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.

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.

Diagnostic problems in suppurative lung disease.

Eleven of 48 (23%) patients diagnosed as having lung abscess or empyema presented diagnostic problems in the localization of infected material. All 11 patients were found eventually to have empyemas, all but one of which was complicated by bronchopleural fistulas. Difficulty in distinguishing abscess from empyema on a chest roentgenogram delayed diagnostic and therapeutic thoracentesis from 1 to 12 days. Pleural effusions were noted in all but one of the patients who did not initially have a bronchopleural fistula. In addition, once the bronchopleural fistula became established, the extension of the air-fluid level to the chest wall, the tapered borders of the air-fluid pocket, and the extension of the lesion across fissure lines were noted, in retrospect, to be suggestive of pleural localization. Delay in the evacuation of empyema fluid can lead to chronic complications and increased morbidity. Early identification and treatment of pleural effusions may avoid these diagnostic and therapeutic problems.

Mechanically assisted ventilation in a community hospital. Immediate outcome, hospital charges, and follow-up of patients.

In 100 consecutive patients undergoing mechanically assisted ventilation, we prospectively determined immediate survival, hospitalization charges, and subsequent one-year outcome. Sixty percent of the patients survived the episode of assisted ventilation. This survival decreased to 50% at the time of hospital discharge and to 33% one year after hospitalization. There were no posthospitalization deaths in patients less than age 50 years. In those patients older than 70 years, however, 51% were dead by the time of hospital discharge and 73% died by one year following discharge. Comparison of features that reflect the magnitude of intensive respiratory care, such as hours of ventilation and intensive care unit (ICU) length of stay, disclosed no statistically significant differences between survivors and nonsurvivors at discharge. Hospitalization charges averaged $10,968 per patient. The total charge for respiratory therapy services (including arterial blood gas determinations) averaged $2,200. Respiratory care service charges were only marginally different between survivors and nonsurvivors. By contrast, total charges and total length of stay were greater for the survivors. Resource use in the intensive care setting as reflected by hours of mechanical ventilation and ICU length of stay was similar in both survivors and nonsurvivors, with the larger total cost for survivors relating primarily to care outside the ICU. Also, we confirm that prognosis is excellent in patients less than 50 years of age who survive mechanically assisted ventilation for acute respiratory failure and that extubation in elderly patients is not necessarily indicative of a good prognosis.

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.

The clinical assessment of roentgenographically atypical pulmonary sarcoidosis.

We studied 89 patients in whom the clinical diagnosis of sarcoidosis was supported by the findings on tissue biopsy. A chest roentgenogram in 14 of the patients showed one of the following atypical features: large pulmonary nodules, an alveolar parenchymal pattern or a pleural effusion. Diagnoses of infection, malignancy or vasculitis were suggested by interpretations of atypical chest roentgenograms in eight of these 14 patients. Nonspecific and misleading clinical information contributed. The diagnosis of sarcoidosis was corroborated by extrathoracic tissue biopsies in 11 of the 14 patients. Over an average observation period of 38 months, the 14 patients remained classified as having sarcoidosis. This suggests that an extrathoracic tissue biopsy, whose findings are consistent with sarcoidosis, is often sufficient to support a clinical diagnosis of some forms of roentgenographically atypical pulmonary sarcoidosis.

Smoking and cotton dust effects in cotton textile workers: an analysis of the shape of the maximum expiratory flow volume curve.

Cotton textile workers have an increased prevalence of both obstructive and restrictive lung function patterns when compared to control subjects. Similar abnormal lung function patterns may occur with other respiratory diseases, notably those associated with cigarette smoking. The shape of the maximum expiratory flow volume (MEFV) curve has been used to characterize patterns of lung function abnormality. We defined a new functional parameter (angle beta) related to the shape of the MEFV curve in order better to characterize the respiratory effects of cotton dust exposure. In this study, 477 cotton textile workers, both current smokers and never smokers 45 years and older, were compared to 932 similarly aged control subjects from three communities: Lebanon and Ansonia, CT, and Winnsboro, SC. Smokers, regardless of their occupational exposure of sex, have smaller values of beta than do nonsmokers. Cotton textile workers who have more abnormal lung function than do controls, cannot be distinguished from controls by beta. We suggest that such functional differences between cotton and smoking effects may reflect injury to different portions of the bronchial tree.

