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STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by multiple “endotypic traits,” including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here, we examined (1) within-night repeatability, (2) long-term consistency, and (3) influences of body position and sleep state, of endotypic traits estimated from in-home polysomnography in mild-to-severe OSA (apnea-hypopnea index, AHI > 5 events/h). METHODS: Within-night repeatability was assessed using Multi-Ethnic Study of Atherosclerosis (MESA): Traits derived separately from “odd” and “even” 30-min periods were correlated and regression (error vs. N windows available) provided a recommended amount of data for acceptable repeatability (R(threshold) = 0.7). Long-term consistency was assessed using the Osteoporotic Fractures in Men Study (MrOS) at two time points 6.5 ± 0.7 years apart, before and after accounting for across-year body position and sleep state differences. Within-night dependence of traits on position and state (MESA plus MrOS data) was estimated using bootstrapping. RESULTS: Within-night repeatability for traits ranged from R = 0.62–0.79 and improved to R = 0.69–0.83 when recommended amounts of data were available (20–35 7-min windows, available in 94%–98% of participants); repeatability was similar for collapsibility, loop gain, and arousal threshold (R = 0.79–0.83), but lower for compensation (R = 0.69). Long-term consistency was modest (R = 0.30–0.61) and improved (R = 0.36–0.63) after accounting for position and state differences. Position/state analysis revealed reduced loop gain in REM and reduced collapsibility in N3. CONCLUSIONS: Endotypic traits can be obtained with acceptable repeatability. Long-term consistency was modest but improved after accounting for position and state changes. These data support the use of endotypic assessments in large-scale epidemiological studies. CLINICAL TRIAL INFORMATION: The data used in the manuscript are from observational cohort studies and are not a part of the clinical trial.

Rationale: Patients managed at a long-term acute-care hospital (LTACH) for weaning from prolonged mechanical ventilation are at risk for profound muscle weakness and disability. Objectives: To investigate effects of prolonged ventilation on survival, muscle function, and its impact on quality of life at 6 and 12 months after LTACH discharge. Methods: This was a prospective, longitudinal study conducted in 315 patients being weaned from prolonged ventilation at an LTACH. Measurements and Main Results: At discharge, 53.7% of patients were detached from the ventilator and 1-year survival was 66.9%. On enrollment, maximum inspiratory pressure (Pi(max)) was 41.3 (95% confidence interval, 39.4–43.2) cm H(2)O (53.1% predicted), whereas handgrip strength was 16.4 (95% confidence interval, 14.4–18.7) kPa (21.5% predicted). At discharge, Pi(max) did not change, whereas handgrip strength increased by 34.8% (P

The objective of this study was to describe trends in the prevalence of opioids in driver fatalities and examine geographic variation in opioid-involved crashes at a county level. Using comprehensive toxicological data from the Office of the Chief Medical Examiner in Maryland, we examined the prevalence of opioids in all motor vehicle crash fatalities in Maryland between 2006-2017 and tested for trends to assess the statistical significance of changes in the prevalence of prescription opioids detected in these drivers over time. Opioid-involved crash deaths accounted for 10.0% of all driver deaths during the study period. The prevalence of opioids detected in fatally injured drivers increased from 8.3% in 2006 to 14.1% in 2017, (Z = -1.9, p .05). The trends in opioid deaths do not follow broader trends in motor vehicle crash deaths; opioid-involved crashes appear to be increasing while overall motor vehicle crashes appear to be decreasing over the same period. To determine if the increase in opioid-involved crash deaths was the result of changes in pain management related to injuries sustained from the crash, we analyzed a subgroup of cases where death occurred at the scene of the crash. Within this group, there was no statistically significant increase in opioid-involved crashes during the study period. Opioid prevalence was higher in middle aged, and white drivers, and in crashes occurring in rural counties. Geographic distribution of opioid-involved crash deaths reflect broader patterns of opioid deaths overdose across the state. Irrespective of the timing of the deaths, of the drivers testing positive for opioids, 28% had elevated blood alcohol concentrations (‡ 0.01 g/dL), and 45% tested positive for other drugs.

Importance One mechanism for teenagers’ elevated crash risk during independent driving may be inadequate learner driving experience. Objective To determine how learner driver experience was associated with crash risk during the first year of independent driving. Design, Setting, and Participants Youth aged 15.5 to 16.1 years at recruitment were eligible to participate. Participants’ vehicles were instrumented with sensors, and driving was recorded during the learner period through 1 year of independent driving. Data were collected from January 2011 through August 2014 in southwestern Virginia. Exposures The amount, consistency and variety of practice, driving errors, and kinematic risky driving (KRD) rates during the learner period were recorded. Surveys, including one on sensation-seeking personality traits, were assessed at baseline. Main Outcomes and Measures Cox proportional hazard regressions examined associations between individual characteristics and learner driving experience with driving time to first crash and all crashes in the first year of independent driving. So that hazard ratios (HRs) can be directly comparable, units of measurement were standardized to the interquartile range. Results Of 298 individuals who responded to recruitment, 90 fulfilled the criteria and 82 completed the study (of whom 75 were white [91%] and 44 were girls [54%]). Teenage participants drove a mean (SD) of 1259.2 (939.7) miles over 89 days during the learner period. There were 49 property-damage crashes and/or police-reportable crashes during independent driving. Factors associated with driving time to first crash included higher sensation-seeking personality scale scores (HR, 1.67 [95% CI, 1.08-2.57] per 0.75-unit increase), learner driving KRD rates (HR, 1.27 [95% CI, 1.12-1.43] per 9.24-unit increase), and learner driving errors (HR, 0.44 [95% CI, 0.22-0.86] per increase of 6.48 errors). Similar results were obtained for all crashes in the first year, with the addition of consistency of learner driving practice (HR, 0.61 [95% CI, 0.38-0.99] per 0.23-unit increase). Conclusions and Relevance Individual characteristics and learner driving experiences were associated with crash risk during independent driving. As expected, there was an association between sensation seeking and crashes. Elevated KRD rates during the learner period may reflect risky driving behavior among novices or tolerance to abrupt maneuvers by parents who supervise driving. Consistent practice throughout the learner period could reduce teenage crash risk, which is supported by learning theories indicating distributed practice is effective for developing expertise. Errors during practice may constitute learning events that reinforce safer driving. Physicians could encourage parents to provide opportunities for regular practice driving and monitor their teenager’s KRD rates during the learner period using in-vehicle or smartphone-based technology.

More than a million polysomnograms (PSGs) are performed annually in the United States to diagnose obstructive sleep apnea (OSA). Third-party payers now advocate a home sleep test (HST), rather than an in-laboratory PSG, as the diagnostic study for OSA regardless of clinical probability, but the economic benefit of this approach is not known.We determined the diagnostic performance of OSA prediction tools including the newly developed OSUNet, based on an artificial neural network, and performed a cost-minimization analysis when the prediction tools are used to identify patients who should undergo HST.The OSUNet was trained to predict the presence of OSA in a derivation group of patients who underwent an in-laboratory PSG (n = 383). Validation group 1 consisted of in-laboratory PSG patients (n = 149). The network was trained further in 33 patients who underwent HST and then was validated in a separate group of 100 HST patients (validation group 2). Likelihood ratios (LRs) were compared with two previously published prediction tools. The total costs from the use of the three prediction tools and the third-party approach within a clinical algorithm were compared.The OSUNet had a higher +LR in all groups compared with the STOP-BANG and the modified neck circumference (MNC) prediction tools. The +LRs for STOP-BANG, MNC, and OSUNet in validation group 1 were 1.1 (1.0-1.2), 1.3 (1.1-1.5), and 2.1 (1.4-3.1); and in validation group 2 they were 1.4 (1.1-1.7), 1.7 (1.3-2.2), and 3.4 (1.8-6.1), respectively. With an OSA prevalence less than 52%, the use of all three clinical prediction tools resulted in cost savings compared with the third-party approach.The routine requirement of an HST to diagnose OSA regardless of clinical probability is more costly compared with the use of OSA clinical prediction tools that identify patients who should undergo this procedure when OSA is expected to be present in less than half of the population. With OSA prevalence less than 40%, the OSUNet offers the greatest savings, which are substantial when the number of sleep studies done annually is considered.

