Air pollution and asthma

The role of air pollution in the increased prevalence and morbidity of asthma has been widely debated, but results to date indicate that the normally encountered levels of air pollution are unlikely to contribute to a worsening of asthma. When the levels of sulphur dioxide (SO2) are exceptionally high it is possible that asthmatic patients may have increased symptoms after exertion, since this irritant gas acts as a trigger to bronchoconstriction. There is also evidence that suspended particles may also act as an inciter of asthma symptoms when concentrations are high. Experimentally, ozone in high concentrations may increase airway responsiveness in both normal and asthmatic subjects by inducing airway inflammation, but asthmatic individuals show the same responses as normal subjects and there is little or no evidence to link increases in ambient ozone with an increase in asthma. There is little evidence that nitrogen dioxide (NO2), even at the peak levels recorded, has any significant effect on airway function in normal or asthmatic individuals. Other air pollutants which are present in lower concentrations have not been studied as extensively, but there is no convincing evidence that they cause significant respiratory symptoms in asthmatic patients. It is still possible that combinations of air pollutants may have greater effects on airway function than exposure to a single pollutant, although there is little evidence to support this. Epidemiological evidence provides little support for the idea that atmospheric pollution levels are related to the frequency of asthma symptoms or the frequency of attacks. More importantly, there is no evidence that asthma prevalence or aetiology is related to the level of air pollution. A review of currently available information therefore provides little evidence for the widely expressed view that atmospheric pollution is related to increased prevalence or morbidity of asthma or is related to the causation of asthma.     

Effect of air pollution on respiratory symptoms of junior high school students in Indonesia

In 1994, 16,187 junior high school students were surveyed in Jakarta and surrounding cities, Indonesia, to study the effect of air pollution on respiratory illnesses. Nitrogen dioxide (NO2) was measured by the filter badge developed by Yanagisawa and Nishimura as a measure of air pollution. The average concentration of NO2 is the highest in central Jakarta and Tangerang (22-30 ppb), the lowest in rural areas (5-11 ppb), and in other cities, 11-20 ppb. Self-administered questionnaires were given to the students in 29 schools to obtain respiratory symptoms of cough, phlegm and wheeze. A significant relationship was found in this study between NO2 exposure levels and prevalence rates of cough, phlegm, and wheezing without cold, which were 27.7 to 38.7%, 15.0 to 21.9%, and 1.4 to 2.9%, respectively. Prevalence rates of persistent cough and persistent phlegm were 7.3 to 10.8% and 4.5 to 5.0% respectively. These rates were higher than those found by other researchers. This difference may be partly due to the survey methods. The more polluted, the higher the prevalence rate of respiratory symptoms.     

Risk factors for sensitisation and respiratory symptoms among workers exposed to acid anhydrides: a cohort study

OBJECTIVES: To examine the relation between exposure to acid anhydrides and the risk of developing immediate skin prick test responses to acid anhydride human serum albumin (AA-HSA) conjugates or work related respiratory symptoms; to assess whether these relations are modified by atopy or smoking. METHODS: A cohort of 506 workers exposed to phthalic (PA), maleic (MA), and trimellitic anhydride (TMA) was defined. Workers completed questionnaires relating to employment history, respiratory symptoms, and smoking habits. Skin prick tests were done with AA-HSA conjugates and common inhalant allergens. Exposure to acid anhydrides was measured at the time of the survey and a retrospective exposure assessment was done. RESULTS: Information was obtained from 401 (79%) workers. Thirty four (8.8%) had new work related respiratory symptoms that occurred for the first time while working with acid anhydrides and 12 (3.2%) were sensitised, with an immediate skin prick test reaction to AA-HSA conjugates. Sensitisation to acid anhydrides was associated with work related respiratory symptoms and with smoking at the time of exposure to acid anhydride. When all subjects were included and all three acid anhydrides were taken into account there was no consistent evidence for an exposure-response relation, but with the analysis restricted to a factory where only TMA was in use there was an increased prevalence of sensitisation to acid anhydrides and work related respiratory symptoms with increasing full shift exposure. This relation was apparent within the current occupational exposure standard of 40 micrograms.m-3 and was not modified significantly by smoking or atopy. CONCLUSIONS: Intensity of exposure and cigarette smoking may be risk factors for sensitisation to acid anhydrides. Exposure is also a risk factor for respiratory symptoms. As there was evidence for sensitisation to TMA at full shift exposures within the occupational exposure standard this standard should be reviewed.     

