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Biomedical subjects

W S Linn

Publications and source records attributed to W S Linn.

At least 19 recordsLinked to original sources

Forced vital capacity in two large outpatient populations with chronic spinal cord injury.

OBJECTIVE: To determine the expected vital capacity in persons with chronic spinal cord injury (SCI) in relation to injury level, completeness of injury, smoking and duration of injury, as an aid to diagnosis and management of respiratory complications. SETTING: A New York City veterans' hospital and a Los Angeles public rehabilitation hospital. METHODS: Case series from the two hospitals were pooled. Participants (adult outpatients with SCI of duration >1 year, not ventilator-dependent) were evaluated by conventional forced expiratory spirometry. Cross-sectional analysis was performed, using multiple regression, on the entire population and defined subgroups. The principal outcome measure was forced vital capacity (FVC). RESULTS: In the subjects with complete-motor lesions, FVC ranged from near 100% of normal predicted values in the group with low paraplegia, to less than 50% in those with high tetraplegia. Incomplete lesions mitigated FVC loss in tetraplegia. In subjects with paraplegia, longer duration of injury was associated with greater loss, and smoking-related loss was evident at older but not at younger ages, presumably due to greater pack years in older subjects. CONCLUSIONS: Vital capacity/SCI level relationships determined here may have diagnostic and prognostic value. Smoking-related FVC loss is important in persons with SCI as in others, although at higher levels it may be obscured by SCI-related loss.

Adult↗

Anti-inflammatory and lung function effects of montelukast in asthmatic volunteers exposed to sulfur dioxide.

BACKGROUND: Sulfur dioxide (SO(2)) gas may induce acute asthmatic responses when inhaled by individuals in the setting of community or occupational air pollution during exercise. Some asthma medications mitigate the SO(2) response, which is not fully understood but appears to involve multiple mechanisms. OBJECTIVE: We tested the hypothesis that pretreatment with the cysteinyl-leukotriene inhibitor montelukast sodium protects against the inflammatory and bronchoconstrictive effects of SO(2) in the airways of asthmatic subjects. METHODS: Asthmatic volunteers (enrolled, 12 subjects; completed study, 11 subjects) were exposed to 0.75 ppm SO(2) for 10-min periods during exercise (mean ventilation, 35 L/min) and were exposed similarly to filtered air (control condition) after double-blinded pretreatments with montelukast (10 mg/d for 3 days) and placebo. RESULTS: After montelukast pretreatment, specific airways resistance, FEV(1), symptoms, and eosinophil counts in induced sputum showed statistically and clinically significant improvements in preexposure measurements and/or decreased responses to SO(2) exposure or exercise. The mean FEV(1) immediately after exposure was 95% of baseline FEV(1) with montelukast pretreatment vs 82% with placebo. CONCLUSION: Montelukast significantly protects against airways eosinophilic inflammation and bronchoconstriction from SO(2) exposure during exercise. This implies a role for leukotrienes in SO(2)-induced lung effects.

Acetates↗

Pulmonary function in chronic spinal cord injury: a cross-sectional survey of 222 southern California adult outpatients.

OBJECTIVES: To evaluate risk factors for respiratory morbidity in chronic spinal cord injury (SCI). SETTING: Model SCI care system based at an urban public rehabilitation medical center. DESIGN: Case series with evaluation of pulmonary function by conventional spirometric testing. PARTICIPANTS: Two hundred twenty-two adults with SCI of more than 1-year duration who were not chronically dependent on mechanical ventilation, including 98 with tetraplegia (62 with complete and 26 with incomplete motor lesions) and 124 with paraplegia (87 with complete and 37 with incomplete motor lesions). MAIN OUTCOME MEASURES: Forced vital capacity (FVC), forced expired volume in 1 second (FEV1), and peak expiratory flow rate (PEFR), all measured in the supine and erect seated positions and compared with predicted normal values for industrial workers. RESULTS: FVC and FEV1 were normal in persons with low-level paraplegia who had never smoked, but both decreased similarly with rising SCI level, more markedly in those with tetraplegia. PEFR decreased with rising SCI level. Incomplete lesions mitigated function loss in those with tetraplegia. In middle-aged individuals with tetraplegia, longer duration of injury was associated with greater function loss, independent of age. Current smokers showed excess function loss, except for those with high tetraplegia. Most people with complete tetraplegia showed FVC and FEV1 increases in the supine position relative to the erect position. CONCLUSIONS: Pulmonary function is compromised by most lesions of the spinal cord, even in those with paraplegia, and is affected relative to the level of lesion. Efforts to help SCI patients minimize respiratory complications-in particular, assistance in smoking cessation-should be given high priority.

