nitrogen-dioxide and Bronchial-Hyperreactivity

Controlled human exposure studies evaluating the effect of inhaled nitrogen dioxide (NO2) on the inherent responsiveness of the airways to challenge by broncho-constricting agents have had mixed results. In general, existing meta-analyses show statistically significant effects of NO2 on the airway responsiveness of individuals with asthma. However, no meta-analysis has provided a comprehensive assessment of the clinical relevance of changes in airway responsiveness, the potential for methodological biases in the original papers, and the distribution of responses. This paper provides analyses showing that a statistically significant fraction (i.e. 70% of individuals with asthma exposed to NO2 at rest) experience increases in airway responsiveness following 30-min exposures to NO2 in the range of 200 to 300 ppb and following 60-min exposures to 100 ppb. The distribution of changes in airway responsiveness is log-normally distributed with a median change of 0.75 (provocative dose following NO2 divided by provocative dose following filtered air exposure) and geometric standard deviation of 1.88. About a quarter of the exposed individuals experience a clinically relevant reduction in their provocative dose due to NO2 relative to air exposure. The fraction experiencing an increase in responsiveness was statistically significant and robust to exclusion of individual studies. Results showed minimal change in airway responsiveness for individuals exposed to NO2 during exercise.

Topics: Air Pollutants; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Exercise; Humans; Nitrogen Dioxide

The effects of 0.1 to 0.6 ppm nitrogen dioxide (NO2) on airway hyper-responsiveness (AHR) to airway challenges in asthmatics have been evaluated in several controlled exposure studies. The authors conducted meta-analyses and meta-regressions of these studies using several effect measures for AHR: a change (in NO2 versus air) in (1) the provocative dose of a challenge agent necessary to cause a specified change in lung function (PD), (2) the change in FEV1 after an airway challenge, and (3) the fraction of subjects with increased AHR. Although several effect estimates from the meta-analyses are statistically significant, they are all so small that they are not likely to be clinically relevant. More importantly, there are no exposure-response associations for any effect estimates based on linear meta-regressions or analyses of effect estimates for exposure groups (0.1 to <0.2 ppm, 0.2 to <0.3 ppm, etc.). This is also generally the case for analyses stratified by airway challenge (specific/nonspecific), exposure method (mouthpiece/whole chamber), and activity during exposure (rest/exercise). The results of these analyses indicate that, to the extent the effects observed are associated with NO2 exposure, they are sufficiently small such that they do not provide evidence that NO2 has a significant adverse effect on AHR at concentrations up to 0.6 ppm.

Topics: Air Pollutants; Asthma; Bronchial Hyperreactivity; Humans; Inhalation Exposure; Nitrogen Dioxide; Regression Analysis; Respiratory Function Tests

In the last decades, many studies have shown an increase in the prevalence of allergic rhinitis and asthma mainly in urban communities, especially in industrialized countries. Airborne pollutants such as diesel exhaust particles, ozone, nitrogen dioxide and sulphur dioxide have been implicated in the initiation and exacerbation of allergic airway diseases. Epidemiologic studies have shown clear associations between air pollution and allergic diseases, in vivo and in vitro studies have provided biologic link and potential molecular mechanisms. Particulate and gaseous pollutants can act both on the upper and lower airways to initiate and exacerbate cellular inflammation through interaction with the innate immune system. As a consequence, increased non-specific airway hyper-responsiveness and airway resistance have been observed in man. Diesel exhaust particles can both induce and exacerbate in vivo allergic responses. They can also modify the immune system's handling of the allergen. The effects of gaseous pollutants on immune responses to allergens are not fully understood. We review the different mechanisms involved in the enhancement of allergic inflammation by urban air pollutants, including effects on cytokine and chemokine production, as well as activation of different immune cells. We discuss the hypothesis that pollutants' effects on the immune system involve hierarchical oxidative stress. Susceptibility genes to air pollution inducing allergic diseases are also discussed.

Topics: Air Pollutants; Air Pollution; Allergens; Animals; Asthma; Bronchial Hyperreactivity; Epithelial Cells; Humans; Immunoglobulin E; Macrophages; Mast Cells; Models, Immunological; Nitrogen Dioxide; Oxidative Stress; Ozone; Respiratory Hypersensitivity; Sulfur Dioxide; Vehicle Emissions

Topics: Air Pollutants; Animals; Bronchial Hyperreactivity; Cytokines; Humans; Hypersensitivity; Immunoglobulin E; Nitrogen Dioxide; Respiratory Mucosa; Sulfur Dioxide; Vehicle Emissions