Respiratory pathogens are frequently isolated from the airways of patients with chronic obstructive pulmonary disease (COPD) in the absence of an exacerbation. This bacterial "colonization" by potential pathogens is associated with host inflammatory and immune responses, which could increase respiratory symptoms.To study whether bacterial colonization impacts daily respiratory symptoms in COPD.In a longitudinal prospective observational study of COPD, patients recorded daily symptoms electronically on the Breathlessness, Cough, and Sputum Scale (BCSS). Sputum cultures and quantitative polymerase chain reaction (PCR) were performed every 2 weeks. The relationship of BCSS and bacterial colonization was analyzed with generalized linear mixed effects models, after controlling for exacerbations, weather conditions, lung function, and demographic variables.A total of 41 patients recorded daily symptoms for 12,527 days. The average BCSS score was higher during the periods of colonization, determined by sputum culture with one or more of the following pathogens: nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa, compared to periods without colonization (5.28 vs. 4.46; P = 0.008) after controlling for confounding variables. The finding did not change when colonization was defined by quantitative PCR (average BCSS, 4.77 vs. 4.25; P = 0.006). Sputum IL-8 levels were elevated with bacterial colonization.Even in the absence of clinical exacerbation, colonization by bacterial pathogens in COPD was associated with a clinically significant moderate increase in daily symptoms, likely mediated by increased airway inflammation. Novel therapies that decrease bacterial colonization in COPD could improve daily symptoms and quality of life.

Animal models have shown a quantal slowing of respiratory pattern when exposed to opioid agonist, in a pattern similar to that observed in central sleep apnea. We postulated that opioid-induced hypoventilation is more likely to be associated with sleep apnea rather than hypoventilation alone. Since we did not have a direct measure of hypoventilation we used hypoxemia as an indirect measure reasoning that significant hypoventilation would not occur in the absence of hypoxemia.We conducted a retrospective analysis of 98 consecutive patients on chronic opioid medications who were referred for overnight polysomnography. All patients on chronic opioids seen in the chronic pain clinic were referred for a sleep study regardless of whether they had sleep symptoms or not. Sleep-related hypoxemia was defined as arterial oxyhemoglobin saturation of less than 90% for more than 5 min with a nadir ofor=85%, or greater than 30% of total sleep time at an oxyhemoglobin saturation of less than 90%.Of the 98 patients, 36% (95% CI 26-46%) had obstructive sleep apnea, 24%, (95% CI 16-33%) had central sleep apnea, 21% (95% CI 14-31%) had combined obstructive and central sleep apnea, in 4% (95% CI 0-10%) sleep apnea was classified as indeterminate, and 15% (95% CI 9-24%) had no sleep apnea. Opioids were potentially responsible for hypoxemia during wakefulness in 10% of patients (95% CI 5-18%) and for hypoxemia during sleep not clearly associated with apneas/hypopneas in 8% of patients (95% CI 4-15%). Two patients (2%, 95% CI 0-7%) had sleep-related hypoxemia in the absence of sleep apnea or hypoxemia during wakefulness.Patients on chronic opiate therapy for chronic pain have an extremely high prevalence of sleep apnea and nocturnal hypoxemia. Hypoxemia can occur during quiet wakefulness in patients on chronic opioid medications with and without sleep apnea. In patients on chronic opioid therapy, isolated nocturnal hypoxemia without coexisting sleep apnea or daytime hypoxemia is very uncommon.

Objectives Three cases are presented in which patients were using opioids as required for nonmalignant pain management and significant central sleep apnea developed. Patients in the first two cases had no evidence of sleep-related breathing disorders on polysomnography until they ingested an opioid for treatment of chronic pain during the night and severe central sleep apnea developed. The patient in our third case had established obstructive sleep apnea but experienced a significant number of central events after the ingestion of an opioid analgesic, leading to worsening severity of his underlying sleep-related breathing disorder. Conclusion The short-term ingestion of opioid analgesics can precipitate central sleep apnea in patients with chronic pain receiving long-term opiate therapy who otherwise show no evidence of central sleep apnea and have no cardiac or neurologic disease that would predispose them to central sleep apnea.

Objective. To assess the relation between medications prescribed for chronic pain and sleep apnea. Design. An observational study of chronic pain patients on opioid therapy who received overnight polysomnographies. Generalized linear models determined whether a dose relation exists between methadone, nonmethadone opioids, and benzodiazepines and the indices measuring sleep apnea. Setting. A private clinic specializing in the treatment of chronic pain. Patients. Polysomnography was sought for all consecutive (392) patients on around-the-clock opi- oid therapy for at least 6 months with a stable dose for at least 4 weeks. Of these, 147 polysomnog- raphies were completed (189 patients declined, 56 were directed to other sleep laboratories by insurance companies, and data were incomplete for seven patients). Available data were analyzed on 140 patients. Outcome Measures. The apnea-hypopnea index to assess overall severity of sleep apnea and the central apnea index to assess central sleep apnea. Results. The apnea-hypopnea index was abnormal ( ≥ 5 per hour) in 75% of patients (39% had obstructive sleep apnea, 4% had sleep apnea of indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea); 25% had no sleep apnea. We found a direct relation between the apnea-hypopnea index and the daily dosage of methadone ( P = 0.002) but not to other around-the-clock opioids. We found a direct relation between the central apnea index and the daily dosage of methadone ( P = 0.008) and also with benzodiazepines ( P = 0.004). Conclusions. Sleep-disordered breathing was common in chronic pain patients on opioids. The dose-response relation of sleep apnea to methadone and benzodiazepines calls for increased vigilance.

Mathematical formulas have been less than adequate in assessing the optimal continuous positive airway pressure (CPAP) level in patients with obstructive sleep apnea (OSA). The objectives of the study were (1) to develop an artificial neural network (ANN) using demographic and anthropometric information to predict optimal CPAP level based on an overnight titration study and (2) to compare the predicted pressures derived from the ANN to the pressures computed from a previously described regression equation.A general regression neural network was used to develop the predictive model. The derivation cohort included 311 consecutive patients who underwent CPAP titration at a University-affiliated Sleep Center. The model was validated subsequently on 98 participants from a private sleep laboratory.The correlation coefficients between the optimal pressure determined by the titration study and the predicted pressure by the ANN were 0.86 (95% confidence interval [CI] 0.83-0.88; p0.001) for the derivation cohort and 0.85 (95% CI 0.78-0.9; p0.001) for the validation cohort, respectively. Whereas there was no significant difference between the optimal pressure obtained during overnight polysomnography and the predicted pressure estimated by the ANN (p=0.4), the estimated pressure derived from the regression equation underestimated the optimal pressure in both the derivation and the validation group, respectively.The optimal CPAP level predicted by the ANN provides a more accurate assessment of the pressure derived from the historic regression equation.

