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Biomedical subjects

W F McDonnell

Publications and source records attributed to W F McDonnell.

At least 37 records · Page 2Linked to original sources
PubMed1993

An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 12. Effects on man, animals, and plants as a function of air pollutant impact.

The impact-effect mathematical model, developed in 1991, improves on a previous mathematical model, and was developed to predict biological response as a function of air pollutant impact. Impact is defined here as exposure duration multiplied by air pollutant concentration raised to an exponent (t.cd). This paper's purpose is to plot and regress example biological effects as a function of air pollutant impact to determine how well the plotted data fit the impact-effect model for three target populations: man, animals, and plants (a wide range of life forms). The three biological effects are: for man, lung function decrease after exposure to ozone (O3); for animals, mouse mortality after exposure to nitrogen dioxide (NO2); and for plants, leaf injury after exposure to O3. The three resultant regression equations account for a substantial amount of the data variance: 95 percent for lung function, 92 percent for leaf injury, and 73 percent for mouse mortality. The model fits the animal and plant data that cover both acute and chronic exposures. The animal exposures ranged from 6 min to 1 yr. The plant exposures ranged from 0.75 to 552 h.

Adult↗
PubMed1993

The pulmonary response of white and black adults to six concentrations of ozone.

Many early studies of respiratory responsiveness to ozone (O3) were done on healthy, young, white males. The purpose of this study was to determine whether gender or race differences in O3 response exist among white and black, males and females, and to develop concentration-response curves for each of the gender-race groups. Three hundred seventy-two subjects (n > 90 in each gender-race group), ages 18 to 35 yr, were exposed once for 2.33 h to 0.0 (purified air), 0.12, 0.18, 0.24, 0.30, or 0.40 ppm O3. Each exposure was preceded by baseline pulmonary function tests and a symptom questionnaire. The first 2 h of exposure included alternating 15-min periods of rest and exercise on a motorized treadmill producing a minute ventilation (VE) of 25 L/min/m2 body surface area (BSA). After exposure, subjects completed a set of pulmonary function tests and a symptom questionnaire. Lung function and symptom responses were expressed as percent change from baseline and analyzed using a nonparametric two factor analysis of variance. Three primary variables were analyzed: FEV1, specific airway resistance (SRaw), and cough. Statistical analysis demonstrated no significant differences in response to O3 among the individual gender-race groups. For the group as a whole, changes in the variables FEV1, SRaw, and cough were first noted at 0.12, 0.18, and 0.18 ppm O3, respectively. Adjusted for exercise difference, concentration-response curves for FEV1 and cough among white males were consistent with previous reports (1).

Adolescent↗
PubMed1993

Predictors of individual differences in acute response to ozone exposure.

The purpose of this study was to identify personal characteristics that predict individual differences in acute FEV1 response to ozone exposure. Response and predictor data were collected on 290 white male volunteers 18 to 32 yr of age who were each exposed to one of six concentrations of ozone between 0.0 and 0.40 part per million. The sample was divided into an exploratory sample of 96 and a confirmatory sample of 194 subjects. Exploratory analysis indicated that ozone, age, and several other variables explained a significant proportion of the variance in response. In the confirmatory sample, only age and ozone concentration predicted FEV1 decrement. For the combined sample ozone explained 31% of the variance, with age accounting for an additional 4%. The model predicted a decreasing response with increasing age for all nonzero ozone concentrations. For exposure to 0.40 ppm, the model predicts decrements in FEV1 of 1.07 and 0.47 L for 18- and 30-yr-old subjects, respectively. We concluded that for white male subjects age was a significant predictor of response, with older subjects being less responsive to ozone. Furthermore, we demonstrated that exploratory analysis without control of type I statistical error rates may result in apparent findings that cannot be replicated.

Adolescent↗
PubMed1993

Utility of controlled human exposure studies for assessing the health effects of complex mixtures and indoor air pollutants.

