Biomedical subjects

M W Frampton

Publications and source records attributed to M W Frampton.

At least 19 recordsLinked to original sources

PubMed2001

Neutrophils in lung inflammation: Which reactive oxygen species are being measured?

The oxidative burst in circulating polymorphonuclear leukocytes (PMN) plays a fundamental role in pulmonary defense and injury. Flow cytometric techniques have been developed for quantitation of oxidative burst activity at the single cell level using 2',7'-dichlorofluorescin (DCFH). However, the specific reactive oxidant species being measured using this method are not clearly defined. Isolated human PMN were loaded with DCFH diacetate, stimulated with phorbol myristate acetate (PMA) in the presence or absence of specific reagents, and analyzed using flow cytometry. Addition of PMA resulted in a 90-fold increase in the fluorescence intensity of DCFH-loaded neutrophils (p <.01). Inhibition of NADPH oxidase activity using a calmodulin antagonist (W-13) decreased PMA-induced DCFH oxidation by 70% (p <.05). Inhibition of nitric oxide synthase using N(G)-monomethyl-L-arginine (NMMA) did not significantly reduce DCFH oxidation, and did not alter the action of W-13. Addition of superoxide dismutase (SOD) had no effect, but catalase, with or without SOD, suppressed DCFH oxidation by 90% (p <.01). These data suggest that hydrogen peroxide, and not NO, is primarily responsible for the PMA-induced oxidation of DCFH in human PMN under these conditions.

Adolescent↗

PubMed2001

Ozone exposure and the production of reactive oxygen species by bronchoalveolar cells in humans.

Exposure to ozone injures respiratory epithelium, and the mechanisms may involve the generation of reactive oxygen species (ROS). This study tested the hypothesis that ozone exposure increases the airway burden of ROS to a greater degree in smokers than nonsmokers, and that this effect is independent of ozone-induced changes in spirometry. Healthy subjects were selected as either responders (decrement in FEV1 > 15%) or nonresponders (decrement in FEV1 < 5%) to ozone; each underwent 2 exposures to ozone and 1 to air, with bronchoalveolar lavage (BAL) performed 30 min (early) and 18 h (late) after exposure. Release of superoxide anion (O2(-)) was used as a measure of ROS release by all BAL cells, and flow cytometry was used to detect ROS production in alveolar macrophages (AM) only. Recovery of AM was approximately threefold greater in smokers than nonsmokers. Unstimulated, but not stimulated, cells obtained by BAL from smokers released approximately twofold greater amounts of O2(-) than cells from nonsmokers, both early and late after ozone exposure (p =.012 and p =.046, respectively). Stimulated, but not unstimulated, ROS generation by AM from smokers increased following ozone exposure, but the ozone effect was not significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p =.014). Total protein, albumin, and immunoglobulin M (IgM) increased in BAL fluid, consistent with an increase in epithelial permeability. In addition, the concentration of alpha2-macroglobulin increased approximately threefold 18 h after exposure in nonsmokers (p <.001). No relationship was found between measures of ROS production and lung function responsiveness to ozone. These studies suggest the airways of smokers experience a greater burden of ROS than those of nonsmokers following ozone exposure.

Administration, Inhalation↗

PubMed2001

Chemiluminescent measurements of nitric oxide pulmonary diffusing capacity and alveolar production in humans.

Measurements of nitric oxide (NO) pulmonary diffusing capacity (DL(NO)) multiplied by alveolar NO partial pressure (PA(NO)) provide values for alveolar NO production (VA(NO)). We evaluated applying a rapidly responding chemiluminescent NO analyzer to measure DL(NO) during a single, constant exhalation (Dex(NO)) or by rebreathing (Drb(NO)). With the use of an initial inspiration of 5-10 parts/million of NO with a correction for the measured NO back pressure, Dex(NO) in nine healthy subjects equaled 125 +/- 29 (SD) ml x min(-1) x mmHg(-1) and Drb(NO) equaled 122 +/- 26 ml x min(-1) x mmHg(-1). These values were 4.7 +/- 0.6 and 4.6 +/- 0.6 times greater, respectively, than the subject's single-breath carbon monoxide diffusing capacity (Dsb(CO)). Coefficients of variation were similar to previously reported breath-holding, single-breath measurements of Dsb(CO). PA(NO) measured in seven of the subjects equaled 1.8 +/- 0.7 mmHg x 10(-6) and resulted in VA(NO) of 0.21 +/- 0.06 microl/min using Dex(NO) and 0.20 +/- 0.6 microl/min with Drb(NO). Dex(NO) remained constant at end-expiratory oxygen tensions varied from 42 to 682 Torr. Decreases in lung volume resulted in falls of Dex(NO) and Drb(NO) similar to the reported effect of volume changes on Dsb(CO). These data show that rapidly responding chemiluminescent NO analyzers provide reproducible measurements of DL(NO) using single exhalations or rebreathing suitable for measuring VA(NO).

