Biomedical subjects

W F McDonnell

Publications and source records attributed to W F McDonnell.

At least 19 recordsLinked to original sources

PubMed2001

Effect of antioxidant supplementation on ozone-induced lung injury in human subjects.

To determine whether antioxidants can influence human susceptibility to ozone (O(3))-induced changes in lung function and airway inflammation, we placed 31 healthy nonsmoking adults (18 to 35 yr old) on a diet low in ascorbate for 3 wk. At 1 wk, subjects were exposed to filtered air for 2 h while exercising (20 L/min/m(2)), and then underwent bronchoalveolar lavage (BAL) and were randomly assigned to receive either a placebo or 250 mg of vitamin C, 50 IU of alpha-tocopherol, and 12 oz of vegetable cocktail daily for 2 wk. Subjects were then exposed to 0.4 ppm O(3) for 2 h and underwent a second BAL. On the day of the O(3) exposure, supplemented subjects were found to have significantly increased levels of plasma ascorbate, tocopherols, and carotenoids as compared with those of the placebo group. Pulmonary function testing showed that O(3)-induced reductions in FEV(1) and FVC were 30% and 24% smaller, respectively, in the supplemented cohort. In contrast, the inflammatory response to O(3) inhalation, as represented by the percent neutrophils and the concentration of interleukin-6 recovered in the BAL fluid at 1 h after O(3) exposure was not different for the two groups. These data suggest that dietary antioxidants protect against O(3)-induced pulmonary function decrements in humans.

Adult↗

PubMed1999

Long-term ambient ozone concentration and the incidence of asthma in nonsmoking adults: the AHSMOG Study.

We conducted a prospective study of a cohort of 3091 nonsmokers, ages 27 to 87 years, to evaluate the association between long-term ambient ozone exposure and development of adult-onset asthma. Over a 15-year period, 3.2% of males and 4.3% of females reported new doctor diagnoses of asthma. For males, we observed a significant relationship between report of doctor diagnosis of asthma and 20-year mean 8-h average ambient ozone concentration (relative risk (RR)=2.09 for a 27 ppb increase in ozone concentration, 95% CI=1.03 to 4.16). We observed no such relationship for females. Other variables significantly related to development of asthma were a history of ever-smoking for males (RR=2.37, 95% CI=1.13 to 4.81), and for females, number of years worked with a smoker (RR=1.21 for a 7-year increment, 95% CI=1.04 to 1.39), age (RR=0.61 for a 16-year increment, 95% CI=0.44 to 0.84), and a history of childhood pneumonia or bronchitis (RR=2.96, 95% CI=1.68 to 5.03). Addition of other pollutants (PM10, SO4, NO2, and SO2) to the models did not diminish the relationship between ozone and asthma for males. These data suggest that long-term exposure to ambient ozone is associated with development of asthma in adult males.

Adult↗

PubMed1999

Ozone-induced respiratory symptoms: exposure-response models and association with lung function.

Ozone-induced respiratory symptoms are known to be functions of concentration, minute ventilation, and duration of exposure. The purposes of this study were to identify an exposure-response model for symptoms, to determine whether response was related to age, and to assess the relationships between symptom and lung function responses to ozone. Four hundred and eighty-five healthy male volunteers (ages 18-35 yrs) were exposed to one of six ozone concentrations at one of three activity levels for 2 h. Symptoms and forced expiratory volume in one second (FEV1) were assessed at the end of 1 and 2 h. The exposure and response data were fitted by a nonlinear exposure-response model previously found to describe FEV1 response. The proportion of individuals experiencing moderate or severe cough, shortness of breath, and pain on deep inspiration were accurately described as functions of concentration, minute ventilation, and time. Response was inversely related to age for shortness of breath (p=0.0001), pain on deep inspiration (p=0.0002), and cough (p=0.0013). Controlling for exposure differences, symptom responses were significantly but weakly (correlation coefficient 0.30-0.41) related to the FEV1 response. In conclusion, the exposure-response model did accurately predict symptoms, response was inversely related to age.

Adolescent↗

PubMed1999

A statistical model for FEV1 response to arbitrary dynamic ozone exposure conditions.

Lung function response to inhaled ozone at ambient air pollution levels is known to be a function of ozone concentration, exposure duration, and minute ventilation. Most data-driven exposure-response models address exposures under static condition (i.e., with a constant ozone concentration and exercise pattern). Such models are simplifications, as both ambient ozone concentrations and normal human activity patterns change with time. The purpose of this study was to develop a dynamic model of response with the advantages of a statistical model (a relatively simple structure with few parameters). A previously proposed mechanistic model for changes in specific airways resistance was adapted to describe the percent change in forced expiratory volume in one second (FEV1). This model was then reduced using the fit to three existing exposure-response data sets as criterion. The resulting model consists of a single linear differential equation together with an algebraic logistic equation. Under restricted static conditions the model reduces to a logistic model presented earlier by the authors.

