Biomedical subjects
Publications and source records attributed to S T Weiss.
We report a case of acute fatal respiratory failure following mitomycin and vinblastine administration in a patient with metastatic breast cancer. This case, the first reported fatal case in a breast cancer patient and also the first fatal case in a nonsmoker, suggests an acute hypersensitivity reaction as the cause of the respiratory distress.
The association of nonspecific bronchial responsiveness (BR) with pulmonary function level has been studied in a random population sample of 2,156 male and female subjects 15 to 64 yr of age participating in the Vlagtwedde-Vlaardingen field survey on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. About 25% of the subjects responded with a decrease in baseline FEV1 of 10% or more after challenge with histamine in a concentration of 16 mg/ml or less inhaled over 30 s (PC10). In a stratified analysis, pulmonary function level appeared to be associated with BR in a dose-response relationship. The mean %FEV1 was consistently lower in the more responsive subjects. This relationship was confirmed in linear regression analyses, adjusting for age, sex, area of residence, and smoking habits. Exclusion of subjects with %FEV1 less than 80% diminished but did not change the association between FEV1 and BR. The magnitude of the effect of responsiveness on level of pulmonary function was considerable and statistically significant. In the subjects older than 21 yr of age, male responders (PC10 at less than or equal to 16 mg/ml) on average had an adjusted FEV1 of 32.5 centiliters less than nonresponders, and female responders had an adjusted FEV1 of 30.5 centiliters less (p less than 0.001). BR appeared to be an independent predictor of pulmonary function level after adjustment for age, sex, area of residence, respiratory symptom prevalence, and cigarette smoking. The effect of cigarette smoking on pulmonary function level in this population sample was significant only in men older than 21 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Epidemiologic investigations into the natural history of airway obstructive disease have focused on both the growth and decline of lung function measurements. Although a general picture has emerged as to overall patterns of growth/decline, uncertainty remains with regard to important details of these patterns. Pulmonary function data from subjects aged 5 yr and and older who participated in any or all of the first 10 annual surveys of the East Boston population-based study have been used to investigate patterns of growth and decline of lung function derived from maximal forced expiratory maneuvers. At each annual survey, subjects completed a standardized respiratory illness and smoking questionnaire and provided forced expiratory volume-time curves from which forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were derived. A nonparametric curve smoothing method was used to provide an overall summary of growth and decline of each measure of function. Asymptomatic, nonsmoking males demonstrated a pattern of growth of FEV1 that included a prolonged plateau phase or period of slow, continued growth from ages 23 to 35 yr. Decline in lung function began after this period and occurred in two phases that averaged about -20 and -30 ml/yr. In contrast, no plateau phase was observed for male current smokers. In these smokers, decline in FEV1 began in the early part of the third decade at a rate only slightly greater than that observed for nonsmokers (-25 to -30 ml/yr). Similar patterns and rates of decline were observed for females, although the presence of a plateau phase was less clearly discernible. These data suggest that a major effect of cigarette smoking on lung function decline involves the premature onset of a "normal" rate of decline in function and, to a lesser extent, more rapid rates of decline later in life and that the pattern and magnitude of decline is similar in males and females.
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.
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The relationship of airway responsiveness to respiratory symptom prevalence has been studied in a cross-sectional analysis of a random subpopulation from a large-scale population study on chronic obstructive pulmonary disease (COPD) being conducted in the Netherlands. In 1,905 subjects with complete data on age, sex, area of residence, smoking habits, and respiratory symptom prevalence, airway responsiveness was assessed by a histamine challenge test. Subjects with a decrease in FEV1 of greater than or equal to 10% at a histamine concentration of less than or equal to 16 mg/ml were considered to be responders. Bronchial hyperresponsiveness appeared to be age dependent, with the proportion of responders increasing from 13% in those 14 to 24 yr of age to 40% in those 55 to 64 yr of age (p less than 0.001). Respiratory symptom outcomes included chronic cough, chronic phlegm, dyspnea, bronchitic episodes, persistent wheeze, and asthmatic attacks. Respiratory symptom prevalence rates were significantly higher in responders (p less than 0.001 for all symptoms). Cigarette smoking is known to be related to respiratory symptom prevalence and possibly to bronchial responsiveness. Because of these associations, we examined the relationship of bronchial responsiveness to respiratory symptoms within cigarette smoking categories. For all respiratory symptoms, it was found that, regardless of smoking category, responders were more likely to be symptomatic than were nonresponders. Odds ratios ranged from 1.7 for chronic cough to 4.4 for asthmatic attacks.(ABSTRACT TRUNCATED AT 250 WORDS)
