The beta-agonist dilemma.
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Biomedical subjects
Publications and source records attributed to M D Lebowitz.
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The objective of this study was to determine the effects of passive smoking on functional lung growth in children and adolescents. It was hypothesized that passive smoking might reduce lung function growth, especially in susceptible children. The assumption was that those most susceptible would be children who started with low lung function, as it had been shown that they had slower growth of lung function, and start to decline earlier. There were 138 non-Hispanic Caucasian children and adolescents, ages 5 through 15, who had at least three satisfactory longitudinal lung function tests over a 13 year period in the Tucson epidemiological study of airway obstructive diseases. Those who started in childhood with normal function did not show any effect of passive smoking, nor did females who started with low lung function. Males starting with low lung function whose parents smoked showed definite changes. Their forced expiratory volume in 1 second (FEV1) grew even more slowly between ages 13 through 16, related primarily to continuous parental smoking. They also had higher rates of decline for FEV1 to forced vital capacity (FVC) ratio and maximum flow at 50% vital capacity to FVC ratios than either the low function group without passive smoking or the normal function groups. This was independent of any symptoms or diagnoses present in this male low function group.
We examined growth of spirometric lung function in 696 children of European ancestry who were followed from ages 9 to 15 years and stratified according to their degree of responsiveness to methacholine inhalation challenge, atopic status, and respiratory symptoms. Subjects were participants in the longitudinal Multidisciplinary Health and Development Study in Dunedin, New Zealand. Forced expired volume in 1 second (FEV1), and vital capacity (VC) were measured at 9, 11, 13, and 15 years of age, concurrently with assessment of airway responsiveness determined by the concentration of methacholine causing a 20% fall in FEV1 (PC20 FEV1). Atopic status was assessed at age 13 by skin-prick testing to 11 allergens. In children demonstrating airway hyperresponsiveness, FEV1 increased with age at a slower rate, and the FEV1/VC ratio had a faster rate of decline through childhood, compared to non-responsive children. Subjects with positive skin tests to house dust mite and cat dander also had lower mean FEV1/VC ratios than the control group. Any reported wheezing was associated with slower growth of FEV1 and VC in males. We conclude that in New Zealand children with airway responsiveness and/or atopy to house dust mite or cat growth of spirometric lung function is impaired.
In this study we examined the longitudinal effects of smoke exposure on lung function in a cohort of New Zealand children observed from 9 to 15 yr of age. Possible exposures included in utero exposure from mothers smoking during pregnancy, passive smoke from parents, and active smoking by the children. Lung function measures of forced expiratory volume in one second (FEV1) and vital capacity (VC) were measured biennially and ratios (FEV1/VC) were computed. The data were analyzed using longitudinal methodology, and all subjects with at least one pulmonary function test and responses to the questions concerning smoke exposures were included (n = 634). Subjects reporting wheeze or asthma were examined as a separate subgroup. In the whole cohort, no significant detrimental effects were detected for absolute FEV1 or VC in either sex, related to active or passive smoke exposures. Parental smoking was, however, associated with persistent but mild and nonprogressive impairment of the FEV1/VC ratio in males, an effect that was present at the time lung function measurements were first made. This effect was not seen in females. In children with reported wheeze or asthma, parental smoking had progressive, more serious, and clinically significant effects on the FEV1/VC ratio among adolescents of both sexes, causing a mean reduction in FEV1/VC ratios by age 15 of 3.9% in males and 2.3% in females, in contrast to the observed increase in FEV1/VC ratios with age seen in nonexposed wheezing children. We conclude that passive smoking is a major contributing factor to the development and persistence of airflow limitation in wheezing children.
BACKGROUND: Insomnia is a common complaint both in the general population and also in physician's offices. However, risk factors for the development of insomnia complaints have not been completely identified. METHODS: To identify population characteristics associated with increased prevalence of insomnia complaints, we surveyed a large general adult population in 1984 through 1985. We evaluated the relationship among current complaints of initiating and maintaining sleep and obesity, snoring, concomitant health problems, socioeconomic status, and documented complaints of difficulty with insomnia 10 to 12 years previously. RESULTS: The strongest risk factor for complaints of initiating and maintaining sleep was previous complaints of insomnia (odds ratio, 3.5). In addition, female gender (odds ratio, 1.5), advancing age (odds ratio, 1.3), snoring (odds ratio, 1.3), and multiple types of concomitant health problems (odds ratios, 1.1 to 1.7) were all risk factors associated with an increased rate of complaints of initiating and maintaining sleep. CONCLUSION: Complaints of insomnia tend to be a persistent or recurrent problem over long periods of time. Female gender, advancing age, and concomitant health problems also are important risk factors.