The study of health effects induced by exposure to mixtures of pollutants is a complex task. The purpose of this paper is to identify areas of research in which the conduct of human controlled exposure (clinical) studies may contribute to better understanding health effects of exposure to indoor air and other mixtures. The strengths and weaknesses of clinical studies in general are reviewed, as well as examples from the literature of approaches that have been used. Human chamber studies play an important role alongside epidemiologic and animal toxicologic studies in such research. Human chamber studies are limited with regard to assessing chronic effects, rare effects, or effects from long-duration exposures but are powerful in assessing acute, reversible effects from short-duration exposures in humans. The areas in which human chamber studies are most likely to contribute include identification of effects or markers of effects for exposure to a given pollutant or mix of pollutants; direct dose-response assessment of effects for individual compounds and mixtures of set composition; identification of individual compounds responsible for the effects of a mixture; study of the joint effects of a binary mixture; development of markers of acute exposure for particular compounds; development of outcome measurements to be used in the field; and identification, characterization, and testing of sensitive subpopulations.

Air Pollutants↗
PubMed1991

An air quality data analysis system for interrelating effects, standards, and needed source reductions: Part 11. A lognormal model relating human lung function decrease to O3 exposure.

Forced expiratory volume in 1 second (FEV1) was measured in 21 men exercising while exposed to four O3 concentrations (0.0, 0.08, 0.10, and 0.12 ppm). A lognormal multiple linear regression model was fitted to their mean FEV1 measurements to predict FEV1 percent decrease as a function of O3 concentration and exposure duration. The exercise level used was probably comparable to heavy manual labor. The longest O3 exposure studied was 6 h. Extrapolating cautiously to an 8-h workday of heavy manual labor, the model predicts that O3 concentrations of 0.08, 0.10, and 0.12 ppm would decrease FEV1 by 9, 15, and 20 percent, respectively.

Adult↗
PubMed1991

Exposure of humans to ambient levels of ozone for 6.6 hours causes cellular and biochemical changes in the lung.

An acute (2 h) exposure of humans to 0.4 ppm ozone initiates biochemical changes in the lung that result in the production of components mediating inflammation and acute lung damage as well as components having the potential to lead to long-term effects such as fibrosis. However, many people are exposed to lower levels of ozone than this, but for periods of several hours. Therefore, it is important to determine if a prolonged exposure to low levels of ozone is also capable of causing cellular and biochemical changes in the lung. Nonsmoking males were randomly exposed to filtered air and either 0.10 ppm ozone or 0.08 ppm ozone for 6.6 h with moderate exercise (40 liters/min). Bronchoalveolar lavage (BAL) was performed 18 h after each exposure, and cells and fluid were analyzed. The BAL fluid of volunteers exposed to 0.10 ppm ozone had significant increases in neutrophils (PMNs), protein, prostaglandin E2 (PGE2), fibronectin, interleukin-6 (IL-6), and lactate dehydrogenase (LDH) compared with BAL fluid from the same volunteers exposed to filtered air. In addition, there was a decrease in the ability of alveolar macrophages to phagocytize yeast via the complement receptor. Exposure to 0.08 ppm ozone resulted in significant increases in PMNs, PGE2, LDH, IL-6, alpha 1-antitrypsin, and decreased phagocytosis via the complement receptor. However, BAL fluid protein and fibronectin were no longer significantly elevated. We conclude that exposure of humans to as low a level as 0.08 ppm for 6.6 h is sufficient to initiate an inflammatory reaction in the lung.

Adolescent↗
PubMed1991

Time-dependent changes of markers associated with inflammation in the lungs of humans exposed to ambient levels of ozone.

