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ABSTRACT: We searched for possible associations between various measures of severity of sleep-disordered breathing (SDB) and indices of cardiac autonomic function in older subjects (>60 years). Twenty four overnight unattended home-based polysomnograms obtained from the Sleep Heart Health Study were analyzed using spectral analysis. For each subject, six autonomic indices reflecting heart rate variability were quantitatively determined during wakefulness, REM sleep and non-REM sleep. Each individual autonomic marker was regressed against each of 4 measures of SDB, including the respiratory disturbance index (RDI), respiratory oscillation index, cumulative oxygen desaturation, and arousal index. In general, we found no correlation between any of these measures of SDB severity and each of the autonomic indices. However, mean heart rate was found to decrease as RDI increased. As well, the ratio of low-frequency to high-frequency power (LHR) decreased with increasing RDI. Contrary to previous reports, our preliminary findings suggest that sympathetic activity decreases with increasing severity of SDB. This paradoxical association between SDB and cardiac autonomic function may be the result of natural compensatory mechanisms at work, allowing some subjects with SDB to be protected from systemic hypertension or other cardiovascular diseases.
Engineering in Medicine and Biology Society, 2005. IEEE-EMBS 2005. 27th Annual International Conference of the; 10/2005
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ABSTRACT: We searched for possible associations between various measures of severity of sleep-disordered breathing (SDB) and indices of cardiac autonomic function in older subjects (>60 years). Twenty four overnight unattended homebased based polysomnograms obtained from the Sleep Heart Health Study were analyzed using spectral analysis. For each subject, six autonomic indices reflecting heart rate variability were quantitatively determined during wakefulness, REM sleep and non-REM sleep. Each individual autonomic marker was regressed against each of 4 measures of SDB, including the respiratory disturbance index (RDI), respiratory oscillation index, cumulative oxygen desaturation, and arousal index. In general, we found no correlation between any of these measures of SDB severity and each of the autonomic indices. However, mean heart rate was found to decrease as RDI increased. As well, the ratio of low-frequency to high-frequency power (LHR) decreased with increasing RDI. Contrary to previous reports, our preliminary findings suggest that sympathetic activity decreases with increasing severity of SDB. This paradoxical association between SDB and cardiac autonomic function may be the result of natural compensatory mechanisms at work, allowing some subjects with SDB to be protected from systemic hypertension or other cardiovascular diseases. Supported in part by NIH Grants HL076375, EB001978, HL63463 and HL53941.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2005; 2:1103-5.
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ABSTRACT: Obstructive sleep apnea/hypopnea (OSAH) has a strong heritable component, although its genetic basis remains largely unknown. One epidemiologic study found a significant association between the APOE epsilon4 allele and OSAH in middle-aged adults, a finding that was not replicated in a cohort of elderly adults. The objective of this study was to further examine the association of the APOE epsilon4 allele with OSAH in a community-dwelling cohort, exploring age dependency of the association.
A genetic association study was performed, nested within a prospective cohort study of the cardiovascular consequences of OSAH. Unattended, in-home nocturnal polysomnography was used to measure apnea-hypopnea index (AHI) in 1,775 participants age 40 to 100 years. OSAH was defined as an AHI > or = 15. The relation of APOE genotype to prevalent OSAH was analyzed using generalized estimating equations to account for non-independent observations of individuals from the same sibship.
At least one APOE epsilon4 allele was present in 25% of subjects, with 1.3% epsilon4/epsilon4 homozygotes. The prevalence of OSAH was 19%. After adjustment for age, sex, and BMI, the presence of any APOE epsilon4 allele was associated with increased odds of OSAH (OR 1.41, 95% CI 1.06 to 1.87, p = 0.02). The effect was approximately twice as great in subjects <75 (OR 1.61, CI 1.02 to 2.54) as in those > or =75 years old (OR 1.32, CI 0.91 to 1.90). Exploratory analyses revealed that the strongest effect of APOE epsilon4 was in subjects age <65 (OR 3.08, CI 1.43 to 6.64), and was stronger in those with hypertension or cardiovascular disease than in those without.