Adult↗

Air pollution and daily hospital admissions in metropolitan Los Angeles.

We used daily time-series analysis to evaluate associations between ambient carbon monoxide, nitrogen dioxide, particulate matter [less than and equal to] 10 microm in aerodynamic diameter (PM(10)), or ozone concentrations, and hospital admissions for cardiopulmonary illnesses in metropolitan Los Angeles during 1992-1995. We performed Poisson regressions for the entire patient population and for subgroups defined by season, region, or personal characteristics, allowing for effects of temporal variation, weather, and autocorrelation. CO showed the most consistently significant (p<0.05) relationships to cardiovascular admissions. A wintertime 25th-75th percentile increase in CO (1.1-2.2 ppm) predicted an increase of 4% in cardiovascular admissions. NO(2), and, to a lesser extent, PM(10) tracked CO and showed similar associations with cardiovascular disease, but O(3) was negatively or nonsignificantly associated. No significant demographic differences were found, although increased cardiovascular effects were suggested in diabetics, in whites and blacks (relative to Hispanics and Asians), and in persons older than 65 years of age. Pulmonary disease admissions associated more with NO(2) and PM(10) than with CO. Pulmonary effects were generally smaller than cardiovascular effects and were more sensitive to the choice of model. We conclude that in Los Angeles, atmospheric stagnation with high primary (CO/NO(2)/PM(10)) pollution, most common in autumn/winter, increases the risk of hospitalization for cardiopulmonary illness. Summer photochemical pollution (high O(3)) apparently presents less risk.

Adult↗

Quality of spirometry test performance in children and adolescents : experience in a large field study.

STUDY OBJECTIVE: To determine the ability of children and adolescents to meet the American Thoracic Society (ATS) goals for spirometry quality that were based on results from adults. DESIGN: Observational. PARTICIPANTS: More than 4,000 public school students, ages 9 to 18 years. MEASUREMENTS: Spirometry was performed annually for 3 years, with the recording of maneuver quality measures of forced expiratory time, end-of-test volume, back-extrapolated volume, and time to peak expiratory flow (PEFT), and the recording of differences between best and second-best FVC, FEV(1), and peak expiratory flow (PEF) values. RESULTS: Regression analyses showed significant influences of participant age, gender, ethnicity, size, clinical status, and previous testing experience, as well as differences among individual test technicians. In general, these influences were small and explained little of the variance in performance. On average, children with a history of asthma or wheeze performed better quality spirometry than did others. Only PEFT improved significantly from year to year. Overall, only 15% of girls' tests and 32% of boys' tests met the PEFT criterion derived from adults in the Lung Health Study. CONCLUSION: Most of the children met adult-based ATS goals for spirometry test performance. Age group-specific criteria are needed to ensure adequately fast PEFT and reproducible PEF values.

Adolescent↗

Day-to-day particulate exposures and health changes in Los Angeles area residents with severe lung disease.