Computer Simulation↗

PubMed1999

Long-term inhalable particles and other air pollutants related to mortality in nonsmokers.

Long-term ambient concentrations of inhalable particles less than 10 microm in diameter (PM10) (1973- 1992) and other air pollutants-total suspended sulfates, sulfur dioxide, ozone (O3), and nitrogen dioxide-were related to 1977-1992 mortality in a cohort of 6,338 nonsmoking California Seventh-day Adventists. In both sexes, PM10 showed a strong association with mortality for any mention of nonmalignant respiratory disease on the death certificate, adjusting for a wide range of potentially confounding factors, including occupational and indoor sources of air pollutants. The adjusted relative risk (RR) for this cause of death as associated with an interquartile range (IQR) difference of 43 d/yr when PM10 exceeded 100 microg/m3 was 1.18 (95% confidence interval [CI]: 1.02, 1.36). In males, PM10 showed a strong association with lung cancer deaths-RR for an IQR was 2.38 (95% CI: 1.42, 3.97). Ozone showed an even stronger association with lung cancer mortality for males with an RR of 4.19 (95% CI: 1.81, 9.69) for the IQR difference of 551 h/yr when O3 exceeded 100 parts per billion. Sulfur dioxide showed strong associations with lung cancer mortality for both sexes. Other pollutants showed weak or no association with mortality.

Adult↗

PubMed1999

Respiratory symptoms and pulmonary function in an elderly nonsmoking population.

OBJECTIVE: To examine risk factors for chronic airway disease (CAD) in elderly nonsmokers, as determined by pulmonary function tests (PFTs), and to correlate reported respiratory symptoms with PFT measures. DESIGN: An observational survey. SETTING: Several communities in California. MEASUREMENTS: Exposures and respiratory history were assessed by standardized questionnaire. PFTs were performed and prediction equations derived. RESULTS: Significant risk factors for obstruction on PFTs in multiple logistic regression included reported environmental tobacco smoke (ETS) exposure (relative risk [RR]=1.44), parental CAD or hay fever (RR=1.47), history of childhood respiratory illness (RR=2.15), increasing age, and male sex. The number of years of past smoking was of borderline significance (RR=1.29 for 10 years of smoking; p=0.06). The prevalence of obstruction on PFTs was 24.9% in those with definite symptomatic CAD, compared with 7.5% in those with no symptoms of CAD. The prevalence of obstruction was 36.0% among those with asthma and 70.6% among those with emphysema. Also, symptomatic CAD correlated with reduction in lung function by analysis of covariance. The mean percent predicted FEV1 adjusted for covariates was 90.6% in persons with definite symptoms of CAD, compared with 97.8% in those without it (p < 0.001). CONCLUSIONS: Age, sex, parental history, childhood respiratory illness, and reported ETS exposures were significant risk factors for obstruction on PFTs. Self-reported respiratory symptoms also correlated significantly with PFTs.

Adult↗

PubMed1999

Particulate and ozone pollutant effects on the respiratory function of children in southwest Mexico City.

We assessed the contributions of particulate matter with aerodynamic diameters < or =10 and < or =2.5 microm (PM2.5 and PM10) and ozone (O3) to peak expiratory flow (PEF) and respiratory symptoms in 40 schoolchildren 8-11 years of age for 59 days during three periods in 1991 at a school in southwest Mexico City. We measured peak expiratory flow in the morning on the children's arrival at school and in the afternoon before their departure from school. Separately for morning and afternoon, we normalized each child's daily measurement of peak flow by subtracting his or her mean peak flow from the daily measurement. Child-specific deviations were averaged to obtain a morning and afternoon mean deviation (APEF) for each day. Mean 24-hour O3 level was 52 parts per billion (ppb; maximum 103 ppb); mean 24-hour PM2.5 and PM10 were 30 microg/m3 (maximum 69 microg/m3) and 49 microg/m3 (maximum 87 microg/m3), respectively. We adjusted moving average and polynomial distributed lag multiple regression analyses of APEF vs pollution for minimum daily temperature, trend, and season. We examined effects of PM2.5, PM10, and O3, on deltaPEF separately and in joint models. The models indicated a role for both particles and O3 in the reduction of peak expiratory flow, with shorter lags between exposure and reduction in peak expiratory flow for O3 than for particle exposure (0-4 vs 4-7 days). The joint effect of 7 days of exposure to the interquartile range of PM2.5 (17 microg/m3) and O3 (25 ppb) predicted a 7.1% (95% confidence interval = 11.0-3.9) reduction in morning peak expiratory flow. Pollutant exposure also predicted higher rates of phlegm; colinearity between pollutants limited the potential to distinguish the relative contribution of individual pollutants. In an area with chronically high ambient O3 levels, school children responded with reduced lung function to both O3 and particulate exposures within the previous 1 to 2 weeks.