Particles, SOx, and acid aerosols are a complex group of distinct pollutants that have common sources and usually covary in concentration. During the past two decades, the chemical characteristics and the geographic distribution of sulfur oxide and particulate pollution have been altered by control strategies, specifically taller stacks for power plants, put in place in response to air pollution regulations adopted in the early 1970s. While the increasing stack heights have lowered local ambient levels, the residence time of SOx and particles in the air have been increased, thereby promoting transformation to various particulate sulfate compounds, including acidic sulfates. These sulfate particles constitute a large fraction of the total mass of smaller particles (< 3 microns in aerodynamic diameter). Epidemiologic studies have consistently provided evidence of adverse health effects of these air pollutants. Particulate and SO2 pollution were strongly implicated in the acute morbidity and mortality associated with the severe pollution episodes in Donora (Pennsylvania), London, and New York in the 1940s, 1950s, and 1960s. There is new evidence that even current ambient levels of PM10 (30 to 150 micrograms/m3) are associated with increases in daily cardiorespiratory mortality and in total mortality, excluding accidental and suicide deaths. These associations have been shown in many different communities, as widely different in particle composition and climate as Philadelphia, St. Louis, Utah Valley, and Santa Clara County, California. It has recently been shown in a long-term prospective study of adults in the United States that chronic levels of higher PM10 pollution are associated with increased mortality after adjusting for several individual risk factors. Daily fluctuations in PM10 levels have also been shown to be related to acute respiratory hospital admissions in children, to school and kindergarten absences, to decrements in peak flow rates in normal children, and to increased medication use in children and adults with asthma. Although some epidemiologic studies suggest that acid aerosols are an important toxic component of PM10, other studies do not support this hypothesis. Dockery and Pope (408) recently reviewed the epidemiologic literature for adverse effects, assuming that reported associations can be attributed to acute particle mass exposures. Combined effects were estimated as percent increase in comparable measures of mortality and morbidit

Topics: Adult; Aerosols; Air Pollutants; Air Pollution; Animals; Asthma; Biomarkers; Bronchial Hyperreactivity; Carbon Monoxide; Cardiovascular Diseases; Cattle; Cells, Cultured; Child; Emergencies; Environmental Health; Female; Hospitalization; Humans; Lead; Lung Diseases, Obstructive; Male; Models, Biological; Nitrogen Dioxide; Occupational Health; Ozone; Pregnancy; Rabbits; Rats; Respiratory Function Tests; Respiratory Tract Diseases; Sulfur Dioxide; United States

A review of the present understanding of asthma leads to the following conclusions: an elevated IgE is the principal risk factor in the development of childhood asthma; secondary exposure to a wide range of environmental agents (including indoor bioallergens) accounts for the variations in prevalence; prevalence (defined by a positive answer to the question "Have you ever had doctor-diagnosed asthma?") ranges between 4 and 8% in children. Black children have a slightly higher prevalence than white children in the United States, and in both races boys have a higher prevalence than girls. A high prevalence is found in Puerto Rican children in the United States. Patterns of utilization of health care resources (hospital emergency departments, individual physicians, etc.) are dependent on economic circumstances. Low-income children have higher annual morbidity (days in hospital, days off school, etc.) than higher income children and are more dependent on hospital emergency departments for primary care. Relatively little is known about nonatopic asthma in adults, although virus infections and occupational exposures play some part in its induction. There are some striking examples of asthma attack periodicity, and much may be learned from these. Hospital admissions for asthma have increased in many regions over the past 15 years; it is unlikely that this represents the increased admission of milder cases and hence would indicate that asthma has become more severe. This is likely to be a more sensitive indicator of change than mortality. Associations between indices of health effects and air pollutants indicate that these are probably playing a role in the worsening of asthma. Adverse effects related to SO2 and NO2 exposures have been documented, and fine particulate pollution (PM10) is also associated with worsening of asthma. Ozone is an intense respiratory irritant, and, together with acid aerosols, may well be playing a role in the worsening of asthma. It is not known whether any of these agents are affecting prevalence.

Topics: Adult; Air Pollutants; Asthma; Bronchial Hyperreactivity; Child; Female; Humans; Male; Nitrogen Dioxide; Oxidants, Photochemical; Sulfur Dioxide; United States

We investigated the effects of NO2 and allergen on lung function in a repeated exposure model. For 4 subsequent days, 16 subjects with mild asthma and allergy to birch or grass pollen were exposed at rest to either purified air or 500 microg x m(-3) NO2 for 30 min in an exposure chamber. Four hours later, an individually determined nonsymptomatic allergen dose was inhaled. Lung function (forced expiratory volume in one second (FEV1)) was measured by a portable spirometer at early phase (EP) 15 min after allergen and at late phase (LP) 3-10 h after allergen. Subjective symptoms and medication were followed by diary cards. Asthmatic response was significantly increased after repeated exposure to NO2 and allergen compared to air and allergen. The 4-day mean fall in FEV1 after NO2 was at EP -25% versus -0.4% for air (p=0.02) and at LP -4.4% versus -1.9% for air (p=0.01, ANOVA). An increase in EP response was seen already after a single NO2 exposure (p=0.03). There was a tendency (p=0.07) towards increased night-time symptoms of asthma after NO2 plus allergen. Although the effects were small, the results indicate that a repeated short exposure to an ambient level of NO2 enhances the airway response to a nonsymptomatic allergen dose.

Topics: Adult; Air Pollutants; Allergens; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Dose-Response Relationship, Drug; Drug Synergism; Female; Forced Expiratory Volume; Histamine; Humans; Male; Nitrogen Dioxide; Pollen; Reproducibility of Results; Rhinitis, Allergic, Seasonal; Risk Factors

We investigated whether exposure to a low level (490 micrograms/m3) of nitrogen dioxide (NO2) affects bronchial responsiveness to allergen and enhances allergen-induced increase in airway responsiveness to histamine. Eighteen subjects with asthma and allergy to pollen were exposed at rest to either purified air or NO2 for 30 min followed 4 h later by an allergen inhalation challenge. Responsiveness to histamine was measured the day after. Lung function during NO2 exposure and allergen challenge was measured by plethysmography and after exposure by a portable spirometer hourly. The order of exposure to NO2 and air was randomized and separated by at least 2 wk. The asthmatic reaction during the late phase was enhanced by NO2, and peak expiratory flow after allergen challenge was on average 6.6% lower (p = 0.02) after NO2 than after air exposure. The number of subjects having a late asthmatic reaction (fall in FEV1 > 15%) was seven after air and 10 after NO2 (NS). Peripheral blood samples were analyzed for differential cell counts before and after NO2/allergen and serum levels of eosinophil cationic protein (ECP). NO2 effect on lung function was neither associated with an increase in eosinophil numbers nor with ECP levels. NO2 did not affect lung function before allergen challenge, early asthmatic reaction, and allergen-induced increase in responsiveness to histamine. These results indicate that short exposure to an ambient level of NO2 followed several hours later by allergen inhalation enhances allergen-induced late asthmatic reaction.

