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Biomedical subjects

D Sparrow

Publications and source records attributed to D Sparrow.

At least 91 records · Page 5Linked to original sources

Recovery of leukotriene E4 from the urine of patients with airway obstruction.

The urinary excretion of leukotriene E4 (LTE4) was measured in subjects presenting for emergency treatment of airway obstruction. A total of 72 subjects presenting with airway obstruction performed peak flow determinations before and after three treatments with nebulized albuterol given at 20-min intervals. Of these subjects, 22 more than doubled their peak flow rates, while 19 failed to increase their peak flow rates more than 25% during the treatment period. These groups were designated "responders" and "nonresponders," respectively. Urinary LTE4 excretion was determined in 16 of the 22 responders and 12 of the 19 nonresponders as well as 13 normal subjects by precolumn extraction, analytic reversed-phase high-performance liquid chromatography, and enzyme immunoassay. In the normal subjects the urinary LTE4 excretion was significantly (p less than 0.0001) less than the urinary LTE4 measured in the responder subjects, but not less than the urinary LTE4 excretion in the nonresponder group (p = 0.071). The enhanced recovery of LTE4 from the urine of subjects with acutely reversible airway narrowing is consistent with a bronchoconstrictor role for the cysteinyl leukotrienes in spontaneous acute asthma.

Acute Disease↗

Relationship of urinary serotonin excretion to cigarette smoking and respiratory symptoms. The Normative Aging Study.

The relationship of 2-h urinary excretion of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) to cigarette smoking and respiratory symptoms was examined among 631 male participants in the Normative Aging Study (age range, 44 to 85 years). The amount of serotonin excreted in urine was inversely related to age (p less than 0.001). Mean 2-h excretion of serotonin varied from 8.01 micrograms for men 40 to 49 years of age to 5.84 micrograms for those 70 years of age or over. No clear relationship was evident between the amount of 5-HIAA excreted in urine and age. After adjustment for age, current smokers were found to excrete more serotonin (p less than 0.001) and 5-HIAA (p = 0.001) than never smokers. Former smokers did not differ significantly from never smokers in these respects. After adjustment for age and smoking status in a multivariate model, chronic cough was a significant predictor of serotonin excretion (p = 0.005); chronic cough was less predictive of 5-HIAA excretion (p = 0.07). Other respiratory symptoms were unrelated to urinary excretion of serotonin and 5-HIAA. The mechanisms underlying the observed relationships of urinary serotonin and 5-HIAA excretion to smoking and to chronic cough and their potential relevance to chronic bronchitis remain to be determined.

Age Factors↗

Changes in urinary catecholamine excretion after smoking cessation.

Excretion levels of norepinephrine, epinephrine, and dopamine were assessed in 17 habitual cigarette smokers while smoking and periodically during 30 days of abstinence to determine whether a pattern of transient change existed, suggestive of sympathetic nervous system (SNS) involvement in tobacco withdrawal. Excretion of all three catecholamines declined 1 day after abstinence but did not return to precessation levels during the rest of the follow-up period. The results suggest that postcessation declines in excretion may be permanent changes caused by loss of tobacco's agonist effects, rather than transient withdrawal phenomena resulting from SNS adaptation to the stimulatory effects of tobacco.

Adult↗

Dopaminergic regulation of gonadotropin and thyrotropin hormone secretion is altered with age.

To determine if age-related changes in glycoprotein pituitary hormone secretion are associated with alterations in dopaminergic regulation, plasma gonadotropins and TSH were measured before and after L-dopa administration in 44 young (31-44 years of age) and 42 old (64-88 years of age) healthy male participants. Plasma GH and PRL were also determined in order to examine the somatotroph and lactotrope response. In the young, following L-dopa, plasma FSH, LH and TSH were unchanged from baseline. However, in older subjects, plasma FSH was significantly increased (p less than 0.001) and a similar trend was noted for LH. Plasma TSH was significantly depressed (p less than 0.002) in older subjects only. Following L-dopa, increases in plasma GH and decreases in plasma PRL were of similar magnitude in each group. These data indicate that dopaminergic modulation of gonadotropins and TSH is altered with age.

