Michael D. Lebowitz

Obstructive sleep apnea-hypopnea and incident stroke: the sleep heart health study.

RATIONALE Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. OBJECTIVES To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. METHODS Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea-hypopnea index (OAHI) and outcome was incident ischemic stroke. MEASUREMENTS AND MAIN RESULTS A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1-7.4). In the mild to moderate range (OAHI, 5-25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2-10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. CONCLUSIONS The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

Distribution of IgE in a community population sample: correlations with age, sex, and allergen skin test reactivity

The distribution of total serum IgE determined by the paper radioimmunosorbent test (PRIST) is examined in a large random stratified community population. Prior to logarithmic conversion the distribution of this immunoglobulin is not normal, with almost 40% of values below 20 IU/ml. A normal distribution occurs following such conversion, with a geometric mean value of 32.1 IU/ml. Both age and sex, in addition to atopic status, relate to IgE level. In both sexes highest levels occur among 6- to 14-year-olds, and males have higher levels than females at any given age. Women over age 75 yr have the lowest levels (geometric mean 9.2 IU/ml). Subjects with positive skin test results have several times the concentration of IgE as their nonatopic counterparts.

Immediate Skin-Test Reactivity in a General Population Sample

To assess the prevalence and distribution of allergic skin-test reactions in a general population sample, allergy prick tests were applied to 3101 subjects older than 2 years of age. Test materials included allergens common to the Tucson environment, and subjects were randomly stratified by age, sex, and socioeconomic status. No difference in the prevalence of measurable reactions was found among male subjects versus female subjects. A definite age relation was apparent, however, with the peak prevalence of reactivity (more than 40%) occurring during the third decade, and falling rapidly past age 50. When present, reactions tended to be multiple, highly reproducible, and more frequent among those in the higher socioeconomic strata. The prick test was judged to be a useful tool for the assessment of atopy.

Longitudinal changes in allergen skin test reactivity in a community population sample

A cohort of 1333 subjects, aged 3 years and older, was followed for a mean of 8.1 years to assess changes in allergen skin test reactivity. The overall prevalence of reactivity to the five antigen mixtures was 39.1% during the initial survey and 50.7% after the follow-up period. The greatest increase in prevalence occurred among children and teenagers (22.2% and 19.5%) with only minimal increases after the age of 65 years (6.0%). No difference in prevalence between male and female subjects was apparent, either initially or at the end of the follow-up period. In-migration to the Tucson area was a major factor in determining changes in reaction prevalence. Among subjects more than 35 years of age, recent in-migrants accounted for most of the increased prevalence. Comparisons of atopy among consistent smoking groups confirmed the previous observation that smokers are less atopic than either nonsmokers or exsmokers, probably because of a self-selection process. In contrast, exsmokers were generally the most atopic, both initially and at the end of the longitudinal observation period. The high overall prevalence of allergen reactivity in this population is believed to be due in large measure to high year-round concentrations of multiple aeroallergens in the Tucson environment.

A longitudinal study of serum IgE in a community cohort: Correlations with age, sex, smoking, and atopic status

A number of factors, including age, sex, smoking habits, and atopic status have been reported in cross-sectional studies to influence levels of serum IgE. We have examined the effects of these variables on serum IgE in a community population cohort of 1109 subjects during a longitudinal study in which two serum samples were obtained 8 years apart from each subject. For the entire cohort, mean serum IgE level changed little during the follow-up period (28.9 versus 26.0 IU/ml). Most of the decreases were observed in children and young adults. Subjects more than the age of 35 years demonstrated no systematic change in serum IgE levels. By the end of follow-up (when there were few subjects still less than 16 years of age), significant relationships of IgE to age could no longer be demonstrated in nonatopic subjects. Also, in the nonatopic subjects of this cohort, there were no significant differences in IgE levels between the sexes. Among atopic subjects, there was a clear tendency for IgE to decrease with age, with atopic women more than 35 years of age demonstrating greater declines in IgE levels during follow-up than men of comparable age. The IgE levels in atopic male subjects were significantly higher than in atopic female subjects after the age of 35 years. Smoking was associated with an elevation in serum IgE. In this cohort, the smoking effect appeared to be limited to male subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

An association of human congenital cardiac malformations and drinking water contaminants

During an informal study in 1973 it was noted that approximately one third of patients with congenital heart disease lived in a small area in the Tucson Valley. In 1981 groundwater for a nearly identical area was found to be contaminated with trichloroethylene and to a lesser extent with dichloroethylene and chromium. Contamination probably began during the 1950s. Affected wells were closed after discovery of contamination. This sequence of events allowed investigation of the prevalence of congenital heart disease in children whose parents were exposed to the contaminated water area as compared with children whose parents were never exposed to the contaminated water area. The contaminated water area contained 8.8% of the Tucson Valley population and 4.5% of the labor force. Using their case registry, the authors interviewed parents of 707 children with congenital heart disease who, between 1969 and 1987, 1) conceived their child in the Tucson Valley, and 2) spent the month before the first trimester and the first trimester of the case pregnancy in the Tucson Valley. Two random dialing surveys showed that only 10.5% of the Tucson Valley population had ever had work or residence contact, or both, with the contaminated water area, whereas 35% of parents of children with congenital heart disease had had such contact (p less than 0.005). The prevalence of congenital cardiac disease (excluding syndromes, children with atrial tachycardia or premature infants with patent ductus arteriosus) in the Tucson Valley was 0.7% of live births and with syndromes was calculated to be 0.82%. The odds ratio for congenital heart disease for children of parents with contaminated water area contact during the period of active contamination was three times that for those without contact (p less than 0.005) and decreased to near unity for new arrivals in the contaminated water area after well closure. The proportion of infants with congenital heart disease as compared with the number of live births was significantly higher for resident mothers in the contaminated water area than for mothers with no exposure. No other environmental agent could be identified that was localized to the contaminated water area, but one could have been missed. The data show a significant association but not a cause and effect relation between parental exposure to the contaminated water area and an increased proportion of congenital heart disease among live births as compared with the proportion of congenital heart disease among live births for parents without contaminated water area contact.

