High Carbon Monoxide Levels from Charcoal Combustion Mask Acute Endothelial Dysfunction Induced by Hookah (Waterpipe) Smoking in Young Adults.

BACKGROUND: Hookah smoking is marketed to youth as a harmless alternative to cigarettes. Although cigarette smoking acutely impairs endothelial function, the effect of smoking fruit-flavored hookah tobacco is unknown. Because charcoal traditionally is used to heat the hookah tobacco in the waterpipe, hookah smoke delivers tobacco toxicants and nicotine plus charcoal combustion products: not only carbon-rich nanoparticles, oxidants that may destroy nitric oxide and impair endothelial function, but also large amounts of carbon monoxide (CO), a putative vasodilator molecule. METHODS: To test the acute effect of hookah smoking on endothelial function, in young adult hookah smokers (n=30, age 26±1 years, mean±SE), we measured plasma nicotine, exhaled CO, and brachial artery flow-mediated dilation (FMD) before and after charcoal-heated hookah smoking. To remove the effect of charcoal combustion, the same measurements were performed when the same flavored hookah tobacco product was heated electrically (n=20). As a positive internal control, we studied age-matched cigarette smokers (n=15) who smoked 1 cigarette. To isolate the effect of the CO boost on FMD, hookah smokers (n=8) inhaled a 0.1% CO gas mixture to approximate their CO boost achieved with charcoal-heated hookah smoking. RESULTS: Nicotine levels increased similarly with all types of smoking, whereas exhaled CO increased 9- to 10-fold more after charcoal-heated hookah than after either electrically heated hookah or cigarette smoking. FMD did not decrease after smoking charcoal-heated hookah but instead increased by +43±7% ( P<0.001). In contrast, FMD decreased by -27±4% ( P<0.001) after smoking electrically heated hookah, comparable to the decrease after cigarette smoking. FMD increased markedly by 138±71% ( P<0.001) after breathing CO gas, 2.8 times more than the increase induced in the same subjects after smoking charcoal-heated hookah ( P<0.001), despite comparable increases in exhaled CO (24±1 versus 28±3 ppm, hookah versus CO). CONCLUSIONS: Smoking hookah tobacco, similar to cigarette tobacco, acutely impairs endothelial function. With traditional charcoal-heated hookah smoking, the acute endothelial dysfunction is masked by high levels of carbon monoxide, a potent vasodilator molecule generated by charcoal combustion. With respect to large-artery endothelial function, smoking hookah is not harmless. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT03616002 and NCT03067701.

Highly sensitive noninvasive early lung cancer detection using DNA methylation topology in sputum-derived epithelial cells.

Objective: Sputum is a source of exfoliated respiratory epithelial cells transformed early in lung carcinogenesis. Malignant cells are hypomethylated and contain less genomic 5-methylcytosine (5mC). Validating a test that recognizes and quantifies aberrantly hypomethylated cells in sputum, we assessed its potential as a screening tool for detecting early-stage non-small cell lung cancer. Methods: Cells extracted from sputum were immunofluorescence labeled with an anti-5-methylcytosine antibody and counterstained with 4',6-diamidino-2-phenylindole (DAPI) delineating global nuclear DNA (gDNA). Via confocal scanning and 3-dimensional image analysis, fluorescence 5mC and DAPI signals were measured in segmented cell nuclei, and a 5mC/DAPI co-distribution map was generated for each imaged cell. Cells were classified as hypomethylated based on 5mC load and 5mC/DAPI co-distribution. The proportion of hypomethylated epithelial cells in the sputum determines whether a patient has lung cancer. Results: A total of 88 subjects were enrolled: 12 healthy subjects; 34 high-risk subjects with benign chronic lung disorders (10 with chronic obstructive pulmonary disease, 24 with idiopathic pulmonary fibrosis), and 43 subjects with non-small cell lung cancer (27 with stage I-II and 16 with stage III-IV). The test identified early-stage non-small cell lung cancer and distinguished it from the high-risk group with 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 41.2% (95% confidence interval, 24.6-59.3) specificity applying only 5mC, 95.8% (95% confidence interval, 78.9-99.9) sensitivity and 26.5% (95% confidence interval, 12.9-44.4) specificity using solely 5mC/DAPI index, and 100% (95% confidence interval, 98.7-100) sensitivity and 26.1% (95% confidence interval, 26.2-27.8) specificity with the combined parameters. Conclusions: We tested and validated a novel, noninvasive, highly sensitive screening test for non-small cell lung cancer. With the use of sputum, our test may impact lung cancer screening, evaluation of pulmonary nodules, and cancer surveillance algorithms.