Adult↗

Relation of obesity and diet to sympathetic nervous system activity.

The hypothesis that dietary intake and obesity stimulate the sympathetic nervous system was investigated in a cross-sectional study of 572 men aged 43-85 years from the Normative Aging Study. Habitus was represented by body mass index, as a measure of overall adiposity, and by the ratio of abdomen-to-hip circumference (abdomen/hip ratio), as a measure of centripetal fat distribution. Sympathetic activity was assessed by measurement of 24-hour urinary norepinephrine excretion. Increased body mass index and total caloric intake were independently associated with increased 24-hour urinary norepinephrine excretion (p = 0.0001 and p = 0.0055, respectively). In addition, mean urinary norepinephrine excretion was higher in subjects classified as either hyperglycemic (serum fasting glucose greater than or equal to 113 mg/dl) and hyperinsulinemic (serum fasting insulin greater than or equal to 19 microIU/ml) (p = 0.0023) or in subjects classified as either hyperglycemic or hyperinsulinemic (p = 0.0063) than the mean urinary norepinephrine excretion in normal subjects. These relations were demonstrated to be independent of age, smoking status, and physical activity. Our results are consistent with the hypothesis that insulin mediates sympathetic stimulation in response to dietary intake and increases sympathetic nervous system activity in the obese.

Adipose Tissue↗

The influence of age and level of pulmonary function on nonspecific airway responsiveness. The Normative Aging Study.

The relationship of age and prechallenge FEV1 to methacholine airway responsiveness was examined among 914 male participants of the Normative Aging Study (age range 41 to 86 yr). Methacholine airway responsiveness was analyzed as both a continuous (dose-response slope) and categorical (PD20 FEV1 greater than 8.6 mumol; PD20 FEV1 less than or equal to 8.6 mumol) variable. Methacholine responsiveness, as assessed by dose-response slope, displayed a significant inverse relationship to the prechallenge level of FEV1 (p less than 0.001). The dose-response slope was directly related to age among former smokers (p = 0.003) but not among current and never smokers. Using a categorical variable rather than the dose-response slope to characterize responder status yielded very similar results. A logistic regression model of the data predicts an approximately threefold greater odds of a positive methacholine challenge test in association with a 500 ml lower FEV1. The model predicts that among former smokers a 20-yr increase in age is associated with an approximately fivefold increase in the odds of a positive methacholine challenge test. This analysis suggests that nonspecific airway responsiveness increases with advancing age among former smokers even after adjustment for prechallenge level of FEV1.

Adult↗

Methacholine airway responsiveness and 24-hour urine excretion of sodium and potassium. The Normative Aging Study.

Prior studies have suggested a direct relationship between dietary sodium intake and nonspecific airway responsiveness. The relationship of dietary sodium and potassium intake to methacholine airway responsiveness was examined among 273 male participants of the Normative Aging Study (age range 44 to 82 yr) using 24-h urinary excretion of these cations as a surrogate for intake. Methacholine airway responsiveness was analyzed as dose-response slope, a continuous measure of responsiveness that represents the slope of a line connecting the origin to the last point of the dose-response plot. Greater airway responsiveness to methacholine was associated with greater potassium excretion. A significant relationship between methacholine dose-response slope and potassium excretion (p = 0.014) was observed in multivariate analysis that took into account other covariates, including age, percentage of predicted FEV1, cigarette smoking, and skin test reactivity. In contrast, methacholine airway responsiveness did not appear related to urinary sodium excretion. These data suggest that dietary potassium may have an influence on airway responsiveness of middle-aged and older men.

Adult↗

Asthma, hay fever, and phlegm production associated with distinct patterns of allergy skin test reactivity, eosinophilia, and serum IgE levels. The Normative Aging Study.

