Nociceptive mechanisms modulate ozone-induced human lung function decrements.

We have previously suggested that ozone (O3)-induced pain-related symptoms and inhibition of maximal inspiration are due to stimulation of airway C fibers (M. J. Hazucha, D. V. Bates, and P. A. Bromberg. J. Appl. Physiol. 67: 1535-1541, 1989). If this were so, pain suppression or inhibition by opioid-receptor agonists should partially or fully reverse O3-induced symptomatic and lung functional responses. The objectives of this study were to determine whether O3-induced pain limits maximal inspiration and whether endogenous opioids contribute to modulation of the effects of inhaled O3 on lung function. The participants in this double-blind crossover study were healthy volunteers (18-59 yr) known to be "weak" (WR; n = 20) and "strong" O3 responders (SR; n = 42). They underwent either two 2-h exposures to air or two 2-h exposures to 0. 42 parts/million O3 with moderate intermittent exercise. Immediately after post-O3 spirometry, the WR were randomly given either naloxone (0.15 mg/kg iv) or saline, whereas SR randomly received either sufentanil (0.2 microgram/kg iv) or saline. O3 exposure significantly (P < 0.001) impaired lung function. In SR, sufentanil rapidly, although not completely, reversed both the chest pain and spirometric effects (forced expiratory volume in 1 s; P < 0.0001) compared with saline. Immediate postexposure administration of saline or naloxone had no significant effect on WR. Plasma beta-endorphin levels were not related to an individual's O3 responsiveness. Cutaneous pain variables showed a nonsignificant weak association with O3 responsiveness. These observations demonstrate that nociceptive mechanisms play a key role in modulating O3-induced inhibition of inspiration but not in causing lack of spirometric response to O3 exposure in WR.

Clinical presentation and pharmacological therapy in corticobasal degeneration.

BACKGROUND: To date, to our knowledge, there is no systematic presentation of treatment outcome in large series of patients clinically diagnosed as having corticobasal degeneration. OBJECTIVE: To evaluate the clinical presentation and treatment outcome of patients clinically diagnosed as having corticobasal degeneration. SUBJECTS: We gathered case patients seen in 8 major movement disorder clinics during the last 5 years who were diagnosed as having corticobasal ganglionic degeneration. METHODS: Using a chart review method, we recorded the clinical presentation, medications used, response to medications, and adverse effects. RESULTS: A total of 147 case patients were reviewed, 7 were autopsy proven. Parkinsonian features were present in all, other movement disorders in 89%, and higher cortical dysfunction in 93%. The most common parkinsonian sign was rigidity (92%), followed by bradykinesia (80%), gait disorder (80%), and tremor (55%). Other movement disorders were dystonia in 71% and myoclonus in 55%. Higher cortical dysfunction included dyspraxia (82%), alien limb (42%), cortical sensory loss (33%), and dementia (25%). Ninety-two percent of the case patients received dopaminergic drugs, which resulted in a beneficial effect for 24%. Parkinsonian signs were the elements improving the most and levodopa was the most effective drug. Benzodiazepines, primarily clonazepam, were administered to 47 case patients, which resulted in improvement of myoclonus in 23% and dystonia in 9%. The most frequent disabling adverse effects of drug trials in these case patients were somnolence (n = 24), gastrointestinal complaints (n = 23), confusion (n = 16), dizziness (n =12), hallucinations (n = 5), and dry mouth (n = 5). CONCLUSIONS: Pharmacological intervention was largely ineffective in the management of corticobasal degeneration, and new treatments are needed for ameliorating the symptoms of this syndrome.

Characterization of fatty acid synthase in cell lines derived from experimental mammary tumors.