Dilated and unreactive pupils and burst-suppression on electroencephalography due to buproprion overdose.

Burst-suppression pattern on electroencephalography (EEG) occurs upon dissociation of the cortex from underlying brain structures. Unless the pattern is a physiologic consequence of administered sedatives, this electroencephalographic pattern is indicative of a poor neurologic outcome and high mortality. We report a case of a 29-year-old female thought to be brain dead based on initial physical examination and EEG findings of burst-suppression, who was later found to have supratherapeutic serum levels of bupropion. This is the second documented case of burst-suppression pattern on EEG in a patient who overdosed on bupropion. We propose that burst-suppression in the setting of bupropion toxicity may revert with drug clearance.

'Physician advocates': a novel strategy for improving the value of hospital care by employing hospitalists part time to support non-hospitalist physicians.

BACKGROUND AND OBJECTIVE: At many hospitals, private-practice physicians still admit their own patients and are accustomed to autonomy in clinical practice. This creates challenges for hospital's efforts to improve the efficiency, quality, and value of care. Experienced inpatient-focused physicians - 'Physician Advocates' - could act as liaisons between private practitioners and the fast-paced inpatient microsystem. METHODS: We conducted a controlled pre-post ('differences-in-differences') analysis at an academic medical center where private-practice physicians care for about 40% of medical inpatients and hospitalist groups care for 60%. In the intervention, 'Physician Advocates' participated in daily multidisciplinary 'Progression of Care Rounds,' offering suggestions to increase care quality for private-practice physicians' patients. Controls were cared for by a large, well-established hospitalist group, which convened separate, unchanged multidisciplinary rounds. Outcomes were length of stay (LOS; primary outcome), 30-day readmissions, and inpatient mortality. RESULTS: In a risk-adjusted analysis of 31,632 medical inpatients, LOS declined by 4 hours more from the baseline period to the post-intervention period in the intervention group relative to the control group (ratio: 0.96, 95% CI: 0.93-0.99, p = 0.004). Readmissions declined 22% more in the intervention group (OR: 0.78, 95% CI: 0.63-0.97, p = 0.023). Mortality was unchanged (OR: 1.23, 95% CI: 0.78-1.93 p-value = 0.378). CONCLUSION: Among inpatients cared for by private practitioners, adding Physician Advocates to multidisciplinary rounds was associated with improved LOS and reduced readmissions - measures of efficiency and value. The Physician Advocates approach should be tested in diverse health systems because it allows hospitals to leverage the expertise of on-site clinicians while respecting the traditional private-practice care model, in which primary care physicians manage their hospitalized patients.

Ascorbic Acid Prevents Vascular Endothelial Dysfunction Induced by Electronic Hookah (Waterpipe) Vaping.