We investigated the relationship of three phenotypic markers of atopy (allergy skin test reactivity, serum IgE level, and eosinophilia) to the prevalence of respiratory symptoms in 1,071 middle-aged and older men participating in the Normative Aging Study. Participants had all been health screened at the onset of the study in the 1960s to exclude individuals with asthma or other chronic respiratory diseases. Respiratory symptoms were grouped into three categories: asthma (adult onset) and other wheezing syndromes; cough and phlegm production; and hay fever. Multivariate logistic regression models were utilized to assess the independent relationship of each phenotypic marker to symptom prevalence adjusted for age, cigarette smoking, and the competing influence of the other markers. In this population, the prevalence of each symptom increased with serum total IgE concentration, this relationship being strongest for asthma. Skin test positivity (greater than or equal to 5 mm induration to one or more aeroallergens) was strongly associated with hay fever but was not significantly associated with symptoms of wheeze or cough and phlegm. Eosinophilia was associated with asthma and with phlegm production. The association of eosinophilia with phlegm production was present in skin test-negative as well as skin test-positive subjects and remained significant even after current smokers and individuals with asthma or hay fever were excluded. These data support the concept that asthma and hay fever are related to different immunologic host factors as reflected by expression of atopy phenotypes. Future investigations of immunologic factors in respiratory disease susceptibility should include, at a minimum, an assessment of all three phenotypic markers of atopy.

Adult↗

Pulmonary function and cardiovascular risk factor relationships in black and in white young men and women. The CARDIA Study.

Pulmonary function is known to be related inversely to incidence of coronary heart disease, congestive heart failure, chronic obstructive lung disease, lung cancer, and death from all causes. Reasons for some of these associations are poorly understood. Relationships between cardiovascular disease risk factors and pulmonary function were examined in 5,115 18- to 30-year-old black and white male and female participants in the study of Coronary Artery Risk Development in Young Adults (CARDIA). Forced expiratory volume in 1 s adjusted for height (FEV1/Ht2) was significantly lower in smokers than nonsmokers and in persons who reported shortness of breath; FEV1/Ht2 was correlated positively with a history of strenuous physical activity, duration of exercise on the treadmill, and high-density lipoprotein cholesterol. It was associated negatively with skinfold thicknesses, serum triglycerides, fasting serum insulin, and the Cook Medley scale of hostility. The association between pulmonary function and heart disease risk may reflect associations with physical fitness, vigor, fatness, and lipid profiles, as well as with cigarette smoking.

Adolescent↗

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans.

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.

Adult↗

The relationship of nonspecific airway responsiveness and atopy to the rate of decline of lung function. The Normative Aging Study.

Nonspecific airway hyperresponsiveness and atopy have been postulated to be risk factors that predispose individuals to the development of chronic obstructive pulmonary disease. The purpose of the present study was to examine the relationship of methacholine airway responsiveness and markers of atopy to rate of decline in lung function among 790 men, age 40 to 79 yr, followed in the Normative Aging Study. Airway responsiveness was assessed at the end of follow-up, which ranged from 14 to 24 yr. Multiple linear regression analysis indicated that greater methacholine airway responsiveness was associated with more rapid annual FEV1 decline. Stratified analysis suggested that this association was stronger among skin test-negative, current smokers. No significant relationship was found between serum IgE level and annual FEV1 decline. A weak but statistically significant correlation between eosinophil count and mean annual FEV1 decline was noted among skin test-negative individuals (r = -0.08; p = 0.03). Results from the present study do not show a clear association between atopy and decline in FEV1. These data, however, do indicate an independent association between heightened methacholine responsiveness on decline in FEV1 in adult males.

Adult↗

The role of allergy and nonspecific airway hyperresponsiveness in the pathogenesis of chronic obstructive pulmonary disease.