Topics: Administration, Inhalation; Adolescent; Adult; Airway Resistance; Allergens; Asthma; Atmosphere Exposure Chambers; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Eosinophil Granule Proteins; Female; Forced Expiratory Volume; Histamine; Humans; Inflammation Mediators; Leukocyte Count; Male; Middle Aged; Nitrogen Dioxide; Peak Expiratory Flow Rate; Pollen; Ribonucleases; Spirometry; Time Factors

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.

Topics: Adolescent; Adult; Aged; Air Pollutants; Air Pollution, Indoor; Analysis of Variance; Asthma; Bronchial Hyperreactivity; Child; Double-Blind Method; Female; Hazardous Substances; Heating; Humans; Male; Middle Aged; Nitrogen Dioxide; Respiratory Function Tests

Both peak flow decrements in children at summer camps and increased hospital admissions for asthma have been associated with summer "acid haze," which is composed of ozone and various acidic species. The objective of this study was to investigate the pulmonary effects of acid summer haze in a controlled laboratory setting. Twenty-eight adolescent subjects with allergic asthma, exercise-induced bronchospasm, and a positive response to a standardized methacholine challenge enrolled in the study; 22 completed the study. Each subject inhaled one of four test atmospheres by mouthpiece on two consecutive days. The order of exposure to the four test atmospheres was assigned via a random protocol: air, oxidants (0.12 parts per million [ppm]* ozone plus 0.30 ppm nitrogen dioxide), oxidants plus sulfuric acid at 70 micrograms/m3 of air, or oxidants plus 0.05 ppm nitric acid. Exposure to each of the different atmospheres was separated by at least one week. The exposures were carried out during alternating 15-minute periods of rest and moderate exercise for a total exposure period of 90 minutes per day. Pulmonary function was measured before and after exposure on both test days and again on the third day as a follow-up measurement. A postexposure methacholine challenge was performed on Day 3. Low methacholine concentrations were chosen for the postexposure challenge to avoid provoking a response. The protocol was designed to detect subtle changes in airway reactivity. The statistical significance of the pulmonary function values was tested using paired t tests. First, we compared the difference between baseline and postexposure measurements after air exposure on Day 1 with the differences between baseline and postexposure measurements after Day 1 exposure to each of the other three atmospheres. Second, we compared the difference between baseline and postexposure measurements after the Day 2 air exposure with the differences between baseline and postexposure measurements after the Day 2 exposure to each of the pollutant atmospheres. Third, we compared the difference between baseline measurements on Day 1 of each exposure atmosphere with measurements after exposure to the same atmosphere on Day 2 to detect delayed effects. No changes in any of the pulmonary function parameters were statistically significant when compared with changes after clean air exposure. Six subjects left the study because of uncomfortable symptoms associated with the exposures. These all occurred

Topics: Acid Rain; Adolescent; Adult; Aerosols; Air Pollutants; Asthma; Bronchial Hyperreactivity; Bronchial Spasm; Child; Female; Follow-Up Studies; Humans; Hypersensitivity; Lung; Male; Nitric Acid; Nitrogen Dioxide; Oxidants; Ozone; Physical Exertion; Sulfuric Acids

The impact of single exposures on asthma development is better understood than the effect of multiple exposures. The objective of the present study was to evaluate the effect of combined early exposure to dog allergen (Can-f1) plus indoor nitrogen dioxide (NO₂) or environmental tobacco smoke (ETS) on asthma and bronchial hyperreactivity (BHR) in a high-risk birth cohort. We also aimed to assess atopy's impact on the effects of these exposures. Peri-birth ETS exposure was measured using cord blood cotinine (CCot). During year 1, atopy, NO₂, Can-f1, and urinary cotinine (UCot) were measured. At 7 yrs of age, 380 children were assessed for asthma and BHR. Exposure effects were determined using stepwise multiple linear regression. Co-exposure to elevated Can-f1 and NO₂, or Can-f1 and ETS (CCot), increased risk for asthma, relative to having neither such exposure (OR 4.8 (95% CI 1.1-21.5) and 2.7 (1.1-7.1), respectively); similar risks resulted when substituting dog ownership for allergen. Atopy increased asthma and BHR risk associated with several exposures; notably, atopy with elevated UCot, relative to atopy without such exposure, increased risk of BHR (OR 3.1 (95% CI 1.1-8.6)). In a high-risk birth cohort, early co-exposure to Can-f1 and NO₂ or ETS increased the risk of incident asthma. Atopy increased the risk of asthma and BHR associated with ETS.