Background Electronic hookah (e-hookah) vaping has increased in popularity among youth, who endorse unsubstantiated claims that flavored aerosol is detoxified as it passes through water. However, e-hookahs deliver nicotine by creating an aerosol of fine and ultrafine particles and other oxidants that may reduce the bioavailability of nitric oxide and impair endothelial function secondary to formation of oxygen-derived free radicals. Methods and Results We examined the acute effects of e-hookah vaping on endothelial function, and the extent to which increased oxidative stress contributes to the vaping-induced vascular impairment. Twenty-six healthy young adult habitual hookah smokers were invited to vape a 30-minute e-hookah session to evaluate the impact on endothelial function measured by brachial artery flow-mediated dilation (FMD). To test for oxidative stress mediation, plasma total antioxidant capacity levels were measured and the effect of e-hookah vaping on FMD was examined before and after intravenous infusion of the antioxidant ascorbic acid (n=11). Plasma nicotine and exhaled carbon monoxide levels were measured before and after the vaping session. Measurements were performed before and after sham-vaping control experiments (n=10). E-hookah vaping, which increased plasma nicotine (+4.93±0.92 ng/mL, P<0.001; mean±SE) with no changes in exhaled carbon monoxide (-0.15±0.17 ppm; P=0.479), increased mean arterial pressure (11±1 mm Hg, P<0.001) and acutely decreased FMD from 5.79±0.58% to 4.39±0.46% (P<0.001). Ascorbic acid infusion, which increased plasma total antioxidant capacity 5-fold, increased FMD at baseline (5.98±0.66% versus 9.46±0.87%, P<0.001), and prevented the acute FMD impairment by e-hookah vaping (9.46±0.87% versus 8.74±0.84%, P=0.002). All parameters were unchanged during sham studies. Conclusions E-hookah vaping has adverse effects on vascular function, likely mediated by oxidative stress, which overtime could accelerate development and progression of cardiovascular disease. Registration URL: https://ClinicalTrials.gov. Unique identifier: NCT03690427.

Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery.

RATIONALE: Lung volume reduction surgery (LVRS) is inconsistently reported to improve arterial oxygenation in patients with chronic obstructive pulmonary disease. OBJECTIVES: We studied the effects of surgery on oxygenation in a large cohort and identified predictors of postoperative oxygenation improvement. METHODS: We evaluated oxygenation in 1,078 subjects with chronic obstructive pulmonary disease enrolled in the National Emphysema Treatment Trial after LVRS compared with medical control subjects, including arterial blood gases, use of supplemental oxygen during treadmill walking, and self-reported use of oxygen during rest, exertion, and sleep. MEASUREMENTS AND MAIN RESULTS: Pa(O(2)) breathing room air was equal in medical and surgical subjects at baseline (64.8 vs. 65.0 mm Hg, P = not significant), but lower in medical subjects at 6 months (63.6 vs. 70.0 mm Hg, P < 0.001), 12 months (63.9 vs. 68.7 mm Hg, P < 0.001), and 24 months (62.4 vs. 68.0 mm Hg, P < 0.001). Fewer medical subjects required oxygen for treadmill walking at baseline compared with surgical subjects (46 vs. 53%, P = 0.02). However, more medical subjects required oxygen for this activity at 6 months (49 vs. 33%, P < 0.001), 12 months (50 vs. 36%, P < 0.001), and 24 months (52 vs. 42%, P = 0.02). Self-reported oxygen use was greater in medical than in surgical subjects at 6, 12, and 24 months. Multivariate modeling of preoperative characteristics showed baseline oxygenation status was the best predictor of postoperative oxygenation. CONCLUSIONS: LVRS increases Pa(O(2)), and decreases treadmill and self-reported use of oxygen for up to 24 months post-procedure. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Longitudinal change in the BODE index predicts mortality in severe emphysema.

RATIONALE: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. OBJECTIVES: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. METHODS: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. MEASUREMENTS AND MAIN RESULTS: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. CONCLUSIONS: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease.

BACKGROUND: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002. METHODS: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%). RESULTS: Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score, >or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score, < 5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population. CONCLUSIONS: Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.

A Case of Henoch-Schonlein Purpura Associated with Rotavirus Infection in an Elderly Asian Male and Review of the Literature.

BACKGROUND Henoch-Schönlein purpura (HSP), a small vessel vasculitis mediated by deposition of immune-complexes containing IgA in the skin, gut, and glomeruli, often presents with abdominal pain, purpuric rash in the lower extremities and buttocks, joint pain, and hematuria. The disease most commonly targets children but can affect adults who tend to have a worse prognosis. CASE REPORT We discuss a case of HSP in an elderly Chinese male who presented with severe proximal bowel inflammation, vasculitic rash, and proteinuria; he was found to have positive stool rotavirus and giardia. He improved significantly with high dose steroids. We believe rotavirus may have been a triggering event in this patient. A brief review of the literature is also presented. CONCLUSIONS This is the first case report describing a classic presentation of HSP in an adult following a rotavirus infection. HSP can cause significant morbidity and mortality in adult patients predominantly from progressive renal failure; therefore careful management and monitoring is important. GI infections seem to be a common trigger for HSP and this case report suggests that rotavirus may be part of the spectrum.

Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease.

BACKGROUND: Fabry disease is an X-linked genetic disorder resulting in the accumulation of glycosphingolipids in various organs, leading to exercise intolerance and early mortality. Enzyme replacement therapy (ERT) has recently been approved for use in Fabry patients. GOALS OF STUDY: To assess baseline cardiopulmonary exercise characteristics in both invasive and noninvasive tests and to study the impact of ERT on exercise. METHODS: A total of 15 patients with Fabry disease underwent baseline cardiopulmonary exercise tests. Six patients were randomized 2:1 to receive either ERT or placebo. We performed serial cardiopulmonary exercise tests at baseline and every 3 months over a period of at least 18 months. The baseline test was compared to the last two exercise tests for each patient. RESULTS: Mean age was 32 years. Mean VO2max was 1.680 +/- 0.67 L/min and increased by 0.459 +/- 0.64 L/min in the patients receiving ERT. Mean VO2max was 1.462 +/- 0.25 L/min and decreased by 0.116 +/- 0.44 L/min in patients on placebo. Mean oxygen pulse (VO2/HR) increased by 1.71 with enzyme, but increased only 0.025 in patients taking placebo. Estimated stroke volume (SV) increased by 10 ml in patients on ERT. CONCLUSIONS: In this small cohort, exercise tolerance increased in patients receiving enzyme replacement therapy. Cardiopulmonary exercise testing is a useful test in measuring the response to therapy in Fabry disease patients.

The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease.

BACKGROUND: Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD. OBJECTIVES: To access the association between IC/TLC and survival in an emphysematous phenotype of COPD. METHODS: We performed a retrospective analysis of a large pulmonary function (PF) database with 39,050 entries, from April 1978 to October 2009. Emphysematous COPD was defined as reduced FEV1/forced vital capacity (FVC), increased TLC, and reduced diffusing capacity of the lungs for carbon monoxide (DLCO; beyond 95% confidence intervals [CIs]). We evaluated the association between survival in emphysematous COPD patients and the IC/TLC ratio evaluated both as dichotomous (≤25% vs >25%) and continuous predictors. Five hundred and ninety-six patients had reported death dates. RESULTS: Univariate analysis revealed that IC/TLC ≤25% was a significant predictor of death (hazard ratio [HR]: 2.39, P<0.0001). Median survivals were respectively 4.3 (95% CI: 3.8-4.9) and 11.9 years (95% CI: 10.3-13.2). Multivariable analysis revealed age (HR: 1.19, 95% CI: 1.14-1.24), female sex (HR: 0.69, 95% CI: 0.60-0.83), and IC/TLC ≤25% (HR: 1.69, 95% CI: 1.34-2.13) were related to the risk of death. Univariate analysis showed that continuous IC/TLC was associated with death, with an HR of 1.66 (95% CI: 1.52-1.81) for a 10% decrease in IC/TLC. CONCLUSION: Adjusting for age and sex, IC/TLC ≤25% is related to increased risk of death, and IC/TLC as a continuum, is a significant predictor of mortality in emphysematous COPD patients.

Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts.

