Controversies in monitoring and testing for sleep-disordered breathing.

Despite significant advances in the understanding of the pathophysiology of the obstructive sleep apnea syndrome, the best index to classify the severity of sleep-disordered breathing has not been established. The use of new measurement techniques suggests that subtle changes in airflow not detected by conventional thermal sensing devices may signal events associated with significant sleep disruption. Recurrent increased respiratory efforts without discernable changes in airflow, which are currently reliably detectable only by invasive means, also may be important. However, it is still uncertain which events should be considered clinically significant, and the correlation of the frequency of various types of respiratory events with long term physiologic consequences is not clear. Outpatient screening with multichannel portable devices or pulse oximetry has important limitations. However, in combination with the clinical pretest probability of significant sleep-disordered breathing, such screening may correctly classify a large proportion of patients. Combining a partial night diagnostic sleep study with a therapeutic titration of continuous positive airway pressure seems to provide adequate information for appropriate management of many patients with obstructive sleep apnea and reduces time between presentation and initiation of treatment.

Epidemiology and pathogenesis of sleep-disordered breathing.

Sleep-disordered breathing is common in the general population, but the observed prevalence depends on the criteria used to establish the diagnosis. Obesity is a strong risk factor, but other conditions such as allergic upper and lower airways disease may also be important. Differences in risk between the sexes and ethnic groups appear to be present even after established risk factors have been considered. The pathogenesis is likely mutifactorial with anatomic and physiologic factors of varying importance in different individuals. The natural history is uncertain, but without treatment or reduction in risk factors, some progression is likely. Ongoing epidemiologic investigations such as the Sleep Heart Health Study are beginning to provide important information on these questions.

Characterization of an aerosol chamber for human exposures to endotoxin.

The objective of this study was to develop and characterize an exposure chamber in which human subjects could be exposed to low dust concentrations carrying an endotoxin coating. An exposure chamber, dust dispersion method, and endotoxin characterization technique were developed for inhalation exposures. A 6.27 m3 exposure chamber was designed and constructed from cinder block, glass windows, and Plexiglas. Using an acetone adhesion process, Enterobacter agglomerans were adsorbed onto respirable cellulose particles to create the endotoxin aerosol. The size distribution of the endotoxin-treated particles was verified using light microscopy and cascade impactors. A dry powder dust generator was refined to consistently disperse small quantities of the aerosol into the chamber to maintain dust concentrations at approximately 250 micrograms/m3. Dust levels during the chamber exposures were monitored using a portable continuous aerosol monitor (PCAM). During initial exposure runs, PCAM monitoring stations were positioned at different locations within a 0.5-meter matrix to document mixing patterns. Total dust and cascade impactor samples were collected throughout each exposure period to characterize the chamber operating system and insure the mean airborne dust concentration fulfilled target levels. A one-factor analysis of variance at the 95 percent confidence interval illustrated that there was not a statistically significant difference in the mean dust concentration throughout the exposure runs compared to the individual runs. Together the consistency of the total dust filters, endotoxin concentrations, and aerosol-monitoring instrument were adequate to allow use of the chamber for experimental studies involving human volunteers.

Eosinophil influx to the nasal airway after local, low-level LPS challenge in humans.

BACKGROUND: Recent observations show that atopic asthmatic subjects have increased sensitivity to respirable endotoxin (or LPS) compared with normal persons. In vitro studies demonstrate that LPS enhances eosinophil survival. These observations suggest that the effects of inhaled LPS in asthmatic subjects may include increases in the number of airway eosinophils. OBJECTIVE: We sought to determine whether low-level nasal LPS challenge causes an increase in eosinophil numbers in the nasal airways of atopic or normal subjects. METHODS: Sixteen volunteers (10 atopic asthmatic subjects and 6 normal subjects) underwent 2 nasal challenge sessions. In one session, one nostril was challenged with saline and the other with 0. 1 microg of LPS. During the second session, 0.3 microg and 1.0 microg of LPS was delivered to each nostril, respectively. Nasal lavage fluid was obtained from each nostril before challenge, as well as 4 and 24 hours after challenge, and examined for the percent of total cells that were eosinophils and neutrophils, as well as cytokine levels. RESULTS: LPS (1.0 microg) increased the percent of eosinophils in nasal lavage fluid 4 hours after challenge in atopic subjects only. There was also a correlation between constitutive nasal GM-CSF and eosinophil response to LPS in atopic subjects. CONCLUSION: LPS challenge increases eosinophils in the airways of atopic subjects.