Air Pollution↗

PubMed1998

Spirometric reference equations for older adults.

The objective of this study was to develop spirometric reference equations for healthy, never-smoking, older adults. It was designed as a cross-sectional observational study consisting of 1510 Seventh Day Adventists, ages 43-79 years enrolled in a study of health effects of air pollutants. Individuals were excluded from the reference group (n = 565) for a history of current respiratory illness, smoking, or chronic respiratory disease, and for a number of 'non-respiratory' conditions which were observed in these data to be related to lower values of FEV1. Gender-specific reference equations were developed for the entire reference group and for a subset above 65 years of age (n = 312). Controlling for height and age, lung function was found to be positively related to the difference between armspan and height, and in males was found to be quadratically related to age. The predicted values for this population generally fell within the range of those of other population groups containing large numbers of adults over the age of 65 years. Individuals with lung function below the 5th percentile in this sample, however, could not be reliably identified by using the lower limits of normal predictions commonly used in North America and Europe.

Adult↗

PubMed1998

Long-term particulate and other air pollutants and lung function in nonsmokers.

The associations between lung function measures (spirometry and peak expiratory flow lability) and estimated 20-yr ambient concentrations of respirable particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were studied in a sample of 1,391 nonsmokers followed since 1977. Differences in air pollutants across the population were associated with decrements of lung function. An increase of 54 d/yr when particles < 10 micro(m) in diameter (PM10) exceeded 100 microg/m3 was associated with a 7.2% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay fever and with increased peak expiratory flow lability of 0.8% for all females and 0.6% for all males. An increase in mean SO4 concentration of 1.6 microg/m3 was associated with a 1.5% decrement in FEV1, as percent of predicted, in all males. An increase of 23 ppb of ozone as an 8-h average was associated with a 6.3% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay fever.

Adult↗

PubMed1997

Prediction of ozone-induced FEV1 changes. Effects of concentration, duration, and ventilation.

The purpose of this analysis of previously published data was to identify a model that accurately predicts the mean ozone-induced FEV1 response of humans as a function of concentration (C), minute ventilation (VE), duration of exposure (T), and age. Healthy young adults (n = 485) were exposed for 2 h to one of six ozone concentrations while exercising at one of three levels. Candidate models were fitted to portions of the data and evaluated on the basis of their ability to predict the mean response of independent samples. A sigmoid-shaped model that is consistent with previous observations of ozone exposure-response (E-R) characteristics was identified and found to accurately predict the mean response with independent data. This model in a more general form may allow the prediction of responses under conditions of changing C and VE. We did not find that response was more sensitive to changes in C than in VE, nor did we find convincing evidence of an effect of body size upon response. We did find that response to ozone decreases with age. In summary, we have identified a biologically plausible, predictive model that quantifies the relationship between the ozone-induced change in FEV1, and C, VE, T, and age.

Adolescent↗

PubMed1997

Peak flow lability: association with asthma and spirometry in an older cohort.

OBJECTIVE: To determine the success rate and correlates of ambulatory peak expiratory flow (PEF) monitoring in an epidemiologic study. DESIGN: An observational survey. SETTING: Several communities in California. PARTICIPANTS: We studied 1,223 nonsmoking men and women (mean age, 66 years) from an established cohort. OUTCOME MEASURES: A standard respiratory symptoms and diagnoses questionnaire, spirometry before and after bronchodilator, and a diary of PEF recorded four times per day for 7 days at home. RESULTS: A physician diagnosis of asthma was reported in 8.6% of the women and 9.4% of the men. Of those who agreed to complete PEF diaries at home, 87% successfully provided a valid measure of PEF lability. The mean PEF lability from those with asthma was significantly higher than the others (12.0% vs 8.9% in women and 10.2% vs 8.1% in men). Independent correlates of higher PEF lability included asthma, wheezing symptoms, airways obstruction by spirometry, older age, and male gender. CONCLUSIONS: Middle-aged and elderly persons are largely successful at providing a measure of PEF lability at home. In nonsmoking adults living in California, increased PEF lability is correlated with asthma, wheezing, airways obstruction, and older age, validating its use in epidemiology studies as an index of airways hyperreactivity.