Topics: Air Pollutants; Allergens; Animals; Asthma; Bronchial Hyperreactivity; Child; Cohort Studies; Cotinine; Dogs; Environmental Exposure; Female; Fetal Blood; Humans; Incidence; Infant; Longitudinal Studies; Male; Nitrogen Dioxide; Tobacco Smoke Pollution

The role of traffic-related air pollution in the development of allergic diseases is still unclear. We therefore investigated if NO₂, an important constituent of traffic-related air pollution, promotes allergic sensitization to the allergen ovalbumin (OVA). We also examined if NO₂ influenced the allergy adjuvant activity of diesel exhaust particles (DEP). For this purpose, mice were exposed intranasally to OVA with or without DEP present, immediately followed by exposure to NO₂ (5 or 25 parts per million [ppm]) or room air for 4 h in whole body exposure chambers. Eighteen hours after the last of three exposures, the lungs of half of the animals were lavaged with saline and markers of lung damage and lung inflammation in the bronchoalveolar lavage fluid (BALF) were measured. Three weeks later, after intranasal booster immunizations with OVA, the levels of OVA-specific IgE and IgG2a antibodies in serum were determined. Both NO₂ (25 ppm) and DEP gave lung damage, measured as increased total protein concentration in BALF, whereas only NO₂ seemed to stimulate release of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast, only DEP significantly increased the number of neutrophils. Furthermore, DEP in combination with OVA stimulated the production of serum allergen-specific IgE antibodies. NO₂, however, neither increased the production of allergen-specific IgE antibodies, nor influenced the IgE adjuvant activity of DEP. Thus, based on our findings, NO₂ seems to be of less importance than combustion particles in the development of allergic diseases after exposure to traffic-related air pollution.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Air Pollutants; Allergens; Animals; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Drug Interactions; Female; Inflammation; Inhalation Exposure; Mice; Mice, Inbred BALB C; Nitrogen Dioxide; Ovalbumin; Vehicle Emissions

Allergen sensitization and allergic airway disease are likely to come about through the inhalation of Ag with immunostimulatory molecules. However, environmental pollutants, including nitrogen dioxide (NO2), may promote adaptive immune responses to innocuous Ags that are not by themselves immunostimulatory. We tested in C57BL/6 mice whether exposure to NO2, followed by inhalation of the innocuous protein Ag, OVA, would result in allergen sensitization and the subsequent development of allergic airway disease. Following challenge with aerosolized OVA alone, mice previously exposed via inhalation to NO2 and OVA developed eosinophilic inflammation and mucus cell metaplasia in the lungs, as well as OVA-specific IgE and IgG1, and Th2-type cytokine responses. One hour of exposure to 10 parts per million NO2 increased bronchoalveolar lavage fluid levels of total protein, lactate dehydrogenase activity, and heat shock protein 70; promoted the activation of NF-kappaB by airway epithelial cells; and stimulated the subsequent allergic response to Ag challenge. Furthermore, features of allergic airway disease were not induced in allergen-challenged TLR2-/- and MyD88-/- mice exposed to NO2 and aerosolized OVA during sensitization. These findings offer a mechanism whereby allergen sensitization and asthma may result under conditions of high ambient or endogenous NO2 levels.

Topics: Administration, Inhalation; Aerosols; Allergens; Animals; Bronchial Hyperreactivity; Eosinophilia; Immunologic Factors; Lung; Metaplasia; Mice; Mice, Inbred C57BL; Mice, Knockout; Mucus; Myeloid Differentiation Factor 88; Nitrogen Dioxide; Ovalbumin; Respiratory Hypersensitivity; Toll-Like Receptor 2

In addition to being an air pollutant, NO2 is a potent inflammatory oxidant generated endogenously by myeloperoxidase and eosinophil peroxidase. In these studies, we sought to determine the effects of NO2 exposure on mice with ongoing allergic airway disease pathology. Mice were sensitized and challenged with the antigen ovalbumin (OVA) to generate airway inflammation and subsequently exposed to 5 or 25 ppm NO2 for 3 days or 5 days followed by a 20-day recovery period. Whereas 5 ppm NO2 elicited no pathological changes, inhalation of 25 ppm NO2 alone induced acute lung injury, which peaked after 3 days and was characterized by increases in protein, LDH, and neutrophils recovered by BAL, as well as lesions within terminal bronchioles. Importantly, 25 ppm NO2 was also sufficient to cause AHR in mice, a cardinal feature of asthma. The inflammatory changes were ameliorated after 5 days of inhalation and completely resolved after 20 days of recovery after the 5-day inhalation. In contrast, in mice immunized and challenged with OVA, inhalation of 25 ppm NO2 caused a marked augmentation of eosinophilic inflammation and terminal bronchiolar lesions, which extended significantly into the alveoli. Moreover, 20 days postcessation of the 5-day 25 ppm NO2 inhalation regimen, eosinophilic and neutrophilic inflammation, pulmonary lesions, and AHR were still present in mice immunized and challenged with OVA. Collectively, these observations suggest an important role for NO2 in airway pathologies associated with asthma, both in modulation of degree and duration of inflammatory response, as well as in induction of AHR.