The lipogenic enzyme fatty acid synthase (FAS) is elevated in various human primary cancers and certain human cancer cell lines. FAS overexpression in human neoplasia has clinical relevance because of its association with tumor aggression and potential chemotherapeutic intervention. Here, we surveyed FAS in cell lines established from normal murine mammary epithelium (NMuMG) and from mammary tumors induced by either rodent polyoma (Py) virus or murine mammary tumor virus (MMTV). Western blotting revealed greater content of FAS in Py-transformed A1-1 and T1 than NMuMG or MMTV-transformed Mm5MT, RIIIMT and MMT060562. These data suggest that signaling events mediated by Py transformation may increase cellular amounts of FAS. Although FAS content was elevated to similar levels in A1-1 and T1, specific activities were significantly different as enzyme activity in T1 was 3-fold higher than A1-1. Likewise, FAS activity in NMuMG was about 0.5-fold higher than the MMTV-transformed lines, even though enzyme content was similar. Immunoprecipitation studies employing anti-phosphoamino acid antibodies followed by immunoblot analysis with anti-FAS antisera (and vice versa) were used to characterize the constitutive phosphorylation state of the enzyme. Phosphoserine and phosphothreonine residues were detected in the more active FAS from T1 and NMuMG, but not in the less active FAS from Mm5MT or A1-1. Discovery of phosphorylated FAS suggests that the enzyme may have more immediate control over lipogenesis than previously thought. High-dose (10-4 M) dexamethasone induced FAS content and activity in NMuMG and MMTV-transformed lines but not Py-transformed cells. Lower concentrations (10-8, 10-6 M) of dexamethasone also activated FAS but without concomitant elevation of its protein content, which was consistent with a phosphorylated form of FAS. Finally, cell lines were treated with the FAS inhibitor cerulenin: almost all breast cancer lines were growth inhibited at significantly lower amounts of drug than normal cell lineages, suggesting that FAS plays a greater role in viability of tumor cells than normal cells. Pretreatment with palmitate (a primary end-product of FAS) prior to cerulenin rescued A1-1 cells only slightly from growth inhibition, whereas pretreatment with oleate (a monounsaturated fatty acid synthesized from palmitate) synergized cerulenin's cytotoxic effects.

Quantitative electroencephalography, with serial subtraction and odour detection in the differentiation of Alzheimer's disease and vascular dementia.

The diagnosis of dementia can be difficult, yet diagnostic accuracy has important prognostic and therapeutic implications. Nevertheless, conventional electroencephalography (EEG) has always played a secondary role in dementia investigation. More recently quantitative EEG (qEEG) has allowed more detailed and objective analysis of EEG data, but there is still no clearly defined clinical role for qEEG. We have used relative power qEEG measures made during resting and active brain conditions (serial subtraction and odour detection tasks) to differentiate between demented and non-demented subjects, and between subjects with different forms of dementia. Electroencephalograms were obtained from 15 subjects with clinically diagnosed Alzheimer's disease (AD), 16 with a clinical diagnosis of vascular dementia (VaD), and 16 non-demented control subjects. Discriminate function analyses were used to differentiate groups according to task, electrode site, and frequency bandwidth. Correct classification, as demented or non-demented, was made for 93% of cases using qEEG comparisons of resting states with eyes closed and eyes opened. Almost all subjects with AD and VaD were correctly classified with qEEG recorded during odour detection (95%). qEEG for serial subtraction correctly classified AD and VaD in 91% of the dementia group. These results have important implications for future qEEG research, and may be pertinent to the precision of diagnosis in patients with dementia.

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.

Intestinal effects of sulfate in drinking water on normal human subjects.

Uncontrolled observations implicate sulfate in drinking water at concentrations exceeding 500-700 mg/liter as a cause of diarrhea, but controlled studies have not been reported. We conducted a controlled study in normal adults to determine the effect of various drinking water sodium sulfate concentrations on bowel function. Ten healthy subjects were given a constant diet and fluid intake. Fluid consisted of 36 ml/kg/day of drinking water of various known sulfate concentrations and 500 ml of other fluid. In a dose-ranging study, four subjects received drinking water with sulfate concentrations of 0, 400, 600, 800, 1000, and 1200 mg/liters for six consecutive two-day periods. In a single-dose study, six other subjects received water with sulfate concentrations of 0 and 1200 mg/liter for two consecutive six-day periods. Stool mass, frequency, and consistency and mouth-to-anus appearance time of colored markers were measured. In the dose-ranging study, the only significant linear trend was decreasing mouth-to-anus appearance time with increasing sulfate concentrations. In the single-dose study, 1200 mg/liter sulfate caused a significant but clinically mild increase in mean stool mass per six-day pool from 621 g to 922 g (P = 0.03). When all 10 subjects were used to compare effects of 0 mg/liter and 1200 mg/liter sulfate, significant differences in stool consistency (P = 0.02) and transit time (P = 0.03) were observed. None of the subjects reported diarrhea or passed more than three stools per day. In 10 normal adult subjects, sulfate in drinking water at a concentration of 1200 mg/liter, which is higher than reported to occur in US municipal water sources, caused a measurable but clinically insignificant increase in stool mass and decrease in stool consistency and appearance time, but no change in stool frequency and no complaint of diarrhea.