The data from a longitudinal population study in Tucson, Arizona, were used to describe the development and decline of maximal expiratory flow-volume (MEFV) measures with age. On the basis of their answers to self-administered questionnaires, in 9 of the first 10 surveys (1972-1988) and having performed at least one MEFV test, 930 nonsmoking healthy subjects were selected, providing 3,848 individual observations. The data were analysed using statistical methods that yield continuous piecewise linear regression equations and allow subjects to have repeated measures which are unequally spaced and at different times for different subjects. In addition, the age intervals for the piecewise linear line segments are estimated for each of the MEFV indices, as part of the modelling procedure. The resulting predicted values are compared between sexes and to previously published cross-sectional results from the same population. All MEFV measures in healthy subjects have an early increase in the rate of development corresponding to the onset of the adolescent growth spurt. This rapid growth period is followed by a plateau phase which lasts around 10 yrs for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in males, in which growth continues, but at a much lower rate. The plateau phase, is followed by a constant rate of decline which lasts throughout adulthood. In contrast, flow measures did not have a detectable plateau period, but did have points of increased rates of decline much later in life.
Data from two longitudinal studies conducted in Cracow, Poland, and Tucson, Arizona, USA, were used to evaluate the differences in period prevalence, incidence and remission rates of respiratory symptoms between two populations, as well as to assess the between-cities similarities in the relationships of the symptoms to age and smoking habit. The analysis was based on data from 3,082 adult Cracow residents, interviewed twice 13 yrs apart, and from 1,452 Tucson adults, with mean period between initial and final survey of 12.2 yrs. Log-linear models were used to consider possible interactions of the symptoms, age, smoking, gender and city. The relationship of the symptoms to smoking was similar in both cities, after adjustment for age and gender, with at least doubled incidence rates of most symptoms in continuous smokers compared to lifetime nonsmokers. The between-population differences in the symptoms were related to age, indicating onset of bronchitic symptoms occurring earlier in life in Cracow, and of asthmatic symptoms in Tucson. These differences were due to factors other than tobacco smoking e.g. various types of ambient air pollution.
The relation of breast feeding and other factors to the incidence of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRI) in the first year of life is examined. The study population is 1,179 healthy infants enrolled at birth between May 1980 and January 1984 into the Tucson Children's Respiratory Study, Tucson, Arizona. Each subject's data were assessed at each month of age during the first year of life, during those months when respiratory syncytial virus was isolated. A number of significant relations were observed, particularly between 1 and 3 months of age. At this age, the risk of having a RSV-LRI increased in association with less than 1-month or no breast feeding, with being male, and with increasing numbers of others sharing the child's bedroom. In multivariate analysis, only sex and the number of others sharing the room remained as significant direct effects. However, a significant interaction demonstrated that breast feeding has a protective role in relation to RSV-LRIs for those infants of mothers with a lower education level. The risk of having a RSV-LRI increases with combinations of risk factors. Being in day care was a significant risk factor in the 7- to 9-month age range. The RSV-LRI rate also varies by birth month. A separate case-control study assessed relations of RSV-LRIs with cord serum RSV antibody. Those with lower cord serum RSV antibody, who also have minimal breast feeding, were found to be especially at risk for RSV-LRIs in the first 5 months of life.
Death certificate reporting of chronic airways disease was examined during 13 years of follow-up in the Tucson Epidemiologic Study of Airways Obstructive Disease. The Tucson study population is a geographically clustered stratified random sample of white, non-Mexican-American households in Tucson, Arizona. The initial survey was performed in 1972-1973. Using clinical and physiologic criteria from nine surveys to define airways obstructive disease in the population, the authors compared death certificate reporting with these criteria as the underlying cause and as reported anywhere on the death certificate. Reporting was related to the degree of antemortem airways obstruction. Sex differences in reporting were also noted. Females showed greater rates of reporting at low levels of impairment while males showed greater reporting at high levels of impairment. When airways obstructive disease was not the underlying cause of death, the type of underlying cause was found to affect reporting of airways obstructive disease on the death certificate.
