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Ambient air pollution and respiratory disease.

OBJECTIVE: To review the literature on ambient air pollution and respiratory disease, and to consider the criteria for defining causation. DATA SOURCES: Medical and scientific journals indexed by Medline, conferences, proceedings and monographs. STUDY SELECTION: Two kinds of study were selected--(i) controlled clinical trials which have exposed normal or asthmatic subjects and/or patients with chronic obstructive airways disease to sulphur dioxide, nitrogen dioxide or ozone; and (ii) epidemiological studies which have investigated the chronic toxicity of these pollutants, acid aerosols and polycyclic aromatic hydrocarbons. DATA EXTRACTION AND SYNTHESIS: Experimental studies were tabulated under the headings "Design", "Subjects", "Pollutant concentration", "Duration of exposure", "Outcome measures" and "Conclusions". Epidemiological studies were summarised and compared in an attempt to reconcile conflicting results. (The experimental and epidemiological evidence has been used by regulatory bodies to develop ambient air quality guidelines.) CONCLUSIONS: At the present state of knowledge, it is not possible to conclude that air pollution can cause respiratory disease de novo, but levels marginally above current guidelines certainly have adverse effects on individuals with pre-existing chronic lung disease.

Air Pollutants↗

Geographic variability in hospital admission rates for respiratory disease among the elderly in the United States.

BACKGROUND: The elderly represent a susceptible subpopulation that experiences disproportionate levels of morbidity and mortality from respiratory disease. As a consequence, they are frequently hospitalized for these conditions. Evaluating the geographic distributions of these hospital admissions can provide useful insights concerning patterns in incidence and medical care for respiratory diseases. METHODS: All hospital admissions for pneumonia, acute respiratory infections, asthma, and chronic obstructive pulmonary disease from the United States for a 6-year period (1984 through 1989) were identified using Medicare admissions records. Age-, race-, and sex-standardized annual admission rates were calculated for each county and spatial clustering of disease specific rates was evaluated using Moran's I statistic. Ecologic analyses were conducted using multiple regression procedures with county-specific measures of average annual temperature, average income, household crowding, median educational level, population density, physicians per capita, and hospital beds per capita together with surrogate measures of cigarette consumption and occupational exposures as predictor variables. RESULTS: Hospital admission rates in the elderly for all four categories of respiratory disease showed marked regional elevations (p < 0.0001), particularly in the southeast and the northern plains states. Low median education level, low per capita income, and household crowding were all associated with elevated hospital admission rates. Surrogate measures of cigarette consumption were strongly associated with hospital admissions in all four disease groups. Hospital beds per capita demonstrated positive associations with hospital admissions, but the number of physicians per capita exhibited consistent inverse relationships with hospital admissions. CONCLUSIONS: Hospital admission rates for respiratory diseases among the elderly show marked geographic variation and are associated with regional indicators of socioeconomic status, availability of medical resources, occupational lung disease rates, and smoking.

Aged↗

Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases.

IgE molecules play a crucial role in allergic respiratory diseases and may cause chronic airway inflammation in asthma through activation of effector cells via high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since the discovery of IgE antibodies our understanding of the mechanisms of allergy has improved to such an extent that we can differentiate allergic/atopic from intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce free IgE levels and to block the binding of IgE to FcepsilonRI without crosslinking IgE and triggering degranulation of IgE-sensitized cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab) binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII. Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma showed that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted effective in reducing asthma-related symptoms, decreasing corticosteroid use and improving quality of life of asthmatic patients. Recent studies show the benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled by optimal pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile and a convenient dosing frequency.

Anti-Asthmatic Agents↗

Diarrheal and respiratory disease aboard the hospital ship, USNS-Mercy T-AH 19, during Operation Desert Shield.

Diarrhea and respiratory disease were common problems among ground troops deployed to the Middle East during Operation Desert Shield. In order to determine the prevalence and impact of diarrheal and upper respiratory disease among shipboard personnel during this period, an epidemiologic survey was conducted on the hospital ship, USNS Mercy T-AH 19. An episode of acute diarrhea was reported by 46% of the surveyed population, and 79% reported upper respiratory symptoms. Six percent of personnel were temporarily unable to perform scheduled duties due to gastrointestinal symptoms and 7% due to respiratory symptoms. Officers were at increased risk of experiencing an episode of diarrhea, and female crew members more often reported respiratory complaints. Improved strategies to prevent diarrhea and respiratory disease among shipboard personnel are needed.