Left atrial tumour mimicking pulmonary embolism.

Primary cardiac tumours have been described as great imitators. They are rare, and clinical presentations are diverse. Diagnosis is usually made by two-dimensional echocardiography. The present case report describes a case where a left atrial fibrosarcoma eluded diagnosis by echocardiography, and was eventually demonstrated by computed tomography. Management was complicated by the presence of persistent mismatch demonstrated by ventilation-perfusion lung scans. The likely mechanism underlying this phenomenon is discussed.

The significance of subnormal serum vitamin B12 concentration in older people: a case control study.

OBJECTIVES: To determine the clinical significance of subnormal serum vitamin B12 concentration in older people by comparing the hematological, neurological, and biochemical findings in patients with subnormal serum B12 with a control group with normal B12 levels. DESIGN: Clinical and laboratory assessment of hospital patients selected to represent a wide range of serum B12 levels. SETTING: Patients in the medical wards of two hospitals, one a general hospital and the other a geriatric hospital. PARTICIPANTS: Ninety-four older patients, 43 with subnormal (< 150 pmol/L) and 51 with normal serum B12 concentrations. MEASUREMENTS: Mini-Mental State Examination, neurological score, full blood examination, mean neutrophil lobe count; serum B12, holotranscobalamin II, total homocysteine, folate, creatinine and gastrin red folate; parietal cell antibodies, intrinsic factor antibodies. RESULTS: Of all the measurements, only mean neutrophil lobe count and mean serum total homocysteine were significantly different in the low serum B12 compared with the control group. There was a significant correlation between serum B12 and homocysteine levels. Eighty-eight percent of patients in the test group compared with 76% in the control group showed at least one of the following; elevated serum total homocysteine, neutrophil hypersegmentation, or elevated MCV. This overlap was much reduced when patients with borderline values for serum B12 (150-250 pmol/L) were included in the low B12 group. Most of the older subjects had little or no B12 on transcobalamin II, irrespective of the serum B12 level. CONCLUSION: Almost 90% of older patients with serum B12 < 150 pmol/L show evidence of tissue vitamin B12 deficiency. Deficiency becomes manifest in older patients at relatively higher concentrations of serum B12 than in younger subjects, possibly because of lower levels of holotranscobalamin II in the older patients.

Effects of age, socioeconomic status, and menstrual cycle on pulmonary response to ozone.

The purpose of this study was to investigate the effects of age, socioeconomic status, and menstrual cycle phase on the pulmonary response to ozone exposure. Three hundred seventy-two healthy white and black young adults, between the ages of 18 and 35 y, were exposed only once to 0.0, 0.12, 0.18, 0.24, 0.30, or 0.40 ppm ozone for 2.3 h. Prior to and after exposure, pulmonary function tests were obtained. Prior to exposure, each subject completed a personal and family-history questionnaire. The responses to this questionnaire were used to investigate age, socioeconomic status, and menstrual cycle phase effects on pulmonary responsiveness to ozone. We concluded that the ages of subjects, within the age range studied, had an effect on responsiveness (i.e., decrements in forced expiratory volume in 1 s decreased as the subjects' ages decreased). Socioeconomic status, as reflected by education of fathers, also appeared to affect forced expiratory volume in 1-s responsiveness to ozone, with the middle socioeconomic group being the most responsive. The phase of menstrual cycle did not have an impact on individual responsiveness to ozone.

Extracellular glucose reduces the responsiveness of mesangial cell ion channels to angiotensin II.