Adult↗

PubMed2001

Systemic and cardiovascular effects of airway injury and inflammation: ultrafine particle exposure in humans.

The concentration of particles in the ambient air is associated with deaths from cardiovascular disease, and determining the biologic mechanisms involved has been identified as a high-priority research need. Hypotheses have focused on the possibility of direct cardiac effects, or indirect effects related to inflammatory responses, including increased blood viscosity or increased blood coagulability. Ultrafine particles (UFPs; those smaller than 100 nm) may be important in cardiovascular effects because of their very high deposition efficiency in the pulmonary region, and their high propensity to penetrate the epithelium and reach interstitial sites. We have initiated human clinical studies of the health effects of UFPs using a mouthpiece exposure system. Healthy, nonsmoking subjects 18-55 years of age are exposed at rest for 2 hr to 10 microg/m3 carbon UFPs and to filtered air as a control. Preliminary findings indicate a relatively high overall deposition fraction (0.66 +/- 0.12 by particle number) consistent with model predictions and an absence of particle-associated symptoms or changes in lung function. Planned studies examine responses in susceptible subject groups, and the effects of particles of varying composition. Human clinical studies using model particles will complement other approaches such as epidemiologic, animal exposure, and in vitro studies in determining the mechanisms for heath effects related to ambient particle exposure.

Air Pollutants↗

PubMed2000

Acute health effects of ambient air pollution: the ultrafine particle hypothesis.

A strong and consistent association has been observed between adjusted mortality rates and ambient particle concentration. The strongest associations are seen for respiratory and cardiac deaths, particularly among the elderly. Particulate air pollution is also associated with asthma exacerbations, increased respiratory symptoms, decreased lung function, increased medication use, and increased hospital admissions. The U.S. Environmental Protection Agency (EPA) has recently promulgated a new national ambient air quality standard for fine particles, and yet the mechanisms for health effects at such low particle mass concentrations remain unclear. Hypotheses to identify the responsible particles have focused on particle acidity, particle content of transition metals, bioaerosols, and ultrafine particles. Because ultrafine particles are efficiently deposited in the respiratory tract and may be important in initiating airway inflammation, we have initiated clinical studies with ultrafine carbon particles in healthy subjects. These studies examine the role of ultrafines in: (1) the induction of airway inflammation; (2) expression of leukocyte and endothelial adhesion molecules in blood; (3) the alteration of blood coagulability; and (4) alteration in cardiac electrical activity. These events could lead to exacerbation of underlying cardiorespiratory disease. For example, airway inflammation may activate endothelium and circulating leukocytes, and induce a systemic acute phase response with transient hypercoagulability; this could explain the epidemiologic linkages between pollutant exposures and cardiovascular events. These approaches should be useful in identifying mechanisms for pollutant-induced respiratory and systemic effects, and in providing data for determining appropriate air quality standards.

Acute Disease↗

PubMed2000

Ozone, but not nitrogen dioxide, exposure decreases glutathione peroxidases in epithelial lining fluid of human lung.

Antioxidants, such as glutathione peroxidases (GPxs), in epithelial lining fluid (ELF) protect against health effects of oxidant pollutants, which includes O(3) or NO(2). We hypothesized that GPxs concentration in ELF is responsive to O(3) or NO(2) exposure. Subjects underwent two 4-h exposures to O(3) (0.22 ppm) and one to air. In another experiment, subjects underwent 3-h exposures to air and NO(2) (0.6 and 1.5 ppm). Bronchoalveolar lavage (BAL) was performed immediately or 18 h after O(3) exposure and 3.5 h after each NO(2) exposure. GPx activity and extracellular GPx (eGPx) protein concentrations were determined in ELF, and their relationships to markers of lung function, inflammation, and epithelial permeability were examined. Although the total amounts were not changed, basal (air) GPx activity (223.6 +/- 24.4 mU/ml), basal eGPx protein concentration (2.62 +/- 0.25 microg/ml), and basal ELF dilution factor (152.3 +/- 8.4) decreased 40% immediately after O(3) exposure and remained 30% decreased 18 h after exposure (p = 0.0001). No effect of NO(2) exposure on GPxs concentration was detected. There was an inverse correlation between baseline ELF eGPx protein concentration and the change in PMN 18 h after O(3) exposure (p = 0.04). Thus, O(3), a strong oxidant, decreases both GPx activity and eGPx protein in ELF, whereas NO(2), a weaker oxidant, does not. eGPx in ELF may protect against O(3)-induced airway inflammation.

