the maximum expiratory flow-volume curves from which the forced vital capacity, the one-second forced expiratory volume, and the maximum expiratory flow rates at 50% and the last 25% were measured. There was a significantly higher prevalence of almost all chronic respiratory symptoms in farmers compared with controls: highest among men for chronic cough (27.2%) and highest among women for dyspnea (28.3%). Typical symptoms of occupational asthma were diagnosed in 3.6% of the male and 1.5% of the female livestock farmers. A logistic regression analysis performed on chronic respiratory symptoms of livestock workers indicate significant effects of smoking (P < 0.001) on all symptoms except occupational asthma. A large number of male and female livestock farmworkers complained of acute work-related symptoms: highest for dry cough (52.2%) and shortness of breath (44.9%). Lung function data among these workers demonstrated a trend toward lower lung function in general. Multivariate analysis of lung function parameters indicate significant effects of length of employment and smoking in male and length of employment in female livestock farmworkers. The data suggest that employment in livestock farming may be associated in a dose-dependent manner with the development of acute and chronic respiratory symptoms and lung function changes.

Pharmacologic properties of brewery dust extracts in vitro.

STUDY OBJECTIVES: To study the effects of extracts of brewery dust on isolated guinea pig tracheal smooth muscle in vitro. DESIGN: Parallel pharmacologic intervention on guinea pig tracheal rings that were obtained from the same animal. SETTING: Mount Sinai School of Medicine, Department of Pulmonary Medicine. MATERIAL: The isolated guinea pig tracheal tissue of 18 guinea pigs. INTERVENTIONS: Pretreatment of guinea pig rings by mediator-modifying agents before challenge with the brewery dust extracts. MEASUREMENTS AND RESULTS: The effect of brewery dust extracts on isolated guinea pig tracheal smooth muscle was studied using water-soluble extracts of dust obtained from brewery materials, including hops, barley, and brewery yeast. Dust extracts were prepared as a 1:10 (wt/vol) aqueous solution. Dose-related contractions of nonsensitized guinea pig tracheas were demonstrated using these extracts. The dust extracts contained significant quantities of bacterial components (eg, endotoxin and n-formyl-methionyl-leucyl-phenylalanine), but these agents were not thought to contribute directly to the constrictor effect of the dusts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with the following drugs known to modulate smooth muscle contraction: atropine; indomethacin; pyrilamine; LY171883; nordihydroguaiaretic acid; captopril; thiorphan; verapamil; and TMB8. The constrictor effects of the dust extracts were inhibited by a wide variety of agents, the patterns of which depended on the dust extract. Atropine consistently and strikingly reduced the contractile effects of these extracts. These observations may suggest an interaction of the extracts with parasympathetic nerves or, more directly, with muscarinic receptors. The inhibition of contraction by the blocking of other mediators was less effective and varied with the dust extract. CONCLUSIONS: We suggest that brewery dust extracts cause a dose-related airway smooth muscle constriction by nonimmunologic mechanisms involving a variety of airway mediators and, possibly, cholinergic receptors. This effect is not dependent on presensitization of the guinea pigs.

Chronic endothelial dysfunction after oversized coronary balloon angioplasty in pigs: a 12-week follow-up of coronary vasoreactivity in vivo and in vitro.

Previous studies have reported the development of vasoconstriction immediately after invasive coronary interventions. Other studies in animals have demonstrated that using oversized balloon angioplasty, vasospasm can be suppressed, even in the presence of endothelial denudation due to important structural alteration in vascular smooth muscle. The regenerated endothelium also appears to be impaired chronically by selective attenuation of in vitro endothelial dependent relaxation related to pertussis toxin-sensitive G proteins. The purpose of this investigation was to verify in vivo and in vitro vasoreactivity to bradykinin (BK) and serotonin (5-hydroxytryptamine; 5-HT) (endothelial dependent agonists) as well as to nitroglycerin (NTG) (exogenous nitric oxide donor) at different times after oversized balloon angioplasty intervention ranging from 1 h to 12 weeks, in normal porcine coronary arteries. BK-induced vasodilatation in vivo was impaired acutely, but it was restored after 4 weeks. Serotonin caused vasoconstriction in vivo that was significantly augmented after 12 weeks. Conversely, endothelium-dependent vasodilatation in vitro to BK and 5-HT remained attenuated during the whole period of follow-up. Finally, relaxation elicited by NTG was reduced in the in vivo experiment until the first week after the procedure. Histological analysis showed severe arterial injury, and complete recovery of endothelial coverage after 4 weeks. In conclusion, this experiment supports evidence for the occurrence of the acute attenuation of vasoresponsiveness and chronic endothelial dysfunction following overstretching coronary balloon angioplasty. Abnormal remodeling associated with the severity of injury may contribute to chronic endothelial dysfunction. Differences found between in vivo and in vitro studies also suggest that multiple endogenous influences present in the former can attenuate the greater endothelial dysfunction demonstrated by endothelial assessment in vitro.

Respiratory findings in chemical workers exposed to low concentrations of organic and inorganic air pollutants.