Topics: Animals; Bronchi; Bronchial Hyperreactivity; Dose-Response Relationship, Drug; Hypersensitivity; Mice; Mice, Inbred C57BL; Nitrogen Dioxide; Ovalbumin; Oxidants, Photochemical; Pneumonia

The impact of air pollution on asthma and allergies still remains a debate.. Our cross-sectional study was intended to analyse the associations between long-term exposure to background air pollution and atopic and respiratory outcomes in a large population-based sample of schoolchildren.. Six thousand six hundred and seventy-two children aged 9-11 years recruited from 108 randomly schools in six French cities underwent a clinical examination including a skin prick test (SPT) to common allergens, exercise-induced bronchial reactivity (EIB) and skin examination for flexural dermatitis. The prevalence of asthma, allergic rhinitis (AR) and atopic dermatitis was assessed by a standardized health questionnaire completed by the parents. Three-year-averaged concentrations of air pollutants (NO2, SO2, PM10 and O3) were calculated at children' schools using measurements of background monitoring stations.. After adjusting for confounders, EIB, lifetime asthma and lifetime AR were found to be positively related to an increase in the exposure to SO2, PM10 and O3. The adjusted odds ratios (aOR) per increase of 5 microg/m3 of SO2 was 1.39 (95% confidence interval (CI)=1.15-1.66) for EIB and 1.19 (1.00-1.41) for lifetime asthma. The aOR for lifetime AR per increase of 10 microg/m3 of PM10 was 1.32 (CI=1.04-1.68). Moreover, SPT positivity was associated with O3 (aOR=1.34; CI=1.24-1.46). Associations with past year symptoms were consistent, even if not always statistically significant. Results persisted in long-term resident (current address for at least 8 years) children. However, no consistent positive association was found with NO2.. A moderate increase in long-term exposure to background ambient air pollution was associated with an increased prevalence of respiratory and atopic indicators in children.

Topics: Air Pollutants; Air Pollution; Asthma; Bronchial Hyperreactivity; Child; Cross-Sectional Studies; Dermatitis, Atopic; Environmental Monitoring; Epidemiological Monitoring; Female; France; Humans; Hypersensitivity, Immediate; Male; Nitrogen Dioxide; Ozone; Prevalence; Rhinitis; Schools; Skin Tests; Sulfur Dioxide; Vehicle Emissions

The purpose of this study was to examine the effects of NO(2), a major component of air pollution, on airway eosinophilic inflammation and bronchial hyperreactivity, using a mouse model of asthma.. BALB/c mice (eight mice per experimental group) were studied in a basic research laboratory at the University of Iowa.. Using a standard murine model of asthma, BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal (IP) injections (days 1 and 7) and were challenged with aerosolized OVA (days 13 and 14). Some mice were exposed to NO(2) (2 ppm) in an exposure chamber for 24 h before undergoing OVA aerosol challenge. A control group was exposed to OVA alone.. The outcomes assessed included airway inflammation, bronchial hyperreactivity to inhaled methacholine, and goblet cell hyperplasia. We found that NO(2) exposure modestly increased airway neutrophilia but not airway eosinophilia in OVA-exposed mice. These mice exhibited epithelial damage and loss of epithelial mucin. Surprisingly, nonspecific bronchial hyperreactivity (ie, enhanced pause index) was not increased, although baseline smooth muscle tone was increased (p < 0.05) in the mice exposed to NO(2).. These data indicate that relatively short-term (24 h) exposure to NO(2) causes epithelial damage, reduced mucin expression, and increased tone of respiratory smooth muscle. Reduced mucin production may be a mechanism of injury following long-term exposure to inhaled NO(2). Despite enhancing epithelial damage in OVA-exposed mice, NO(2) exposure does not otherwise alter the expression of allergen-induced airway responses.

Topics: Animals; Asthma; Bronchial Hyperreactivity; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Nitrogen Dioxide; Ovalbumin; Oxidants, Photochemical; Respiratory Mucosa

Nitrogen dioxide (NO(2)) is a common indoor and outdoor air pollutant whose role in the induction of asthma is unclear. We investigated the effects of NO(2) on the development of asthma-like responses to allergenic challenge in BALB/c mice. Ovalbumin (OVA)-immunized mice were intranasally challenged with OVA or saline solution just before starting a 3 h exposure to 5 or 20 ppm NO(2) or air. Twenty parts per million of NO(2) induced a significant increase of bronchopulmonary hyperreactivity in OVA-challenged mice and of permeability according to the fibronectin content of the bronchoalveolar lavage fluid (BALF) 24 h after exposure, as compared with air or 5 ppm NO(2). Eosinophilia (cell counts in the BALF and eosinophil peroxidase of lung tissue) was detected at 24 and 72 h with similar levels for air and 20 ppm NO(2), whereas a marked reduction was unexpectedly observed for 5 ppm NO(2). At 24 h, interleukin-5 in the BALF was markedly reduced at 5 ppm compared with 20 ppm NO(2) and was also more intense for 20 ppm NO(2) than for the air group. In contrast to specific IgG1 titers, anti-OVA IgE titers and interleukin-4 in the BALF were not affected by NO(2) exposure. Irrespective of the concentration of NO(2), OVA-challenged mice did not develop late mucosal metaplasia compared with those exposed to OVA-air. These results indicate that a short exposure to NO(2) can exacerbate or inhibit some features of the development of allergic disease in mice and may depend on the concentration of pollutant.