Adolescent↗

PubMed2000

Toxicologic methods: controlled human exposures.

The assessment of risk from exposure to environmental air pollutants is complex, and involves the disciplines of epidemiology, animal toxicology, and human inhalation studies. Controlled, quantitative studies of exposed humans help determine health-related effects that result from breathing the atmosphere. The major unique feature of the clinical study is the ability to select, control, and quantify pollutant exposures of subjects of known clinical status, and determine their effects under ideal experimental conditions. The choice of outcomes to be assessed in human clinical studies can be guided by both scientific and practical considerations, but the diversity of human responses and responsiveness must be considered. Subjects considered to be among the most susceptible include those with asthma, chronic obstructive lung disease, and cardiovascular disease. New experimental approaches include exposures to concentrated ambient air particles, diesel engine exhaust, combustion products from smoking machines, and experimental model particles. Future investigations of the health effects of air pollution will benefit from collaborative efforts among the disciplines of epidemiology, animal toxicology, and human clinical studies.

Air Pollutants↗

PubMed1999

Effects of aqueous extracts of PM(10) filters from the Utah valley on human airway epithelial cells.

We hypothesized that the reduction in hospital respiratory admissions in the Utah Valley during closure of a local steel mill in 1986-1987 was attributable in part to decreased toxicity of ambient air particles. Sampling filters for particulate matter < 10 micrometer (PM(10)) were obtained from a Utah Valley monitoring station for the year before (year 1), during (year 2), and after (year 3) the steel mill closure. Aqueous extracts of the filters were analyzed for metal content and oxidant production and added to cultures of human respiratory epithelial (BEAS-2B) cells for 2 or 24 h. Year 2 dust contained the lowest concentrations of soluble iron, copper, and zinc and showed the least oxidant generation. Only dust from year 3 caused cytotoxicity (by microscopy and lactate dehydrogenase release) at 500 microgram/ml. Year 1 and year 3, but not year 2, dust induced expression of interleukin-6 and -8 in a dose-response fashion. The effects of ambient air particles on human respiratory epithelial cells vary significantly with time and metal concentrations.

Air Pollutants, Occupational↗

PubMed1999

Rate of nitric oxide production by lower alveolar airways of human lungs.

This report describes methods for measuring nitric oxide production by the lungs' lower alveolar airways (VNO), defined as those alveoli and bronchioles well perfused by the pulmonary circulation. Breath holding or vigorous rebreathing for 15-20 s minimizes removal of NO from the lower airways and results in a constant partial pressure of NO in the lower airways (PL). Then the amount of NO diffusing into the perfusing blood will be the pulmonary diffusing capacity for NO (DNO) multiplied by PL and by mass balance equals VNO, or VNO = DNO(PL). To measure PL, 10 normal subjects breath held for 20 s followed by exhalation at a constant flow rate of 0.83 +/- 0.14 (SD) l/s or rebreathed at 59 +/- 15 l/min for 20 s while NO was continuously measured at the mouth. DNO was estimated to equal five times the single-breath carbon monoxide diffusing capacity. By using breath holding, PL equaled 2.9 +/- 0.8 mmHg x 10(-6) and VNO equaled 0.39 +/- 0.12 microl/min. During rebreathing PL equaled 2.3 +/- 0.6 mmHg x 10(-6) and VNO equaled 0.29 +/- 0.11 microl/min. Measurements of NO at the mouth during rapid, constant exhalation after breath holding for 20 s or during rebreathing provide reproducible methods for measuring VNO in humans.

Adult↗

PubMed1999

Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans.