Density dependence of maximal expiratory air flow (DD) has been used in adults as a test of early obstructive airway disease (OAD). Whether DD is useful as an epidemiologic tool to identify childhood risk factors for OAD is not known. In a population-based sample of 133 children 8 to 23 yr of age, we calculated density dependence at 50 and 25% of vital capacity (DD50 and DD25) (the ratios between maximal expiratory flow rates breathing helium-oxygen and air gas mixtures at each of these lung volumes), and the volume of isoflow (VisoV) (the lung volume, expressed as a percentage of vital capacity, at which maximal flow rates when breathing each gas mixture are equal), measured airway responsiveness using eucapnic hyperventilation with cold air, and obtained health and household information with questionnaires. Mean levels (+/- SD) of DD50, DD25, and VisoV were: 1.49 +/- 0.14, 1.37 +/- 0.18, and 10.7 +/- 10%. The DD50 significantly increased with age in these growing children (p less than 0.05), but DD50 was found to be significantly lower (1.42 +/- 0.14 versus 1.52 +/- 0.13; p less than 0.01) among children with nonspecific bronchial hyperresponsiveness. The DD50 also was significantly reduced among children with a history of a recent upper respiratory tract illness (URI) (p less than 0.01). There were no significant associations of DD with history of asthma, personal smoking, parental smoking, or respiratory illness during infancy. The reproducibility of DD50 was assessed on a subsample of 90 subjects in whom DD was measured during 2 surveys 1 yr apart.(ABSTRACT TRUNCATED AT 250 WORDS)
To evaluate the role of the use of different analytical techniques in determining differences in the reported effects of passive smoking in children and adolescents, data sets from 2 studies that had previously reported divergent results were subjected to a uniform analytic procedure using a first-order autoregressive model (AR1). Although the populations studied differed in age distribution and the frequency of both personal and maternal smoking, the assumptions of the AR1 model were met by both data sets, and the models developed fit both data sets well. Coefficients for personal smoking from the study-specific models were almost identical. An effect of maternal smoking on FEV1, which has been reported for the East Boston data, again was observed, but no such effect was observed for the Tucson data set. These findings suggest that the differences in reported results are not related simply to model specificity and that real differences in exposure or response to exposure may be occurring in different climatic situations. Such differences need to be taken into account in any assessment of indoor exposure to potentially noxious agents.
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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.
Data from various different types of cross-sectional studies are reviewed in order to examine hypotheses about the etiology of asthma and to more precisely define its relationship with nonspecific bronchial hyperreactivity (NSBH). Although cross-sectional studies have not clarified the precise etiologic links, they have established that NSBH and atopy are linked to the occurrence of asthma and to each other. In children, evidence supports the hypothesis both that atopy is a cause of asthma and that atopic diathesis is the most frequent trigger for NSHB. In adults, the associations are more complex, although in a small subset findings are similar to those in children. It is concluded that further general population-based or clinical epidemiologic cross-sectional studies based on questionnaires will contribute little more to explaining these associations. Criteria are presented for the further application of case-control studies to maximize their use in examining hypotheses of asthma etiology.
To assess the relation of initial blood pressure (BP) taken in sitting, supine and standing positions to subsequent development of systemic hypertension, 1,564 men were followed for an average of 6.6 years. The men were participants in the Normative Aging Study, a longitudinal study of aging initiated in 1963 at the Veterans Administration Outpatient Clinic in Boston. After controlling for sitting levels of systolic BP and diastolic BP in a Cox regression model, supine systolic BP was found to be a significant predictor of subsequent hypertension. This effect of position was not solely a result of decreases in measurement error associated with using additional BP measurements. Although the physiologic mechanism for the observed predictive influence of postural BP on the development of hypertension are unknown, these findings may have important influences on identifying subjects at risk and also providing insight into disease pathogenesis.
The relationship of lead exposure to blood pressure has been examined in a longitudinal study of a cohort of 89 Boston, Massachusetts, policemen. At the baseline examination, subjects had a blood lead determination and three consecutive blood pressure measurements. Triplicate blood pressure measurements were also taken at years 3, 4, and 5. Multivariate analysis revealed that, after correction for previous systolic blood pressure, body mass index, age, and smoking, a high level of blood lead was a significant predictor of subsequent elevation of systolic pressure. Bootstrap simulations of these models provided supporting evidence for the observed associations. These data suggest that lead exposure can significantly affect systolic pressure.
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A population-based, epidemiologic investigation conducted in children, adolescents, and young adults analyzed the response to eucapneic hyperventilation with cold air as a continuous variable to better define factors that influence the expression of bronchial responsiveness. Among respiratory illness/symptom variables, only the report of asthma or persistent wheeze in the previous year and the report of a respiratory illness that led to activity restriction were significantly associated with response to cold air. Furthermore, a low, prechallenge FEF/FVC ratio was a significant predictor of response, especially among those subjects who reported a respiratory illness that led to activity restriction. This relationship was not observed for a low prechallenge FEF.
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