We measured particulate matter (PM2.5 and PM10) exposures, home temperature, arterial blood oxygen saturation, blood pressure, and lung function in 30 volunteer Los Angeles area residents during four-day intervals. Continuous Holter electrocardiograms were recorded in a subgroup on the first two days. Subjects recorded symptoms and time-activity patterns in diaries during monitoring, and during a reference period one week earlier/later. All subjects had severe chronic obstructive pulmonary disease. PM10 (24-hr mean) at monitoring stations near subjects' homes averaged 33 micrograms/m3, and ranged from 9 to 84 micrograms/m3. In longitudinal analyses, day-to-day changes in PM2.5 and PM10 outside subjects' homes significantly tracked concurrent station PM10 (r2 = 0.22 and 0.44, respectively). Indoor and personal concentrations were less related to station readings (r2 < or = 0.1), but tracked each other (r2 > or = 0.4). In-home temperatures tracked outdoor temperatures more for lows (r2 = 0.27) than for highs (r2 = 0.10). These longitudinal relationships of subject-oriented and station PM measurements were generally similar to cross-sectional relationships observed previously in similar subjects. Among health measurements, only blood pressure showed reasonably consistent unfavorable longitudinal associations with particulates, more with station or outdoor PM than with indoor or personal PM.

Aged↗

The 21st century environment and air quality influences on asthma.

"Criteria" air pollutants are federally regulated pollutants that occur widely outdoors and have diverse sources, most often related to combustion. They include ozone (O3), particulate matter, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and lead. All except lead may interfere with oxygen delivery, and so may be of special concern to asthmatics. In controlled experiments, SO2 causes acute asthma symptoms and bronchoconstriction, preventable by beta-agonist medications. Ozone causes acute irritant symptoms, restrictive lung dysfunction, increased bronchial reactivity, and lower-airway inflammation in healthy people and asthmatics. Exposures to O3, and possibly to other pollutants, appear to exacerbate bronchoconstrictive or inflammatory responses to inhaled aeroallergens (bioaerosols); this may represent an important health risk to asthmatics. Exposure levels known to evoke acute responses to O3 or SO2 are uncommon in community air pollution; however, some asthmatics might be susceptible to lesser, more common exposures. Evidence concerning NO2 is equivocal, but it may have O3-like effects in some asthmatics. Epidemiology has often associated particulate pollution with asthma exacerbations and other cardiorespiratory illnesses, even in cities with relatively mild air pollution. Current laboratory research cannot fully explain this association. Advances in emission controls should further reduce ambient pollution levels, but probably will not reduce asthma morbidity. Better asthma management, with improved anti-inflammatory medications, more careful monitoring by patients and health care providers, and reasonable efforts to reduce pollutant and aeroallergen exposures, offers the best hope to reduce asthma morbidity in the new century.

Air Pollutants↗

A study of twelve Southern California communities with differing levels and types of air pollution. I. Prevalence of respiratory morbidity.

To study possible chronic respiratory effects of air pollutants, we initiated a 10-yr prospective cohort study of Southern California children, with a study design focused on four pollutants: ozone, particulate matter, acids, and nitrogen dioxide (NO2). Twelve demographically similar communities were selected on the basis of historic monitoring information to represent extremes of exposure to one or more pollutants. In each community, about 150 public school students in grade 4, 75 in grade 7, and 75 in grade 10 were enrolled through their classrooms. Informed consent and written responses to surveys about students' lifetime residential histories, historic and current health status, residential characteristics, and physical activity were obtained with the help of the parents. In the first testing season, 3,676 students returned questionnaires. We confirmed associations previously reported between respiratory morbidity prevalence and the presence of personal, demographic, and residential risk factors. Rates of respiratory illness were higher for males, those living in houses with pets, pests, mildew, and water damage, those whose parents had asthma, and those living in houses with smokers. Wheeze prevalence was positively associated with levels of both acid (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.14-1.83) and NO2 (OR = 1.54; 95% CI, 1.08-2.19) in boys. We conclude, based on this cross-sectional assessment of questionnaire responses, that current levels of ambient air pollution in Southern California may be associated with effects on schoolchildren's respiratory morbidity as assessed by questionnaire.

Acids↗

A study of twelve Southern California communities with differing levels and types of air pollution. II. Effects on pulmonary function.