Acute exposure of humans to 0.4 ppm 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. Changes in neutrophils and PGE2 have been observed in humans as early as 3 hr (28) and as late as 18 hr post exposure (19). The purpose of this study was to determine whether inflammatory changes occur relatively rapidly (within 1 hr) following exposure to ozone, or if the cascade of events which are initiated by ozone and lead to inflammation, take some time to develop. We exposed 10 healthy volunteers twice: once to filtered air and once to 0.4 ppm ozone. Each exposure lasted for 2 hr at an exercise level of 60 L/min, and bronchoalveolar lavage was performed 1 hr following exposure. The data from this study were compared to those from a previous study in which 10 subjects were exposed to O3 under identical conditions except that bronchoalveolar lavage was performed 18 hr following exposure. The results of the present study demonstrate that O3 is capable of inducing rapid cellular and biochemical changes in the lung. These changes were detectable as early as 1 hr following a 2 hr exposure of humans to ozone. The profiles of these changes were different at 1 hr and 18 hr following ozone exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Relationships between lung function and physical characteristics in young adult black and white males and females.

The relationships of lung function to physical characteristics in young adults have not been adequately described for different gender-race groups in the United States. As part of a study of the effects of ozone exposure upon Black and White men and women, we measured lung volumes, expiratory flow rates, and airways resistance on a sample of 314 healthy 18-35 yr old nonsmokers. Regression analysis indicated that lung function was adequately described as a linear function of either height or sitting height in each of the four groups, and that while not always significant, gender and race differences in the height and sitting height coefficients were consistently present with those of males and Whites larger than those of females and Blacks, respectively. Lung volumes were frequently observed to be associated with body mass index as measured by Quetelet Index (weight.height.2). The best fitting gender-race specific multiple regression models including these terms and occasional age terms are presented. Two additional models are presented, one of which simultaneously adjusts for both gender and race, and the other of which adjusts for gender for a given race. Comparison of predicted values from our study to those of other studies suggests that the population samples from this study may be similar to those of other American populations reported upon by others.

Adolescent↗
PubMed1990

Ozone concentration and pulmonary response relationships for 6.6-hour exposures with five hours of moderate exercise to 0.08, 0.10, and 0.12 ppm.

The magnitudes of pulmonary responses we previously observed (1) following 6.6-h exposures to 0.12 ppm ozone (O3) suggested that responses would also occur with similar exposures at lower O3 concentrations. The objective of this study was to determine the extent of pulmonary function decrements, respiratory discomfort, and increased airway reactivity to methacholine induced by exposure to O3 below 0.12 ppm. Separate 6.6-h chamber exposures to 0.00, 0.08, 0.10, and 0.12 ppm O3 included six 50-min periods of moderate exercise (VE approximately equal to 39 L/min, HR approximately equal to 115 bpm, and VO2 approximately equal to 1.5 L/min). Each exercise period was followed by 10 min of rest. A 35-min lunch break was included midway through the exposure. Although not intended as an exact simulation, the overall duration, intensity, and metabolic requirements of the exercise performed were representative of a day of moderate to heavy work or play. Preexposure FEV1 averaged 4.39 L, and essentially no change (+0.03 L) occurred with exposure to 0.00 ppm O3. Significant decreases (p less than 0.01) of -0.31, -0.30, and -0.54 L were observed with exposures to 0.08, 0.10, and 0.12 ppm, respectively. The provocative dose of methacholine required to increase airway resistance by 100% (PD100) was 58 cumulative inhalation units (CIU) following exposure to 0.00 ppm and was significantly reduced (p less than 0.01) to 37 CIU at 0.08, 31 CIU at 0.10, and 26 CIU at 0.12 ppm O3; reductions in PD100 are considered indicative of increases in nonspecific airway responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Ozone-induced inflammation in the lower airways of human subjects.