Attitudes of respiratory care practitioners and students regarding pulmonary prevention.

STUDY OBJECTIVES: (1) To examine attitudes of respiratory care practitioners (RCPs) and RCP students toward pulmonary disease prevention behaviors and their role in promoting them. (2) To compare RCPs' attitudes regarding pulmonary prevention with existing medical student survey data. DESIGN: Cross-sectional survey. SETTING: Three sites (Valhalla, NY; Winston-Salem, NC; Houston, TX). PARTICIPANTS: One hundred ninety RCPs and 164 RCP students compared with 5,744 medical students. MEASUREMENT AND RESULTS: Subjects completed a 35-item RCP Preventive Pulmonary Attitude (PPA) Survey using a five-point scale (1 = strongly disagree to 5 = strongly agree). A higher score indicates a more positive attitude toward prevention. RCP total scores averaged 117.6 (SD, 15.7; range, 52 to 160). RCP student total scores were significantly higher than RCP practitioners. No significant differences were observed by gender or by type of patient served (pediatric vs adult). RCPs with a history of tobacco smoking had significantly lower scores than RCPs who had never smoked. Most, but not all, respondents acknowledged the importance of patients with chronic lung disease receiving a yearly influenza vaccination. Total PPA scores for medical students were significantly lower than scores for both RCPs and RCP students. Significant differences were noted for a number of individual items. CONCLUSIONS: In general, RCPs had positive attitudes regarding the importance of prevention counseling and their role in providing this to patients. This is important given their potential as a resource in pulmonary prevention efforts. More attention to inclusion of training and evaluation of RCP effectiveness in promoting respiratory health is needed.

Prolonged acute exposure to 0.16 ppm ozone induces eosinophilic airway inflammation in asthmatic subjects with allergies.

BACKGROUND: Increased ambient ozone levels have been associated with increased asthma morbidity in epidemiologic studies. Given that asthma is characterized by airway inflammation and increased sensitivity to airway irritants, it has been suggested that asthmatic subjects may be particularly sensitive to the effect of ozone. OBJECTIVE: The objective of this study was to determine whether exposure to 0.16 ppm ozone induces eosinophilic inflammation in the lower airways of asthmatic subjects. METHODS: Eight asthmatic subjects sensitive to mites were exposed to 0.16 ppm ozone and clean air on separate occasions no less than 4 weeks apart in a double-blind, randomized fashion followed by bronchoscopy 18 hours later. Bronchoalveolar lavage fluid and bronchial lavage fluid were examined for eosinophils. RESULTS: Ozone induced significant increases in airway eosinophils, especially in bronchial lavage fluid. CONCLUSIONS: Ozone exposure results in increased eosinophilic inflammation in the lower airways of asthmatic subjects with allergies.

Smoking history-taking skills: a simple guide to teach medical students.

Many doctors rate themselves as ineffective smoking cessation counsellors. It is logical to initiate training efforts with medical students. We incorporated smoking history-taking in the physical diagnosis course at the University of North Carolina at Chapel Hill using a simple method to teach smoking history-taking skills and to assess its effectiveness as an educational intervention. The principal intervention was the distribution of a one-sheet Smoking-History Taking and Counseling Guide, adapted from the American Lung Association's Freedom From Smoking for You and Your Family self-help manual. The second intervention was a single prompt for 50% of the course preceptors. Students' smoking history-taking skills were evaluated in the Objective Structured Clinical Examination (OSCE) at the end of the course. Students who received the guide did significantly better on the OSCE, even after controlling for having discussed taking a smoking history with their preceptors. A simple guide combined with a one-time prompting of preceptors has a positive effect on the acquisition of smoking history-taking skills by the medical students. This strategy may also be useful for teaching and evaluating smoking-cessation counselling skills, for which good smoking history-taking is a necessary basis.

A mathematical model of bronchial absorption of vapors in the human lung and its significance in pharmacokinetic modeling.

This work formulates a model description of moderately soluble gas and vapor uptake in the bronchial region of the lung during initial inhalation exposure. The mass transport problem is solved using an iterative-analytical approach in which inhaled chemical is partitioned to alveolar blood-gas exchange, bronchial wall absorption, and exhalation. Results of 109 simulations allowed regression analysis to provide simple algebraic equations to describe the fraction of total inhaled mass taken up by the two alternative absorption pathways. These fractions are dependent on the chemical's solubility and liquid diffusivity. The derived relationships are then used in a modified physiologically based pharmacokinetic (PBPK) model which accounts for bronchial uptake. The results are compared to identical results from a traditional (unmodified) PBPK model to draw conclusions concerning the effect of bronchial uptake on systemic chemical distribution in addition to elevated bronchial tissue concentrations.