There are data about the relationship between morphologic findings on high-resolution computed tomography (HRCT) and the number of acid-fast bacilli (AFB) on sputum smears in patients with pulmonary tuberculosis (PTB). It was also shown that existence of cavities and airspace consolidation might be related to smear positivity in PTB patients. However, there is no study suggesting a relationship between AFB on sputum smears and radiologic extent of disease based on HRCT findings.In this study, we investigated a relationship between the degree of smear positivity and radiologic extent of disease based on HRCT findings and, the degree of smear positivity and different pulmonary parenchymal changes on HRCTs of the PTB patients.Sixty-one male patients with PTB (mean age: 22+/-3.2) were included into the study. HRCT images were assessed for patterns, distribution, and profusion of pulmonary abnormalities. Dividing the lungs into 3 zones, profusion of abnormalities was assessed. A profusion score was given. Patients were divided as smear positive and smear negative and compared for the scores of HRCT findings. Smear-positive patients were divided into 4 groups as per grading of the sputum AFB smear: group I (sputum 1+), group II (sputum 2+), group III (sputum 3+), and group IV (sputum 4+). Correlations were investigated between the degree of smear positivity and the scores of HRCT findings.A significant correlation between radiologic extent of the disease based on HRCT and the degree of smear positivity was found (r=0.63, P=0.0001). There were also significant correlations between the degree of smear positivity and the scores of different HRCT findings. Nodule, cavity, and bronchial lesions are the most important contributors of the predictive properties of the total score. There was significant differences for the scores of HRCT findings between smear-positive and smear-negative patients.Our study suggests that radiologic extent of disease based on HRCT findings in patients with PTB correlated with the degree of smear positivity. Different HRCT findings such as nodule, cavitation, ground-glass opacity, consolidation, and bronchial lesion are significantly associated with smear-positive PTB. Particularly, nodules, cavities, and bronchial lesions might be predictors of smear positivity in patients with PTB. This study also suggests that the thickness of cavity wall and the distance of cavity from central airways might be related to the degree of smear positivity.

Current recommendations for management of obese patients post-extubation are based on clinical experience and expert opinions. It was hypothesised that the application of noninvasive ventilation (NIV) during the first 48 h after extubation in severely obese patients would reduce post-extubation failure and avert the need for reintubation. Following protocol-driven weaning trials, 62 consecutive severely obese patients (body mass index > or =35 kg x m(-2)) were assigned to NIV via nasal mask immediately post-extubation and compared with 62 historically matched controls who were treated with conventional therapy. The primary end-point was the incidence of respiratory failure in the first 48 h post-extubation. Compared with conventional therapy, the institution of NIV resulted in 16% (95% confidence interval 2.9-29.3%) absolute risk reduction in the rate of respiratory failure. There was a significant difference in the intensive care unit and lengths of hospital stay between the two groups. Subgroup analysis of hypercapnic patients showed reduced hospital mortality in the NIV group compared with the control group. In conclusion, noninvasive ventilation may be effective in averting respiratory failure in severely obese patients when applied during the first 48 h post-extubation. In selected patients with chronic hypercarbia, early application of noninvasive ventilation may confer a survival benefit.

BACKGROUND: Residency training programs use the night float system increasingly to meet the new resident work hour regulations. OBJECTIVE: To assess and compare residents’, attendings’, and nurses’ perceptions of the night float system. DESIGN: A survey study. PARTICIPANTS: One hundred and seven residents, 48 attendings, and 69 nurses in a university-based multicenter internal medicine residency program. MEASUREMENTS: Perceived impact on patient care, resident training, and resident performance. RESULTS: The overall response rate was 75%. In general, more residents than both attendings and nurses had positive opinions regarding the night float system, particularly in relation to patient care. Only a small proportion of residents and attendings thought positively about the night float’s impact on training quality (29.9%; 18.2%), daily feedback (23.0%; 9.1%), and end of rotation evaluation (21.8%; 6.1%). Less than half of the nurses had positive perceptions of the night residents’ performance in terms of promptness (40.9%), physical availability (38.6%), familiarity with the patients’ cases, and management plans (15.9%), communication of management plans to nurses (36.4%), professional respect and trust (43.2%), and teamwork (45.5%). CONCLUSIONS: Residents had more positive perceptions than attendings and nurses. Nurses, in particular, had negative perceptions of resident performance in the setting of the night float system.

Increased oxidative stress in obstructive sleep apnoea is thought to contribute to endothelial dysfunction. The objective of this study was to test the hypothesis that inhibition of xanthine oxidase by allopurinol can improve endothelial function in patients with obstructive sleep apnoea. A randomised double-blind placebo-controlled crossover study was performed on 12 patients with moderate-to-severe obstructive sleep apnoea, comparing 300 mg allopurinol daily for 2 weeks with placebo. Endothelial function was assessed using hyperaemia-induced flow-mediated vasodilation (FMD) at baseline and following treatment. Plasma malondialdehyde levels were compared in order to assess significant changes in oxidative stress. Baseline FMD correlated significantly with the severity of sleep apnoea and the time spent with an arterial oxygen saturation of

Background: The prevalence of obesity is increasing, and there is evidence that obesity, in particular abdominal obesity as a marker of insulin resistance, is negatively associated with pulmonary function. The mechanism for this association and the best marker of abdominal adiposity in relation to pulmonary function is not known. Study objective: We assessed the association between pulmonary function and weight, body mass index (BMI), waist circumference, waist/hip ratio, and abdominal height as markers of adiposity and body fat distribution. We used multiple linear regression to analyze the association of pulmonary function (ie, FEV1 and FVC) [with maneuvers performed in the sitting position] with overall adiposity markers (ie, weight and BMI) and abdominal adiposity markers, stratified by gender, and adjusted for height, age, race, smoking, and other covariates. Setting and participants: A random sample of individuals (n 2,153) from the general population living in western New York state, 35 to 79 years of age. Results: In women, abdominal height and waist circumference were negatively associated with FEV1 percent predicted, while all five adiposity markers were negatively associated with FVC percent predicted. In men, all overall and abdominal adiposity markers were inversely associated with FEV1 percent predicted and FVC percent predicted. Conclusion: These results suggest that abdominal adiposity is a better predictor of pulmonary function than weight or BMI, and investigators should consider it when investigating the determinants of pulmonary function. (CHEST 2006; 129:853–862)

The primary aim of this study was to determine the prevalence of positional obstructive sleep apnea using a functional definition. Positional sleep apnea was defined as a total apnea-hypopnea index (AHI)or = 5 with a50% reduction in the AHI between the supine and nonsupine postures, and an AHI that normalizes (AHI5) in the nonsupine posture. A secondary aim was to determine if positional sleep apnea can be diagnosed accurately during a split-night study.Retrospective chart review.Two sleep centers in Buffalo, NY, one a Veterans Affairs Western New York Healthcare System Sleep Center (VAWNY) and the other a freestanding ambulatory center (Associated Sleep Center [ASC]).Three hundred twenty-six patients from the VAWNY, including 57 patients who underwent a split-night study and 242 patients from the ASC who underwent polysomnography.None.Patient characteristics and sleep study results.Positional sleep apnea was seen in 49 of 99 patients (49.5%) with mild sleep apnea (AHI, 5 to 15/h), 14 of 72 patients (19.4%) with moderate sleep apnea (AHI, 15 to 30/h), and 5 of 77 patients (6.5%) with severe sleep apnea (AHI30/h). Sufficient sleep (15 min) in both postures was not seen in 104 of 269 patients (38.7%) and 80 of 242 overnight studies (33.1%) at the VAWNY and ASC, respectively, and was not seen in 47 of 57 split-night studies (82.5%). The percentage of studies with insufficient sleep in both postures was significantly greater for split-night studies (p0.0001).Positional sleep apnea is common particularly in patients with mild disease. Positional sleep apnea cannot usually be assessed during a split-night study.

Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.

s: To compare the relative usefulness of the different indexes derived from pulse oximetry in the diagnosis of obstructive sleep apnea (OSA), and to determine if a combination of these indexes improves the prediction of the apnea-hypopnea index (AHI) measured by polysomnography.Prediction model developed from 224 patients, validated prospectively in 101 patients from the same center (group 1) and in 191 patients from a different sleep center (group 2).Two independent sleep clinics run by university sleep specialists.Patients who underwent polysomnography for suspicion of OSA.The following indexes were calculated from pulse oximetry recordings performed simultaneously during polysomnography: (1) Delta index, the average of the absolute differences of oxygen saturation between successive 12-s intervals; (2) desaturation events per hour to 2%, 3%, and 4% levels; and (3) cumulative time spent below 90%, 88%, 86%, 84%, 82%, and 80% saturation.The best predictor was the Delta index, although desaturation events provided similar levels of diagnostic accuracy. An aggregation of multivariate models using combination of indexes reduced the prediction error (r(2) = 0.70) significantly (p0.05) compared to using the Delta index alone (r(2) = 0.60). The proportion of subjects from the validation groups within 95% confidence interval (CI) of the derivation group was 90% (95% CI, 83 to 95%) and 91% (95% CI, 86 to 95%) for groups 1 and 2, respectively. The overall likelihood ratios for the aggregated model in all patient groups were 4.2 (95% CI, 3.3 to 15.3), 3.4 (95% CI, 2.7 to 4.3), 3.0 (95% CI, 2.2 to 4.1), and 6.7 (95% CI, 4.9 to 9.2) for normal (AHI5/h), mild (AHI 5 to15/h), moderate (AHI 15 to30/h), and severe (AHIor = 30/h) disease, respectively.The Delta index and oxygen desaturation indexes provided similar levels of diagnostic accuracy. The combination of indexes improved the precision of the predicted AHI and may offer a potentially simpler alternative to polysomnography.

Study objectives Pulmonary function is dependent not only on smoking, but also on nutritional status. Since an increased RBC distribution width (RDW) has been associated with nutritional deficiencies, we postulated that RDW has an inverse relation to pulmonary function. The purpose of this study was to test this hypothesis. Design and setting A cross-sectional study was conducted of a random sample of the general population in western New York. Participants A total of 1,616 subjects of both genders who were aged 35 to 79 years and were free of respiratory disease. Interventions None. Measurements Pulmonary function was assessed from FEV1, FVC, height, body weight, total pack-years of smoking, smoking status, hemoglobin concentration, and hematologic indexes, eosinophil count, education, and blood levels of retinol, β-cryptoxanthin, and vitamin E. Results We found a direct relation between RDW and the number of pack-years of smoking and smoking status, and an inverse relation between FEV1 and FVC with RDW, even when potentially confounding variables such as smoking were taken into account. When the variability of FEV1 due to smoking was used for comparison, an additional 27% of that variability in FEV1 was explained by variations in antioxidant vitamin levels, and another 24% by RDW. Conclusions The results confirmed our hypothesis that there is an inverse relation between RDW and pulmonary function, and raise the possibility that RDW may be a biomarker for as-yet unidentified nutrients that affect pulmonary function.

The purpose of this work was to study the impact of a patient-self-completed history questionnaire upon the quality of the information in the medical record, resource utilization, patient satisfaction, and physician satisfaction. A controlled trial was performed in a primary care clinic of a public supported, urban, university hospital. The patients were mainly poor, minority, urban individuals visiting the clinic for their first primary care visit. The providers were attending physicians, nurse practitioners, and medical residents associated with the Department of Medicine teaching program. A self-administered history questionnaire was given to approximately half the new patients in a randomized, prospective manner. The physicians completed an assessment form on all new patients estimating the time spent, complexity of the case, and listing studies requested. If a history questionnaire was completed by the patient, the physician completed an assessment irrespective of whether it helped or hindered the evaluation of the patient. After the visit, nurses called the patient by telephone and asked questions concerning the patient's satisfaction. The patients' records were reviewed for the initial history papers. There were 127 patients receiving the history questionnaire and 114 controls. The presence of the history questionnaire in the medical record added to both the quantity and the quality of the information present. Of the provider responses, 87% (95% confidence interval: 78-93%) wanted all new patients to complete the questionnaire. Of the patients who received the questionnaire, all who were asked felt that all their issues were addressed, compared with only 83% in the control group (P = .015). No increases in physician time or in utilization of medical resources were found. The implementation of a self-administered history questionnaire in an urban primary care clinic resulted in improved chart quality and improved satisfaction of physicians and patients.

Background: Less than one third of patients with fatal pulmonary embolism (PE) are identified prior to autopsy. Objective: To determine whether the clinical syndromes of acute PE are effective at identifying patients who die of this condition. Method: Seven hundred seventy-eight autopsy reports at the Buffalo General Hospital from 1991 to 1996 inclusive were reviewed. Inpatient medical records of 67 patients who were identified as having PE as the primary or major cause of death then were analyzed. Results: Thirty patients (45% [95% confidence interval, 33 to 57%]) had received a diagnosis of PE prior to death, which was marginally higher than the number previously reported (p < 0.05). The diagnosis of PE was significantly lower (13%; p < 0.01) in patients with COPD or coronary artery disease (33%; p < 0.01). In contrast to the prospective investigation of PE diagnosis data, only a minority of patients (6%) presented with pleuritic pain or hemoptysis, while a significantly larger proportion (24%; p < 0.01) of our patients experienced circulatory collapse. Only 55% were identified as having PE from the following clinical syndromes of PE: isolated dyspnea; pleuritic pain and/or hemoptysis; and circulatory collapse. Among the 30 patients suspected of having PE, only 14 (47%) received IV heparin in therapeutic doses, despite clinical suspicion. Conclusion: Our results show a modest increase in the correct antemortem diagnosis of fatal PE. The current clinical syndromes used as markers for suspecting PE are not sufficient to detect patients who ultimately die of PE. Physicians should maintain a higher index of suspicion since fatal PE does not always present as one of the three clinical syndromes of PE. Once PE is suspected, heparin therapy should be started early. (CHEST 2001; 120:791–795)

Reduced pulmonary function and indicators of airway obstruction have been shown to be strong predictors of mortality in numerous epidemiologic studies (1—3). Interestingly, even mild reductions in pulmonary function in nonsmokers have been linked to increased mortality (4). Although smoking is the major risk factor for chronic obstructive pulmonary disease (COPD), several issues remain to be resolved (5). For example, why do only 10-20 percent of smokers develop COPD (6)? The balance between the negative effects resulting from exposure to oxidants, for example, from cigarette smoke and air pollutants, and the defense by antioxidants has been suggested to play a role in both the pathogenesis of airway obstruction and the link between reduced pulmonary function and mortality (7-12). In particular, the role of antioxidant vitamins in protection against lung disease has attracted considerable clinical and epidemiologic interest because diseases associated with airway obstruction, such as COPD and asthma, present immense public health problems (13-15). This subject, however, has not been reviewed systematically. The present article is a qualitative systematic review of the epidemiologic and other evidence that deals with the association of antioxidant vitamins with pulmonary function and airway obstruction (16-18).

Objective: To evaluate the predictive accuracy of the severity of illness scoring systems in a single institution. Design: A prospective study conducted by collecting data on consecutive patients admitted to the medical intensive care unit over 20 months. Surgical and coronary care admissions were excluded. Setting: Veterans Affairs Medical Center at Buffalo, New York. Patients and participants: Data collected on 302 unique, consecutive patients admitted to the medical intensive care unit. Interventions: None. Measurements and results: Data required to calculate the patients' predicted mortality by the Mortality Probability Model (MPM) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems were collected. The probability of mortality for the cohort of patients was analyzed using confidence interval analyses, receiver operator characteristic (ROC) curves, two by two contingency tables and the Lemeshow–Hosmer chi-square statistic. Predicted mortality for all three scoring systems lay within the 95 % confidence interval for actual mortality. For the MPM II, SAPS II and APACHE II, the c-index (equivalent to the area under the ROC curve) was 0.695 ± 0.0307 SE, 0.702 ± 0.063 SE and 0.672 ± 0.0306 SE, respectively, which were not statistically different from each other but were lower than values obtained in previous studies. Conclusion: Although the overall mortality was consistent with the predicted mortality, the poor fit of the data to the model impairs the validity of the result. The observed outcoume could be due to erratic quality of care, or differences between the study population and the patient population in the original studies. The data cannot be used to distinguish between these possibilities. To increase predictive accuracy when studying individual intensive care units and enhance quality of care assessments it may be necessary to adapt the model to the patient population.