Biologic activity of purified cotton bract extracts in man and guinea pig.

Purified aqueous extracts of cotton bract induce acute airway constriction in healthy volunteers never before exposed to cotton bract. The response is similar to that of textile workers who inhale cotton dust. Approximately 60% of volunteers respond to bract extract with significant decreases in lung function, and these volunteers show an increased number of lymphocytes present in their lungs. Following inhalation of bract, the percent of polymorphonuclear leukocytes increases. Macrophages obtained by bronchoalveolar lavage from volunteers pre-challenged with bract extract release increased amounts of chemotactic factor and superoxide anion. Efforts to detect release of histamine and leukotrienes in volunteers following challenge with bract show no increase in urinary histamine and no significant release of leukotrienes in lung lavage fluid. Purified extracts exhibit chemotactic activity in vitro. They also contract guinea pig ileal longitudinal muscle in vitro. This preparation contains mast cells but no basophils, and the H-1 blocker, mepyramine blocks the contraction. Purified bract extracts contain no histamine or endotoxin but other contractors of smooth muscle may be present. The purified extract exhibits spectral, fluorescent, and radioimmune assay properties similar to a leukotriene B-like component. Cotton bract appears to have direct as well as cell-mediated activities.

Detection of sulfur dioxide in bronchodilator aerosols.

Several bronchodilator drugs commonly used in respiratory therapy contain sodium metabisulfite as an antioxidant preservative. When aerosolized, these agents may release the irritant gas SO2 as a result of bisulfite decomposition. We found that agents that contain bisulfites generated SO2 concentrations of 2.0 ppm and greater, while bronchodilator solutions without bisulfite did not. Such levels are known to induce or to exacerbate asthmatic symptoms. Levels of SO2 were higher when solutions were nebulized with compressed air from a tank or electric compressor than when they were nebulized from a hand-bulb nebulizer. No significant lot-to-lot variations were found in the solutions tested.

Relationship of the ventilatory response to cotton bract extract and the cells and proteins of the lung.

Many healthy subjects who have had no exposure to cotton textile dusts will experience significant reductions in expired flow rate following an inhalational challenge with an aqueous extract of cotton bracts (CBE). Differences noted among individuals in the magnitude of the bronchial response to a standardized preparation of CBE suggest variable airway reactivity. The mechanism of this response and the reasons for its variability among these naive subjects are unknown. We have studied this problem by performing bronchoalveolar lavage on 13 volunteer subjects with no history of textile dust exposure. Two to three months later, a bronchial provocation with aqueous CBE was performed by an investigator blinded to the lavage results. Subjects with greater than 20 percent drop in flow rate at 40 percent of vital capacity during a partial forced expiration (MEF 40 percent [P]) following CBE had a reduction in total recoverable alveolar macrophages, with a resultant increase in the percentage of recoverable lymphocytes. The magnitude of response (MEF 40 percent [P]) correlated directly with the measured lymphocyte percentage (r = 0.69 p less than 0.01) and inversely with the total numbers of recovered cells.

A prospective study of asthma in a rural community.