Adult↗

PubMed1996

Time-dependent changes of inflammatory mediators in the lungs of humans exposed to 0.4 ppm ozone for 2 hr: a comparison of mediators found in bronchoalveolar lavage fluid 1 and 18 hr after exposure.

Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and biochemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and prostaglandins (PGE2) have been reported in humans as early as 3 hr and as late as 18 hr after exposure. The purpose of this study was to determine whether a broad range of inflammatory mediators are elevated in BAl fluid within 1 hr of exposure. We exposed eight healthy volunteers twice: once to 0.4 ppm ozone and once to filtered air. Each exposure lasted for 2 hr during which the subjects underwent intermittent heavy exercise (66 liters/min). BAL was performed 1 hr after the exposure. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE2, thromboxane B2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the recovery of total cells and alveolar macrophages, and decreased ability of alveolar macrophages to phagocytize Candida albicans. A comparison of these changes with changes observed in an earlier study in which subjects underwent BAL 18 hr after an identical exposure regimen indicates that IL-6 and PGE2 levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a were present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time.

Adolescent↗

PubMed1995

Proportion of moderately exercising individuals responding to low-level, multi-hour ozone exposure.

The purpose of this study was to describe the proportion of moderately exercising individuals experiencing significant respiratory responses to low-level, multi-hour ozone exposure as a function of ozone concentration and exposure duration. Sixty-eight healthy, nonsmoking adults, ages 18 to 34 yr, underwent two or more 6.6-h exposures to 0.0, 0.08, 0.10, or 0.12 ppm ozone. Five hours of exercise was performed during exposure, and lung function was measured before exposure and following each hour of exposure. For each combination of concentration and duration, each individual was determined to either have or not have experienced a 10% or greater decrement in FEV1. A logistic function was used to model the proportion of individuals experiencing such a decrement as a function of concentration and exposure duration. Bootstrap 90% confidence intervals (CIs) were calculated around the predictions. The model was found to give predictions that were in good agreement with observed data. The lowest level of exposure (C x T) for which the 90% CI excluded zero was approximately 0.2 ppm-h. For exposure to 0.12 ppm ozone for 6.6 h, 47% (90% CI = 30 to 65%) of exposed individuals were predicted to experience a 10% decrement in FEV1. A greater proportion of younger adults than of older adults were found to experience a given effect for a given exposure.

Adolescent↗

PubMed1995

Acute effects of ozone on the pulmonary function of exercising schoolchildren from Mexico City.

The acute effects of ozone (O3) on the change in lung function before and after exercise was assessed in 22 boys and 18 girls from 7 1/2 to 11 yr of age tested up to eight times over a 1 1/2-yr period outdoors (under a tarpaulin) at a school in Mexico City. Ozone and particulates were monitored at an adjacent government station, in the school yard, and under the tarp. Subjects were selected to oversample children with chronic respiratory symptoms, although children with active asthma under regular medication or FEV1 < 80% predicted were excluded. Of the participants, 21 had chronic cough, chronic phlegm, or ever wheeze with colds or apart from colds. Children performed two cycles of treadmill exercise (15 min) and rest (15 min) for a total of 1 h of intermittent exercise. Most subjects attained the target minute ventilation of 35 L/min/m2. Subjects exercised alternately during low ozone hours (8:00-10:00 A.M.) and during peak O3 hours (12:00-2:00 P.M.), to assure a range of exposures. On 85% of exercise days, the maximum daily 1-h average for ambient O3 exceeded the Mexican guideline of 110 parts per billion (ppb). O3 exposure during the hour of exercise was divided into quintiles, and the response was adjusted for repeated measures, subject having a cold, and prior outdoor exercise. Ambient O3 in the fifth quintile (mean = 229 ppb) was associated with a percentage change in FVC (-1.43% +/- 0.70), FEV1 (-2.85% +/- 0.79), FEF25-75% (-6.32 +/- 1.87) and FEV1 (-1.41% +/- 0.46).(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗

PubMed1994

The relationship between delivered ozone dose and functional responses in humans.