Although ozone (O3) has been shown to induce inflammation in the lungs of animals, very little is known about its inflammatory effects on humans. In this study, 11 healthy nonsmoking men, 18 to 35 yr of age (mean, 25.4 +/- 3.5), were exposed once to 0.4 ppm O3 and once to filtered air for 2 h with intermittent exercise. Eighteen hours later, bronchoalveolar lavage (BAL) was performed and the cells and fluid were analyzed for various indicators of inflammation. There was an 8.2-fold increase in the percentage of polymorphonuclear leukocytes (PMN) in the total cell population, and a small but significant decrease in the percentage of macrophages after exposure to O3. Immunoreactive neutrophil elastase often associated with inflammation and lung damage increased by 3.8-fold in the fluid while its activity increased 20.6-fold in the lavaged cells. A 2-fold increase in the levels of protein, albumin, and IgG suggested increased vascular permeability of the lung. Several biochemical markers that could act as chemotactic or regulatory factors in an inflammatory response were examined in the BAL fluid (BALF). The level of complement fragment C3 alpha was increased by 1.7-fold. The chemotactic leukotriene B4 was unchanged while prostaglandin E2 increased 2-fold. In contrast, three enzyme systems of phagocytes with potentially damaging effects on tissues and microbes, namely, NADPH-oxidase and the lysosomal enzymes acid phosphatase and beta-glucuronidase, were increased neither in the lavaged fluid nor cells. In addition, the amounts of fibrogenic-related molecules were assessed in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Tolerance to methacholine inhalation challenge in nonasthmatic subjects.

Airway responses to inhalation challenge with methacholine in healthy nonasthmatic subjects were examined to determine whether attenuation of response occurred upon repeated challenge. In one experiment, progressively increasing tolerance to multiple-dose challenges was seen with 4 challenges at 4-h intervals. In another study, a smaller degree of tolerance was also seen when a single-dose challenge was conducted 3 times at 24-h intervals. In these studies, the doses of methacholine used to obtain responses in nonasthmatic subjects were higher than are required under conditions of clinical methacholine challenge as a diagnostic test for asthma. Consequently, these findings may be relevant only to investigations or epidemiologic studies in which serial methacholine challenges are performed at intervals of 24 h or less in nonasthmatic subjects requiring higher cumulative doses of methacholine than do asthmatics.

Adolescent↗
PubMed1987

The respiratory responses of subjects with allergic rhinitis to ozone exposure and their relationship to nonspecific airway reactivity.

Ozone exposure in man produces changes in respiratory function and symptoms. There is a large degree of unexplained intersubject variability in the magnitude of these responses. There is concern that individuals with chronic respiratory diseases may also be more responsive to ozone than normal individuals. The purpose of this study was to describe the responses of subjects with allergic rhinitis to ozone exposure and to compare these responses to those previously observed in normal individuals. A further purpose was to measure the association of baseline nonspecific airway reactivity with changes in lung function and respiratory symptoms following ozone exposure. A group of 26 nonasthmatic subjects with allergic rhinitis performed a bronchial inhalation challenge with histamine and subsequently underwent two hour exposures to both clean air and to 0.18 part per million ozone with alternating periods of rest and heavy exercise. The airway reactivity of this group of subjects was no greater than that of a comparable group of subjects without allergic rhinitis. The respiratory responses of these subjects to ozone exposure were similar to those previously reported for subjects without allergic rhinitis with the exception that the allergic rhinitis subjects appeared to have a modestly increased bronchoconstrictor response compared to normals. Furthermore, we observed no significant relationships between nonspecific airway reactivity and response to ozone as measured by changes in lung function or the induction of symptoms.

Adolescent↗
PubMed1985

Role of the parasympathetic nervous system in acute lung response to ozone.

We conducted an ozone (O3) exposure study using atropine, a muscarinic receptor blocker, to determine the role of the parasympathetic nervous system in the acute response to O3. Eight normal subjects with predetermined O3 responsiveness were randomly assigned an order for four experimental exposures. For each exposure a subject inhaled either buffered saline or atropine aerosol followed by exposure either to clean air or 0.4 ppm O3. Measurements of lung mechanics, ventilatory response to exercise, and symptoms were obtained before and after exposure. O3 exposure alone resulted in significant changes in specific airway resistance, forced vital capacity (FVC), forced expiratory flow rates, tidal volume (VT), and respiratory rate (f). Atropine pretreatment prevented the significant increase in airway resistance with O3 exposure and partially blocked the decrease in forced expiratory flow rates but did not prevent a significant fall in FVC, changes in f and VT, or the frequency of reported respiratory symptoms after O3. These results suggest that the increase in pulmonary resistance during O3 exposure is mediated by a parasympathetic mechanism and that changes in other measured variables are mediated, at least partially, by mechanisms not dependent on muscarinic cholinergic receptors of the parasympathetic nervous system.