Changes in symptoms and pulmonary function among asthmatic subjects in the general population remain poorly characterized. We studied 1,303 white residents aged seven years and older in Lebanon, Conn, a rural community largely unaffected by air pollution or major occupational exposures. These residents were examined in 1972 and again in 1978. There were 73 asthmatic subjects seen in 1972 who were followed. In addition, we identified 278 persons in 1972 who complained of wheezing who were also seen in 1978. Of the original asthmatic subjects, 50 (68 percent) were in remission; and from the original nonasthmatic population, 19 (1.4 percent) new asthmatic subjects were identified. Similarly, the condition of 215 (77 percent) of those who initially complained of wheeze had improved, whereas 56 (4.6 percent) of those initially studied either developed new wheeze or saw their wheezing worsen. When the groups of persons complaining of wheeze and the asthmatic subjects were analyzed for the presence of chronic bronchitis, we found a significant correlation between wheeze and chronic bronchitis in individuals aged 18 years and older (p less than 0.001) for both men and women, and a significant correlation (p less than 0.001) between asthma and chronic bronchitis in women aged 18 years and older. Loss of pulmonary function over time measured in terms of the forced expiratory volume in one second and the forced expiratory flow at 50 percent of total lung capacity was consistently greater for asthmatic adults than for nonasthmatic adults. Furthermore, when individuals were studied by the severity and duration of their asthmatic symptoms, a trend of worse pulmonary function was seen in those individuals with chronic asthma. We conclude that remission rates among asthmatic subjects and persons with wheeze are high in individuals aged seven years and older, that chronic bronchitis is frequently associated with wheezing and a history of asthma in adults, and that significant abnormalities in pulmonary function as well as accelerated loss of pulmonary function are associated with asthma.

Diaphragm pacing. Application to a patient with chronic obstructive pulmonary disease.

In a 66-year-old patient with chronic obstructive pulmonary disease (COPD) complicated by arterial hypoxemia and repeated episodes of respiratory and right ventricular failure, a satisfactory level of oxygenation could not be maintained despite controlled oxygen therapy. To enable oxygen to be administered without depression ventilation, artificial respiration by means of phrenic nerve stimulation (diaphragm pacing) has been employed. Evidence of clinical improvement since pacing was begun 32 months ago include fewer episodes of respiratory failure and better control of congestive heart failure despite a gradual worsening of pulmonary function.

Histamine blocking agents in healthy and asthmatic subjects.

We compared the effects of two histamine receptor blocking agents, chlorpheniramine (H1) and cimetidine (H2) on the airways of healthy and asthmatic subjects. Eleven healthy subjects and ten asthmatic patients underwent histamine aerosol challenge. A threshold dose (T) for response to histamine was determined for each subject using maximal expiratory flow rates on partial expiratory flow rates on partial expiratory flow volume curves (MEF40 %[P]). On subsequent study days, the subjects were pre-treated with 8 mg of chlorpheniramine, 300 mg of cimetidine or a lactose placebo. Histamine challenge was performed two hours later with the individual's own T dose and doses one dilution below (T-1) and one dilution above (T+1) that dose. In both asthmatic and healthy subjects chlorpheniramine significantly reduced the bronchoconstrictor responses to histamine (p less than 0.02 and 0.05, respectively) as measured by MEF40 percent (P) at the T dose. When treated with cimetidine asthmatic patients displayed significantly more bronchospasm at T than with placebo (p less than 0.035). By contrast, pretreatment with cimetidine did not alter airway responses to histamine in healthy subjects when compared to placebo. We conclude that H2 receptors mediating bronchodilatation can be demonstrated in asthmatic patients but not in healthy subjects.

Acute effects of herbal tea dust extracts on lung function.

The acute effect of herbal tea dust extracts on lung function was studied in 15 of 25 healthy subjects responding to the inhalation of these extracts. Bronchial inhalation challenge was performed with tea extracts (sage, dog rose and gruzyan) and with normal saline solution as a control substance to assess their baseline airway reactivity to an isotonic aerosol. Lung function testing was performed before exposure and at 0, 15, 30, and 60 minutes after the cessation of exposure. The same subjects were also tested by challenge with methacholine. Lung function was measured by recording FVC, FEV1, FEF50, FEF25, SGaw, and Raw. Subjects were skin tested by the skin prick method and serum IgE levels were determined. The findings suggested that neither baseline nonspecific airway reactivity nor specific markers of immediate sensitivity to tea predict airway responses to tea extracts. Further evaluation of immunologic markers may help to explain the onset and progression of airway disease in workers.

The shape of the maximum expiratory flow volume curve.