Human airways produce nitric oxide (NO), and exhaled NO increases as expiratory flow rates fall. We show that mixing during exhalation between the NO produced by the lower, alveolar airways (VL(NO)) and the upper conducting airways (VU(NO)) explains this phenomenon and permits measurement of VL(NO), VU(NO), and the NO diffusing capacity of the conducting airways (DU(NO)). After breath holding for 10-15 s the partial pressure of alveolar NO (PA) becomes constant, and during a subsequent exhalation at a constant expiratory flow rate the alveoli will deliver a stable amount of NO to the conducting airways. The conducting airways secrete NO into the lumen (VU(NO)), which mixes with PA during exhalation, resulting in the observed expiratory concentration of NO (PE). At fast exhalations, PA makes a large contribution to PE, and, at slow exhalations, NO from the conducting airways predominates. Simple equations describing this mixing, combined with measurements of PE at several different expiratory flow rates, permit calculation of PA, VU(NO), and DU(NO). VL(NO) is the product of PA and the alveolar airway diffusion capacity for NO. In seven normal subjects, PA = 1.6 +/- 0.7 x 10(-6) (SD) Torr, VL(NO) = 0.19 +/- 0.07 microl/min, VU(NO) = 0.08 +/- 0.05 microl/min, and DU(NO) = 0.4 +/- 0.4 ml. min(-1). Torr(-1). These quantitative measurements of VL(NO) and VU(NO) are suitable for exploring alterations in NO production at these sites by diseases and physiological stresses.

Humans↗

PubMed1999

Ozone exposure increases aldehydes in epithelial lining fluid in human lung.

We hypothesized that exposure of healthy humans to ozone causes both ozonation and peroxidation of lipids in lung epithelial lining fluid. Twelve smokers and 15 nonsmokers (eight lung function "responders" and seven "nonresponders") were exposed once to air and twice to 0. 22 ppm ozone for 4 h with exercise in an environmental chamber, with each exposure separated by at least 3 wk. Bronchoalveolar lavage (BAL) was performed immediately after one ozone exposure and 18 h after the other ozone exposure. BAL fluid was analyzed for the aldehyde products of ozonation and lipid peroxidation, nonanal (C9) and hexanal (C6), as well as total protein, albumin, and immunoglobulin M as markers of changes in epithelial permeability. Ozone exposure resulted in a significant early increase in C9 (p = 0. 0001), with no statistically significant relationship between increases in C9 and lung function changes, airway inflammation, or changes in epithelial permeability. Increases in C6 levels were not statistically significant (p = 0.16). Both C9 and C6 levels returned to baseline by 18 h after exposure. These studies confirm that exposure to ozone with exercise, at concentrations relevant to urban outdoor air, results in ozonation of lipids in the airway epithelial lining fluid of humans.

Adolescent↗

PubMed1999

Aldehydes (nonanal and hexanal) in rat and human bronchoalveolar lavage fluid after ozone exposure.

We hypothesized that exposure of healthy humans to ozone at concentrations found in ambient air causes both ozonation and peroxidation of lipids in lung epithelial lining fluid. Smokers (12) and nonsmokers (15) were exposed once to air and twice to 0.22 ppm ozone for four hours with exercise in an environmental chamber; each exposure was separated by at least three weeks. Bronchoalveolar lavage (BAL) was performed immediately after one ozone exposure and 18 hours after the other ozone exposure. Lavage fluid was analyzed for two aldehyde products of ozonation and lipid peroxidation, nonanal and hexanal, as well as for total protein, albumin, and immunoglobulin M (IgM) as markers of changes in epithelial permeability. Ozone exposure resulted in a significant early increase in nonanal (p < 0.0001), with no statistically significant relationship between increases in nonanal and lung function changes, airway inflammation, or changes in epithelial permeability. Increases in hexanal levels were not statistically significant (p = 0.16). Both nonanal and hexanal levels returned to baseline by 18 hours after exposure. These studies confirm that exposure to ozone with exercise at concentrations relevant to urban outdoor air results in ozonation of lipids in the airway epithelial lining fluid of humans.

Adult↗

PubMed1998

Mutational spectra of a 100-base pair mitochondrial DNA target sequence in bronchial epithelial cells: a comparison of smoking and nonsmoking twins.