Topics: Air Pollutants; Animals; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Eosinophils; Fibronectins; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-5; Lung; Male; Mice; Mice, Inbred BALB C; Nitrogen Dioxide; Ovalbumin

Previous epidemiological studies have shown acute effects of increased amounts of ambient air pollution on the prevalence of respiratory symptoms in children with respiratory disorders. We investigated whether children with bronchial hyperresponsiveness (BHR) and relatively high serum concentrations of total IgE (>60 kU/L, the median value) are susceptible to air pollution.. We collected data from children during three winters (1992-95) in rural and urban areas of the Netherlands. Lower respiratory symptoms (wheeze, attacks of wheezing, shortness of breath), upper respiratory symptoms (sore throat, runny or blocked nose), and peak expiratory flow were recorded daily for 3 months. The acute effects of airborne particulate matter with a diameter of less than 10 microm, black smoke, sulphur dioxide, and nitrogen dioxide were estimated by logistic regression.. 459 (73%) of 632 children had complete data. Of these, 26% had BHR and relatively high (above median) serum total IgE, 36% had no BHR and total IgE of 60 kU/L or less, 15% had BHR and total IgE of 60 kU/L or less, and 23% had a total IgE of more than 60 kU/L but no BHR. In children with BHR and relatively high serum total IgE the prevalence of lower respiratory symptoms increased significantly by between 32% and 139% for each 100 microm/m3 increase in particulate matter, and between 16% and 131% for each 40 microm/m3 increase in black smoke, SO2, or NO2. Decrease in peak expiratory flow of more than 10% in that group was more common with increased airborne particulate matter and black smoke. There were no consistent positive or negative associations between increased air pollution and prevalence of respiratory symptoms or decrease in peak expiratory flow in the other three groups of children.. Children with BHR and relatively high concentrations of serum total IgE are susceptible to air pollution. Although our odds ratios were rather low (range 1.16-2.39) the overall effect of air pollution on public health is likely to be substantial since these odds ratios refer to large numbers of people.

Topics: Air Pollutants; Air Pollution; Bronchial Hyperreactivity; Child; Female; Health Surveys; Humans; Immunoglobulin E; Logistic Models; Male; Netherlands; Nitrogen Dioxide; Peak Expiratory Flow Rate; Prevalence; Rural Health; Seasons; Smoke; Sulfur Dioxide; Urban Health

To identify characteristics associated with respiratory symptoms due to an episode of air pollution.. Mail survey.. In October 1992, the population of the city of Winnipeg was exposed to elevated levels of particulate matter (total and <10 microm size), carbon monoxide, nitrogen dioxide, and volatile organic compounds due to smoke from adjacent fields where farmers were burning agricultural residue (straw and stubble).. We surveyed 428 participants in the ongoing Lung Health Study (35 to 64 years old, both sexes) with mild to moderate airways obstruction (mean FEV1 percent predicted 73+/-12%), and a high level of airways hyperreactivity (23% of men and 37% of women).. While 37% of subjects were not bothered by smoke at all, 42% reported that symptoms (cough, wheezing, chest tightness, shortness of breath) developed or became worse due to the air pollution episode and 20% reported that they had breathing trouble. Those with symptoms were more likely to be female than male and were more likely to be ex-smokers than smokers. Subjects with asthma and chronic bronchitis were also more likely affected. The degree of airways obstruction and the level of bronchial hyperresponsiveness were not associated with increased susceptibility.. Gender, smoking habit, and respiratory symptoms but not bronchial hyperresponsiveness or the degree of airways obstruction are factors influencing susceptibility to symptoms due to air pollution in adult smokers and former smokers.

Topics: Adult; Agriculture; Air Pollutants; Air Pollution; Airway Obstruction; Asthma; Bronchial Hyperreactivity; Bronchitis; Carbon Monoxide; Chest Pain; Chronic Disease; Cough; Disease Susceptibility; Dyspnea; Female; Forced Expiratory Volume; Humans; Male; Manitoba; Middle Aged; Nitrogen Dioxide; Organic Chemicals; Respiration; Respiratory Sounds; Sex Factors; Smoke; Smoking

Bronchial hyperresponsiveness (BHR) and peak expiratory flow (PEF) variability are associated expressions of airway lability, yet probably reflect different underlying pathophysiologic mechanisms. We investigated whether both measures can be used interchangeably to identify subjects who are susceptible to ambient air pollution. Data on BHR (>= 20% fall in FEV1), PEF variability (ampl%mean PEF > 5% on any day during an 8-d period with low air pollution levels) and diary data on upper and lower respiratory symptoms, cough, and phlegm were collected in 189 subjects (48-73 yr). The acute effects (lag0) of particulate matter with a diameter less than 10 micrometers (PM10), black smoke, SO2 and NO2 on the prevalence of symptoms were estimated with logistic regression. In subjects with airway lability, both when expressed as PEF variability (69%) and BHR (28%), the prevalence of symptoms increased significantly with increasing levels of air pollution, especially in those with the greater PEF variability (n = 55, 29%). We found no such consistent positive associations in adults without airway lability. PEF variability, and to a smaller extent BHR, can be used to identify adults who are susceptible to air pollution. Though odds ratios were rather low (ranging from 1.13 to 1.41), the impact on public health can be substantial because it applies to large populations.