BACKGROUND: Occupational exposure to respiratory irritants may effect respiratory function in workers exposed to ambient air pollutants in the workplace. METHODS: We studied 567 male and 135 female workers employed in two chemical plants in Zagreb, Croatia. Measurements of the ambient concentrations of air pollutants were performed. The mean age of the men was 37 years and mean duration of employment was 12 years; a majority of these workers were smokers. The mean age of the women was 37 years with a mean duration of employment of 14 years; only one-third of the women smoked. An unexposed group of 340 male and 110 female unexposed workers was also studied. Acute and chronic work related symptoms were recorded for all workers. Ventilatory capacity was measured by recording maximum expiratory flow-volume (MEFV) curves. RESULTS: There were higher prevalences for all chronic respiratory symptoms in exposed than in unexposed workers particularly among women, a majority of which were nonsmokers. Occupational asthma was recorded in three (0. 5%) of the men and in two (1.5%) of the women workers. Logistic regression analysis indicated that the presence of chronic respiratory symptoms among exposed workers was primarily associated with the amount of smoking. Additionally, there were high prevalences of acute symptoms during the work shift. Among the chemical workers these were greatest for eye irritation (male: 43. 9%; female: 51.9%), dryness of the throat (male: 43.4%; female: 57. 0%) and irritation of the throat (male: 37.4%; female: 56.6%). Ventilatory capacity data among the chemical workers demonstrated that most of the measured tests, particularly the FVC and FEV1 were significantly decreased compared to predicted (P < 0.01 or P < 0. 05)). In particular nonsmoking women exhibited abnormal lung function. The effect of smoking among exposed workers was demonstrated on all ventilatory capacity tests by regression analysis for all measured respiratory parameters. Both length of exposure and age were correlated with lung function loss for FVC. Measured pollutant levels were for the most part within acceptable standard limits. CONCLUSIONS: Our data suggest that in this population of chemical workers exposed to low levels of pollutants respiratory symptoms were primarily associated with smoking. Environmental effects, possibly due to an interaction of pollutants were also suggested.

Respiratory findings in mail carriers.

The results of the recording of respiratory symptoms and the measurement of lung function in 136 male postal workers employed as mail carriers were studied. In addition, the prevalence of chronic respiratory symptoms in 87 male nonexposed control workers was also examined. There was a significantly higher prevalence of chronic bronchitis (25.0%) and sinusitis (38.9%) in mail carriers than in control workers (13.8%; P < 0.05 and 2.3%; P < 0.01). A logistic regression analysis performed on the results of the study of chronic respiratory symptoms of mail carriers indicated a significant (P < 0.001) effect of smoking in this cohort, with the exception of occupational asthma. Mail carriers who smoked had a significantly higher prevalence of chronic cough (45.3%), chronic phlegm (39.1%), chronic bronchitis (39.1%) and sinusitis (53.1%) than mail carriers who were nonsmokers (18.1%; 12.5%; 12.5% and 26.4% respectively.) (P < 0.01). A high prevalence of acute symptoms developing during the work-shift was recorded, in both smokers and nonsmokers, being highest for upper airway symptoms, headache (50.0%), nasal catarrh (42.6%), and eye irritation (57.4%). The results of tests for average measured ventilatory capacity (as a percentage of predicted capacity) were significantly lower than expected, particularly for maximum flow rates at the last 25% of the vital capacity (FEF25), in both smokers (68.5%) and in nonsmokers (74.2%). A multivariate analysis of lung function parameters indicated a significant effect of employment conditions. The only major identifiable occupational exposure of mail carriers was to ambient air pollution for an average of 6 h per day as well as to adverse meteorological conditions. The measured ambient concentrations of major outdoor pollutants, primarily total suspended particulates, sulfur dioxide (SO2) and black smoke exceeded considerably the recommended Croatian maximum air quality standards over the past 10 years. Our study of mail carriers demonstrated that these workers were subject to respiratory symptoms associated with their smoking habits. Lung function findings suggested that occupational exposures, possibly to atmospheric pollution in combination with adverse meteorological conditions, may have led to lung function impairment in these workers.

Respiratory function in female workers occupationally exposed to organic dusts in food processing industries.

Respiratory consequences of work in food processing industry were studied in 764 female workers exposed to organic dusts associated with the processing of green and roasted coffee, tea, spices, dried fruits, cocoa and flour. A group of 387 female workers not exposed to respiratory irritants served as controls for the prevalence of acute (during work shift) and chronic respiratory symptoms. A greater prevalence of all acute and chronic respiratory symptoms was consistently found among exposed workers than among control workers. The highest prevalence of chronic respiratory symptoms was recorded for chronic cough (40%), followed by acute symptoms of dry cough (58.7%). The difference in the prevalence of chronic respiratory symptoms between the exposed and control workers was in general significant (p < 0.01 or p < 0.05). Mean acute reductions of lung function over the work shift were recorded in all of the studied groups; the mean across-shift decrease as a percentage of preshift values was particularly marked in FEF25 (-26.7%), FEF50 (-21.6%), followed by FEV1 (-9.9%) and FVC (-3.7%). The preshift (baseline) values of ventilatory capacity were decreased in comparison to the predicted ones, and were lowest for FEF50 and FEF25. This finding indicated an effect of organic dust on small airways. Our analysis suggested that both dust exposure and smoking history contributed independently to these respiratory findings. Disodium cromoglycate (DSCG) significantly diminished across-shift reductions for FEF50 and FEF25 in a subgroup of the examined workers. Our data suggested the female workers employed in food processing industry to be at risk of developing both acute and chronic respiratory symptoms as well as ventilatory capacity impairment as the result of occupational exposures.