Seventeen separate mitochondrial hot spot mutations in a 100-bp target sequence (mitochondrial bp 10,030-10,130) were detected and measured in bronchial epithelial cell samples isolated from smokers and nonsmokers. Among the individuals sampled were three pairs of monozygotic twins in which one twin had never smoked and had a nonsmoking spouse, and the other had a smoking history of >10 pack-years. Individual point mutations present at frequencies as low as 10(-6) were detected. Partially denaturing electrophoresis was used to separate mutant from nonmutant sequences on the basis of their melting temperatures, and the target sequence was subsequently amplified via high-fidelity PCR with Pfu DNA polymerase. Tests were performed to determine whether mismatch intermediates or DNA adducts present in the cellular DNA were converted to mutants during PCR. Hot spot mutations were clearly observed in bronchial epithelial cells, and the same hot spots were observed consistently in different samples. Significant numerical variability in the mutant fractions for individual mutants was observed among samples and are ascribed to unequal mitochondrial segregation in stem and transition cells. The mutational spectra in smokers' samples did not differ significantly from the mutational spectra in nonsmokers' samples for this 100 bp of mitochondrial DNA. No smoking-specific hot spots were detected. The overall mutant fractions in smokers' samples were not elevated compared to those of nonsmokers. As much variability was observed between two samples from the same individual's lung as between a sample from a smoker and a sample from a nonsmoker. These findings demonstrate that inhaled tobacco smoke does not induce prominent point mutations in this 100-bp target mitochondrial sequence in smokers' bronchial epithelial cells. Endogenous factors (e.g., DNA replication errors or DNA damage by endogenous reactive chemicals) are suggested to be more likely to represent the most important contributors to mitochondrial mutagenesis.

Adult↗

PubMed1998

Acute respiratory exposure of human volunteers to octamethylcyclotetrasiloxane (D4): absence of immunological effects.

Humans are exposed to silicones in a number of commercial and consumer products. Some of these silicones, including octamethylcyclotetrasiloxane (D4), are volatile. Therefore, there is a potential for respiratory exposure. A pharmacokinetic analysis of respiratory exposure to D4 is presented in the accompanying paper (M. J. Utell et al., 1998, Toxicol. Sci. 44, 206-213). Possible immune effects of respiratory exposure to D4 are investigated in this paper. Normal volunteers were exposed to 10 ppm D4 or air for 1 h via a mouthpiece using a double-blind, crossover study design. Assays were chosen to screen for immunotoxicity or a systemic inflammatory response. Assessment of immunotoxicity included enumeration of peripheral lymphocyte subsets and functional assays using peripheral blood mononuclear cells. Because in humans there is no direct test for adjuvant effect of respiratory exposure, we analyzed proinflammatory cytokines and acute-phase reactants in peripheral blood, markers for a systemic inflammatory response, as surrogate markers for adjuvancy. These tests were repeated when the volunteers were reexposed to D4 approximately 3 months after this initial exposure. Blood was obtained prior to exposure, immediately postexposure, and 6 and 24 h postexposure. In these short-term, controlled human exposures, no immunotoxic or proinflammatory effects of respiratory exposure to D4 were found.

Adult↗

PubMed1998

Measurement of cytochrome P450 2A6 and 2E1 gene expression in primary human bronchial epithelial cells.

Bronchogenic carcinomas arise from bronchial epithelial cells (BECs). Inhalation exposure of BECs to nitrosamines in cigarette smoke is an important exogenous risk factor for malignant transformation of BECs. Thus, an important endogenous risk factor is likely to be the capacity of BECs to metabolize nitrosamines. Among the cytochrome P450 enzymes capable of metabolizing nitrosamines, CYP2A6, CYP2E1 and CYP2B6 are expressed in BECs. In this study, we used quantitative RT-PCR to evaluate expression of CYP2A6 and CYP2E1 in primary human BECs from 12 non-smokers and eight smokers. CYP2A6 was expressed in 20/20 cases and quantifiable in 18/20 cases, with a mean level of 580 mRNA/10(6) beta-actin mRNA. CYP2E1 expression was observed in 9/20 cases, but in all cases it was expressed at levels below our limit of quantification (10 mRNA/10(6) beta-actin mRNA). There was significant (P < 0.05) 20-fold inter-individual variation in expression of CYP2A6. Further, the mean level of CYP2A6 among smokers (260 mRNA/10(6) beta-actin mRNA) was significantly lower than among non-smokers (740 mRNA/10(6) beta-actin mRNA). It is hypothesized that: (i) inter-individual variation in CYP2A6 gene expression may contribute to inter-individual variation in risk for bronchogenic carcinoma; (ii) smoking may reduce the level of expression of CYP2A6 in the BECs of some individuals; and (iii) CYP2A6 is more important than CYP2E1 for metabolic activation of nitrosamines in bronchial epithelial cells.