Abnormal cellular ion homeostasis is a well-recognized component of diabetic glomerular disease. In cultured rat glomerular mesangial cells, we have previously shown that insulin regulates Ca(2+)-dependent activation of 4-pS Cl- channels and 27-pS nonselective cation channels (NSCC) by angiotensin II (ANG II). To assess whether extracellular glucose also affects mesangial ion channels, we applied patch-clamp techniques to cells incubated in constant insulin (100 mU/ml) and either "normal" (5 mM) or "high" (30 mM) glucose for 1 wk. In normal glucose, 100 nM ANG II increased Cl- and NSCC activity by > 16-fold and > 60-fold, respectivley. Direct release of intracellular Ca2+ ([Ca2+]i) stores (0.25 microM thapsigargin) mimicked ANG II-induced channel stimulation. In high glucose, Cl- and NSCC stimulation by ANG II was attenuated (< 7-fold), whereas channel activation by thapsigargin was unaffected. Protein kinase C (PKC) inhibition (30-min exposure to 0.5 microM calphostin) or downregulation (24-h exposure to 0.1 microM 4 beta-phorbol 12-myristate 13-acetate), but not aldose reductase inhibition (0.5 mM sorbinil), restored channel responsiveness to ANG II despite high glucose. Channel responsiveness was also restored if mesangial cells were coincubated in both high glucose and 500 microM myo-inositol. Acute exposure to a synthetic diacylglycerol (100 microM 1-oleoyl-2-acetyl glycerol) reestablished channel unresponsiveness to ANG II. We conclude the following in rat mesangial cell cultures: 1) Activation of Ca(2+)-dependent Cl- and NSCCs by ANG II is reduced by high extracellular glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

High levels of inorganic sulfate cause diarrhea in neonatal piglets.

Artificially reared neonatal piglets were used to study the effect of inorganic sulfate on bowel function in human infants. Two experiments were conducted to evaluate the effect of high levels of inorganic sulfate on the growth, feed intake and feces consistency of artificially reared piglets, and to determine the dose at which at least 50% of piglets develop nonpathogenic diarrhea. The effect of sulfate level on kidney weight and concentration of inorganic sulfate in urine was also assessed. In each experiment, 40 pigs with an average initial age of 5 d were individually caged and reared with an automatic feeding device. Ten pigs per dietary treatment were fed one of four diets containing the following levels of added inorganic sulfate (mg/L of diet), as anhydrous sodium sulfate (USP): 0, 1200, 1600 and 2000 for Experiment 1 (18-d study), and 0, 1800, 2000 and 2200 for Experiment 2 (16-d study). The levels of added sulfate did not affect (P > 0.05) the growth of piglets, or their feed intake. Whereas 1200 mg added sulfate/L had essentially no effect on feces consistency, levels > 1800 mg/L of diet resulted in a persistent, nonpathogenic diarrhea in neonatal piglets. Added sulfate did not affect (P > 0.05) relative kidney weight. Inorganic sulfate in urine reached maximum concentration (P < 0.05) in pigs fed diets with 1600 and 1800 mg added sulfate/L in Experiments 1 and 2, respectively, but declined at higher levels. The results suggest that the level of added dietary inorganic sulfate at which 50% of piglets develop nonpathogenic diarrhea is between 1600 and 1800 mg/L.

Gallstone ileus: a new role for abdominal computed tomography.

This case report illustrates the difficulties in making the clinical diagnosis of gallstone ileus. In addition to an unusual clinical picture, the changes normally expected on abdominal X-ray in gallstone ileus were subtle and missed in our patient. The diagnosis was made using abdominal computerised tomography (CT). We recommend the early use of abdominal CT scanning in the investigation of clinical bowel obstruction, especially in the elderly, where gallstone ileus is a more common condition.

Lung function response of healthy women after sequential exposures to NO2 and O3.