The APOE epsilon4 allele is associated with increased risk of OSAH, particularly in individuals under age 65. The mechanisms underlying this association are uncertain. Age-dependency of the APOE-OSAH association may explain previous conflicting results.
Neurology 09/2004; 63(4):664-8. · 8.31 Impact Factor
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ABSTRACT: There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV(1), FVC, and FEV(1)/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV(1), FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions.
American Journal of Respiratory and Critical Care Medicine 12/2001; 164(9):1655-9. · 11.08 Impact Factor
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ABSTRACT: Previous studies have reported an association between obstructive sleep apnea (OSA) and proteinuria, but are limited in their ability to assess proteinuria accurately, to adjust for confounders such as obesity, or to exclude confidently underlying renal disease in patients with OSA and nephrotic-range proteinuria.
The spot urine protein/creatinine ratio was measured in a prospective consecutive series of 148 patients referred for polysomnography who were not diabetic and had not been treated previously for OSA. The urine protein/creatinine ratio was compared across four levels of OSA severity, based on the frequency of apneas and hypopneas per hour: <5 (absent), 5 to 14.9 (mild), 15 to 29.9 (moderate), and > or =30 (severe).
The median level of urine protein/creatinine ratio in all categories of OSA was <0.2 (range 0.03 to 0.69; median 0.06 in patients with normal apnea hypopnea index, 0.06, 0.07, 0.07 in patients with mild, moderate, and severe OSA, respectively). Eight subjects had a urine protein/creatinine ratio greater than 0.2. Univariate analysis showed a significant association between urine protein/creatinine ratio and older age (P < 0.0001), hypertension (P < 0.0001), coronary artery disease (P = 0.003), and arousal index (P = 0.003). Body mass index (P = 0.16), estimated creatinine clearance (P = 0.17), and apnea hypopnea index (P = 0.13) were not associated with the urine protein/creatinine ratio. In multiple regression analysis, only age and hypertension were independent positive predictors of the urine protein/creatinine ratio (P < 0.0001, R2 = 0.17).
Clinically significant proteinuria is uncommon in sleep apnea. Nephrotic range proteinuria should not be ascribed to sleep apnea and deserves a thorough renal evaluation.
Kidney International 10/2001; 60(4):1484-9. · 6.61 Impact Factor
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ABSTRACT: The effect of sleep-disordered breathing (SDB) on right heart structure and function is controversial. Studies of patients referred for evaluation of possible sleep apnea have yielded conflicting results, and the impact of SDB on the right heart has not been investigated in the general population. We examined the echocardiographic features of subjects with SDB at the Framingham Heart Study site of the Sleep Heart Health Study. Of 1,001 polysomnography subjects, 90 with SDB defined as a respiratory disturbance index (RDI) score > 90th percentile (mean RDI = 42) were compared with 90 low-RDI subjects (mean RDI = 5) matched for age, sex, and body mass index. Right heart measurements, made without knowledge of clinical status, were compared between groups. The majority of the subjects were male (74%). After multivariable adjustment, right ventricle (RV) wall thickness was significantly greater (p = 0.005) in subjects with SDB (0.78 +/- 0.02 cm) than in the low-RDI subjects (0.68 +/- 0.02 cm). Right atrial dimensions, RV dimensions, and RV systolic function were not found to be significantly different between subjects with SDB and the low-RDI subjects. We conclude that in this community-based study of SDB and right heart echocardiographic features, RV wall thickness was increased in subjects with SDB. Whether the RV hypertrophy observed in persons with SDB is associated with increased morbidity and mortality remains unknown.
American Journal of Respiratory and Critical Care Medicine 09/2001; 164(6):933-8. · 11.08 Impact Factor
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ABSTRACT: We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.