Differences in the shape of the maximum expiratory flow volume (MEFV) curve have been associated with pathologic states and physiologic differences between normal individuals. We describe variations in a new parameter, angle beta, which characterizes the general configuration of the MEFV curve among healthy subjects and subjects with disease in 5,140 white individuals. Women had consistently larger beta angles than men. There was a progressive decline in beta with advancing age. Cigarette smokers had lower beta angles than did lifetime never-smokers. Subjects with abnormal lung function patterns had lower beta angles than individuals with a normal pattern. Finally, individuals with asthma, chronic bronchitis, dyspnea and wheezing had significantly lower beta angles than healthy individuals. Further clinical and epidemiologic studies are needed to evaluate this measurement's possible value in pulmonary function evaluation.

Bronchoalveolar lavage. Its safety in subjects with mild asthma.

It has been suggested that fiberoptic bronchoscopy may induce life-threatening bronchospasm in persons with asthma. The safety of bronchoscopy and bronchoalveolar lavage (BAL) with bilateral installation of 300 ml of saline solution was assessed prospectively in ten adults with mild asthma as a part of a study of the lower respiratory tract in bronchospastic disease. Asthmatic subjects had pretreatment with intravenous aminophylline prior to bronchoscopy. Pulmonary function tests were performed prior to and immediately after the procedure, and values were compared to results in 12 normal adults undergoing bronchoscopy with BAL. One subject had mild bronchospasm (the third subject) before BAL could be performed. There were no major complications in the remaining asthmatic or normal subjects. Mean forced expiratory volume in one second (FEV1) did not change significantly in either group, and the mid-flow rate at 50 percent of vital capacity (Vmax 50%) decreased significantly only in normal subjects (p = 0.002). Moreover, none of the nine asthmatic subjects completing bronchoscopy with BAL had clinically significant bronchospasm. These results suggest that elective fiberoptic bronchoscopy and BAL can be performed safely in subjects with mild asthma.

Airway reactivity and exercise in healthy subjects.

The interaction of exercise, methacholine challenge, and beta-adrenergic blockade was investigated in eight healthy subjects. We measured the response to increasing doses of aerosolized methacholine, examining maximum expiratory flow rates. These responses were compared with those obtained on separate days when each methacholine challenge followed submaximal exercise or submaximal exercise in the presence of Beta-blockade. The possible independent effect of increased ventilation (20 +/- 6.7 L/min) was also studied during methacholine challenge. Methacholine-induced bronchospasm was not augmented by exercise alone or by exercise in the presence of beta-blockade, nor was this response significantly altered by hyperventilation during methacholine aerosol challenge. These findings suggest that airway hyperreactivity cannot be induced in healthy subjects by levels of exercise that commonly provoke exercise-induced bronchospasm in asthmatic patients.

Airway reactivity and cotton bract-induced bronchial obstruction.

Most seemingly healthy persons challenged with an aerosol of cotton bract extract develop some degree of bronchospasm. The role of nonspecific reactivity of the airways in this reaction to cotton bract extract is undefined. We examined the relationship between airway responses to cotton bract extract and to methacholine, as well as between airway responses to cotton bract extract and to a bronchodilator. Twenty-two healthy subjects were screened for sensitivity to inhaled cotton bract extract. Pulmonary function was measured using partial expiratory flow-volume curves on which flow at 60 percent of the control vital capacity below total lung capacity was measured (MEF40%[P]) following ten minutes of inhalation of cotton bract extract. In the group screened, 12 were found to be responders to the extract, with drops in MEF40%(P) of 20 percent or more, and ten were found to be nonresponders. On separate days, we measured the responses of our subjects' airways to inhaled metaproterenol and methacholine. The mean threshold dose for methacholine in the responding group was 26.8 mg/ml, as compared to 55.6 mg/ml for the nonresponders (t = 2.52; p less than 0.05). Furthermore, the mean percent increase in MEF40%(P) following inhalation of metaproterenol was 41 percent in responders and 24 percent in nonresponders (t = 2.19; p less than 0.05). We conclude that some responders to cotton bract extract exhibit greater reactivity of the airways than nonresponders.