Actins↗

PubMed1997

Determination of production of nitric oxide by lower airways of humans--theory.

Exercise and inflammatory lung disorders such as asthma and acute lung injury increase exhaled nitric oxide (NO). This finding is interpreted as a rise in production of NO by the lungs (VNO) but fails to take into account the diffusing capacity for NO (DNO) that carries NO into the pulmonary capillary blood. We have derived equations to measure VNO from the following rates, which determine NO tension in the lungs (PL) at any moment from 1) production (VNO); 2) diffusion, where DNO(PL) = rate of removal by lung capillary blood; and 3) ventilation, where V A(PL)/(PB - 47) = the rate of NO removal by alveolar ventilation (V A) and PB is barometric pressure. During open-circuit breathing when PL is not in equilibrium, d/dt PL[V(L)/ (PB - 47)] (where V(L) is volume of NO in the lower airways) = VNO - DNO(PL) - V A(PL)/(PB - 47). When PL reaches a steady state so that d/dt = 0 and V A is eliminated by rebreathing or breath holding, then PL = VNO/DNO. PL can be interpreted as NO production per unit of DNO. This equation predicts that diseases that diminish DNO but do not alter VNO will increase expired NO levels. These equations permit precise measurements of VNO that can be applied to determining factors controlling NO production by the lungs.

Air Pressure↗

PubMed1997

Ozone responsiveness in smokers and nonsmokers.

Short-term exposure to ozone causes decrements in lung function, but predictors of responsiveness remain largely unknown. Ninety healthy volunteers (56 never-smokers, age [mean +/- SD] 25 +/- 4 yr; 34 current smokers, 13 +/- 9 pack-yr, age 28 +/- 1 yr) were exposed to 0.22 ppm ozone for 4 h, with exercise, in an environmental chamber. We measured spirometry and specific airway conductance before, during, and immediately after exposure, and assessed symptoms by questionnaire. Smokers experienced a smaller increase in respiratory symptoms following exposure to ozone than did nonsmokers. Decrements in FEV1 were significantly less than for smokers than for nonsmokers (p = 0.0013). Ozone responsiveness (> 15% fall in FEV1) occurred in 16 of 56 never-smokers (28.6%) and 4 of 34 smokers (11.8%). Multiple logistic regression analysis found pack-yr of smoking to be associated with decreased ozone responsiveness (odds ratio [OR] 0.87, p = 0.017). Age, gender, and methacholine responsiveness were not predictive of responder status. Fourteen smokers and 25 nonsmokers were subsequently exposed once to air and twice to ozone; smokers as well as nonsmokers were consistent in their subsequent responsiveness (or lack of responsiveness) to ozone. Healthy smokers have smaller decrements in lung function and fewer symptoms in response to ozone exposure than do nonsmokers.

Adolescent↗

PubMed1997

Airway inflammation in smokers and nonsmokers with varying responsiveness to ozone.

Exposure to ozone causes symptoms, changes in lung function, and airway inflammation. We studied whether individuals who differ in lung-function responsiveness to ozone, or in smoking status, also differ in susceptibility to airway inflammation. Healthy subjects were selected on the basis of responsiveness to a classifying exposure to 0.22 ppm ozone for 4 h with exercise (responders, with a decrease in FEV1 > 15%; and non-responders, with a decrease in FEV1 < 5%). Three groups were studied: nonsmoker-nonresponders (n = 12), nonsmoker-responders (n = 13), and smokers (n = 13, 11 nonresponders and two responders). Each subject underwent two exposures to ozone and one to air, separated by at least 3 wk; bronchoalveolar and nasal lavages were performed on three occasions: immediately (early) and 18 h (late) after ozone exposure, and either early or late after air exposure. Recovery of polymorphonuclear leukocytes (PMN) increased progressively in all groups, and by up to 6-fold late after ozone exposure. Interleukin-6 (IL-6) and IL-8 increased early (by up to 10-fold and up to 2-fold, respectively), and correlated with the late increase in PMN. Lymphocytes, mast cells, and eosinophils also increased late after exposure. We conclude that ozone-induced airway inflammation is independent of smoking status or airway responsiveness to ozone.

Adolescent↗