Multivariate analysis of ambient environmental factors and respiratory effects

Relationships between respiratory health and environmental conditions (pollen, pollution and meteorology) are investigated in 204 subjects in four symptom groups in four geographical clusters in Tucson. Techniques used are principal components, factor and path analysis. Daily respiratory symptoms and peak expiratory flows were recorded during a three-year period. Ambient pollutants, meteorological conditions and pollen types were monitored in or near the clusters. Factor-based scales, which are climate and season specific, are developed for the environmental variables. Three pollutant/meteorological scales represent 'Summer', 'Winter', and 'Humidity'. Four pollen scales represent early and late spring, summer and fall pollen types. Relationships between environmental variables, respiratory symptoms and peak expiratory flow are analyzed with path diagrams, after accounting for age, sex, smoking habits and stove type. The different effects of the environment on asthmatics, allergics and airways obstructive disease subjects have been demonstrated. Many relationships were found between environmental factors and respiratory responses. The pollutant and meteorological variables are related to respiratory symptoms and peak flow directly as well as through interactions with pollen types. Some of the largest positive coefficients are seen in association with seasonal pollen types, specifically, rhinitis and dyspnoea.     

Correlates of peak expiratory flow lability in elderly persons.

OBJECTIVE: To determine the correlates of the lability of peak expiratory flow (PEF) in the elderly. METHODS: A community sample of 4,581 persons > or = 65 years old from the Cardiovascular Health Study completed an asthma questionnaire and underwent spirometry. During a follow-up examination of the cohort, 1,836 persons agreed to measure PEF at home twice daily for 2 weeks, and 90% successfully obtained at least 4 days of valid measurements. PEF lability was calculated as the highest daily (PEF maximum - PEF minimum)/mean PEF. RESULTS: Mean PEF measured at home was accurate when compared to PEF determined by spirometry in the clinic. Mean PEF lability was 18% in those with current asthma (n = 165) vs 12% in healthy nonsmokers (upper limit of normal, 29%). Approximately 26% of those with asthma and 14% of the other participants had abnormally high PEF lability (> 29%). After excluding participants with asthma, other independent predictors of high PEF lability included black race, current and former smoking, airway obstruction on spirometry, daytime sleepiness, recent wheezing, chronic cough, emphysema, and wheezing from lying in a supine position. Despite having a lower mean PEF, those reporting congestive heart failure (n = 82) did not have significantly higher PEF lability. CONCLUSIONS: Measurement of PEF lability at home is highly successful in elderly persons. PEF lability > or = 30% is abnormal in the elderly and is associated with asthma.     

Urinary tract calculi that form on surgical staples: a characteristic radiologic appearance

An autostapler is frequently used when bowel is interposed in the urinary tract during reconstructive urologic surgery in children. Usually the metallic staples are buried beneath the intestinal mucosa. However, if a portion of a staple is unintentionally left exposed or becomes exposed through migration and is then bathed by urine, it can become the nidus for formation of a calculus. The radiologic studies of 30 patients having surgery of this type in our hospital from 1980 to 1990 were reviewed prospectively, and stones were found to have developed on staples in eight patients. None of the patients had metabolic abnormalities. The stones were easily visible on plain radiographs because they were calcified. They formed in the lumen of the bladder or the bowel segment on the exposed portion of the staple. Thus, the staple was eccentric in the calculus and not central, as is usually the case with a stone forming on a foreign body. This experience suggests that stones forming on surgical staples during reconstructive urologic surgery have a characteristic radiologic appearance that may aid in their identification.     

Decreased deformability of erythrocytes from smokers

The deformability of erythrocytes from smoking and non-smoking human subjects was examined by filtration through 3-mu pores and capillary viscometry of cell suspensions. In both cases, small but significant differences were found between the two groups that are consistent with a reduction in the surface area-to-volume ratio and/or a diminished membrane flexibility in erythrocyte from smokers. Additional evidence suggests that these findings represent a chronic rather than an acute effect of smoking on erythrocyte deformability.     

Collaborative study to assess risk of lung disease in Pi MZ phenotype subjects

We studied 143 Pi MZ heterozygous (MZ) subjects from random populations that had been examined previously for alpha 1-antitrypsin phenotype. Each Pi MZ subject was closely matched with a Pi M control subject from the same population at each of 6 centers. An expanded National Heart, Lung and Blood Institute (NHLBI) respiratory symptom questionnaire was completed by each subject. Pulmonary function tests designed to detect established as well as early obstructive airway abnormalities were administered. Multivariate analysis of the variance of data from the questionnaire and pulmonary function tests corrected for age, race, sex, and smoking history showed no significant difference (p less than 0.05) between subjects of Pi MZ and Pi M phenotype. The size of the populations studied and number of observations made for each variable were sufficient to assure that small differences could be detected with 95% power. We conclude that MZ phenotype alone carries no greater risk of developing lung disease than M phenotype.     