Effect of nitrogen dioxide and other combustion products on asthmatic subjects in a home-like environment

Nitrogen dioxide (NO2) is one of a number of nitrogen compounds that are by-products of combustion and occur in domestic environments following the use of gas or other fuels for heating and cooking. In this study, we examined the effect of two levels of NO2 on symptoms, lung function and airway hyperresponsiveness (AHR) in asthmatic adults and children. In addition, in the same subjects, we examined the effects of the same levels of NO2 mixed with combustion by-products from a gas space heater. The subjects were nine adults, aged 19-65 yrs, and 11 children, aged 7-15 yrs, with diagnosed asthma which was severe enough to require daily medication. All subjects had demonstrable AHR to histamine. Exposures were for 1 h on five separate occasions, 1 week apart, to: 1) ambient air, drawn from outside the building; 2) 0.3 parts per million (ppm) NO2 in ambient air; 3) 0.6 ppm NO2 in ambient air; 4) ambient air+combustion by-products+NO2 to give a total of 0.3 ppm; and 5) ambient air+combustion by-products+NO2 to give a total of 0.6 ppm. Effects were measured as changes in lung function and symptoms during and 1 h after exposure, in AHR 1 h and 1 week after exposure, and in lung function and symptoms during the week following exposure. Exposure to NO2 either in ambient air or mixed with combustion by-products from a gas heater, had no significant effect on symptoms or lung function in adults or in children. There was a small, but statistically significant, increase in AHR after exposure to 0.6 ppm NO2 in ambient air. However, there was no effect of 0.6 ppm NO2 on AHR when the combustion by-products were included in the test atmosphere nor of 0.3 ppm NO2 under either exposure condition. We conclude that a 1 h exposure to 0.3 or 0.6 ppm NO2 has no clinically important effect on the airways of asthmatic adults or children, but that 0.6 ppm may cause a slight increase in airway hyperresponsiveness.     

The role of rhinovirus in allergic airway inflammation

Epidemiological data demonstrate that viral infections are the most important trigger for acute asthma symptoms in children, and this association persists in many adults with asthma. Studies on volunteers experimentally infected with rhinoviruses (RV) suggest that atopy alone does not predispose to unusually severe symptoms. In contrast, experimental models combining viral infection and allergen exposure have identified potential links between virus-induced and allergen-induced inflammation. While in vitro studies suggest that cytokines may be an important part of this association, their role must be verified by sampling lower airway fluids and tissues in vivo after experimental and/or natural rhinovirus infections. Although it has long been recognized that the common cold is a potent trigger for symptoms of asthma, the mechanisms underlying the association between upper respiratory infection and increased lower airway obstruction remain obscure. The use of experimental infection of volunteers with or without respiratory allergies has enabled direct comparisons of common cold symptoms in these two groups. Furthermore, techniques such as bronchoalveolar lavage and segmental antigen challenge have been used to directly sample lower airway fluids and tissues during acute viral infection.     

Bupivacaine 0.01% and/or epinephrine 0.5 microg/ml improve epidural fentanyl analgesia after cesarean section

The Pollution Effects on Asthmatic Children in Europe (PEACE) study is a multicentre study of the acute effects of particles with a 50% cut-off aerodynamic diameter of 10 microm (PM10), black smoke (BS), sulphur dioxide (SO2) and nitrogen dioxide (NO2) on the respiratory health of children with chronic respiratory symptoms. The study was conducted in the winter of 1993/1994 by 14 research centres in Europe. A total of 2,010 children, divided over 28 panels in urban and suburban locations, was followed for at least 2 months. Exposure to air pollution was monitored on a daily basis. Health status was monitored by daily peak expiratory flow (PEF) measurements and a symptom diary. The association between respiratory health and air pollution levels was calculated with time series analysis. Combined effect estimates of air pollution on PEF or the daily prevalence of respiratory symptoms and bronchodilator use were calculated from the panel-specific effect estimates. Fixed effect models were used and, in cases of heterogeneity, random effect models. No clear associations between PM10, BS, SO2 or NO2 and morning PEF, evening PEF, prevalence of respiratory symptoms or bronchodilator use could be detected. Only previous day PM10 was negatively associated with evening PEF, but only in locations where BS was high compared to PM10 concentrations. There were no consistent differences in effect estimates between subgroups based on urban versus suburban, geographical location or mean levels of PM10, BS, SO2 and NO2. The lack of association could not be attributed to a lack of statistical power, low levels of exposure or incorrect trend specifications. In conclusion, the PEACE project did not show effects of particles with a 50% cut-off aerodynamic diameter of 10 microm, black smoke, sulphur dioxide or nitrogen dioxide on morning or evening peak expiratory flow or the daily prevalence of respiratory symptoms and bronchodilator use.     