American Journal of Respiratory and Critical Care Medicine 01/2001; 162(6):2069-72. · 11.08 Impact Factor
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ABSTRACT: Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI >/= 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score >/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.
American Journal of Respiratory and Critical Care Medicine 11/2000; 162(4 Pt 1):1512-7. · 11.08 Impact Factor
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ABSTRACT: Current understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD), a source of substantial morbidity and mortality in the United States, suggests that chronic inflammation leads to the airways obstruction and parenchymal destruction that characterize this condition. Environmental factors, especially tobacco smoke exposure, are known to accelerate longitudinal decline of lung function, and there is substantial evidence that upregulation of inflammatory pathways plays a vital role in this process. Genetic regulation of both inflammatory responses and anti-inflammatory protective mechanisms likely underlies the heritability of COPD observed in family studies. In alpha-1 protease inhibitor deficiency, the only genetic disorder known to cause COPD, lack of inhibition of elastase activity, results in the parenchymal destruction of emphysema. Other genetic polymorphisms have been hypothesized to alter the risk of COPD but have not been established as causes of this condition. It is likely that multiple genetic factors interacting with each other and with a number of environmental agents will be found to result in the development of COPD.
Environmental Health Perspectives 09/2000; 108 Suppl 4:733-42. · 7.04 Impact Factor
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ABSTRACT: Varying approaches to measuring the respiratory disturbance index (RDI) may lead to discrepant estimates of the severity of sleep-disordered breathing (SDB). In this study, we assessed the impact of varying the use of corroborative data (presence and degree of desaturation and/or arousal) to identify hypopneas and apneas. The relationships among 10 RDIs defined by various definitions of apneas and hypopneas were assessed in 5,046 participants in the Sleep Heart Health Study (SHHS) who underwent overnight unattended 12-channel polysomnography (PSG). The magnitude of the median RDI varied 10-fold (i.e., 29.3 when the RDI was based on events identified on the basis of flow or volume amplitude criteria alone to 2.0 for an RDI that required an associated 5% desaturation with events). The correlation between RDIs based on different definitions ranged from 0.99 to 0.68. The highest correlations were among RDIs that required apneas and hypopneas to be associated with some level of desaturation. Lower correlations were observed between RDIs that required desaturation as compared with RDIs defined on the basis of amplitude criteria alone or associated arousal. These data suggest that different approaches for measuring the RDI may contribute to substantial variability in identification and classification of the disorder.
American Journal of Respiratory and Critical Care Medicine 03/2000; 161(2 Pt 1):369-74. · 11.08 Impact Factor
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ABSTRACT: Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21% in subjects with RDI < 5 to 35% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.
American Journal of Respiratory and Critical Care Medicine 03/1999; 159(2):502-7. · 11.08 Impact Factor
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ABSTRACT: Unattended, home-based polysomnography (PSG) is increasingly used in both research and clinical settings as an alternative to traditional laboratory-based studies, although the reliability of the scoring of these studies has not been described. The purpose of this study is to describe the reliability of the PSG scoring in the Sleep Heart Health Study (SHHS), a multicenter study of the relation between sleep-disordered breathing measured by unattended, in-home PSG using a portable sleep monitor, and cardiovascular outcomes.
The reliability of SHHS scorers was evaluated based on 20 randomly selected studies per scorer, assessing both interscorer and intrascorer reliability.
Both inter- and intrascorer comparisons on epoch-by-epoch sleep staging showed excellent reliability (kappa statistics >0.80), with stage 1 having the greatest discrepancies in scoring and stage 3/4 being the most reliably discriminated. The arousal index (number of arousals per hour of sleep) was moderately reliable, with an intraclass correlation (ICC) of 0.54. The scorers were highly reliable on various respiratory disturbance indices (RDIs), which incorporate an associated oxygen desaturation in the definition of respiratory events (2% to 5%) with or without the additional use of associated EEG arousal in the definition of respiratory events (ICC>0.90). When RDI was defined without considering oxygen desaturation or arousals to define respiratory events, the RDI was moderately reliable (ICC=0.74). The additional use of associated EEG arousals, but not oxygen desaturation, in defining respiratory events did little to increase the reliability of the RDI measure (ICC=0.77).