Since NOx emissions bear a precursor-product relation with ambient ozone (O3) levels, the sequence of peak ambient concentrations is first nitrogen dioxide (NO2) followed later in the day by ozone (O3). We ascertained whether preliminary exposure to 0.6 parts per million (ppm) NO2 would affect the lung function response to subsequent exposure to 0.3 ppm O3. Twenty-one healthy young nonsmoking women (18 to 35 yr of age) underwent two sets of exposures on two different days separated by a minimum of 2 wk. On one day, subjects were exposed to air for 2 h followed 3 h later by a 2-h exposure to O3. On the other day, the first exposure was to NO2; order of the days was randomized. During each exposure subjects intermittently exercised, alternating 15 min of rest with 15 min of exercise (Ve approximately 40 L/min). Spirometry was performed before the first exposure and at 1-h intervals until the end of the 2-h (O3) exposure. Plethysmography measurements were made before and after NO2 and O3 exposures. Nonspecific airway reactivity (AR) was determined at least 1 wk prior to the first exposure and following each O3 exposure. AR to methacholine (MCh) was expressed as dose required to decrease FEV1 by 10% (PD10FEV1). Nitrogen dioxide exposure alone did not reduce FEV1 but did significantly enhance O3-induced spirometric changes. No significant effects were observed in plethysmography. On both exposure days, the median PD10FEV1 was significantly reduced (p < 0.05) from control PD10FEV1 (14.3 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of mesangial cell ion channels by insulin and angiotensin II. Possible role in diabetic glomerular hyperfiltration.

We used patch clamp methodology to investigate how glomerular mesangial cells (GMC) depolarize, thus stimulating voltage-dependent Ca2+ channels and GMC contraction. In rat GMC cultures grown in 100 mU/ml insulin, 12% of cell-attached patches contained a Ca(2+)-dependent, 4-picosiemens Cl- channel. Basal NPo (number of channels times open probability) was < 0.1 at resting membrane potential. Acute application of 1-100 nM angiotensin II (AII) or 0.25 microM thapsigargin (to release [Ca2+]i stores) increased NPo. In GMC grown without insulin, Cl- channels were rare (4%) and unresponsive to AII or thapsigargin in cell-attached patches, and less sensitive to [Ca2+]i in excised patches. GMC also contained 27-pS nonselective cation channels (NSCC) stimulated by AII, thapsigargin, or [Ca2+]i, but again only when insulin was present. In GMC grown without insulin, 15 min of insulin exposure increased NPo (insulin > or = 100 microU/ml) and restored AII and [Ca2+]i responsiveness (insulin > or = 1 microU/ml) to both Cl- and NSCC. GMC AII receptor binding studies showed a Bmax (binding sites) of 2.44 +/- 0.58 fmol/mg protein and a Kd (binding dissociation constant) of 3.02 +/- 2.01 nM in the absence of insulin. Bmax increased by 86% and Kd was unchanged after chronic (days) insulin exposure. In contrast, neither Kd nor Bmax was significantly affected by acute (15-min) exposure. Therefore, we concluded that: (a) rat GMC cultures contain Ca(2+)-dependent Cl- and NSCC, both stimulated by AII. (b) Cl- efflux and cation influx, respectively, would promote GMC depolarization, leading to voltage-dependent Ca2+ channel activation and GMC contraction. (c) Responsiveness of Cl- and NSCC to AII is dependent on insulin exposure; AII receptor density increases with chronic, but not acute insulin, and channel sensitivity to [Ca2+]i increases with both acute and chronic insulin. (d) Decreased GMC contractility may contribute to the glomerular hyperfiltration seen in insulinopenic or insulin-resistant diabetic patients.

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).

Effects of steady-state and variable ozone concentration profiles on pulmonary function.

Measurements of ambient ozone (O2) concentration during daylight hours have shown a spectrum of concentration profiles, from a relatively stable to a variable pattern usually reaching a peak level in the early afternoon. Several recent studies have suggested that in estimating exposure dose (O3 concentration [C] x exposure time [T] x ventilation [V]), O3 concentration needs to be weighted more heavily than either ventilation or duration of exposure in the estimates. In this study we tested the hypothesis that regardless of concentration pattern and exposure rate the same exposure dose of O3 will induce the same spirometric response. We exposed 23 healthy male volunteers (20 to 35 yr of age) for 8 h to air, 0.12 ppm O3 (steady-state), and a triangular exposure pattern (concentration increased steadily from zero to 0.24 ppm over the first 4 h and decreased back to zero by 8 h). During the first 30 min of each hour, subjects exercised for 30 min at minute ventilation (VE) approximately 40 L/min. The order of the exposures was randomized, and the exposures were separated by at least 7 days. The response patterns over the 8-h periods for spirometric variables in both O3 exposures were statistically different from air exposure changes and from each other. For FEV1 the p values were 0.017 between air and steady-state profile, 0.002 between air and triangular profile, and 0.037 between steady-state and triangular profiles. Although in the triangular pattern of exposure the maximal O3 concentration was reached at 4 h, the maximum FEV1 decrement (10.2%) was observed at 6 h of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of ozone exposure on the dispersion of inhaled aerosol boluses in healthy human subjects.