Traffic-related NO2 and the prevalence of asthma and respiratory symptoms in seven year olds

The aim of this study was to determine whether outdoor nitrogen dioxide (NO2) was associated with the prevalence of asthma and respiratory symptoms. In eight nonurban communities, 843 children resident for a minimum of 2 yrs were studied. Since industrial sources of air pollution were at least 20 km away from the study communities, NO2 was considered to primarily indicate traffic-related air pollution. NO2 was recorded at central monitors, and the 3 yr mean exposure was calculated. Asthma and respiratory symptoms were assessed according to the International Study on Asthma and Allergy in Childhood. Prevalence of asthma at some time ("ever asthma") was associated with long-term NO2. In parallel with increasing levels of NO2 (community specific 3 yr mean 6.0-17.0 parts per billion (ppb)), asthma prevalence was 2.5, 1.4, 1.6, 2.3, 3.4, 3.6, 7.6 and 8.5%, respectively (p=0.002 for trend). The prevalence odds ratios (PORs) for "ever asthma", following adjustment for gender, age, parental education, passive smoke exposure, type of indoor heating, and parental asthma, were 1.28 (95% confidence interval (95% CI) 0.20-7.98), 2.14 (95% CI 0.40-11.3) and 5.81 (95% CI 1.27-26.5), when each of two communities with low, regular and high NO2, respectively, were compared with the two communities with very low NO2. For symptoms "wheeze" (adjusted PORs for increased NO2: 1.47, 1.23 and 2.27) and "cough apart from colds" (adjusted PORs for increased NO2: 1.49, 1.93 and 2.07), a similar trend was seen. In this study a significant relationship was observed between traffic-related nitrogen dioxide and the prevalence of asthma and symptoms. Whether this association is causal has to be tested in longitudinal studies.     

Respiratory effects associated with indoor nitrogen dioxide exposure in children

BACKGROUND: The human health effects of exposure to indoor nitrogen dioxide (NO2) are unclear, and few studies have examined the effects of short-term peak levels of exposure. METHODS: The association between indoor exposure to NO2 and respiratory illness was examined in 388 children aged 6-11 years. The NO2 levels were monitored during winter in 41 classrooms, from four schools with unflued gas heating and four schools with electric heating. Each classroom was monitored daily with 6-hour passive diffusion badge monitors over nine alternate weeks, and with hourly monitors over two of those weeks. Children living in homes with unflued gas appliances were also monitored daily over four evenings during times of gas use. RESULTS: Exposure to NO2 at hourly peak levels of the order of > or = 80 ppb, compared with background levels of 20 ppb, was associated with a significant increase in sore throat, colds and absences from school. An increase in cough with phlegm was marginally significant. Significant dose-response relationships were demonstrated for these four measures with increasing levels of NO2 exposure. CONCLUSIONS: Short-term peak levels of exposure are important to consider in relation to adverse respiratory effects associated with NO2 exposure.     

Seeing is believing

BACKGROUND: Nitric oxide (NO) may be an important component of the host defence against infections. Endogenously produced NO is present in exhaled air and may be representative of respiratory tract production of NO. Since subjects infected with HIV are prone to develop respiratory infections, it was postulated that exhaled NO might be reduced in such individuals. METHODS: The exhaled concentration of NO (nl/l) and minute ventilation (l/min) were measured and exhaled NO release (nl/min/m2) calculated in 36 subjects infected with HIV (20 non-smokers, 16 smokers) and 31 non-smoking subjects with no active medical conditions. RESULTS: Exhaled NO from HIV positive individuals was less than from control subjects of similar age, height, and weight. Cigarette smoking did not account for the decreased exhaled NO in HIV positive individuals as both smoking and non-smoking HIV positive subjects had decreased exhaled NO compared with control subjects. CONCLUSION: Exhaled NO is decreased in subjects infected with the HIV. Since NO functions in host defence against bacterial, viral, and fungal infections, reduced exhaled NO may indicate a mechanism of impaired host defence in HIV infection.     