Adolescent↗

[Prevalence of tuberculosis and respiratory disease in persons older than 15 years of age in the northeastern sector of Medellín, Colombia].

A survey was conducted in 1988 to estimate the prevalence of tuberculosis and respiratory disease (cases of tuberculosis and patients with respiratory symptoms who tested negative for the presence of bacilli) in persons over the age of 15 and of low socioeconomic status in the northeastern commune of Medellín. A cluster sample was selected and 3,731 adults were interviewed. The interviews were carried out in the interviewees' homes. For those patients classified as having respiratory symptoms (two weeks with cough, without considering other symptoms), samples of sputum were taken and a series of three examinations for bacilli were performed in order to confirm the diagnosis. When the interviewee could not be located, the material for collection of samples was delivered to family members. The prevalence of tuberculosis was estimated to be 2.68 per 1,000 population, and that of respiratory disease, 70 per 1,000 population. Of those who initiated treatment, 37.5% abandoned it. The prevalence of respiratory disease was higher among persons who did their cooking and sleeping in the same room, those living in poorly ventilated and overcrowded dwellings, and those with the fewest years of schooling.

Adolescent↗

Functionally relevant changes occur in HIV-infected individuals' alveolar macrophages prior to the onset of respiratory disease.

OBJECTIVE: We have compared the phenotypic and functional changes found in alveolar macrophages recovered from the lungs of 39 HIV-positive individuals with no respiratory disease with those from 33 HIV-positive individuals with pneumonitis and 31 healthy controls. METHODS: Bronchoalveolar lavage (BAL) cell cytospin preparations were stained using monoclonal antibody immunoperoxidase and double immunofluorescence techniques. Cytokine levels within supernatant BAL were determined using enzyme immunoassay. RESULTS: There were marked differences in alveolar macrophage phenotype between the three groups. In particular, the relative proportion of cells staining RFD1+RFD7- (inducer cells) was reduced in the HIV-positive individuals without respiratory disease. This was correlated with measures of declining systemic immunity. Patients with pneumonitis had the highest levels of measured cytokines [interleukin-1 beta, tumour necrosis factor-alpha and transforming growth factor (TGF)-beta 2], followed by the HIV-positive individuals without respiratory disease. In this latter population a negative correlation was found between active (non acid dissociated) TGF-beta 2 and blood CD4 cell count. CONCLUSIONS: The differences between the three groups suggest that alterations of potential relevance to the pulmonary immune response are occurring in alveolar macrophages prior to the onset of respiratory disease. This study confirms the importance of investigating asymptomatic HIV-positive individuals.

AIDS-Related Opportunistic Infections↗

Field study of undifferentiated respiratory disease in housed beef calves.

A severe outbreak of undifferentiated respiratory disease affecting 119 of 144 (82.6 per cent) two- to five-month-old housed beef calves was studied by monitoring their clinical signs and rectal temperatures daily or every second day for two months. New cases of respiratory disease, which were first identified three weeks after the calves were housed, occurred over a period of 29 days. The cause of the outbreak was not conclusively determined although 20 per cent of the calves sampled showed serological evidence of recent infection with bovine respiratory syncytial virus and parainfluenzavirus 3. Seventeen of 61 calves (27.9 per cent) which were treated with tilmicosin had to be treated again, compared with nine of 58 calves (15.5 per cent) which were treated with both tilmicosin and flunixin meglumine and did not need further treatment, but this difference was not statistically significant.

Animal Husbandry↗

Respiratory disease in pregnancy.

Respiratory disorders seem to be better tolerated during pregnancy than disorders of the cardiovascular system. Pregnancy seems to have a variable effect on bronchial asthma although respiratory function in general shows little change. Similarly patients with bronchiectasis do not tend to show functional deterioration. Fetal growth, however, may be adversely affected in these conditions if arterial hypoxaemia is present. The problems of drug treatment of respiratory disorders in pregnancy, particularly asthma and tuberculosis, are discussed.

Adolescent↗

Respiratory disease and wasting in athymic mice infected with pneumonia virus of mice.