The recent outbreaks of multidrug-resistant strains of M. tuberculosis in health care facilities has increased concern over its transmission in health care facilities. Isolation has been recommended for all patients suspected to have tuberculosis even though the feasibility and the cost of this recommendation can be substantial. We have developed a classification tree using clinical and radiographic data from 277 isolation episodes in patients admitted between August 1992 and March 1994 who required isolation for suspicion of tuberculosis. The classification tree was developed with a sensitivity and negative predictive value of 100% by binary recursive partitioning to predict those patients who are unlikely to require isolation. The predictor variables were upper zone disease on chest radiograph, a history of fever, weight loss, and CD4 count. The tree was validated in a separate cohort of 286 isolation episodes between April 1994 and December 1995. In this validation cohort, no erroneous prediction was made of not isolating a patient with active pulmonary tuberculosis. The classification tree had a sensitivity of 100% (95% confidence interval [CI]: 92.5 to 100%), a specificity of 48.1% (95% CI: 43.8 to 52.4%), and a negative predictive value of 100% (95% CI: 98.5 to 100%). We estimate that the use of the tree could have reduced the number of patients requiring isolation by more than 40% without increasing the risk of cross infection.

Study objective To evaluate the predictive ability of three scoring systems, acute physiology and chronic health evaluation (APACHE II), simplified acute physiology score (SAPS II), and mortality probability models (MPM II) in critically ill obstetric patients compared to a control group of nonobstetric female patients of similar age group (range, 17 to 41 years). Design A retrospective medical chart review of obstetric and nonobstetric female patients between 17 and 41 years of age. Setting Two university hospitals. Patients Ninety-three obstetric patients and 96 nonobstetric female patients were identified from 12, 740 consecutive ICU admissions. Results The actual mortality of the obstetric and the nonobstetric group was 10.8% (95% confidence interval [CI], 5.3 to 19.0%) and 12.5% (95% CI, 6.6 to 21.0%), respectively. The observed mortality was not statistically different from the mortality predicted by APACHE II, SAPS II, and MPM II (14.7%, 7.8%, and 9.1% for the obstetric group and 10.9%, 9.0%, and 9.9% for the nonobstetric group). Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic (ROC) curve. There were no significant differences in the c-index for APACHE II, SAPS II, and MPM II within or between the obstetric group ([mean±SE], 0.93±0.02, 0.90±0.04, and 0.91±0.04, respectively) and the nonobstetric group (0.97±0.02, 0.95±0.03, and 0.96±0.02, respectively). Conclusions We conclude that APACHE II, SAPS II, and MPM II assess the ICU outcome of critically ill obstetric patients as accurately as nonobstetric critically ill female patients of similar age group.

Importance Patients requiring prolonged mechanical ventilation (>21 days) are commonly weaned at long-term acute care hospitals (LTACHs). The most effective method of weaning such patients has not been investigated. Objective To compare weaning duration with pressure support vs unassisted breathing through a tracheostomy collar in patients transferred to an LTACH for weaning from prolonged ventilation. Design, Setting, and Participants Between 2000 and 2010, a randomized study was conducted in tracheotomized patients transferred to a single LTACH for weaning from prolonged ventilation. Of 500 patients who underwent a 5-day screening procedure, 316 did not tolerate the procedure and were randomly assigned to receive weaning with pressure support (n = 155) or a tracheostomy collar (n = 161). Survival at 6- and 12-month time points was also determined. Main Outcome Measure Primary outcome was weaning duration. Secondary outcome was survival at 6 and 12 months after enrollment. Results Of 316 patients, 4 were withdrawn and not included in analysis. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned; 22 (14.5%) died. Of 160 patients in the tracheostomy collar group, 85 (53.1%) were weaned; 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; interquartile range [IQR], 8-25) than with pressure support (19 days; IQR, 12-31), P = .004. The hazard ratio (HR) for successful weaning rate was higher with tracheostomy collar use than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = .033) after adjusting for baseline clinical covariates. Use of the tracheostomy collar achieved faster weaning than did pressure support among patients who did not tolerate the screening procedure between 12 and 120 hours (HR, 3.33; 95% CI, 1.44-7.70; P = .005), whereas weaning time was equivalent with the 2 methods in patients who did not tolerate the screening procedure within 0 to 12 hours. Mortality was equivalent in the pressure-support and tracheostomy collar groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI, −6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI, −4.2% to 17.1%). Conclusion and Relevance Among patients requiring prolonged mechanical ventilation and treated at a single long-term care facility, unassisted breathing through a tracheostomy, compared with pressure support, resulted in shorter median weaning time, although weaning mode had no effect on survival at 6 and 12 months. Trial Registration clinicaltrials.gov Identifier: NCT01541462

The purpose of the study was to determine if the adverse effect of body position on obstructive sleep apnea (OSA) is worsened during rapid eye movement (REM) sleep and if patients with OSA decrease the time spent supine during REM sleep.Overnight polysomnography from 80 sequential patients referred to Buffalo VA Sleep Lab for suspected OSA were analyzed with 20 patients in each of the following groups: normal with apnea-hypopnea indices (AHI)5/h, mild (AHI, 5-15/h), moderate (AHI, 15-30/h), and severe (AHI,30/h). We used extended Cox models with the Anderson-Gill modification for multiple events with two time varying covariates: sleep stage and body position. Generalized estimating equations with logit link were used to take into account correlated data within each patient for the relation between sleep stage and body position.The hazard ratios for events in REM vs non-REM sleep was significant for the normal, mild, and moderate groups only: 1.71 (95% CI 1.4-2.08), 1.45 (95% CI 1.22-1.73), 1.28 (95% CI 1.1-1.5), respectively. The hazard ratio for events in the supine vs non-supine position was significant for the mild and moderate groups only: 1.25 (95% CI 1.02-1.52) and 1.24 (95% CI 1.04-1.47), respectively. The addition of an interaction effect between sleep stage and body position was not statistically significant for any group. The odds ratios of sleeping in supine position for REM vs non-REM sleep were 0.47 (95% CI 0.27-0.82) for moderate OSA group and 0.54 (95% CI 0.3-0.95) for severe OSA.In summary, we found significant effects of both sleep stage and body position in mild and moderate but not severe OSA. Patients with moderate and severe OSA were less likely to spend time in the supine position during REM compared with non-rapid eye movement sleep.

Autotitrating continuous positive airway pressure (auto-CPAP) devices now have a smart card (a pocket-sized card with embedded integrated circuits which records data from the CPAP machine such as CPAP usage, CPAP pressure, large leak, etc.) which can estimate the Apnea–Hypopnea Index (AHI) on therapy. The aim of this study was to determine the accuracy of auto-CPAP in estimating the residual AHI in patients with obstructive sleep apnea (OSA) who were treated with auto-CPAP without a CPAP titration study. We studied 99 patients with OSA from April 2005 to May 2007 who underwent a repeat sleep study using auto-CPAP. The estimated AHI from auto-CPAP was compared with the AHI from an overnight polysomnogram (PSG) on auto-CPAP using Bland–Altman plot and likelihood ratio analyses. A PSG AHI cutoff of five events per hour was used to differentiate patients optimally treated with auto-CPAP from those with residual OSA on therapy. Bland and Altman analysis showed good agreement between auto-CPAP AHI and PSG AHI. There was no significant bias when smart card estimates of AHI at home were compared to smart card estimates obtained in the sleep laboratory. An auto-CPAP cutoff for the AHI of six events per hour was shown to be optimal for differentiating patients with and without residual OSA with a sensitivity of 0.92 (95% confidence interval (CI) 0.76 to 0.98) and specificity of 0.90 (95% CI 0.82 to 0.95) with a positive likelihood ratio (LR) of 9.6 (95% CI 5.1 to 21.5) and a negative likelihood ratio of 0.085 (95% CI 0.02 to 0.25). Auto-CPAP AHI of eight events per hour yielded the optimal sensitivity (0.94, 95% CI 0.73 to 0.99) and specificity (0.90, 95% CI 0.82 to 0.95) with a positive LR of 9.6 (95% CI 5.23 to 20.31) and a negative LR of 0.065 (95% CI 0.004 to 0.279) to identify patients with a PSG AHI of ≥ 10 events per hour. Auto-CPAP estimate of AHI may be used to estimate residual AHI in patients with OSA of varying severity treated with auto-CPAP.

Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (±18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating >1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P < 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue. (Cancer Epidemiol Biomarkers Prev 2008;17(1):33–42)

Increased bacterial concentration (load) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease (COPD) exacerbations. Bacterial concentrations are higher during exacerbation than during stable disease; however, these studies are cross sectional and devoid of strain typing.To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition.In a prospective, longitudinal cohort of patients with COPD, the relationship between exacerbation occurrence, sputum bacterial concentrations, and new strain acquisition was examined.Clinical information, quantitative sputum cultures, and molecular typing of potential bacterial pathogen isolates. Over 81 months, 104 subjects completed 3,009 clinic visits, 560 (19.6%) during exacerbations and 2,449 (80.4%) during stable disease. Among preexisting strains, sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease. Moraxella catarrhalis (stable, 10(8.38 +/- 0.13) [mean +/- SEM] vs. exacerbation, 10(7.78 +/- 0.26); p = 0.02) and Streptococcus pneumoniae (stable, 10(8.42 +/- 0.21) vs. exacerbation, 10(7.76 +/- 0.52); p = 0.07) concentrations were lower during exacerbations compared with stable periods. Concentrations of new strains of H. influenzae (stable, 10(7.28 +/- 0.15) vs. exacerbation, 10(7.76 +/- 0.17); p = 0.04) and M. catarrhalis (stable, 10(7.85 +/- 0.15) vs. exacerbation, 10(8.37 +/- 0.14); p = 0.02), were increased during exacerbations; however, the differences were small.Change in bacterial load is unlikely to be an important mechanism for exacerbations. Better understanding of the host-pathogen interaction, rather than enumerating bacteria in respiratory samples, is required to provide new insights into bacterial infection in COPD.

Study objective: To determine if obesity-related changes in lung volume might contribute to airway reactivity, we investigated the effects of simulated mild obesity-related lung volume reductions on airway responsiveness in lean, nonasthmatic subjects. Participants and methods: We simulated the lung volume reductions of class 1 obesity in eight lean, nonasthmatic subjects by externally mass loading the chest wall and abdomen, and shifting blood volume into the lung with lower limb compression (LLC). Airway responsiveness was assessed by measuring FEV1 before and after methacholine challenge tests (1, 2.5, 5, 10, and 25 mg/mL) with the following: (1) no intervention (control); (2) external chest loading (CL); (3) LLC; and (4) CL and LLC (COMB) on separate days. Lung function was measured before and after CL, LLC, and COMB were applied. Results: The application of CL, LLC, and COMB decreased expiratory reserve volume, functional residual capacity, and total lung capacity compared with baseline. FVC and FEV1 decreased significantly with CL and COMB, while FEV1/FVC did not change compared to baseline. The maximal response to the methacholine challenge increased with CL, LLC, and COMB, with a mean maximal fall of FEV1 of 9%, 11%, and 18%, respectively, compared to a 6% fall with control. Conclusions: We conclude that decreases in lung volume increase airway responsiveness and may account for the increased propensity for increased airway responsiveness in the obese. (CHEST 2006; 130:834–840)

Background Several studies investigated the association of anemia with health related quality of life (HRQL) in patients with chronic disease. However, there is little evidence regarding the association of anemia with HRQL in patients with chronic obstructive pulmonary disease (COPD). Methods This is a post-hoc analysis of a study which enrolled a population of adults aged 35–79 randomly selected from residents of Erie and Niagara Counties, NY, between 1996 and 2000. In addition to demographic information and physical measurements, we obtained spirometry data and hemoglobin levels. We used modified Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria to define COPD, and World Health Organization (WHO) criteria to define anemia. To assess HRQL we used the Short Form-36 (SF-36) to assess physical functioning (PF), physical component summary (PCS) measures and mental component summary (MCS) measures. Results In the entire study population (n = 2704), respondents with anemia had lower scores on the physical functioning domain [45.4 (SD10.9) vs. 49.2 (SD 9.1); p < 0.0001]. Among patients with COPD (n = 495) the PF scores (39.9 vs. 45.4) and the PCS (41.9 vs. 45.9) were significantly lower in individuals with anemia compared to those without. In multiple regression analysis, the association between hemoglobin and PCS was positive (regression coefficient 0.02, p = 0.003). There was no significant association of hemoglobin with PF scores or the mental component summary measure after adjusting for covariates in patients with COPD. Conclusion In patients with moderate to very severe COPD anemia may be associated with worse HRQL. However, co-morbidities may explain part or all of this association in these patients.

The objective of this study was to investigate the association between antioxidant nutrients and markers of oxidative stress with pulmonary function in persons with chronic airflow limitation.Cross-sectional study exploring the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%).The study data included 218 persons with chronic airflow limitation recruited randomly from the general population of Erie and Niagara counties, New York State, USA.After adjustment for covariates, multiple linear regression analysis showed that serum beta-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, vitamin C, and lycopene were positively associated with FEV1% (P0.05, all associations). Serum vitamins beta-cryptoxanthin, lutein/zeaxanthin, and lycopene, and dietary beta-cryptoxanthin, beta-carotene, vitamin C, and lutein/zeaxanthin were positively associated with FVC% (P0.05, all associations). Erythrocytic glutathione was negatively associated with FEV1%, while plasma thiobarbituric acid-reactive substances (TBARS) were negatively associated with FVC% (P0.05).These results support the hypothesis that an imbalance in antioxidant/oxidant status is associated with chronic airflow limitation, and that dietary habits and/or oxidative stress play contributing roles.

Studies have shown increased oxidative stress in patients with chronic airflow limitation; however, the population-based evidence for the association of oxidative stress with pulmonary function is limited. The authors analyzed the association of plasma thiobarbituric acid-reactive substances (TBARS), glutathione, glutathione peroxidase, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox)-equivalent antioxidant capacity with forced expiratory volume in 1 second and forced vital capacity using data collected from 1996 to 2000 in a general population sample from western New York State (n = 2,346). After adjustment for covariates including smoking status, lifetime pack-years of smoking, education, weight, and eosinophils, multivariate analysis showed an inverse association of TBARS with forced expiratory volume in 1 second and forced vital capacity as the percentage of the predicted value (FEV1% and FVC%, respectively), positive associations of glutathione peroxidase with FEV1% and FVC%, and an inverse association of glutathione with FEV1% in men (p < 0.05). The associations of TBARS and glutathione peroxidase with FVC% in men remained statistically significant after adjustment for serum carotenoid levels. There were no statistically significant associations of oxidative stress with pulmonary function in women. These results suggest that oxidative stress may be associated with airflow limitation in men, and that gender differences may exist in the relation of oxidative stress to pulmonary function.