Topics: Acute Disease; Adult; Air Pollutants; Air Pollution; Bronchial Hyperreactivity; Cough; Disease Susceptibility; Female; Forced Expiratory Volume; Humans; Logistic Models; Male; Middle Aged; Nitrogen Dioxide; Odds Ratio; Particle Size; Peak Expiratory Flow Rate; Prevalence; Public Health; Respiratory Tract Diseases; Rural Health; Smoke; Sputum; Sulfur Dioxide; Urban Health

To estimate the prevalence of bronchial asthma (BA) basing on the complex of the disease symptoms within the last year associated with bronchial obstruction (BO) and bronchial hyperreactivity (BHR).. A questionnaire survey (IUATLD) has covered 1572 individuals (mean age 40.1 +/- 0.3 years, 837 females). The responders were divided into 3 age groups. BO and BHR were examined, concentration of air pollutants NO2, SO2, CO were measured.. The most typical BA symptoms were defined in males and females in different age groups. The relationship between frequency of BA symptoms on concentration of air pollutants was determined. BO and BHR were found in 13.3% of the respondents.. Prevalence of BA in a large industrial region is 16.4% (17.5% in males and 14.0% in females).

Topics: Adolescent; Adult; Age Factors; Air Pollutants; Asthma; Bronchial Hyperreactivity; Carbon Monoxide; Cross-Sectional Studies; Female; Humans; Industry; Male; Middle Aged; Nitrogen Dioxide; Risk Factors; Sex Factors; Sulfur Dioxide

The time-kinetics of NO2 induced effects on bronchial responsiveness are poorly known as most observations have been made shortly after exposure. The aim of this study was to measure nonspecific bronchial responsiveness, lung function and inflammatory markers at different times after NO2 exposure in asthmatics. Nineteen subjects with mild asthma were exposed to either purified air or 488 micrograms.m-3 (0.26 ppm) NO2 for 30 min during intermittent exercise. Airway responsiveness to histamine, specific airway resistance (sRaw) and thoracic gas volume (TGV) were measured 30 min, 5 h, 27 h and 7 days after exposure. Peripheral blood inflammatory mediators and the expression of an adhesion molecule, (Mac1) on granulocytes, were analysed 30 min and 27 h after exposure. Bronchial responsiveness to histamine was significantly increased 5 h after NO2 exposure when compared to air (median provocative dose of histamine required to cause 100% increase of sRaw ((PDsRaw,100%) 110 micrograms after NO2 exposure vs 203 micrograms on air). There was a tendency for an increase after 30 min, which was nonsignificant (median PDsRaw,100% 100 vs 153 micrograms). NO2 exposure did not affect sRaw, but TGV was significantly reduced after exposure. We found an increased expression of Mac-1 on granulocytes 30 min after NO2 exposure when compared to pre-exposure values. No effect was seen on tryptase, eosinophil cationic protein (ECP), or myeloperoxidase (MPO). These results suggest that exposure to an ambient level of NO2 causes a delayed effect on bronchial responsiveness in asthmatics. The increased expression of an adhesion molecule in peripheral blood may indicate a NO2-induced priming of human granulocytes.

Topics: Adult; Asthma; Blood Proteins; Bronchial Hyperreactivity; Bronchial Provocation Tests; Chymases; Eosinophil Granule Proteins; Female; Granulocytes; Histamine; Humans; Kinetics; Macrophage-1 Antigen; Male; Middle Aged; Nitrogen Dioxide; Peroxidase; Respiratory Function Tests; Ribonucleases; Serine Endopeptidases; Time Factors; Tryptases

The aims of this work were (1) to determine the dose-response relationship between ex vivo exposure to oxidizing pollutants such as nitrogen dioxide (NO2), the aldehyde acrolein, and ozone (O3), and the reactivity to agonists in isolated human bronchial smooth muscle; and (2) to investigate the alterations in the cellular mechanisms of human airway smooth muscle contraction induced by such exposures. Experiments were performed in isolated human bronchi obtained at thoracotomy. Isometric contraction in response to a variety of agonists was compared between pollutant-exposed preparations and paired controls. Short exposures to NO2, acrolein, or O3 altered the subsequent airway smooth muscle responsiveness in a dose-dependent manner. The cellular mechanisms producing the airway hyperresponsiveness observed in vitro are shared by the three pollutants and include alterations in airway smooth muscle excitation-contraction coupling as well as indirect effects on neutral endopeptidase activity.

Topics: Acrolein; Air Pollutants; Bronchi; Bronchial Hyperreactivity; Humans; In Vitro Techniques; Muscle, Smooth; Nitrogen Dioxide; Oxidation-Reduction; Ozone

In the present study utilizing male Hartley guinea pigs, we investigated (1) the concentration and time dependency of the effects of subchronic exposure to nitrogen dioxide (NO2) on airway responsiveness and (2) the concentration and time dependency of the effects on specific airway resistance under room air (SRaw0). Animals were exposed to filtered air, 0.06, 0.5, 1.0, 2.0, or 4.0 ppm NO2 for 6 and 12 weeks (24 hr/day). Airway responsiveness and SRaw0 were determined 1 week before the beginning of exposure at 10 weeks of age and on the day of termination of the exposure. Our results revealed that (1) subchronic exposure to NO2 induces airway hyperresponsiveness, both concentration and time dependently, (2) such exposure also induces an increase in SRaw0, both concentration and time dependently, and (3) subsequent to the airway hyperresponsiveness induced by NO2 is an increase in the SRaw0. Therefore, NO2 could be a potent risk factor for alteration of pulmonary function and airway responsiveness.