A relatively small change in sodium chloride concentration has a strong effect on adhesion of ocular bacteria to contact lenses

We studied the effect of the nitric oxide synthase (NOS) inhibitor asymmetric dimethyl arginine (ADMA) and the inactive enantiomer N G-methyl-D-arginine (D-NMMA) on Pseudomonas aeruginosa infection of the respiratory mucosa in nasal turbinate organ cultures. We also investigated the effect of P. aeruginosa culture filtrate on the expression of inducible NOS (iNOS) messenger RNA (mRNA) by an epithelial cell line (A549). Organ cultures were preincubated with ADMA (0.1 to 4 x 10(-4) M) or D-NMMA (2 x 10(-4) M) for 30 min prior to bacterial infection. Infected organ cultures (8 h) had significantly (P <= 0.05) greater epithelial damage and fewer ciliated and unciliated cells than did control cultures. There was an increased level of nitrite in the medium feeding infected organ cultures as compared with control cultures. ADMA significantly (P <= 0.05) reduced both bacterially induced epithelial damage and loss of ciliated cells in a concentration-dependent manner. D-NMMA did not influence the effect of P. aeruginosa infection of the mucosa. ADMA, but not D-NMMA, significantly (P <= 0.04) reduced total bacterial numbers adherent to the respiratory mucosa. P. aeruginosa culture filtrates (24 h and 36 h) significantly (P = 0.02) increased iNOS with respect to glyceraldehyde-3-phosphate dehydrogenase mRNA expression. These results show that P. aeruginosa stimulates iNOS expression by a cell line and NO production by an organ culture. ADMA reduces mucosal damage and loss of ciliated cells, which suggests that NO may be a mediator of epithelial damage caused by P. aeruginosa.     

Pollution and allergy: the contributions of animal and in vitro experimentation

The respiratory pathological symptoms induced by atmospheric pollutants are closely dependent on the action of the aerocontaminants on the cells of the respiratory tract that are exposed to their effects. Two methods of experimental investigation are used to specify the effects of pollutants on the respiratory system: Study of the morphological and functional alterations of animal respiratory systems after exposure to different pollution constituents. Exposure of bronchitic or pulmonary cells to microquantities of pollutants, using different techniques that create direct contact between the pollutant and target cells. In animals gaseous pollutants alter the means of defence (muco-ciliary purification and antibacterial defence), inducing development of a neutrophil inflammatory reaction and, for ozone and NO2 favouring sensitisation by allergen-dependent IgE; diesel particles are responsible for restrictive ventilation problems, an inflammatory reaction, a sensitisation develops to pneumoallergens and in some cases of the development of pulmonary tumours. In vitro studies specify the cellular mechanisms and the molecules that are responsible for the observed phenomena: increase in the synthesis and expression of messenger DNA the codes for the pro-inflammatory cytokines, adherance molecules and chimiokines.     

Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione

Both reversible and irreversible inhibition of mitochondrial respiration have been reported following the generation of nitric oxide (NO) by cells. Using J774 cells, we have studied the effect of long-term exposure to NO on different enzymes of the respiratory chain. Our results show that, although NO inhibits complex IV in a way that is always reversible, prolonged exposure to NO results in a gradual and persistent inhibition of complex I that is concomitant with a reduction in the intracellular concentration of reduced glutathione. This inhibition appears to result from S-nitrosylation of critical thiols in the enzyme complex because it can be immediately reversed by exposing the cells to high intensity light or by replenishment of intracellular reduced glutathione. Furthermore, decreasing the concentration of reduced glutathione accelerates the process of persistent inhibition. Our results suggest that, although NO may regulate cell respiration physiologically by its action on complex IV, long-term exposure to NO leads to persistent inhibition of complex I and potentially to cell pathology.     

Bipotential primitive-definitive hematopoietic progenitors in the vertebrate embryo