Monocyte responsiveness and a T-cell subtype predict the effects induced by cotton dust exposure.

The aim of the study was to evaluate whether peripheral cellular parameters could predict susceptibility to decreased lung function and associated symptoms, in response to a single exposure to cotton dust. Previously nonexposed subjects (n = 42) inhaled an aerosol of cotton dust in a model cardroom during a period of 5 h. The subjects were examined before the exposure for FEV1, procoagulant activity (PCA) in blood mononuclear cells (BMNC), and serum IgE antibodies against a pool of inhalant antigens. Blood lymphocytes were typed into the helper/inducer (CD4+) and cytotoxic/suppressor (CD8+) T cells in combination with surface markers subdividing these populations. A questionnaire was used to identify atopic and nonatopic subjects. Immediately after exposure, the subjects were tested for FEV1 and PCA, and symptoms were recorded with a questionnaire. The dust exposure induced a decrease in FEV1 that was larger for the atopic group, but did not change the PCA in BMNC. The decrease in FEV1 was positively related to the preexposure PCA in both atopics and nonatopics. Symptoms from the airways after the exposure were reported to the same extent in the atopic and nonatopic group, and the subject group reporting chest tightness had a larger preexposure PCA. The atopic group had a larger proportion of blood CD8+ T lymphocytes negative for the monoclonal antibody anti-S6F1 (CD8+S6F1-), and in this group the decrease in FEV1 was significantly related to the proportion of this cell type. Also, in the atopic group, the proportion of CD8+S6F1- cells correlated positively with the preexposure PCA, and a negative correlation was found for this cell and serum levels of IgE.(ABSTRACT TRUNCATED AT 250 WORDS)

Do waste incinerators induce adverse respiratory effects? An air quality and epidemiological study of six communities.

The purpose of the study presented here was to simultaneously measure air quality and respiratory function and symptoms in populations living in the neighborhood of waste incinerators and to estimate the contribution of incinerator emissions to the particulate air mass in these neighborhoods. We studied the residents of three communities having, respectively, a biomedical and a municipal incinerator, and a liquid hazardous waste-burning industrial furnace. We compared results with three matched-comparison communities. We did not detect differences in concentrations of particulate matter among any of the three pairs of study communities. Average fine particulate (PM2.5) concentrations measured for 35 days varied across study communities from 16 to 32 micrograms/m3. Within the same community, daily concentrations of fine particulates varied by as much as eightfold, from 10 to 80 micrograms/m3, and were nearly identical within each pair of communities. Direct measurements of air quality and estimates based on a chemical mass balance receptor model showed that incinerator emissions did not have a major or even a modest impact on routinely monitored air pollutants. A onetime baseline descriptive survey (n = 6963) did not reveal consistent community differences in the prevalence of chronic or acute respiratory symptoms between incinerator and comparison communities, nor did we see a difference in baseline lung function tests or in the average peak expiratory flow rate measured over a period of 35 days. Based on this analysis of the first year of our study, we conclude that we have no evidence to reject the null hypothesis of no acute or chronic respiratory effects associated with residence in any of the three incinerator communities.

Bronchial reactivity, atopy, and airway response to cotton dust.

Studies of cotton textile workers have found an association between atopy and drop in FEV1 over a workshift. We studied the response of previously nonexposed volunteers with and without a history of mild atopy to a 5-h exposure to 1 mg/m3 of respirable cotton dust in a model cardroom. All participants were nonsmokers, had no history of asthma, and had normal spirometry. Twenty atopic subjects gave a personal history of mild respiratory allergy to pollen, dusts, or animals that had been confirmed by a physician. Thirty-two nonatopic subjects had no history of allergy. Spirometry and a methacholine challenge test were performed 1 to 2 days prior to exposure. Spirometry was repeated immediately before exposure to cotton dust; spirometry and a methacholine challenge were performed immediately after exposure. Atopic subjects showed a significantly higher mean serum IgE level to Phadiatop, a screening test to common inhalant allergens, than did nonatopic subjects (mean percent binding, 32.1 versus 1.5; p < 0.001). Atopic subjects had a significantly greater mean fall in FEV1 during exposure (8.3% versus 4.9%, p < 0.05). The difference in FEV1 decline between atopic and nonatopic subjects was similar in magnitude to that reported for workshift FEV1 declines between textile workers with and without mild atopy. Atopic subjects had significantly higher baseline methacholine responsiveness than did nonatopic subjects (26% versus 0% reaching a PD20, p < 0.0005). After cotton dust exposure, there was a significant increase in airway reactivity in both groups (68% versus 20% reaching a PD20, p < 0.0005). For all subjects combined baseline responsiveness was significantly related to the change in FEV1 after exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Preventive medicine: what do future practitioners really need? Are they getting it in medical school?