Topics: Administration, Inhalation; Air Pollutants; Airway Resistance; Animals; Bronchial Hyperreactivity; Guinea Pigs; Histamine; Male; Nitrogen Dioxide; Time Factors

Our aim was to determine whether daily exposure to 4 ppm nitrogen dioxide (NO2) from birth until 3 months of age influenced the development of airways hyperresponsiveness and atopic sensitivity in immunized rabbits. Littermate New Zealand white (NZW) rabbits were immunized within 24 h of birth by i.p. injection of house dust mite antigen in AI(OH)3 gel, and exposed to either ambient air or 4 ppm NO2 for 2 h.day-1, 5 days.week-1. At 3 months, bronchoalveolar lavage (BAL) and serum samples were obtained. Airways responsiveness was measured as the provocative concentrations (mg.ml-1) of histamine or methacholine required to elicit a 50% increase in airway resistance (RLPC50) and a 35% decrease in dynamic compliance (CdynPC35). There were no differences in total cell or differential cell counts recovered in BAL fluid between control and NO2 exposed animals. Airways responsiveness did not differ between groups of animals (histamine RLPC50 values: air (n = 15) versus NO2 (n = 13), respectively, 9.98 +/- 1.32 versus 16.43 +/- 1.45 mg.ml-1; CdynPC35 values: 16.60 +/- 1.44 versus 14.95 +/- 1.43 mg.ml-1; methacholine RLPC50 values: air (n = 14) versus NO2 (n = 12), respectively, 2.18 +/- 1.51 versus 2.21 +/- 1.32 mg.ml-1; CdynPC35 values: 2.64 +/- 1.41 versus 2.85 +/- 1.31 mg.ml-1). There was no difference in sensitization between groups of animals exposed to air or NO2, evaluated either by cutaneous responsiveness to intradermal antigen, or serum immunoglobulin E (IgE) levels assessed by the passive cutaneous anaphylaxis (PCA) reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Allergens; Animals; Asthma; Bronchial Hyperreactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid; Female; Hypersensitivity, Immediate; Immunization; Immunoglobulin E; Male; Mites; Nitrogen Dioxide; Passive Cutaneous Anaphylaxis; Rabbits; Skin Tests; Time Factors

The aim of this study was to develop an in vitro system in which an isolated bronchus from human lung was exposed, during 30 min, to a constant flow of either air or nitrogen dioxide (NO2), and to examine subsequently the contractile response of airway smooth muscle rings to carbachol, histamine, and substance P. Two proximal bronchi were mounted in an organ bath, perfused externally with Krebs-Henseleit solution and ventilated with clean air, 1.0 or 2.0 ppm NO2. The exposed bronchi were then cut into rings and mounted in a computerized organ bath system. Contractile responses to agonists were measured isometrically. In each ring, a cumulative concentration response curve was obtained to the desired agonist. We found that in vitro exposure of human lumen bronchus to a constant flow of air did not alter the contractility of the smooth muscle. Whereas in vitro exposure of the bronchus to 1.0 ppm NO2 did not significantly increase the efficacy or the potency of carbachol, exposure to 2.0 ppm NO2 increased airway smooth muscle contractions in response to carbachol, histamine, and substance P. These results indicate that our experimental preparation is well suited to study the respiratory toxicity of inhaled pollutants in order to understand further the mechanisms underlying toxicant-induced airway hyperresponsiveness.

Topics: Acetylcholine; Airway Resistance; Bronchial Hyperreactivity; Bronchial Provocation Tests; Carbachol; Dose-Response Relationship, Drug; Evaluation Studies as Topic; Histamine; Humans; In Vitro Techniques; Nitrogen Dioxide; Substance P

In the present study, we investigated (1) whether airway responsiveness to inhaled histamine-aerosol could be induced during 7-d exposure of guinea pigs to 4 ppm NO2 and, if so, (2) whether thromboxane A2 may be involved in such increase. Female Hartley guinea pigs were divided into 6 groups (n = 15/group). Three groups were exposed to filtered air and the other 3 groups were exposed to NO2 for 1, 3, or 7 d (24 h/d). Baseline specific airway resistance (SRaw0) did not change significantly after exposure to 4 ppm NO2 or air. Airway responsiveness was determined 1 wk before the beginning of exposure and on the day of termination of the exposure. Prior to exposure to NO2, the EC200His, the concentrations of inhaled histamine necessary to double SRawNaCl (SRaw after inhalation of 0.9% NaCl), were 1.07 +/- 0.20, 1.30 +/- 0.20, and 1.01 +/- 0.18 mM for the 3 groups later given NO2 for 1, 3, and 7 d, respectively. Following exposure to NO2 for 1, 3, or 7 d, EC200His values were 1.42 +/- 0.25, 0.66 +/- 0.10 (p < .05), and 1.05 +/- 0.22 mM, respectively. These results show that 7-d exposure to 4 ppm NO2 induced a significant increase in airway responsiveness on d 3. Exposure to air had no significant effect on the airway responsiveness. This transient hyperresponsiveness was inhibited by a specific inhibitor of thromboxane synthetase, OKY 046. These results indicated that (1) a lower concentration (4 ppm) of NO2 than that previously reported can induce transient hyperresponsiveness in guinea pigs during appropriate long-term exposure, and (2) thromboxane A2 may play an important role in this transient airway hyperresponsiveness.

Topics: Administration, Inhalation; Air Pollutants; Airway Resistance; Animals; Asthma; Bronchial Hyperreactivity; Drug Hypersensitivity; Female; Guinea Pigs; Histamine; Lung; Methacrylates; Nitrogen Dioxide; Thromboxane A2; Thromboxane-A Synthase; Time Factors