To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described in the accompanying paper. Pulmonary function tests were completed on 3,293 subjects. We evaluated cross-sectionally the effects of air pollution exposures based on data collected in 1986-1990 by existing monitoring stations and data collected by our study team in 1994. Expected relationships were seen between demographic, physical, and other environmental factors and pulmonary function values. When the data were stratified by sex, an association was seen between pollution levels and lower pulmonary function in female subjects, with the associations being stronger for the 1994 exposure data than the 1986-1990 data. After adjustment, PM10, PM2.5, and NO2 were each significantly associated with lower FVC, FEV1, and maximal midexpiratory flow (MMEF); acid vapor with lower FVC, FEV1, peak expiratory flow rate (PEFR), and MMEF; and O3 with lower PEFR and MMEF. Effects were generally larger in those girls spending more time outdoors. Stepwise regression of adjusted pulmonary function values for girls in the 12 communities showed that NO2 was most strongly associated with lower FVC (r = -0.74, p < 0.01), PM2.5 with FEV1 (r = -0.72, p < 0.01), O3 with PEFR (r = -0.75, p < 0.005), and PM2.5 with MMEF (r = -0.80, p < 0.005). There was a statistically significant association between ozone exposure and decreased FVC and FEV1 in girls with asthma. For boys, significant associations were seen between peak O3 exposures and lower FVC and FEV1, but only in those spending more time outdoors. These findings underline the importance of follow-up of this cohort.

Acids↗

Temperature standardization of multiple spirometers.

In respiratory health surveys involving multiple spirometers, spirometer differences may introduce important biases. We investigated temperature measurement variability as a cause of spirometer differences. Digital thermometers recorded internal (cylinder) and external (outer casing) temperatures of six similar rolling-seal spirometers during field use and in laboratory tests at controlled room temperatures. Internal and external thermometers substantially agreed in recording spirometer temperature changes, which lagged room temperature changes. Offsets of individual thermometers from overall mean readings were roughly the same in field testing of 3908 students in > 60 schools over 5 months and in subsequent laboratory tests. Thermometers differed by as much as 1.3 degrees C, causing differences as large as 0.8% in vital capacity measurements. We conclude that (1) interior and exterior temperatures of typical rolling-seal spirometers do not differ greatly, although both may differ from surrounding air temperature; and (2) variations between individual digital thermometers may be large enough to bias spirometric data appreciably in large-scale surveys. Variations should be controlled by selection of similar-reading thermometers and/or correction to a uniform standard.

Analysis of Variance↗

Cardiovascular effects of ozone exposure in human volunteers.

We hypothesized that ozone (O3) exposure acutely affects cardiovascular hemodynamics in humans and, in particular, in subjects with essential hypertension. We studied 10 nonmedicated hypertensive and six healthy male adults. Each subject, after catheterization of the right heart and a radial artery, was exposed in an environmentally controlled chamber to filtered air (FA) on one day and to 0.3 ppm O3 on the following day for 3 h with intermittent exercise. Relative to FA exposure, O3 exposure induced no statistically significant changes in cardiac index, ventricular performance, pulmonary artery pressure, pulmonary and systemic vascular resistances, ECG, serum cardiac enzymes, plasma catecholamines and atrial natriuretic factor, and SaO2. The overall results did not indicate major acute cardiovascular effects of O3 in either the hypertensive or the control subjects. However, mean preexposure to postexposure changes were significantly (p < 0.02) larger with O3 than with FA for rate-pressure product (1,353 beats/min/mm Hg) and for heart rate (8 beats/min); these responses were not significantly different between the hypertensive and the control subjects. Significant O3 effects were also observed for mean FEV1 (-6%), and AaPO2 (> 10 mm Hg increase), which were not significantly different between the two groups. These results suggest that O3 exposure can increase myocardial work and impair pulmonary gas exchange to a degree that might be clinically important in persons with significant preexisting cardiovascular impairment, with or without concomitant lung disease.

Adult↗

Projection of health benefits from ambient ozone reduction related to the use of methyl tertiary butyl ether (MTBE) in the reformulated gasoline program.