Pharmacologic effects of cocoa and rye flour extracts on isolated guinea pig trachea.

Confectionery workers are exposed to a wide variety of organic dusts and aerosols. Previous studies with workers in a confectionery plant working with cocoa and rye flour indicate that these workers are at risk of developing adverse respiratory symptoms and lung function impairment. The effects of cocoa and rye flour extract on isolated guinea pig tracheal smooth muscle were studied using water-soluble extracts from cocoa and rye flour obtained from the studied confectionery plant. Dose-related contractions of nonsensitized guinea pig tracheal rings were demonstrated using both cocoa and rye flour extracts. Pharmacologic studies were performed by pretreating guinea pig tracheal tissue with drugs known to modulate smooth muscle contraction: atropine, indomethacin, pyrilamine, nordihydroguaiaretic acid (NDGA), acivicin, bromophenacyl bromide (BPB), 3,4,5-trimethoxybenzoate 8-(N,N-diethylamino)octyl ester (TMB8), captopril, and capsaicin. Constrictor effects of the dust extracts were inhibited by these agents, the pattern of which depended on the dust extract. Atropine consistently and significantly reduced the contractile effects of both extracts. These observations suggest a release of parasympathetic mediators by these extracts or more directly an interaction with muscarinic receptors. In addition, the constrictor effect of cocoa and rye flour extracts was significantly, but only partially, reduced by indomethacin, pyrilamine, BPB, and TMB8. Acivicin also partially decreased the constrictor effect of cocoa extract. Pretreatment of tracheal tissue with capsaicin also decreased the constrictor effects of high concentrations of cocoa and rye flour extracts. Data suggest that cocoa and rye flour extracts cause a dose-related constriction of airway smooth muscle by non immunological mechanisms involving cholinergic pathways and airway mediators such as histamine and the products of the arachadonic acid cascade. This effect is not dependent on the presensitization of guinea pigs.

Respiratory and immunological findings in brewery workers.

BACKGROUND: Occupational exposure of brewery workers to organic dusts such as hops, barley, and brewery yeast has the potential to change respiratory function and immunological status. METHODS: Ninety-seven male workers employed in a brewery plant were studied. The mean age of the workers in this plant was 40 years, the mean duration of their employment was 16 years. In addition, a group of 76 unexposed workers was studied as a control. Respiratory symptoms were recorded. Lung function was measured by recording maximum expiratory flow-volume (MEFV) curves. Immunological testing was performed on all brewery workers and some control volunteers using skin prick testing with hops, barley, and yeast antigens as well as other nonoccupational allergens, and by determining total serum IgE levels. RESULTS: There was a significantly higher prevalence of most of the chronic respiratory symptoms in brewery workers compared to controls (P < 0.01). Occupational asthma, however, was recorded in only 2 (2.1%) of the brewery workers. Logistic regression analysis showed that smoking was the major studied factor responsible for the high prevalence of chronic respiratory symptoms in workers. A large number of brewery workers complained of acute symptoms that developed during the work shift. Lung function tests were decreased compared to predicted. Multivariate analysis of these respiratory function parameters suggested the importance of workplace exposure in explaining lung function abnormalities. Significantly higher prevalences of positive skin prick tests were recorded in 37 brewery workers for molds, hops, and barley than in controls. Increased serum levels of total IgE were documented in 34/97 (45.1%) brewery workers and in 1/76 (2.7%) of the control workers (P < 0.01). However, workers with positive skin prick tests had prevalences of chronic respiratory symptoms and lung function changes similar to those of workers with negative skin prick tests. CONCLUSION: Our data suggest that both smoking and dust exposure in the brewery industry may be responsible for the development of respiratory impairment and immunological reactions.

Integrins inhibit angiotensin II-induced contraction in rat aortic rings.

Many extracellular matrix proteins contain the tripeptide sequence arginine-glycine-aspartate (RGD). This RGD motif is recognized by integrins, a family of adhesion receptors present on vascular smooth muscle cells. In the present study, we examined the ability of different RGD-containing peptides to affect the contraction of rat aortic rings in response to different agonists. We found that the peptide RGDS inhibited angiotensin-induced contraction in a dose dependent manner. In contrast, the peptides RGDW and RGES had no effect on angiotensin-induced contractility. We show that function-blocking antibodies to the integrins alphavbeta3 and alpha5beta1 also inhibit angiotensin-induced contraction. These effects were observed in the absence of an intact endothelium. In contrast, neither an antibody directed against the beta1 subunit nor the peptide RGDS had an effect on phenylephrine or 5-hydroxytryptamine-induced contraction. These data suggest that interactions of vascular smooth muscle with components of the surrounding extracellular matrix may influence the response of smooth muscle to agonists.