The SHHS achieved a high degree of intrascorer and interscorer reliability for the scoring of sleep stage and RDI in unattended in-home PSG studies.
Sleep 11/1998; 21(7):749-57. · 5.05 Impact Factor
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ABSTRACT: This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.
Sleep 11/1998; 21(7):759-67. · 5.05 Impact Factor
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ABSTRACT: Urinary levels of collagen- and elastin-crosslink amino acids have been used as biologic markers for degradation of collagen and elastin in the body. Circadian variation of collagen-crosslink amino acids is well known. The current study was undertaken to determine whether there is also circadian variation in excretion of elastin-crosslink amino acids. We used an isotope dilution-HPLC assay to measure the elastin-crosslink amino acids, desmosine (DES) and isodesmosine (IDES), and the collagen-crosslink amino acids, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP), in urine. Sixteen apparently healthy subjects collected urine from 5:00 to 7:00 AM, and from 5:00 to 7:00 PM. Mean urinary excretion of DES and IDES in women was 56% and 41% higher (P < 0.001), respectively, in AM versus PM specimens when normalized by the creatinine content of the urine specimen. For men, the corresponding values were 11% and 13% higher (not statistically significant). Mean urinary excretion of HP and LP in women was 61% and 71% higher (P < 0.001), respectively, in AM versus PM specimens. For men, the corresponding values were 11% and 19% higher (not statistically significant). Differences were not found in the AM versus PM rates of excretion of creatinine in men or women. These findings demonstrate the occurrence of circadian variation in HP, LP, DES and IDES in women but not in men. We conclude that the time of collection of urine specimens, especially from women, must be taken into consideration in using the urinary levels of these crosslink amino acids as biologic markers for collagen or elastin degradation.
Proceedings of The Society for Experimental Biology and Medicine 07/1998; 218(3):229-33.
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ABSTRACT: Familial aggregation of cross-sectional pulmonary function was examined in 5,003 subjects from 1,408 families participating in the Framingham Study. Subjects, who were members of either the Original Cohort (recruited from 1948 to 1952) or the Offspring Cohort (recruited from 1971 to 1974), underwent spirometry at a mean age of 53 yr. The effects of age, height, weight, and smoking status on FEV1 were evaluated through linear-regression analysis, with separate models for men and women in each cohort. The gender- and cohort-specific standardized residual FEV1 from these models was used as the phenotypic variable in familial correlation and segregation analyses to assess inheritance patterns. In models that assumed no major gene determining FEV1, correlation of pulmonary function was greater for mothers and offspring than for fathers and offspring (p[mo] = 0.190, p[fo] = 0.112; p = 0.06), and sibling correlation exceeded parent-offspring correlation (p[sib] = 0.225; p < 0.01). By comparison with a general model, in which transmission probabilities and residual familial correlations are arbitrary, models that imposed a Mendelian gene were rejected (p < 0.001). A model with no parent-offspring transmission of a major factor, but with residual familial correlation, provided as good a fit as the general model, suggesting that environmental and/or polygenic genetic influences determine FEV1.