Rationale: Moraxella catarrhalis is frequently present in the sputum of adults with chronic obstructive pulmonary disease (COPD). Little is known about the role of M. catarrhalis in this common disease. Objective: To elucidate the burden of disease, the dynamics of carriage, and immune responses to M. catarrhalis in COPD. Methods: Prospective cohort study of 104 adults with COPD in an outpatient clinic at the Buffalo Veterans Affairs Medical Center. Measurements: Clinical information, sputum cultures, molecular typing of isolates, and immunoassays to measure antibodies to M. catarrhalis. Main Results: Over 81 months, 104 patients made 3,009 clinic visits, 560 during exacerbations. Molecular typing identified 120 episodes of acquisition and clearance of M. catarrhalis in 50 patients; 57 (47.5%) of the acquisitions were associated with clinical exacerbations. No instances of simultaneous acquisition of a new strain of another pathogen were observed. The duration of carriage of M. catarrhalis was shorter with exacerbations compared with asymptomatic colonization (median, 31.0 vs. 40.4 days; p = 0.01). Reacquisition of the same strain was rare. The intensity of the serum IgG response was greater after exacerbations than asymptomatic colonization (p = 0.009). Asymptomatic colonization was associated with a greater frequency of a sputum IgA response than exacerbation (p = 0.009). Conclusions: M. catarrhalis likely causes approximately 10% of exacerbations of COPD, accounting for approximately 2 to 4 million episodes annually. The organism is cleared efficiently after a short duration of carriage. Patients develop strain-specific protection after clearance of M. catarrhalis from the respiratory tract.

The original chronic respiratory questionnaire (CRQ), one of the most widely used measures of health-related quality of life (HRQL) in chronic respiratory disease (CRD), is traditionally interviewer administered (IA) and includes an individualised dyspnoea domain. The present authors studied the impact of self-administered (SA) and standardised dyspnoea questions on CRQ measurement properties. In a factorial design multicentre trial, 177 patients with CRD (mean age 67.7 yrs; mean forced expiratory volume in one second per cent predicted 44.6%) were randomised to CRQ-IA (n = 86) or CRQ-SA (n = 91), and to initially complete the standardised or individualised items before and after respiratory rehabilitation. While maintaining validity, the CRQ-SA proved more responsive to changes in HRQL than the CRQ-IA in all domains. Compared with the standardised dyspnoea domain, the individualised dyspnoea domain indicated greater responsiveness. The correlations of baseline scores and change scores with other HRQL instruments indicated good validity of the CRQ-SA. In conclusion, self-administration and standardisation of the chronic respiratory questionnaire maintains validity and responsiveness relative to the interviewer-administered chronic respiratory questionnaire. These results challenge the assumption that interviewer-administered questionnaires are superior to self-administered questionnaires in older patients with chronic respiratory disease.

Breastfeeding reduces the risk of asthma and respiratory infections in infants. Since respiratory infections are associated with reduced pulmonary function in adolescents, pulmonary function impairment may be carried into adulthood. Our aim was to determine whether a history of having been breastfed as an infant is a determinant of adult pulmonary function.We analyzed data from a general population sample of residents of Erie and Niagara Counties between September 1995 and December 1999. We calculated forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC) prediction equations and used multiple linear regression models to study the association between having been breastfed as an infant and percentage predicted FEV(1) (FEV(1)%) and percentage predicted FVC (FVC%) after adjustment for covariates.Of 2305 subjects, 62% reported having been breastfed. After controlling for age, gender, weight, smoking status, pack-years of smoking, eosinophil counts and dietary factors, there was no association between having been breastfed (yes/no) and FEV(1)% or FVC% (regression coefficients 0.0049, p = 0.46 and 0.0055, p = 0.43, respectively).We did not find a strong or consistent association between having been breastfed as an infant and pulmonary function in adulthood.

Individuals with cystic fibrosis (CF) have large amounts of infected mucus in their lungs, which causes irreversible lung tissue damage. Although patient-administered positive expiratory pressure (PEP) breathing has been promoted as an effective therapeutic modality for removing mucus and improving ventilation distribution in these patients, the effects of PEP on ventilation distribution and gas mixing have not been documented. Therefore, this preliminary investigation described responses in distribution of ventilation and gas mixing to PEP breathing for patients with moderate to severe CF lung disease.The effects of PEP breathing on ventilation distribution, gas mixing, lung volumes, expiratory airflow, percentage of arterial blood oxyhemoglobin saturation (SpO(2)), and sputum volume were studied in 5 patients with CF (mean age=18 years, SD=4, range=13-22) after no-PEP, low-PEP (10-20 cm H(2)O), and high-PEP (20 cm H(2)O) breathing conditions. Single-breath inert gas studies and lung function tests were performed before, immediately after, and 45 minutes after intervention. Single-breath tests assess ventilation distribution homogeneity and gas mixing by observing the extent to which an inspired test gas mixes with gas already residing in the lung.Improvements in gas mixing were observed in all PEP conditions. By 45 minutes after intervention, the no-PEP group improved by 5%, the low-PEP group improved by 15%, and the high-PEP group improved by 23%. Slow vital capacity increased by 1% for no PEP, by 9% for low PEP, and by 13% for high PEP 45 minutes after intervention. Residual volume decreased by 13% after no PEP, by 20% after low PEP, and by 30% after high PEP. Immediate improvements in forced expiratory flow during the middle half of the forced vital capacity maneuver (FEF(25%-75%)) were sustained following high PEP but not following low PEP.This study demonstrated the physiologic basis for the efficacy of PEP therapy. The results confirm that low PEP and high PEP improve gas mixing in individuals with CF, and these improvements were associated with increased lung function, sputum expectoration, and SpO(2). The authors propose that improvements in gas mixing may lead to increases in oxygenation and thus functional exercise capacity.

Objective: Quality control in the clinical pulmonary function laboratory has been well developed for spirometry and diffusing capacity but not for the measurement of TLC. The purpose of the present study was to test two approaches to this problem. First, we compared TLC by body plethysmography (TLCb) with a value predicted from TLC measured by multibreath helium dilution (TLCm). Concordance between the measured and predicted values would imply the validity of the measurements. Second, we measured the test–retest variability of TLCb, TLCm and TLC measured by single breath helium dilution (TLCs) to assess the consistency of the measurements. Methodology: We performed a prospective study of 815 veterans. Results: The prediction of TLCb from TLCm improved (r2 increased from 0.44 to 0.64) when FEV1/FVC and the difference between TLCm and TLCs were added to the model. The coefficient of variation for test–retest of TLCs, TLCm and TLCb were 8.9, 7.1 and 5.4%, respectively. Of all tests, 5.9% were inconsistent based on pathophysiology or measurement error and attributed mostly to TLCm. Conclusions: Prediction of TLCb from TLCm was not sufficiently accurate as to be useful for quality control. Comparison of TLCs, TLCm and TLCb may be useful for determining the internal data validity.

The aim of this study was to design a diagnostic model to identify patients with Cheyne-Stokes respiration (CSR-CSA) based on indices of oximetric spectral analysis. A retrospective analysis of oximetric recordings of 213 sleep studies conducted over a one-year period at a Veterans Affairs medical facility was performed. A probabilistic neural network (PNN) was developed from salient features of the oximetric spectral analysis, desaturation events and the delta index. A fivefold cross-validation was used to assess the accuracy of the neural network in identifying CSR-CSA. When compared to overnight polysomnography, the PNN achieved a sensitivity of 100% (95% confidence interval [CI] 85%-100%) and a specificity of 99% (95% 97%-100%) with a corresponding area under the curve of 99% (95% CI 99%-100%). When combined with overnight pulse oximetry, PNN offers an accurate and easily applicable tool to detect CSR-CSA.