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A mathematical procedure is described for fitting piecewise linear equations constrained to join at estimable multiple junctions or breakpoints. The model parameters, a combination of both linear and nonlinear, are estimated using a "Separable Least Squares" algorithm. In this algorithm the linear parameters, estimated using the General Linear Model, are nested within the iterations of a nonlinear optimization routine. This formulation allows additional covariates to be included in the model and can be easily expanded to include any number of line segments, both linear and nonlinear. The procedure is demonstrated by estimating continuous lung function reference equations for healthy normal subjects. Comparison of these reference equations with previously published equations derived for the same subjects, illustrates the advantages of having continuous equations throughout the age range of the data.
Forty elderly subjects who denied ever having asthma or emphysema on enrollment in a longitudinal epidemiologic study later reported consulting a doctor for asthma when they were older than 60 years of age. The average age at which the diagnosis was reported was 70.8 years, after a mean follow-up of 8.5 years. Findings on enrollment in the newly diagnosed subjects with asthma are compared with findings in the 1145 subjects who provided follow-up information when they were older than age 60 years but had never developed asthma. At the time of enrollment, most subjects later diagnosed as having asthma already had wheezing symptoms, suggesting at least a mild asthmatic state, and many subjects had impaired ventilatory function, a positive allergy skin test (especially in association with rhinitis), and blood eosinophilia. Thirty-five percent of the subjects recalled "respiratory trouble before age 16" despite denying prior asthma. The likelihood of a new asthma label was very closely related to the age-sex-standardized serum-IgE level before diagnosis. Newly diagnosed subjects with asthma demonstrated much greater rates of decline in FEV1 than control subjects or than subjects who already had known asthma on enrollment. We conclude that (1) symptoms suggesting asthma are usually present for many years before the diagnosis of the disease in elderly subjects, (2) the serum-IgE level is closely related to the likelihood of a subsequent asthma diagnosis, even in this age group, and (3) a rapid fall in lung function often occurs around the time of initial diagnosis.
Data from four consecutive surveys of Tucson longitudinal study of airways obstructive disease were used to examine the relation of respiratory symptoms and pulmonary function to non-tobacco cigarette smoking. The surveys were conducted over a six-year period and provided data on 1802 subjects 15-60 years of age, with a total of 5659 individual questionnaires. Estimated odds ratio (OR) of current non-tobacco smoking for chronic cough was 1.73, for chronic phlegm: 1.53, and for wheeze: 2.01 (p less than 0.05). These estimates were adjusted for age, tobacco smoking and occurrence of the symptom in preceding survey. The increased risk of the symptoms was related to the habit continued for several years, and there was no immediate remission of the symptoms after quitting smoking. A significant (p less than 0.05) reduction in pulmonary function (FEV1, Vmax50 and their ratios with FVC) was found a year or more after current non-tobacco smoking was reported. Although the average consumption of non-tobacco cigarettes, believed to be marijuana smoking, was less than one per day, significant effects were still detectable in both pulmonary function and respiratory symptoms.
The data from consecutive surveys of the Tucson Epidemiologic Study (1981-1988) were used to evaluate the relationship in cigarette smokers of respiratory symptoms and pulmonary function to tar, nicotine, and carbon monoxide (CO) yields of the cigarette. There were 690 subjects who reported smoking regularly in at least one survey, over age 15. After adjustment for intensity and duration of smoking and for depth of inhalation, the risk of chronic phlegm, cough, and dyspnea were not related to the tar and nicotine yields. In 414 subjects with pulmonary function tested in at least one of the three surveys the spirometric indices used were significantly related to the daily dose of tar, nicotine, and CO (product of the cigarette yield and daily number of cigarettes smoked). The effects were more pronounced for past than for current doses. However, the differentiation of pulmonary function due to various yields of cigarettes was small in comparison to the difference in pulmonary function between smokers and nonsmokers.