Adolescent↗
PubMed1985

Reproducibility of individual responses to ozone exposure.

Because large intersubject differences in the magnitudes of response to a single ozone (O3) exposure have been observed, we undertook to determine if this variability were due to differences in intrinsic responsiveness to O3 or to other factors. Thirty-two subjects were exposed to 1 of 5 O3 concentrations (0.12, 0.18, 0.24, 0.30, or 0.40 ppm), and each underwent one or more repeat exposures separated by from 3 wk to 14 months. Magnitudes of change for pulmonary function variables, respiratory rate and tidal volume, and for reported symptoms were compared for the repeated exposures. Changes induced in forced expiratory spirometric measurements were highly reproducible for as long as 10 months and for all tested O3 concentrations of 0.18 ppm or greater. This high degree of reproducibility indicates that the magnitude of response to a single exposure is a precise estimate of that subject's intrinsic O3 responsiveness. We conclude that the previously observed intersubject variability in magnitude of O3-induced effects is the result of large differences in intrinsic responsiveness to O3.

Adolescent↗
PubMed1985

Respiratory responses of vigorously exercising children to 0.12 ppm ozone exposure.

Changes in respiratory function have been suggested for children exposed to less than 0.12 ppm ozone (O3) while engaged in normal activities. Because the results of these studies have been confounded by other variables, such as temperature or the presence of other pollutants or have been questioned as to the adequacy of exposure measurements, we determined the acute response of children exposed to 0.12 ppm O3 in a controlled chamber environment. Twenty-three white males 8 to 11 yr of age were exposed once to clean air and once to 0.12 ppm O3 in random order. Exposures were for 2.5 h and included 2 h of intermittent heavy exercise. Measures of forced expiratory volume in one second (FEV1) and the symptom cough were determined prior to and after each exposure. A significant decline in FEV1 was found after the O3 exposure compared to the air exposure, and it appeared to persist for 16 to 20 h. No significant increase in cough was found due to O3 exposure. Forced vital capacity, specific airways resistance, respiratory frequency, tidal volume, and other symptoms were measured in a secondary exploratory analysis of this study.

Child↗
PubMed1983

Effects of 0.1 ppm nitrogen dioxide on airways of normal and asthmatic subjects.

It has been reported (J. Clin. Invest. 57: 301-307, 1976) that inhalation of nitrogen dioxide (NO2) will enhance the bronchial reactivity of asthmatics. This study was designed to evaluate the respiratory effect of a 1-h exposure of normal subjects and of atopic asthmatics to 0.1 parts per million (ppm) NO2. Fifteen normal and 15 asthmatic subjects were exposed to air and to NO2 in a randomized double-blind crossover design. Exposure to either atmosphere was bracketed by bronchial inhalation challenge using aerosolized metacholine chloride solutions. Plethysmographic measurements of specific airway resistance (sRaw) and the forced random noise impedance spectrum (5-30 Hz) were obtained immediately after each methacholine dose. Following acute exposure to NO2, there was a slight but not significant increase in mean base-line sRaw in both normals and asthmatics. The overall base-line resistive properties of the respiratory system determined by forced random noise excitation were not significantly affected by NO2 inhalation either. Finally, there was no change in bronchial response to methacholine challenge in either group. These findings indicate that 0.1 ppm NO2 exposure for 1 h without exercise had no demonstrable airways effects in either young atopic asthmatics with mild disease or young normal subjects.

Adolescent↗