BACKGROUND: Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists. OBJECTIVE: To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV(1) to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible. DESIGN: Individual subject data analysis of 10 European and American cohorts (n=13 914). SETTING: Population-based, primary, secondary and tertiary care. PATIENTS: COPD GOLD stages I-IV. MEASUREMENTS: We validated the original ADO index. We then obtained an updated ADO index in half of our cohorts to improve its predictive accuracy, which in turn was validated comprehensively in the remaining cohorts using discrimination, calibration and decision curve analysis and a number of sensitivity analyses. RESULTS: 1350 (9.7%) of all subjects with COPD (60% male, mean age 61 years, mean FEV(1) 66% predicted) had died at 3 years. The original ADO index showed high discrimination but poor calibration (p<0.001 for difference between predicted and observed risk). The updated ADO index (scores from 0 to 14) preserved excellent discrimination (area under curve 0.81, 95% CI 0.80 to 0.82) but showed much improved calibration with predicted 3-year risks from 0.7% (95% CI 0.6% to 0.9%, score of 0) to 64.5% (61.2% to 67.7%, score of 14). The ADO index showed higher net benefit in subjects at low-to-moderate risk of 3-year mortality than FEV(1) alone. INTERPRETATION: The updated 15-point ADO index accurately predicts 3-year mortality across the COPD severity spectrum and can be used to inform patients about their prognosis, clinical trial study design or benefit harm assessment of medical interventions.

Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.

BACKGROUND: In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume. METHODS: In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months. Medical and surgical patients were divided into "deflators" and "non-deflators" based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75% of surgical patients. We examined changes in O(2) pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs. RESULTS: In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O(2) pulse (median ∆RV/TLC -18.0% vs. -9.3%, p=0.0003; median ∆O(2) pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In the validation cohort, surgical deflators experienced a greater improvement in peak O(2) pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32 mL/beat, p<0.0001 and 0.47 mL/beat, p<0.0001, respectively) corresponded with significant reductions in HR and improvements in VO(2). On multivariate analysis, deflators were 88% more likely than non-deflators to have an improvement in O(2) pulse (OR 1.88, 95% CI 1.30-2.72, p=0.0008). CONCLUSION: In COPD, decreased hyperinflation through lung volume reduction is associated with improved O(2) pulse.

High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation.

BACKGROUND: This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery. METHODS: Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests. RESULTS: Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was <1 year for 56 (13.6%), 1-10 years for 110 (26.8%), 11-20 years for 87 (21.2%), 21-30 years for 66 (16.1%), 31-40 years for 44 (10.7%), 41-50 years for 40 (9.7%) and 51-60 years for 8 (1.9%). The mean cessation was 18.1 ± 15.7 years (n = 411 former smokers). Fifty-nine percent had stage 1 disease and 68.0% had adenocarcinoma. Squamous cell carcinoma was more prevalent in smokers (15.6% vs. 8.3%, p = 0.028); adenocarcinoma was more prevalent in never-smokers (79.9% versus 64.3%, p = 0.0004). The prevalence of adenocarcinoma varied inversely with pack year (p < 0.0001) and directly with years of smoking cessation (p = 0.0005). CONCLUSIONS: In a surgical lung cancer cohort, the majority of patients were smoking abstinent greater than one decade before the diagnosis of lung cancer.

Differentiating COPD from asthma in clinical practice.

Asthma and chronic obstructive pulmonary disease (COPD) are interrelated diseases of airflow limitation. They share several common origins, symptoms, and treatments, but there are important differences that affect both diagnosis and recommended treatments. In fact, the most important reason for distinguishing COPD from asthma is the difference in treatment strategies. Although both asthma and COPD use the same types of treatments, the timing of their use in the disease course can have dramatic and important effects. Spirometry should be used to detect COPD in patients with symptoms. Many patients do not recognize their COPD symptoms so the primary care physician should be proactive in asking about symptoms. This article summarizes the key pathophysiologic, epidemiologic, and clinical differences and similarities between asthma and COPD, as well as recommended treatment strategies for both diseases and criteria for referring patients to a pulmonologist.

Effects of lung volume reduction surgery on gas exchange and breathing pattern during maximum exercise.