The purposes of our study were (1) to determine preventive medicine topics most relevant to clinical practice, and (2) to determine if medical education affects medical students' attitudes regarding preventive medicine. Our method of study was two surveys. The first survey asked practicing physicians to rank the 23 topics identified in the Healthy People 2000 monograph and determine their usefulness in clinical practice. The second survey assessed medical students' attitudes about preventive medicine. Practitioners ranked tobacco, cancer, and diabetes as most relevant to the actual clinical practice of medicine. There were no correlations between practitioners' gender, age, or region and their rankings of topics. In terms of specialties, surgeons felt preventive medicine was less important than did family practitioners. Medical students' attitudes about preventive practices became significantly more positive as they progressed through medical school. Survey scores also improved significantly in second year students after their preventive medicine course. Students planning to be surgeons were less positive about preventive medicine. There is a continuing need for prevention education in medical school curricula, especially about tobacco, cancer, diabetes, and nutrition. Epidemiology and disease reporting might best be presented as "how to read the literature."

Silicon nephropathy mimicking Fabry's disease.

Percutaneous renal biopsy was performed in a surface coal miner with radiographic and histopathologic pulmonary changes consistent with acute silicolipoproteinosis who developed proteinuria and hematuria. Electron microscopic evaluation of the renal tissue specimen revealed a diffusely thickened glomerular basement membrane, foot process effacement, and dense lamellar inclusions in swollen glomerular epithelial cells, similar to those seen in Fabry's disease. However, normal levels of plasma alpha-galactosidase A, normal urinary sediment glycosphingolipids and the absence of the clinical characteristics of Fabry's disease excluded this diagnosis. This case illustrates that electron-dense lamellar inclusions, similar to those seen in Fabry's disease, may be seen in other entities such as nephropathy associated with silicosis.

Silicosis in silica flour workers.

In July 1979, the health of 86 current and ex-workers at 2 silica mining and milling operations in southern Illinois was examined using a respiratory questionnaire, spirometry, and chest radiographs. None of 25 current workers with less than 1 yr of exposure to silica dust had radiographic evidence of silicosis. For 61 current workers and ex-workers with 1 or more yr of exposure, chest radiographs showed 16 (26%) with simple silicosis and 7 (11%) with progressive massive fibrosis. Of these 23, 8 with simple silicosis and 3 with progressive massive fibrosis began work after the first Mine Safety and Health Administration inspection in 1973. These data and a review of federal dust inspection results between 1973 and 1979 showed that these cases of silicosis could have been prevented by effecting compliance with the existing dust standard.

The use of pulmonary function testing and questionnaires as epidemiologic tools in the study of occupational lung disease.

Pulmonary function testing and questionnaires are valuable tools in epidemiologic studies of occupational lung disease. Accurate equipment and standardized methodology are vital to obtain reproducible responses. For spirometry, the FVC and FEV show the least intrasubject variability and on questionnaires, occupational and smoking history are more reproducible than symptoms. The limitations of any method used to define a lower limit of normal should be kept in mind and, whenever possible, groups should be compared by use of the distribution of observations in the two groups--not just the prevalence of "abnormal" findings.

Cotton dust and complement in vivo.

Cotton grown in Stoneville, Mississippi and harvested by three different methods was examined for anticomplementary activity in human serum in vivo. Subjects exposed to cotton dust in a model cardroom for six hours showed changes in C3c and CH50 after exposure to closed boll harvested, bract removed cotton dust when compared with a group of normal, unexposed controls. Decreases in C3c, :C4, and C3A were associated with decreases in FEV1 after exposure to closed boll harvested bract intact cotton dust. The data from this preliminary study suggest in vivo associations between inhalation of cotton dusts and complement which appear to be independent of endotoxin contamination. These findings suggest a relationship between cotton dust inhalation and complement-mediated respiratory impairment.