The relationship between delivered ozone dose and variability of pulmonary function response to ozone was investigated in 20 young, healthy, nonsmoking male volunteers. The subjects were exposed to 0.4 ppm ozone for 1 hr during which time they walked on a treadmill at a speed and inclination sufficient to induce a minute ventilation (VE) of 20 liter/min/m2 body surface area. Prior to and immediately following exposure spirometric and plethysmographic measurements of lung function were made. In addition, 5 min after the beginning of exposure and 5 min before the end of exposure the uptake efficiency of ozone in the upper and lower respiratory tract, spontaneous tidal volume (Vt), and breathing frequency (f) were measured. During exposure subjects wore a noseclip in order to constrain breathing to the oral pathway. Uptake efficiencies in the upper (FURT) and lower (FLRT) respiratory tracts were determined by continuously drawing air from the posterior pharynx into a rapidly responding chemiluminescent ozone analyzer. Linear regression models were constructed to examine the relationships between pulmonary function and breathing pattern responses, and the instantaneous and average values of FLRT and VE. Initial VE and average VE (VE) were found to be significant predictors of FEV1 decrement (p = 0.011 and p = 0.006, respectively). In addition the cross-product term FLRT x VE was a significant predictor of Vt decrement (p = 0.02). These results suggest that delivered dose, as determined primarily by VE, is responsible for some of the intersubject variability of ozone response. The failure of FLRT to play a significant role may be due to the fact that it primarily reflects ozone uptake in the lung periphery distal to anatomical sites where the ozone response may be mediated.

Adult↗

PubMed1994

Description of acute ozone response as a function of exposure rate and total inhaled dose.

The magnitude of respiratory responses to short-term ozone exposure is known to be a function of the exposure variables concentration (C), duration of exposure (T), and minute ventilation (VE) during exposure. The purpose of this study was to identify a mathematical model that described ozone-induced mean decrements in forced expiratory volume in 1 s (FEV1) as a function of exposure rate (C x VE) and total inhaled dose (C x VE x T). Three hundred seventy-four young male nonsmokers participated in 504 exposures to several concentrations of ozone for 2 or 6.6 h. Mean percent change in FEV1 was calculated for each hour of exposure and was fit to the exposure variables by use of nonlinear models. We identified a general sigmoid-shaped model that well described the observed mean response in terms of exposure rate and total inhaled dose over a wide range of C and T. By fixing the value of a single parameter, this model reduces to a simpler form, which was adequate for description of responses over narrower ranges of exposure conditions. We concluded that the observed mean responses to short-term ozone exposure were adequately described by the nonlinear models identified in this study and that models of this form may be useful for description of responses over a wide range of C and T.

Administration, Inhalation↗

PubMed1994

Ozone dose and effect in humans and rats. A comparison using oxygen-18 labeling and bronchoalveolar lavage.

In an effort to improve risk assessments for ozone (O3) we compared the incorporation of inhaled oxygen-18-labeled O3 (18O3) into the lungs of humans and laboratory rats. Cells and fluids obtainable through bronchoalveolar lavage (BAL) were examined after exposure to 18O3 to determine whether excess 18O concentrations (presumed to be reaction products of 18O3) could be detected and equated to the O3 dose to the lung. Three O3 effect measurements (increased BAL protein and neutrophils and decreased BAL macrophages) were also made in subjects or animals exposed in parallel to determine whether there was a correspondence between dose and effect measurements. Eight human male volunteers 18 to 35 yr of age were exposed to 18O3 (0.4 ppm for 2 h) with 15-min alternating periods of heavy treadmill exercise and rest. Rats (F344) were exposed identically, except without exercise. 18O3 was generated directly from pure 18O2. BAL cells and centrifugally separable surfactant material were freeze-dried and analyzed by mass spectrometer for excess 18O. Results showed that the exercising humans had four- to fivefold higher 18O concentrations in all of their BAL constituents than did the rats. The humans also had significant increases in all of the effects markers after 0.4 ppm O3, whereas the rats did not. Rats that were exposed to higher concentrations of 18O3 (2.0 ppm) had levels of 18O in BAL that were more comparable to but still lower than those of exercising humans. Changes in all of the effects markers in these rats were comparable or higher than in exercising humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

U.S. Environmental Protection Agency's Ozone Epidemiology Research Program: a strategy for assessing the effects of ambient ozone exposure upon morbidity in exposed populations.

The Clean Air Act Amendments of 1990 mandate a future reduction of ambient ozone levels in many areas of the country, the cost of which will be great. In order to assess the current public health burden of ambient ozone exposure and to provide information for assessment of potential health benefits of improved air quality, the Health Effects Research Laboratory of the U.S. EPA has undertaken an Ozone Epidemiology Research Program. The research strategy which will guide this scientific program is described in this paper. Criteria for selection of important research questions as well as issues which cut across all questions and study designs are discussed. In particular, this program emphasizes the study of effects which reflect morbidity in the population. The three questions identified as being of most immediate importance involve the relationship of short-term ambient ozone exposure to acute respiratory illness, the relationship of recurrent exposure to chronic respiratory disease, and the relationship of recurrent exposure to development of acute respiratory illness. Specific research approaches and initial projects to address these three questions are described.

Animals↗