The "horse-racing effect" and predicting decline in forced expiratory volume in one second from screening spirometry

Longitudinal spirometric data on adults in a general population sample confirmed an overall relationship between rate of change in FEV1 (delta FEV1) and mean FEV1/Ht3. This relationship between FEV1 "slope" and "level" has been called a "horse-racing effect" and is the basis for the widely accepted concept that detecting a low FEV1 will predict a rapid decline in FEV1 and the development of clinically significant COPD. However, when both age and smoking habits were taken into account, the effect persisted only in male smokers. Even in them, it was dependent on the inclusion of part of the delta FEV1 in calculation of the mean FEV1 value. While neither a low initial FEV1/Ht3 nor percent predicted FEV1 significantly predicted a subsequent rapid fall in FEV1, presumably because of regression toward the mean, other initial spirometric variables proved better predictors, at least among male smokers. In them, a low FEV1/FVC ratio on entry was almost uniformly associated with a high rate of decline in FEV1. This was not seen in ex-smokers with similar initial spirometric findings. Also, delta FEV1 could not be predicted with any precision in women regardless of their smoking status. The findings strongly support the concept that detection of early airway disease by spirometric screening will identify those male smokers who are likely to develop clinically significant illness if they continue to smoke and that smoking cessation, even at this point, can markedly improve the prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exposure assessment approaches to evaluate respiratory health effects of particulate matter and nitrogen dioxide.

Several approaches can be taken to estimate or classify total personal exposures to air pollutants. While personal exposure monitoring (PEM) provides the most direct measurements, it is usually not practical for extended time periods or large populations. This paper describes the use of indirect approaches to estimate total personal exposure for NO2 and particulate matter (PM), summarizes the distributions of these estimates, and compares the effectiveness of these estimates with microenvironmental concentrations for evaluating effects on respiratory function and symptoms. Pollutant concentrations were measured at several indoor and outdoor locations for over 400 households participating in an epidemiological study in Tucson, Arizona. Central site monitoring data were significantly correlated with samples collected directly outside homes, but the former usually had higher pollutant concentrations. Integrated indices of daily total personal exposure were calculated using micro-environmental (ME) measurements or estimates and time-budget diary information. Peak expiratory flow rates (PEFR) were measured for up to four times a day during two-week study periods. In thirty children (ages 6-15 years) with current diagnosed asthma, a significant reduction in PEFR was associated with NO2 levels measured outside of their homes. Additional decrements of morning PEFR were found in those children sleeping in bedrooms with higher measured NO2 levels. Morning and noon PEFR decrements were also linked to higher morning NO2 levels that were measured at central monitoring stations. Effects of PM were also found, but were limited to morning PEFR. No effects were found in non-asthmatic children. The relationship of PEFR to the calculated indices of daily average total exposure were weaker than to the microenvironment concentrations. This suggests that diary and ME monitoring data need to yield better time resolution in order to incorporate short-term average exposures to higher concentrations into the exposure indices and into the analysis of within day health responses.     

Myelinated and nonmyelinated nerves: comparison of proton MR properties

The magnetic resonance (MR) relaxation rates of protons were compared in the myelinated and nonmyelinated nerves of the garfish. The long, large olfactory nerve of the garfish, as an easily accessible source of nonmyelinated axons, is uniquely suited for such a comparison. The T1 and T2 measurements revealed distinct and consistent differences between nonmyelinated olfactory nerves and myelinated optic and oculomotor nerves. Comparisons between water content, lipid content, and relaxation rates indicated that the differences in MR properties represent complex differences in the distribution and physical environment of the constituent lipid and water protons.     

Identifying the Relative Contributions of Rac1 and Rac2 to Osteoclastogenesis

Rac small GTPases may play an important regulatory role in osteoclastogenesis. Our in vitro and in vivo results show that both Rac1 and Rac2 are required for optimal osteoclast differentiation, but Rac1 is more critical. Rac1 is the key Rac isoform responsible for regulating ROS generation and the actin cytoskeleton during the multiple stages of osteoclast differentiation. Introduction: Recent evidence suggests that the Rac small GTPases may play an important regulatory role in osteoclastogenesis. This finding is important because bisphosphonates may regulate their antiresorptive/antiosteoclast effects through the modification of Rho family of small GTPases. Materials and Methods: To elucidate the specific roles of the Rac1 and Rac2 isoforms during osteoclastogenesis, we used mice deficient in Rac1, Rac2, or both Rac1 and Rac2 in monocyte/osteoclast precursors. Macrophage‐colony stimulating factor (M‐CSF)– and RANKL‐mediated osteoclastogenesis in vitro was studied by using bone marrow‐derived mononucleated preosteoclast precursors (MOPs). The expression of osteoclast‐specific markers was examined using quantitative real‐time PCR and Western blot analysis. Free actin barbed ends in bone marrow MOPs after M‐CSF stimulation was determined. The ability of MOPs to migrate toward M‐CSF was assayed using Boyden chambers. Margin spreading on heparin sulfate‐coated glass and RANKL‐induced reactive oxygen species generation were also performed. Functional assays of in vitro‐generated osteoclasts were ascertained using dentine sections from narwal tusks. Osteoclast levels in vivo were counted in TRACP and immunohistochemically stained distal tibial sections. In vivo microarchitexture of lumbar vertebrate was examined using μCT 3D imaging and analysis. Results: We show here that, although both Rac isoforms are required for normal osteoclast differentiation, Rac1 deletion results in a more profound reduction in osteoclast formation in vitro because of its regulatory role in pre‐osteoclast M‐CSF‐mediated chemotaxis and actin assembly and RANKL‐mediated reactive oxygen species generation. This Rac1 cellular defect also manifests at the tissue level with increased trabecular bone volume and trabeculae number compared with wildtype and Rac2‐null mice. This unique mouse model has shown for the first time that Rac1 and Rac2 play different and nonoverlapping roles during osteoclastogenesis and will be useful for identifying the key roles played by these two proteins during the multiple stages of osteoclast differentiation. Conclusions: Rac1 and Rac2 play different and nonoverlapping roles during osteoclastogenesis. This model showed that Rac1 is the key Rac isoform responsible for regulating ROS generation and the actin cytoskeleton during the multiple stages of osteoclast differentiation.