To estimate potential public health benefits from ozone (O3) pollution reduction attributable to the use of methyl tertiary-butyl ether (MTBE) in gasoline, O3 dose-response estimates from the biomedical literature were combined with model estimates of O3 reduction. Modeling employed EPA MOBILE5a and Complex models to predict emission changes, industry AQIRP techniques to predict ambient O3 changes, and the National Exposure Model to predict human exposures. Human health effects considered were lung function decrements and respiratory irritant symptoms (using dose-response functions measured in laboratory and field studies), and increased death rates (using concentration-response functions inferred statistically from public-health data). Other reported health effects, such as lung inflammation, increases in asthma attacks, and hospitalizations, were not addressed because of inadequate dose-response information. Even for the health responses considered, quantitation of improvements due to MTBE use is problematical, because MTBE affects only a small percentage of existing O3 pollution, and because exposure-response relationships are not well understood for population subgroups most likely to be affected. Nevertheless, it is reasonable to conclude that even small MTBE-associated reductions in peak ambient O3 levels (1-5 ppb, according to model estimates) should yield considerable public health benefits. Tens of millions of Americans are potentially exposed to O3 in the concentration range associated with health effects. Even if only a small percentage of them are susceptible, any incremental reduction in O3 (as with MTBE use) must mitigate or prevent effects for a meaningful number of people. Better quantitative estimates of benefit must await a more detailed understanding of each link in the chain of causation.

Air Pollutants↗

Standardization of multiple spirometers at widely separated times and places.

We designed a system for a multiyear longitudinal study of lung function in 12 widely separated communities, intending to minimize variation in instrument-related data. We used multiple rolling-seal spirometer/personal computer systems. Calibrations were checked before, during, and after each day's field testing, using multiple calibration syringes with electronic readouts. The syringes were rotated to obtain data for each syringe-spirometer combination. Before and after each annual field testing season, a laboratory reference spirometer system was calibrated against a water-displacement device and an electronic frequency counter, and then compared against each field spirometer and syringe. Field equipment consistently met American Thoracic Society (ATS) specifications. Variance among spirometers exceeded variance among syringes. A spirometer occasionally changed its volume readout by approximately 1 to 2 %. More rarely, a syringe changed its delivered volume by approximately 1%. Syringes' electronic readouts tracked changes in delivered volume. Syringe readouts were the most stable component of the system, and were more reproducible than the laboratory water-displacement calibration. We conclude that variation in spirometers may limit the reliability of epidemiologic findings, even when these spirometers meet ATS specifications. Frequent calibration checks traceable to an independent standard, and adjustment of individual test results, can reduce measurement error.

Calibration↗

Effect of inhaled salmeterol on sulfur dioxide-induced bronchoconstriction in asthmatic subjects.

UNLABELLED: This study tested the capability of a single 42-microgram dose of inhaled salmeterol xinafoate, a long-acting beta 2-agonist, to protect against bronchoconstrictive effects of exposure to 0.75 ppm sulfur dioxide (SO2) during exercise, for up to 24 h. Ten SO2-responsive adult volunteers with stable asthma were studied under 4 conditions of drug pretreatment/exposure, administered in random order, double-blind: salmeterol/SO2, placebo/SO2, salmeterol/clean air, and placebo/clean air. Each subject underwent 10-min exposure/exercise challenges in a chamber 1, 12, 18, and 24 h after pretreatment. Exercise ventilation rates averaged 29 L/min. Response was measured as the decrement in FEV1 between preexposure and postexposure (lowest value within 30 min). After salmeterol, mean decrement post-SO2 was 7% at 1 h and 12% at 12 h. At 18 and 24 h after salmeterol, and at all times after placebo, mean decrements were 25 to 30%. After 18 and 24 h, salmeterol still improved base-line FEV1 relative to placebo, although improvement was not statistically significant at 24 h. Acute symptom increases accompanied FEV1 decrements. CONCLUSION: In our asthmatic subjects, pretreatment with salmeterol imparted clinically and statistically significant (p < 0.01) protection against bronchoconstriction induced by SO2/exercise for at least 12 h, and maintained an improvement in lung function for as much as 18 h.

Administration, Inhalation↗

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Adolescent↗