American Journal of Respiratory and Critical Care Medicine 06/1998; 157(5 Pt 1):1445-51. · 11.08 Impact Factor
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ABSTRACT: It is hypothesized that smoking-related chronic obstructive pulmonary disease (COPD) results in part from excess lung elastin degradation. Taking advantage of spirometry performed over a 12-yr period at the Normative Aging Study, we conducted a nested case-control study of elastin and collagen degradation rates in current smokers with (n = 10) and without (n = 8) rapid decline of lung function, using a biochemical assay for urinary desmosine (DES), a specific marker for mature elastin degradation, and hydroxylysylpyridinoline (HP), a specific marker for mature fibrillar collagen degradation. Mean urinary excretion of DES in rapid decliners was 36% greater than in slow decliners (9.8 +/- 0.7 [mean +/- SE] versus 7.2 +/- 0.4 microg/g creatinine, p < 0.01); after adjustment for age and lean body mass (LBM), DES excretion in rapid decliners was 30% greater than in slow decliners (9.6 +/- 0.6 versus 7.4 +/- 0.7 microg/g creatinine, p = 0.06). Among rapid decliners, there was no difference in DES excretion between those with and those without computed tomogaphic evidence of emphysema. There was no significant difference between rapid and slow decliners in mean urinary excretion of HP (24.7 +/- 1.4 versus 21.6 +/- 1.8 nmol/mmol creatinine, p = 0.18). Among all subjects, rate of decline of FEV1 was significantly correlated with DES excretion (r = 0.61, p < 0.01). In a linear regression model adjusting for age and LBM, an increase in DES excretion of 1 microg/g creatinine was associated with an excess decline of FEV1 of 10.6 ml/yr (p = 0.04). This study provides further evidence in support of the elastase-antielastase hypothesis of the pathogenesis of COPD, and it suggests a role for elastin degradation in both emphysema and small airways disease. Moreover, it suggests that urinary DES excretion may be a useful biochemical marker for the study of interventions designed to prevent the development or progression of COPD.
American Journal of Respiratory and Critical Care Medicine 12/1996; 154(5):1290-5. · 11.08 Impact Factor
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ABSTRACT: An epidemic of isoniazid (INH)- and streptomycin (SM)-resistant tuberculosis began among Boston's homeless population in 1984. Individuals with skin test conversions who agreed to preventive therapy received either INH, rifampin, or a combination of INH and rifampin. A total of 204 individuals with documented tuberculin skin test conversions who did not have active tuberculosis at the time of the clinical evaluation for their positive skin test were eligible for preventive therapy. Data on type and length of preventive therapy were obtained from the Tuberculosis Clinic and the Boston Tuberculosis Registry records at Boston City Hospital. The individuals were followed for development of active tuberculosis. Six of 71 (8.6%) individuals who received no therapy, 3 of 38 (7.9%) in the INH group, and none in the rifampin or rifampin plus INH groups (49 and 37 persons, respectively) developed active tuberculosis. Patients in the rifampin group were significantly less likely to develop tuberculosis than patients in the no therapy group (p = 0.04; odds ratio [OR] = 0.00, 95% confidence interval [CI] = 0.00-0.91). Treatment with any rifampin-containing preventive therapy (rifampin or rifampin plus INH) was effective (p < 0.01 ) in preventing development of active disease. The three INH failures were with organisms that were resistant to INH.
American Journal of Respiratory and Critical Care Medicine 11/1996; 154(5):1473-7. · 11.08 Impact Factor
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ABSTRACT: It has been hypothesized that allergy is associated with an increased risk of developing chronic irreversible airflow obstruction. We have investigated the relation between immediate cutaneous hypersensitivity to common aeroallergens and the subsequent rate of decline of lung function in 1,025 men participating in the Normative Aging Study; subjects had a mean age of 61 +/- 8 (SD) yr and denied any history of asthma. Subjects performed spirometry and underwent allergen skin testing at a baseline visit and performed repeat spirometry after a median of 3.1 yr. Skin prick tests were performed using four glycerin-preserved allergens (house dust, mixed grasses, mixed trees, and ragweed); wheal size was measured at 20 min. Multiple linear regression analysis was used to examine the annual rate of change of lung function in relation to skin test reactivity, defined as a mean wheal size to the 4 allergens > or = 2 mm, after adjustment for age, height, smoking status, and initial lung function. Skin test reactivity was a significant predictor of the annual rates of decline of FEV1 and FEV1/FVC ratio. The regression model predicted an excess decline of FEV1 of 9.45 ml/yr for subjects with mean wheal diameter > or = 2 mm (p < 0.05); the excess rate of decline of FEV1/FVC ratio was 0.29 percent/yr (p = 0.001). There was no significant relation between mean wheal diameter and rate of decline of FVC. The magnitude of the effects of a mean wheal diameter > or = 2 mm on rates of decline of FEV1 and FEV1/FVC ratio are 34% and 49%, respectively, of the magnitude of the effects of current cigarette smoking in these models. We conclude that cutaneous hypersensitivity to common aeroallergens is a significant independent predictor of subsequent decline of lung function among middle-aged and older men with no history of asthma.