ContextPrivate for-profit and private not-for-profit dialysis facilities provide the majority of hemodialysis care in the United States. There has been extensive debate about whether the profit status of these facilities influences patient mortality.ObjectiveTo determine whether a difference in adjusted mortality rates exists between hemodialysis patients receiving care in private for-profit vs private not-for-profit dialysis centers.Data SourcesWe searched 11 bibliographic databases, reviewed our own files, and contacted experts in June 2001–January 2002. In June 2002, we also searched PubMed using the "related articles" feature, SciSearch, and the reference lists of all studies that fulfilled our eligibility criteria.Study SelectionWe included published and unpublished observational studies that directly compared the mortality rates of hemodialysis patients in private for-profit and private not-for-profit dialysis centers and provided adjusted mortality rates. We masked the study results prior to determining study eligibility, and teams of 2 reviewers independently evaluated the eligibility of all studies. Eight observational studies that included more than 500 000 patient-years of data fulfilled our eligibility criteria.Data ExtractionTeams of 2 reviewers independently abstracted data on study characteristics, sampling method, data sources, and factors controlled for in the analyses. Reviewers resolved disagreements by consensus.Data SynthesisThe studies reported data from January 1, 1973, through December 31, 1997, and included a median of 1342 facilities per study. Six of the 8 studies showed a statistically significant increase in adjusted mortality in for-profit facilities, 1 showed a nonsignificant trend toward increased mortality in for-profit facilities, and 1 showed a nonsignificant trend toward decreased mortality in for-profit facilities. The pooled estimate, using a random-effects model, demonstrated that private for-profit dialysis centers were associated with an increased risk of death (relative risk, 1.08; 95% confidence interval, 1.04-1.13; P

There is some evidence that glucose and other factors related to glucose metabolism, such as insulin and insulin-like growth-factors (IGFs) may contribute to breast cancer development. The present study analyzed the hypothesis that serum glucose, insulin levels, and IGF-I pattern are associated with breast cancer using a nested case-control study. Between 1987 and 1992, 10,786 women ages 35-69 were recruited in a prospective study in Italy. Women with history of cancer and on hormone therapy were excluded at baseline. At recruitment, blood samples were collected after a 12-h fast between 7:30 and 9:00 a.m. from all of the study participants. After 5.5 years, 144 breast cancer cases were identified among the participants of the cohort. Four matched controls were chosen for each breast cancer case from members of the cohort who did not develop breast cancer during the follow-up period. In premenopausal women, glucose was associated with breast cancer risk: the age, body mass index, and reproductive variable adjusted relative risk (RR) for the highest quartile of serum glucose versus the lowest was 2.8 [95% confidence interval (CI), 1.2-6.5], and P for trend was 0.02. Insulin showed a weaker association with breast cancer, the adjusted RR of the highest quartile versus the lowest was 1.7 (95% CI, 0.7-4.1), and P for trend was 0.14, whereas the adjusted RR of the highest quartile of IGF-I was 3.1 (95% CI, 1.1-8.6), and P for trend was 0.01. Increased levels of insulin-like growth factor binding protein-3 (IGFBP)-3 were related to breast cancer risk: the adjusted RR for the highest quartile was 2.1 (95% CI, 0.95-4.75), and P for trend was 0.02. In postmenopausal women, the associations of glucose, insulin, and IGF-1 pattern were associated with breast cancer risk in heavier subjects characterized by a body mass index higher than 26. These results indicate that chronic alteration of glucose metabolism is related to breast cancer development.

The role of bacterial pathogens in acute exacerbations of chronic obstructive pulmonary disease is controversial. In older studies, the rates of isolation of bacterial pathogens from sputum were the same during acute exacerbations and during stable disease. However, these studies did not differentiate among strains within a bacterial species and therefore could not detect changes in strains over time. We hypothesized that the acquisition of a new strain of a pathogenic bacterial species is associated with exacerbation of chronic obstructive pulmonary disease.We conducted a prospective study in which clinical information and sputum samples for culture were collected monthly and during exacerbations from 81 outpatients with chronic obstructive pulmonary disease. Molecular typing of sputum isolates of nonencapsulated Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa was performed.Over a period of 56 months, the 81 patients made a total of 1975 clinic visits, 374 of which were made during exacerbations (mean, 2.1 per patient per year). On the basis of molecular typing, an exacerbation was diagnosed at 33.0 percent of the clinic visits that involved isolation of a new strain of a bacterial pathogen, as compared with 15.4 percent of visits at which no new strain was isolated (P0.001; relative risk of an exacerbation, 2.15; 95 percent confidence interval, 1.83 to 2.53). Isolation of a new strain of H. influenzae, M. catarrhalis, or S. pneumoniae was associated with a significantly increased risk of an exacerbation.The association between an exacerbation and the isolation of a new strain of a bacterial pathogen supports the causative role of bacteria in exacerbations of chronic obstructive pulmonary disease.

Elevated plasma endothelin-1 (ET-1) levels have been reported in association with hypoxia and congestive heart failure (CHF). Furthermore, Cheyne-Stokes respiration-central sleep apnea (CSR-CSA) has been found to correlate with the degree of pulmonary hypertension and the severity of CHF; however, the association between ET-1 levels and CSR-CSA has not been investigated previously.Veterans Affairs Medical Center.We studied 46 consecutive patients with CHF (left ventricular functionor = 40%) who underwent right-heart catheterization and overnight polysomnography. Thirty-nine patients completed the study. Sixteen patients (41%) had CSR-CSA, 5 patients (13%) had obstructive apnea, and 18 patients (46%) had no sleep-disordered breathing. Circulating plasma ET-1 levels were assayed in patients with CSR-CSA and in patients with no sleep-disordered breathing using commercially available enzyme-linked immunosorbent assay kits.ET-1 levels were significantly elevated in patients with CSR-CSA (mean +/- SD, 5.4 +/- 1.3 pg/mL) compared to those without central apnea (3.9 +/- 1.1 pg/mL; p0.01), and correlated with mean pulmonary artery pressure (r = 0.66, p0.01), pulmonary capillary wedge pressure (r = 0.56, p0.03), and central apnea frequency (r = 0.66, p0.01). In multivariate analysis, the severity of CSR-CSA was the only variable independently associated with plasma ET-1.We conclude that elevated plasma ET-1 levels are linked to the severity of CSR-CSA. Whether ET-1 represents an important pathogenic factor in CSR-CSA or marker of its occurrence requires further evaluation.

Study objectives: It has been suggested that obstructive sleep apnea (OSA)-induced hypoxic stress might contribute to cardiovascular disorders by promoting expression of soluble adhesion molecules. The reported increase of circulating adhesion molecules in patients with OSA remains controversial because confounders such as cardiovascular risk factors and left ventricular function have not been adequately controlled for. We hypothesized that soluble intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, L-selectin, and Eselectin levels are correlated with OSA independent of coexisting coronary artery disease (CAD). Settings: University-affiliated teaching hospitals. Design and participants: A prospective study of 61 consecutive subjects with angiographically proven CAD deemed to have stable angina. Interventions: Fifteen patients (mean SD) 61.2 1.9 years old with moderate-to-severe OSA (apnea-hypopnea index [AHI] > 20/h) were matched to a control group (AHI < 5/h) for age, gender, body mass index, and severity of CAD. Venous blood samples were collected the morning of the sleep study and assayed for human ICAM-1, VCAM-1, L-selectin, and E-selectin with commercially available enzyme-linked immunosorbent assay kits. Results: All but L-selectin were significantly increased in the OSA group compared to the control subjects (ICAM-1, 367.4 85.2 ng/mL vs 252.8 68.4 ng/mL, p 0.008; VCAM-1, 961.5 281.7 ng/mL vs 639.1 294.4 ng/mL, p 0.004; E-selectin, 81.0 30.4 ng/mL vs 58.1 23.2 ng/mL, p 0.03, respectively). The increased levels of adhesion molecules correlated with the AHI and the oxygen desaturation index but not with the severity of hypoxemia or the frequency of arousals. Conclusions: These findings suggest that OSA modulates the expression of proinflammatory mediators. Further studies should evaluate the influence of adhesion molecules on cardiovascular outcome in CAD patients with OSA. (CHEST 2002; 121:1541–1547)