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A decision analysis was used to evaluate the economic effectiveness of respiratory syncytial virus immune globulin (RSVIG) prophylaxis on selected pediatric populations at risk for developing RSV bronchiolitis or all respiratory illness-related hospitalizations. We compared costs, outcomes, and cost-effectiveness of administering RSVIG to no treatment in different pediatric populations, including those at risk of developing RSV-bronchiolitis and those at risk of developing any respiratory illness-related hospitalization. We observed that if only infants at high risk of severe RSV infections received treatment with RSVIG, a calculated cost saving of about 27,000 dollars per hospitalization prevented were realized. If the Food and Drug Administration (FDA)-approved indications for RSVIG were followed, the cost to prevent one hospitalization due to RSV bronchiolitis would be over 53,000 dollars. If the aim, however, was to prevent all respiratory illness-related hospitalizations for this broader population, a much lower cost (4,000 dollars) to prevent one hospitalization would result. In this situation, cost neutrality was possible, with a therapy cost of 2,843 dollars compared to the actual average therapy cost of 4,444 dollars. Sensitivity analysis showed that the model was relatively insensitive to all variables, with the exceptions of costs related to RSVIG and intensive care unit (ICU) admissions. We conclude that RSVIG resulted in cost savings if therapy were reserved for the infants who are at highest risk for developing severe RSV infections. RSVIG is not cost-effective for preventing RSV bronchiolitis when used according to the FDA-approved indications. Education that emphasizes frequent hand-washing, avoidance of passive smoking, and lessening exposure to sick children remains the least expensive prevention tool.

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Nedocromil sodium is a nonsteroidal anti-inflammatory drug used to control asthmatic attacks. Our hypothesis is that nedocromil sodium inhibits virus-induced airway inflammation, a common trigger of asthma. We nebulized nedocromil sodium into beagle dogs (n = 10, mean +/- SEM ages: 149 +/- 13 days) before and after inoculation with canine adenovirus type 2 (CAV2). Control dogs (n = 10) received saline aerosols and were either infected with CAV2 (Sal/CAV2, n = 7, mean +/- SEM ages: 140 +/- 11 days) or were not infected (Sal/Sal, n = 3, ages: 143 +/- 0 days). All dogs were anesthetized with choralose (80 mg/kg i.v.), intubated, and mechanically ventilated. Pulmonary function tests and bronchoalveolar lavage (BAL) were performed using standard techniques. Pulmonary function tests revealed no significant change between the nedocromil sodium and non-nedocromil-treated groups. The percentage of infected bronchioles was quantitated as the number of inflamed airways of 40 bronchioles examined times 100 for each dog. Nedocromil-treated dogs had significantly (p < 0.05) less mucosal inflammation (mean +/- SEM, 39% +/- 5%), epithelial denudation (36% +/- 5%), and BAL neutrophilia (11 +/- 3) than did Sal/CAV2 dogs (51% +/- 6%, 57% +/- 4%, and 33% +/- 8%, respectively). We concluded that pretreatment with nedocromil sodium aerosols attenuated CAV2-induced airway inflammation in these beagle puppies.

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The author argues that the special knowledge of individual professionals confers upon them personal responsibility to monitor governmental standards and regulations in their field and to intervene in their formulation and, where necessary, remediation. An occupational and environmental health professional in such a role needs first to identify the persons in charge of the entity in question. Influencing their actions then calls for conviction, courage, ethical principles and moral behavior, and willingness to get involved.

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In ragweed (RW)-sensitized beagle dogs, we tested the hypothesis that reactivity of the pulmonary vasculature was enhanced with aerosolized histamine (Hist) and RW. Seven dogs were neonatally sensitized with repeated intraperitoneal RW injections, and 12 dogs were controls (Con). The dogs were anesthetized with intravenous chloralose, mechanically ventilated, and instrumented with femoral arterial and pulmonary artery catheters. Specific lung compliance (CLsp), specific lung conductance (Gsp), systemic vascular resistance index, and pulmonary vascular resistance index (PVRI) were measured before and after bronchoprovocation with Hist and RW. After Hist inhalation (5 breaths of 30 mg/ml), both Con and RW dogs had significant (P < 0.05) decreases in CLsp (-51 +/- 4 and -53 +/- 5%, respectively) and Gsp (-65 +/- 5 and -69 +/- 3%, respectively), but only RW-sensitized dogs had a significant increase in PVRI (38 +/- 10%). After RW inhalation (60 breaths of 0.8 mg/ml), only RW-sensitized dogs had significant increases (62 +/- 20%) in PVRI and decreases in Gsp (-77 +/- 4%) and CLsp (-65 +/- 7%). We conclude that, compared with Con, RW-sensitized beagle dogs have increased pulmonary vasoconstrictive responses with Hist or RW inhalation.

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Discussion of the major milestones in the history of the modern uses of asbestos and the first knowledge of the health effects associated with such usage. Highlights of the studies associating exposure to asbestos with non-malignant lung diseases, lung cancer, and mesothelioma are discussed.

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Acute viral respiratory infections are commonly associated with alterations in lung growth. Recently, fractal techniques have been demonstrated to show changes in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle puppy model. In the present study, we investigated whether the fractal dimension (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after inoculation, 131d CAV2 group) or during the recovery phase (approximately 22 weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The Df of alveolar perimeter length was significantly increased in the 235d CAV2 puppies compared to all of the other beagle puppy groups. On the other hand, the fractal dimensions for alveolar perimeter length for the other beagle puppy groups were very similar. In a related human study of patients (age range of 25 h to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change in Df of alveolar perimeter length with normal lung growth and development. We conclude that fractal analysis of alveolar perimeter length can be used as an index of permanent lung injury after insult to the growing lungs.