American Journal of Respiratory and Critical Care Medicine 02/1996; 153(2):561-6. · 11.08 Impact Factor
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ABSTRACT: Hospitalization rates for asthma in New York City are highest in poor urban neighborhoods, although the reasons for this are unknown. We performed a small area analysis of asthma hospitalization rates in Boston, to determine whether this pattern of asthma hospitalization also obtained in a medium-sized city and to identify characteristics of neighborhoods with high hospitalization rates, including the relative use of inhaled anti-inflammatory medication. Zip codes were used to define 22 small areas within Boston. The number of asthma hospitalizations for residents of each area in 1992 was obtained from the Codman Research Group. Population and demographic characteristics of each area were obtained from the 1990 US Census. Estimates of inhaled asthma medications (beta-agonists, steroids, and cromolyn) dispensed in each area in 1992 were obtained from IMS America. Asthma hospitalization rates for each of the six areas with the highest rates (5.3 to 9.8 per 1,000 persons) were significantly greater than the city-wide average of 4.2 hospitalizations per thousand persons (p < 0.001 for each comparison). Asthma hospitalization rate was positively correlated with poverty rate and with the proportion of nonwhite residents and inversely correlated with income and educational attainment. Asthma hospitalization rate was inversely correlated with the ratio of inhaled anti-inflammatory to beta-agonist medication use (r = -0.55, p = 0.008). We conclude that asthma hospitalization rates in Boston are highest in poor inner city neighborhoods, and that these high rates affect both genders and all age groups. Underuse of inhaled anti-inflammatory medication may be one of the many factors that contributes to this excess hospitalization.
Chest 08/1995; 108(1):28-35. · 5.25 Impact Factor
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ABSTRACT: It has been hypothesized that emphysema results from damage to the elastic fiber network of the lungs as a result of elastase-antielastase imbalance. We used a new assay for urinary desmosine (DES) and isodesmosine (IDES), specific markers for the degradation of mature crosslinked elastin, and hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP), specific markers for the degradation of mature crosslinked collagen, in order to examine elastin and collagen degradation in relation to current cigarette smoking and the presence of chronic obstructive pulmonary disease (COPD). The study sample consisted of 22 never-smokers (NSM group), 13 current smokers without airflow obstruction (SM group), and 21 patients with COPD (COPD group), including both current and former smokers. The relation between the creatinine-height index and FEV1 was used to correct for possible loss of muscle mass and decreased excretion of creatinine in the COPD group. Mean urinary excretion of elastin-derived crosslinks in the COPD group (DES, 11.8 +/- 5.1 [mean +/- SD]; IDES, 11.3 +/- 5.0 micrograms/g creatinine) and in the SM group (DES, 11.0 +/- 4.2; IDES, 10.2 +/- 2.5 micrograms/g creatinine) was significantly higher than in the NSM group (DES, 7.5 +/- 1.4; IDES, 6.9 +/- 1.3 micrograms/g creatinine). In multivariate analysis, current smoking and the presence of COPD were significantly and independently associated with higher urinary excretion of elastin degradation products, and there was no significant interaction between current smoking and the presence of COPD.(ABSTRACT TRUNCATED AT 250 WORDS)
American Journal of Respiratory and Critical Care Medicine 05/1995; 151(4):952-9. · 11.08 Impact Factor