Although pneumonia virus of mice (PVM) is ubiquitous among rodent colonies in the United States, it has not been reported to cause clinically apparent disease in euthymic mice. However, PVM has been reported to cause respiratory disease and death in experimentally infected euthymic and athymic mice. A group of nu/nu mice, housed in quarantine in a Trexler-type isolator, had weight loss and dyspnea. Gross necropsy findings included cachexia and diffuse pulmonary edema or lobar consolidation. Histologically there was diffuse interstitial pneumonia. Electron microscopy revealed filamentous virions budding from plasma membranes, and immunohistochemical staining of lung tissue was positive for PVM antigen. PVM was isolated from affected lung tissue in BHK 21 cells and mouse antibody production tests resulted in seroconversion to PVM. Experimental inoculation of athymic mice with lung homogenate from spontaneously infected mice resulted in clinically apparent respiratory disease and histologic lung changes similar to those in naturally infected mice. Inoculation of athymic mice with infected BHK 21 cell culture fluid resulted in pneumonia which was qualitatively similar to, but less severe than, that observed in mice with spontaneous disease. These findings indicate that naturally occurring PVM infection in athymic mice may cause respiratory disease and wasting.

Animals↗

[Mortality from respiratory diseases among agricultural and non-agricultural workers in France from 1970 to 1974].

The mortality due to respiratory disease was studied in France between 1970 and 1974 as well as in seven other countries in the European Economic Community. The French results were presented as an index of mortality by cause of death, enabling a comparison of the mortality in different groups of the population. Data was supplied for 7 diagnostic groups defined according to List A of the International Classification of Diseases. The population studied consisted of men and women between 15 to 64 years, classified according to residence (urban or rural) and profession (agricultural worker or not). In addition the indices of mortality for farmers or agricultural employees were compared to men of the same social class, for the same period. The comparisons between the urban and the rural background revealed an excess mortality for respiratory tuberculosis, lung cancer, bronchitis, emphysema and asthma for those in urban areas. In the rural environment an excess mortality was noted for acute respiratory diseases in both men and women; this was also found comparing agricultural to non-agricultural workers. Lastly, if one compared agricultural and non-agricultural workers of the same social class, deaths due to acute and chronic respiratory infections were higher in the agricultural workers. These results show the relative importance already stressed in other studies, of acute respiratory diseases in agricultural workers.

Adult↗

Respiratory viruses in children younger than five years old with acute respiratory disease from 2001 to 2004 in Uberlândia, MG, Brazil.

The main viruses involved in acute respiratory diseases among children are: respiratory syncytial virus (RSV), influenzavirus (FLU), parainfluenzavirus (PIV), adenovirus (AdV), human rhinovirus (HRV), and the human metapneumovirus (hMPV). The purpose of the present study was to identify respiratory viruses that affected children younger than five years old in Uberlândia, Midwestern Brazil. Nasopharyngeal aspirates from 379 children attended at Hospital de Clínicas (HC/UFU), from 2001 to 2004, with acute respiratory disease, were collected and tested by immunofluorescence assay (IFA) to detect RSV, FLU A and B, PIV 1, 2, and 3 and AdV, and RT-PCR to detect HRV. RSV was detected in 26.4% (100/379) of samples, FLU A and B in 9.5% (36/379), PIV 1, 2 and 3 in 6.3% (24/379) and AdV in 3.7% (14/379). HRV were detected in 29.6% (112/379) of the negative and indeterminate samples tested by IFI. RSV, particularly among children less than six months of life, and HRV cases showed highest incidence. Negative samples by both IFA and RT-PCR might reflect the presence of other pathogens, such as hMPV, coronavirus, and bacteria. Laboratorial diagnosis constituted an essential instrument to determine the incidence of the most common viruses in respiratory infections among children in this region.

Acute Disease↗

Ethnic differences in the prevalence of nonmalignant respiratory disease among uranium miners.

OBJECTIVES: This study (1) investigates the relationship of nonmalignant respiratory disease to underground uranium mining and to cigarette smoking in Native American, Hispanic, and non-Hispanic White miners in the Southwest and (2) evaluates the criteria for compensation of ethnic minorities. METHODS: Risk for mining-related lung disease was analyzed by stratified analysis, multiple linear regression, and logistic regression with data on 1359 miners. RESULTS: Uranium mining is more strongly associated with obstructive lung disease and radiographic pnuemoconiosis in Native Americans than in Hispanics and non-Hispanic Whites. Obstructive lung disease in Hispanic and non-Hispanic White miners is mostly related to cigarette smoking. Current compensation criteria excluded 24% of Native Americans who, by ethnic-specific standards, had restrictive lung disease and 4.8% who had obstructive lung disease. Native Americans have the highest prevalence of radiographic pneumoconiosis, but are less likely to meet spirometry criteria for compensation. CONCLUSIONS: Native American miners have more nonmalignant respiratory disease from underground uranium mining, and less disease from smoking, than the other groups, but are less likely to receive compensation for mining-related disease.