The effects of the diatomic radical, nitric oxide (NO), on melphalan-induced cytotoxicity in Chinese hamster V79 and human MCF-7 breast cancer cells were studied using clonogenic assays. NO delivered by the NO-releasing agent (C2H5)2N[N(O)NO]- Na+ (DEA/NO; 1 mM) resulted in enhancement of melphalan-mediated toxicity in Chinese hamster V79 lung fibroblasts and human breast cancer (MCF-7) cells by 3.6- and 4.3-fold, respectively, at the IC50 level. Nitrite/nitrate and diethylamine, the ultimate end products of DEA/NO decomposition, had little effect on melphalan cytotoxicity, which suggests that NO was responsible for the sensitization. Whereas maximal sensitization of melphalan cytotoxicity by DEA/NO was observed for simultaneous exposure of DEA/NO and melphalan, cells pretreated with DEA/NO were sensitized to melphalan for several hours after NO exposure. Reversing the order of treatment also resulted in a time-dependent enhancement in melphalan cytotoxicity. To explore possible mechanisms of NO enhancement of melphalan cytotoxicity, the effects of DEA/NO on three factors that might influence melphalan toxicity were examined, namely NO-mediated cell cycle perturbations, intracellular glutathione (GSH) levels and melphalan uptake. NO pretreatment resulted in a delayed entry into S phase and a G2/M block for both V79 and MCF-7 cells; however, cell cycle redistribution for V79 cells occurred after the cells returned to a level of cell survival, consistent with treatment with melphalan alone. After 15 min exposure of V79 cells to DEA/NO (1 mM), GSH levels were reduced to 40% of control values; however, GSH levels recovered fully after 1 h and were elevated 2 h after DEA/NO incubation. In contrast, DEA/NO (1 mM) incubation did not reduce GSH levels significantly in MCF-7 cells (approximately 10%). Melphalan uptake was increased by 33% after DEA/NO exposure in V79 cells. From these results enhancement of melphalan cytotoxicity mediated by NO appears to be complex and may involve several pathways, including possibly alteration of the repair of melphalan-induced lesions. Our observations may give insights for improving tumour kill with melphalan using either exogenous or possibly endogenous sources of NO.     

Respiratory symptoms and lung function abnormalities among machine operators in automobile production

This cross-sectional study was designed to assess differences in prevalence of respiratory symptoms and lung function between machine operators exposed to semisynthetic or soluble metal-working fluids (MWFs) and unexposed assemblers and to assess exposure-response relationships with MWF type, total aerosol, endotoxin, culturable bacteria and fungi. We evaluated 183 machine operators and 66 assemblers from one large automobile transmission plant using questionnaires, spirometry data, and cross-shift assessment of both lung function and respiratory symptoms. We found that airborne exposures to total aerosol, endotoxin, culturable bacteria and fungi were higher in machine operations than in the assembly area. There was a correlation between bulk and airborne culturable bacteria, but not between bulk and airborne culturable fungi. Machine operators had significantly more usual cough, usual phlegm, work-related chest tightness and post-shift symptoms of chest tightness, throat irritation, and cough compared with assemblers. We found exposure-response relationships between respiratory symptoms and total aerosol, as well as culturable fungi and bacteria. Associations with endotoxin were not strong or consistent, possibly because airborne levels were generally low. Cross-shift lung function decrements did not differ between machine operators and assemblers and there were no associations with MWF or specific exposures. The finding of respiratory symptoms at low levels of exposure in this study suggests the need to re-assess total aerosol thresholds. Associations between airborne fungal exposures and respiratory symptoms need further study to characterize sources of exposure other than MWF in machining operations.     

Detection of Mycobacterium tuberculosis DNA in lobular granulomatous panniculitis (erythema induratum-nodular vasculitis)

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.     

Respiratory syncytial virus bronchiolitis

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.     

Assessment of the indoor environment in respiratory allergy

Many types of allergens may be present in the indoor environment and may lead to sensitization and respiratory allergy. Common indoor allergens include dust mites, animal dander, cockroach exposure and molds. Exposure to indoor pollutants, such as tobacco smoke, wood-burning stoves or fireplaces and chemical sprays, can precipitate and exacerbate symptoms. An allergic reaction in the airways caused by natural exposure to allergens has been shown to lead to an increase in inflammatory reaction, increased airway hyperresponsiveness and increased eosinophils in bronchoalveolar lavage. Other research has demonstrated that asthma symptoms correlate with levels of domestic dust mite and cockroach exposure. In the case of dust mites, ending exposure results in symptomatic relief.     

Management of advanced duodenal polyposis in familial adenomatous polyposis

Farmers are exposed to high levels of organic dust with a high content of bacteria, fungi and endotoxins. The main exposure takes place during the many hours of work in closed animal confinement buildings, and working in swine confinement buildings gives the highest exposure. Corresponding to this, farmers have a high prevalence of respiratory symptoms and cross-sectional studies show evidence of airways obstruction. Swine farming seems to be an important risk factor for this in the farming community. Allergy plays a minor role in the development of symptoms, the most important allergy being towards storage mites. Longitudinal studies suggest that exposure to high concentrations of organic dust is associated with an accelerated decline in forced expiratory volume in one second.