Acute exposure of humans to low levels of ozone are known to cause decreases in FVC and increases in SRaw. These alterations in lung function do not, however, elucidate the potential for acute small airway responses. In this study we employed a test of aerosol dispersion to examine the potential effects of ozone on small airways in humans. Twenty-two healthy nonsmoking male volunteers were exposed to 0.4 ppm ozone for 1 h while exercising at 20 L/min/m2 body surface area. Before and immediately after exposure, tests of spirometry (FVC, FEV1, and FEF25-75) and plethysmography (Raw and SRaw) were performed. Subjects also performed an aerosol dispersion test before and after exposure. Each test involved a subject inhaling five to seven breaths of a 300-ml bolus of a 0.5 micron triphenyl phosphate aerosol injected into a 2-L tidal volume. The bolus was injected into the tidal breath at three different depths: at Depth A the bolus was injected after 1.6 L of clean air were inhaled from FRC, at Depth B after 1.2 L, and at Depth C after 1.2 L but with inhalation beginning from RV. The primary measure of bolus dispersion was the expired half-width (HW). Secondary measures were the ratio (expressed as percent) of peak exhaled aerosol concentration to peak inhaled concentration (PR), shift in the median bolus volume between inspiration and expiration (VS), and percent of total aerosol recovered (RC). Changes in pulmonary function after ozone exposure were consistent with previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Pulmonary function, airway responsiveness, and respiratory symptoms in asthmatics following exercise in NO2.

Two experiments were conducted to determine respiratory responses of persons with asthma performing intermittent moderate exercise while exposed to low concentrations of NO2. In the first, preliminary experiment, 13 male subjects, aged 19-35, with mild asthma were exposed on separate days in a chamber (natural breathing, 20 degrees C, 40% RH) to 0.30 ppm NO2 and to a control or "clean air" exposure (0.0 ppm NO2). Exposure included three 10-min periods of moderate treadmill exercise (VE = 44.5 liter/min), each followed by symptom measurement and pulmonary function testing. The average decrease in FEV1 following the initial 10 min exercise in 0.30 ppm was 11% which was significantly greater (p less than 0.05) than that observed in clean air (7%). Differences in FVC and SRaw were not significantly different at this time. Slight cough and dry mouth and throat were apparent only after the first exercise in NO2. After the second and third exercises, decreases in FEV1 and FVC and increases in SRaw were significantly greater in 0.30 than in 0.0 ppm NO2. Individual subject responses were variable. These results suggested that some asthmatics who perform moderate exercise while exposed to 0.30 ppm NO2 may experience bronchoconstriction and reduction in spirometric performance. Because of these preliminary findings, a more comprehensive, concentration-response experiment was conducted. Twenty-one male volunteers with mild asthma were exposed for 75 min with natural breathing to 0.0, 0.15, 0.30, and 0.60 ppm NO2. Exposure included three 10-min periods of moderate treadmill exercise (VE = 43 liter/min), each exercise followed by symptoms measurement and pulmonary function testing. In addition, airway responsiveness was measured two hr after each exposure by methacholine bronchial challenge testing. In the control exposures (0.0 ppm NO2), the exercise alone caused substantial decrements in pulmonary function. These decrements (as measured by decreases in FEV1 and FVC, and increases in SRaw) were not increased relative to the control exposure after any exercise session in any concentration of NO2. Furthermore, there was no overall group-averaged indication of a concentration-related effect of the NO2 on pulmonary function. Likewise, symptoms reported after NO2 exposure were not significantly different from those reported in clean air. Group-averaged airway responsiveness after exercise in NO2 was also not different from responsiveness after exercise in clean air. For only two subjects was there any indication of a concentration-related increase in airway responsiveness due to exposure to NO2.(ABSTRACT TRUNCATED AT 400 WORDS)