Although the information that has been reviewed leaves many questions unanswered, some conclusions can be drawn from available data. (1) Smoking appears to increase the risk of sensitization to certain inhaled antigens encountered in the workplace; however, there is no definite evidence that smoking increases the frequency or intensity of allergy to common aeroallergens in the general population. On average, smokers have higher serum total IgE concentrations and blood eosinophil counts than do nonsmokers, but the mechanisms underlying these alterations are not clear. Analysis of these relationships is complicated by observations suggesting that atopic persons are less likely to become and to remain regular cigarette smokers. (2) Long-term cigarette smoking may be associated with increased nonspecific airway responsiveness, although the magnitude of this effect is relatively small when one adjusts for prechallenge level of pulmonary function. This effect of smoking may be more pronounced in atopic persons. (3) Atopy, as assessed by skin testing and serum IgE concentrations, is associated with asthma, nonspecific airway hyperresponsiveness, and reduced pulmonary function level in population data. However, there is no clear evidence that atopy is a risk factor for irreversible airflow obstruction in persons without asthma. Population data do not indicate how much of the reduction in pulmonary function associated with atopy and asthma is potentially reversible. (4) Blood eosinophil count appears inversely related to the level of pulmonary function and directly related to the rate of decline of pulmonary function among nonsmokers. Reports vary concerning whether the relationship of eosinophil count to level of pulmonary function remains after excluding subjects with diagnosed asthma. This relationship may be determined largely by a clinically distinguishable subset of nonsmokers with "asthmatic bronchitis." Presumably, these observations reflect an adverse impact of eosinophilic inflammation in the airways or lung parenchyma. It is not clear whether this represents an allergic response because skin-test reactivity to common aeroallergens and serum total IgE concentration do not show similar relationships to reduced level and rapid decline of pulmonary function. (5) Among smokers, nonspecific airway hyperresponsiveness appears to be associated with an accelerated longitudinal decline of pulmonary function, although most studies indicating this association are limited by either a retrospective design or lack of adjustment for prechallenge level of pulmonary function.(ABSTRACT TRUNCATED AT 400 WORDS)

Bronchi↗

Smoking, atopy, and methacholine airway responsiveness among middle-aged and elderly men. The Normative Aging Study.

The interrelationships between smoking history, objective markers of allergy and inflammation, and methacholine responsiveness were examined among 778 middle-aged and elderly men (age range 41 to 86 yr). Methacholine responsiveness was analyzed using dose-response slope to describe each subject's responsiveness. Current smokers were observed to have significantly greater total serum IgE concentration ([IgE]), blood total leukocyte count, and blood eosinophil count than nonsmokers. Current smokers with at least one positive skin test reaction to common aeroallergens displayed significantly greater methacholine dose-response slope than smokers with negative skin test results (p less than 0.01). Among nonsmokers, skin test positivity was associated with slightly but not significantly greater methacholine responsiveness. Among subjects with negative skin test results, smoking was not associated with greater methacholine responsiveness. Blood eosinophil count and serum total [IgE] displayed weak but statistically significant direct relationships to methacholine dose-response slope (p less than 0.01), and these relationships were not significantly modified by smoking status. In a multivariate model, the cigarette smoking/skin test positivity interaction, total serum [IgE], and blood eosinophil count displayed significant, independent relationships to methacholine dose-response slope, although only a small portion of the variance of dose-response slope was accounted for by these covariates. These data suggest that smoking and atopy may act synergistically to increase the degree of nonspecific airway responsiveness displayed by middle-aged and elderly individuals. Allergic airway inflammation, as reflected by total serum [IgE] and blood eosinophil count, may also influence nonspecific airway responsiveness in this age group.

Adult↗

Forced vital capacity and the risk of hypertension. The Normative Aging Study.