Chronic respiratory effects of indoor formaldehyde exposure

The relation of chronic respiratory symptoms and pulmonary function to formaldehyde (HCHO) in homes was studied in a sample of 298 children (6-15 years of age) and 613 adults. HCHO measurements were made with passive samplers during two 1-week periods. Data on chronic cough and phlegm, wheeze, attacks of breathlessness, and doctor diagnoses of chronic bronchitis and asthma were collected with self-completed questionnaires. Peak expiratory flow rates (PEFR) were obtained during the evenings and mornings for up to 14 consecutive days for each individual. Significantly greater prevalence rates of asthma and chronic bronchitis were found in children from houses with HCHO levels 60-120 ppb than in those less exposed, especially in children also exposed to environmental tobacco smoke. In children, levels of PEFR decreased linearly with HCHO exposure, with the estimated decrease due to 60 ppb of HCHO equivalent to 22% of PEFR level in nonexposed children. The effects in asthmatic children exposed to HCHO below 50 ppb were greater than in healthy ones. The effects in adults were less evident: decrements in PEFR due to HCHO over 40 ppb were seen only in the morning, and mainly in smokers.

Respiratory effects of non-tobacco cigarettes.

Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 9% were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controlled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking. These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.

Respiratory Disorders and Allergy Skin-Test Reactions

This study examines the relations of allergy skin-test reactivity, assessed by prick testing, to a variety of respiratory symptoms, findings, and diagnoses in a general population sample consisting of more than 3000 subjects. The independent and combined relations of skin-test reactivity and cigarette smoking are reported. Prevalences of asthma and allergic rhinitis are closely related to the severity of skin-test reactions; all of the 39 subjects with the largest skin-test reactions observed have had one or both of these conditions. A variety of other respiratory findings, not generally considered allergic in nature, are also related to skin-test reactivity, especially in children and in young to middle-aged adults. In subjects 15 to 54 years of age, an atopic predisposition, as manifested by reactions to allergy skin tests, appears to be associated with an increased susceptibility to the bronchoconstrictor effects of cigarette smoking and to recurrent chest infections. It is suggested that an atopic predisposition relatively early in life may be a risk factor for the later development of chronic obstructive lung diseases.

Residential environmental measurements in the national human exposure assessment survey (NHEXAS) pilot study in Arizona: preliminary results for pesticides and VOCs.

A major objective of the National Human Exposure Assessment Survey (NHEXAS) performed in Arizona was to conduct residential environmental and biomarker measurements of selected pesticides (chlorpyrifos, diazinon), volatile organic compounds (VOCs; benzene, toluene, trichloroethene, formaldehyde, 1,3-butadiene), and metals for total human exposure assessments. Both personal (e.g., blood, urine, dermal wipes, 24 h duplicate diet) and microenvironmental (e.g., indoor and outdoor air, house dust, foundation soil) samples were collected in each home in order to describe individual exposure via ingestion, inhalation, and dermal pathways, and to extrapolate trends to larger populations. This paper is a preliminary report of only the microenvironmental and dermal wipe data obtained for the target pesticides and VOCs, and provides comparisons with results from similar studies. Evaluations of total exposure from all sources and pathways will be addressed in future papers. The pesticides and VOCs all showed log-normal distributions of concentrations in the Arizona population sampled, and in most cases were detected with sufficient frequency to allow unequivocal description of the concentration by media at the 90th, 75th, and 50th (median) percentiles. Those combinations of pollutant and media, in which a large fraction of the measurements were below the detection limit of the analysis method used, included trichloroethene, 1,3-butadiene, and formaldehyde in outdoor air; chlorpyrifos and diazinon in outdoor air; and diazinon in dermal and window sill wipes. In general, indoor air concentrations were higher than outdoor air concentrations for all VOCs and pesticides investigated, and VOC levels were in good agreement with levels reported in other studies. In addition, the agreement obtained between co-located VOC samplers indicated that the low-cost diffusional badges used to measure concentrations are probably adequate for use in future monitoring studies. For the pesticides, the median levels found in indoor samples agreed well with other studies, although the levels corresponding to the upper 0.1–1% of the population were considerably higher than levels reported elsewhere, with indoor air levels as high as 3.3 and 20.5 µg/m3 for chlorpyrifos and diazinon, respectively. These data showed excellent correlation (Pearson and Spearman correlation coefficients of 0.998 and 0.998, respectively) between chlorpyrifos in indoor air and in the corresponding dermal wipes, and relatively poor correlation between chlorpyrifos in dust (µg/g or µg/m2) and dermal wipes (Pearson=0.055 µg/g and 0.015 µg/m2; Spearman=0.644 µg/g and 0.578 µg/m2). These data suggest the importance of dermal penetration of semi-volatiles as a route of residential human exposure.