Measuring peak expiratory flow rates (PEFR) several times a day can provide an objective assessment of functional changes relative to environmental or occupational exposures. This report describes the pattern of diurnal changes in PEFR in a reference population, and defines ranges of "normal" between- and within-day variability. An index of diurnal changes was defined as the ratio between maximal and minimal values, where the maximal value was restricted to PEFR measured at noon or in the evening (N, E) and the minimal value was restricted to the morning or at bedtime (M, B). A ratio greater than normal represented an exaggeration of the normal diurnal pattern in PEFR. Normal limits, based on the ninety-fifth percentile in the reference population, were larger for children (130%) than for adults 15 to 35 yr of age (117%) and those older than 35 yr of age (118%). The meaningfulness of excessive diurnal changes in PEFR was examined by relating this ratio (Max/Min), and a similar measure (the amplitude percent mean) to chronic respiratory symptoms and diseases in 938 adults and children who recorded PEFR values 2 to 4 times per day for as long as 14 days. There was a strong relationship of diurnal changes in PEFR that exceed normal limits with physician-confirmed asthma (relative risk of 2.99 with Max/Min), with exertional dyspnea (Grade 2+), and with more frequent reporting of acute symptoms of wheeze, attacks of wheezing dyspnea, cough, and chest colds. In addition, those exceeding the normal limits had about 2.9 times greater risk of having a FEV1 below 80% of predicted, and nearly 7 times greater risk of being below 70%.(ABSTRACT TRUNCATED AT 250 WORDS)
We assessed the effects of occupational exposure in a general population sample living in an unpolluted rural area of North Italy. In the age range of 18 to 64 yr, there were 417 participants who reported any exposure to dusts, chemicals, or gases and 1,218 who reported no exposure. Each subject completed a standardized interviewer-administered questionnaire (CNR-questionnaire). A variable proportion of participants succeeded in performing flow-volume curves, diffusing capacity of carbon monoxide, and slope of alveolar plateau of nitrogen. There was no significant difference for symptom prevalence rates between exposed and nonexposed in men and women who smoke. In nonsmoking women, those exposed showed significantly higher prevalence rates for exertional dyspnea and asthma. Regarding lung function, in exposed male smokers there was a significantly higher slope of the alveolar plateau. In exposed female nonsmokers, FEV1 and forced expiratory flows were significantly lower. Multiple logistic models in the overall group, accounting for age, smoking, and pack-years, showed that work exposure was associated significantly with higher risks for all symptoms in men (e.g., odds ratio: 2.76 for dyspnea, 2.31 for asthma, 1.69 for cough, and 1.64 for phlegm); in females, the association was significant for dyspnea (OR = 3.74) and asthma (OR = 3.29). Exposed men also had a significantly higher risk for %FEV1 or FEV1/FVC% below 70 (OR = 1.45). Our findings confirm those of the other few epidemiologic surveys in general population samples and contribute to the suggestion of a causal association between occupational exposure and chronic obstructive pulmonary disease.
Numerous studies have examined the natural time course of human lung function growth and decline throughout life. In most of these studies the investigators used statistical models that required a priori assumptions concerning the underlying form or structure of the lung function data, thus introducing possible biases. In this study we used recently developed nonparametric regression (spline) techniques to describe the evolution of lung function measures with age. This procedure yields an optimally fitted smooth curve through the data and estimates of the process velocity and does not require assumptions concerning the underlying shape of the data curves. The lung function growth-velocity curves are used to estimate the age of growth cessation. This technique was applied to the FVC, FEV1, and the FEV1/FVC ratios of 1,295 females and 1,230 males who were tested in at least one of the first nine surveys of the Tucson epidemiologic study of airway obstructive diseases. Data were analyzed stratified according to gender, smoking status, and respiratory symptoms or diseases. The results indicate large differences between the fitted FEV1 and FEV1/FVC smoothed curves of the various subgroups compared with asymptomatic nonsmokers. These differences were most pronounced in the adult symptomatic smokers, who had higher rates of lung function loss that also began at earlier ages, for both sexes. No significant differences were observed between asymptomatic and symptomatic nonsmokers, most likely because of the reduced number of symptomatic nonsmokers, particularly among the males.
Some individuals in the population may be sensitive or susceptible be to the effects of air pollutants. Such sensitivity may be to specific pollutants or classes of pollutants. However, sensitivity or susceptibility in some individuals can be to all irritants, but the sensitivity is likely to be response specific or organ specific. The U.S. Clean Air Act specifically recognizes that some individuals in the population are sensitive to air pollutants and indicates that such individuals need to be protected by air quality standards. It is usually difficult to determine the cause of sensitivity, though various biological mechanisms have been studied. Biological age may be a factor, with the young being most sensitive and susceptible to being affected. An example is the heightened bronchial lability and responsiveness in the very young that appears to disappear with growth. Susceptibility may be innate (e.g., genetic) and/or induced by events/exposures. Frequently, those with preexisting illnesses are part of the sensitive population because they may often respond, sometimes hyperrespond, to a pollutant exposure that may not affect most people. Asthmatics are excellent examples of individuals who were susceptible to the disease and, once inflicted, are susceptible to the effects of many environmental and nonenvironmental agents. Usually only a fraction of the general population will respond with heightened reactions at lower doses. Such individuals require special evaluation and attention in all exposure-response studies and risk assessments. Thus, the conditions defining populations at risk and the methodologies to discover and study them can be reviewed.