This report describes the development of hypertension among 1,270 males (aged 23-80 years at the time of entry into the study) observed prospectively for 10 years who had a baseline blood pressure of less than 140/90 mmHg and who underwent baseline spirometry. Subjects were participants in the Normative Aging Study, a longitudinal study on aging initiated in 1961 at the Veterans Administration Outpatient Clinic in Boston, Massachusetts. Blood pressures were taken at five- and 10-year follow-up examinations. The age-adjusted incidence of hypertension during the follow-up period was found to be inversely related to forced vital capacity. Multiple logistic regression was employed to assess the relation of forced vital capacity to the subsequent development of hypertension after controlling for baseline levels of age, weight, cigarettes smoked per day, and systolic and diastolic blood pressures. Forced vital capacity was a statistically significant and negative predictor, indicating that lower values of forced vital capacity were associated with the subsequent development of hypertension. This was consistently found in several logistic regression analyses with a standardized odds ratio associated with forced vital capacity of approximately 0.7. Although the physiologic mechanism for this association is unknown, these findings may have importance in identifying subjects at risk and may also provide insight into disease pathogenesis.

Adult↗

The relationship of blood lead to systolic blood pressure in a longitudinal study of policemen.

We examined the relationship of blood lead level to systolic and diastolic blood pressure in a longitudinal study of 89 Boston, MA, policemen. At the second examination blood lead level and blood pressure were measured in triplicate. Blood pressure measurements were taken in a similar fashion in years 3, 4, and 5. Multivariate analysis using a first-order autoregressive model revealed that after adjusting for previous systolic blood pressure, body mass index, age, and cigarette smoking, an elevated blood lead level was a significant predictor of subsequent systolic blood pressure. Bootstrap simulations of these models provided supporting evidence for the observed association. These data suggest that blood lead level can influence systolic blood pressure even within the normal range.

Adult↗

Analysis of dose-response curves to methacholine. An approach suitable for population studies.

Dose-response curves to methacholine were examined in 9 normal and 10 asthmatic volunteers to determine whether the relationship between dose and response can be adequately summarized by means of a single, continuous measure that is not censored at lower levels of bronchial responsiveness. Subjects underwent a standard methacholine challenge test. There was a strong linear relationship between percent decline FEV1 and cumulative dose methacholine. We summarized each dose-response curve by the slope of a line extending from the origin to the last data point obtained. This summary dose-response slope effectively separated asthmatic from normal subjects, and there was a greater than 3,000-fold difference between the least and most responsive subjects. There was a high degree of correlation between the dose-response slope determined by the standard methacholine challenge protocol and that determined by an abbreviated protocol currently being used to examine nonspecific airway responsiveness in a large, longitudinal study of aging. Among the participants of the latter study, there is a unimodal, skewed distribution of dose-response slope. Dose-response slope is proposed as a quantitative measure of nonspecific airway responsiveness that avoids censoring and that may be particularly useful in epidemiologic studies.

Aging↗

The relationship of nonspecific bronchial responsiveness to the occurrence of respiratory symptoms and decreased levels of pulmonary function. The Normative Aging Study.

Nonspecific bronchial responsiveness was assessed by an abbreviated methacholine challenge test in 458 male participants of the Normative Aging Study, who also completed a respiratory questionnaire and spirometry. A positive response to the methacholine challenge test was defined as a greater than or equal to 20% decline in FEV1 during the test. Cigarette smoking was significantly associated with a positive methacholine response (p less than 0.001). Logistic regression analyses indicated that there was a significant association between a positive response to methacholine and both any wheeze (p = 0.002) and persistent wheeze (p less than 0.001) after taking into account smoking status and age; an association between responsiveness and chronic cough was of borderline significance (p = 0.06). Multiple linear regression analyses indicated that positive methacholine responsiveness was independently associated with lower levels of FEV1 (p less than 0.001) and FEF25-75 (p less than 0.001). Using the log of the dose-response slope rather than a dichotomous variable to characterize responder status yielded very similar results in the linear and logistic models. The findings of this cross-sectional study suggest that increased level of nonspecific responsiveness is significantly associated with wheeze and cough symptoms and decreased levels of pulmonary function in adult men. Longitudinal follow-up of these men should shed light on the importance of nonspecific responsiveness as a risk factor for the subsequent development of chronic obstructive pulmonary disease.

Adult↗