Colorado↗

[Donato G Alarcón, founder of institutions devoted to respiratory diseases in Mexico].

Dr. Donato G. Alarcón was the founder director of the National Institute of Respiratory Diseases recently named "Ismael Cosío Villegas ", officially established on December 31, 1935. He was also the first president of the Mexican Society of Tuberculosis Studies, and the first director of its journal: the Mexican Journal of Tuberculosis and Respiratory Diseases, both starting in 1939 and the first general director of the National Committee of Fight Against Tuberculosis. In Mexico only Dr. Donato G. Alarcón, in the respiratory diseases, and Dr. Ignacio Chávez, in the cardiovascular diseases, took the initial responsability of the three equivalent institutions: the National Institute, the Society of Specialists and the journal of the specialty. He was also the first pulmonologist elected director of the National Academy of Medicine of Mexico and director of the Faculty of Medicine of the National Autonomous University of Mexico.

Academies and Institutes↗

Hospitalization for lower respiratory disease during 20 yrs among under 5 yr old children in Stockholm County: a population based survey.

Lower respiratory disease (LRD) is a common cause of hospitalization in infants, and episodes of obstructive LRD increase the risk for asthma later in life. The purpose of this study was to assess time trends and geographical variation of first time hospitalization for LRD among children in Stockholm County, Sweden. Data on first time admittance for LRD among children aged up to 5 yrs from 1973 through 1992 were obtained from the Stockholm County Council hospital discharge register, and population register data were used for estimation of the population at risk. Municipal data were available for 1982-1992 on outbreaks of respiratory syncytial virus (RSV) infections and socio-economic factors. A total of 12,450 children had been hospitalized for the first time with LRD. For children aged <2 yrs a 100% increase in the rate of first time hospitalization for LRD was observed during the study period and children aged up to 1 yr predominated (50%). The average yearly increase in the population based first time hospital admission rate for LRD was 1.82%. Males constituted 65% of the cases. Of the diagnoses, 89.6% were consistent with obstructive LRD, e.g. asthma and obstructive bronchitis. In children aged up to 1 yr, peaks in the rate of hospitalization tended to coincide with outbreaks of RSV infections. Differences in hospitalization between municipalities seemed to be partly explained by differences in the admission practices of the four paediatric hospitals in the area. We conclude that the increased rate of hospitalization for lower respiratory disease in infants of Stockholm County may reflect a true increase in the incidence of obstructive respiratory disease. However, several factors determine admittance to hospital and the results need to be interpreted with caution.

Age Distribution↗

A potential role for tumour necrosis factor-alpha in synergy between porcine respiratory coronavirus and bacterial lipopolysaccharide in the induction of respiratory disease in pigs.

This study examined whether exposure of pigs to both porcine respiratory coronavirus (PRCV) and bacterial lipopolysaccharide (LPS) can potentiate respiratory disease and lung secretion of tumour necrosis factor-a (TNF-alpha) and interleukin-1 (IL-1). Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with PRCV, with LPS from Escherichia coli O111:B4 (20 microg/kg), or with a combination of the two, and killed at set times after inoculation. Clinical signs, virus replication and (histo)pathological changes in the lungs, percentage of neutrophils and bioactive TNF-alpha and IL-1 in broncho-alveolar lavage (BAL) fluids were examined. The effects of separate virus or LPS inoculations were subclinical and failed to induce high and sustained cytokine levels. In a preliminary study, pigs were inoculated with PRCV and then with LPS 24 h later and killed sequentially. Severe respiratory disease and significantly enhanced TNF-alpha titres (208-3601 U/ml versus 40-89 U/ml after LPS only) were seen during the first 12 h after LPS inoculation. IL-1 levels (106-1631 U/ml versus 28-654 U/ml after LPS only) were also increased, but persisted for longer after clinical recovery than TNF-alpha. In a second study, pigs were inoculated with PRCV and subsequently with LPS at various time intervals ranging from 0 to 24 h, and killed 5 h after inoculation with LPS. A time interval of at least 12 h between inoculations was necessary for prominent respiratory signs to develop. Production of TNF-alpha, but not IL-1, was also dependent on the time interval between inoculations and was tightly correlated with disease. Lung neutrophil infiltration and pathological changes were comparable after combined PRCV-LPS and single LPS inoculations, and were not associated with disease. These data show that exposure to high endotoxin concentrations in swine buildings can precipitate respiratory disease in PRCV-infected pigs, and that TNF-alpha is probably an important mediator of these effects. This is the first in-vivo demonstration of synergy between respiratory viruses and LPS.

Animals↗