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Respiratory syncytial virus (RSV) bronchiolitis is associated with the clinical signs and symptoms of small airway obstruction. A major public health problem throughout the world, this condition is responsible for significant morbidity and mortality. Management is primarily preventive, through strict hand washing, avoidance of exposure during the respiratory illness season and intravenously administered prophylactic anti-RSV Immune globulin, especially in selected small infants with underlying cardiopulmonary disease. Supportive measures, including fluid hydration, good nutrition, aerosolized bronchodilators and steroids, may be helpful. Ribavirin may be useful in severely ill children or those with underlying cardiopulmonary disease. A significant number of patients have recurrent episodes of bronchiolitis and wheezing, and may develop asthma later in life. Avoidance of exposure to tobacco smoke, cold air and air pollutants is also beneficial to long-term recovery from RSV bronchiolitis. A number of vaccines to prevent this infection are currently being studied.

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We have determined that fractal analysis of the alveolar perimeter (Df) changes with aging in human lung tissue in twenty-nine patients, age range of 25 hours to 76 years, who died of non-respiratory related causes. There was a very significant difference (p = 0.0004) in Df between the young (less than 16 years old, N = 9, mean Df of 1.047 [0.01]) and adult (greater than 16 years old, N = 20, mean Df of 1.093 [0.013]) groups. Furthermore, there was a significant difference in Df between the Adult group and the group of patients who died of chronic obstructive pulmonary disease (COPD, N = 10) (p = 0.012). Additionally, the Df values for the COPD and cystic fibrosis (CF, N = 5) groups were virtually identical; 1.061 and 1.070, respectively. Regression analysis showed a significant (p = 0.0041) exponential relationship with a correlation coefficient of 0.59 between aging and Df. We have demonstrated that the correlation between Df and aging in humans is an exponential function and that the end-stage pulmonary diseases of COPD and CF decrease Df.

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OBJECTIVES: To evaluate alternative models and estimate risk of mortality from lung cancer and asbestosis after occupational exposure to chrysotile asbestos. METHODS: Data were used from a recent update of a cohort mortality study of workers in a South Carolina textile factory. Alternative exposure-response models were evaluated with Poisson regression. A model designed to evaluate evidence of a threshold response was also fitted. Lifetime risks of lung cancer and asbestosis were estimated with an actuarial approach that accounts for competing causes of death. RESULTS: A highly significant exposure-response relation was found for both lung cancer and asbestosis. The exposure-response relation for lung cancer seemed to be linear on a multiplicative scale, which is consistent with previous analyses of lung cancer and exposure to asbestos. In contrast, the exposure-response relation for asbestosis seemed to be nonlinear on a multiplicative scale in this analysis. There was no significant evidence for a threshold in models of either the lung cancer or asbestosis. The excess lifetime risk for white men exposed for 45 years at the recently revised OSHA standard of 0.1 fibre/ml was predicted to be about 5/1000 for lung cancer, and 2/1000 for asbestosis. CONCLUSIONS: This study confirms the findings from previous investigations of a strong exposure-response relation between exposure to chrysotile asbestos and mortality from lung cancer, and asbestosis. The risk estimates for lung cancer derived from this analysis are higher than those derived from other populations exposed to chrysotile asbestos. Possible reasons for this discrepancy are discussed.

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OBJECTIVES: This article examines the credibility and policy implications of the "amphibole hypothesis," which postulates that (1) the mesotheliomas observed among workers exposed to chrysotile asbestos may be explained by confounding exposures to amphiboles, and (2) chrysotile may have lower carcinogenic potency than amphiboles. METHODS: A critical review was conducted of the lung burden, epidemiologic, toxicologic, and mechanistic studies that provide the basis for the amphibole hypothesis. RESULTS: Mechanistic and lung burden studies do not provide convincing evidence for the amphibole hypothesis. Toxicologic and epidemiologic studies provide strong evidence that chrysotile is associated with an increased risk of lung cancer and mesothelioma. Chrysotile may be less potent than some amphiboles for inducing mesotheliomas, but there is little evidence to indicate lower lung cancer risk. CONCLUSIONS: Given the evidence of a significant lung cancer risk, the lack of conclusive evidence for the amphibole hypothesis, and the fact that workers are generally exposed to a mixture of fibers, we conclude that it is prudent to treat chrysotile with virtually the same level of concern as the amphibole forms of asbestos.

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In the United States workers are still exposed to asbestos, and particularly to chyrsotile, mainly in mines, in manufacturing of asbestos-containing products, and in construction, with the extent of exposure widely varying according to the job; familial exposure must also be taken into account. It is quite difficult to evaluate the entity of previous exposures, which have sometimes occurred 30-40 years ago. The risk furthermore varies according to the intensity of exposure and smoking habits. As far as allowed exposure levels are concerned, there is not homogeneity among the laws of different countries; above all it is no longer justifiable to regulate chrysotile differently than the amphiboles.

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Viral bronchiolitis is a common world-wide disease of infants and children resulting in respiratory failure and occasionally death. The major underlying pathophysiology is airway inflammation of peripheral airways and airway hyperresponsiveness to bronchoprovocation. Management is primarily prevention through strict hand washing and avoidance of exposures during respiratory seasons, especially in small infants who have underlying heart or lung disease. Careful supportive therapy, including fluid hydration, good nutrition, and aerosolized bronchodilators, steroids or ribavirin may be helpful. Long term follow-up for these children is important because a significant number will have recurrent episodes of bronchiolitis and wheezing, and many will develop clinical asthma. There's some evidence that long term abnormalities of airway function, perhaps secondary to airway fibrosis, may result from bronchiolitis infections. Avoidance of exposure to passive smoking, cold air and air pollutants is also beneficial to long term recovery from RSV bronchiolitis.

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