BACKGROUND: The National Emphysema Treatment Trial studied lung volume reduction surgery (LVRS) for its effects on gas exchange, breathing pattern, and dyspnea during exercise in severe emphysema. METHODS: Exercise testing was performed at baseline, and 6, 12, and 24 months. Minute ventilation (Ve), tidal volume (Vt), carbon dioxide output (Vco(2)), dyspnea rating, and workload were recorded at rest, 3 min of unloaded pedaling, and maximum exercise. Pao(2), Paco(2), pH, fraction of expired carbon dioxide, and bicarbonate were also collected in some subjects at these time points and each minute of testing. There were 1,218 patients enrolled in the study (mean [+/- SD] age, 66.6 +/- 6.1 years; mean, 61%; mean FEV(1), 0.77 +/- 0.24 L), with 238 patients participating in this substudy (mean age, 66.1 +/- 6.8 years; mean, 67%; mean FEV(1), 0.78 +/- 0.25 L). RESULTS: At 6 months, LVRS patients had higher maximum Ve (32.8 vs 29.6 L/min, respectively; p = 0.001), Vco(2), (0.923 vs 0.820 L/min, respectively; p = 0.0003), Vt (1.18 vs 1.07 L, respectively; p = 0.001), heart rate (124 vs 121 beats/min, respectively; p = 0.02), and workload (49.3 vs 45.1 W, respectively; p = 0.04), but less breathlessness (as measured by Borg dyspnea scale score) [4.4 vs 5.2, respectively; p = 0.0001] and exercise ventilatory limitation (49.5% vs 71.9%, respectively; p = 0.001) than medical patients. LVRS patients with upper-lobe emphysema showed a downward shift in Paco(2) vs Vco(2) (p = 0.001). During exercise, LVRS patients breathed slower and deeper at 6 months (p = 0.01) and 12 months (p = 0.006), with reduced dead space at 6 months (p = 0.007) and 24 months (p = 0.006). Twelve months after patients underwent LVRS, dyspnea was less in patients with upper-lobe emphysema (p = 0.001) and non-upper-lobe emphysema (p = 0.007). CONCLUSION: During exercise following LVRS, patients with severe emphysema improve carbon dioxide elimination and dead space, breathe slower and deeper, and report less dyspnea.

Multivariate models of determinants of health-related quality of life in severe chronic obstructive pulmonary disease.

Persons with severe chronic obstructive pulmonary disease (COPD) and similar levels of forced expiratory volume in 1 second (FEV(1)), exercise capacity, and dyspnea have a wide range of health-related quality of life (HRQL). We identified the independent determinants of HRQL in persons with COPD. Comprehensive assessments of physiological, psychosocial, and clinical variables from the National Emphysema Treatment Trial were used. HRQL was assessed by the Medical Outcomes Study 36-Item Short Form Physical Component Summary (PCS) and Mental Component Summary (MCS) scores and the St. George's Respiratory Questionnaire total score (SGRQ-TS). In multivariate linear regression models, exercise capacity, dyspnea, age, single-breath diffusing capacity of the lung for carbon monoxide percent predicted, and self-report of being disabled were significant determinants of PCS score. Dyspnea, depression, antidepressant use, daytime sleepiness, and education were significant determinants of MCS score. Prior participation in pulmonary rehabilitation, supplemental oxygen use, and oral corticosteroid use were significant determinants of SGRQ-TS. Although FEV(1), 6-minute walk test distance, and dyspnea significantly correlated with HRQL, their effects on HRQL were reduced when other variables were considered. Greater exercise capacity, prior participation in pulmonary rehabilitation, and use of supplemental oxygen were significantly associated with better HRQL. Self-perception of being disabled, (Abstract continued) depression, dyspnea, oral corticosteroid use, and daytime sleepiness were associated with worse HRQL. To optimize HRQL, clinicians should pay attention to a number of clinical and physiological factors.

Do faculty intensivists have better outcomes when caring for patients directly in a closed ICU versus consulting in an open ICU?

BACKGROUND: Intensivists have been associated with decreased mortality in several studies, but in one major study, centers with intensivist-staffed units reported increased mortality compared with controls. We hypothesized that a closed unit, in which a unit-based intensivist directly provides and coordinates care on all cases, has improved mortality and utilization compared with an open unit, in which individual attendings and consultants provide care, while intensivists serve as supervising consultants. METHODS: We undertook the retrospective study of outcomes in 2 intensive care units (ICUs)-a traditional open unit managed by faculty intensivists and a second closed unit overseen by the same faculty intensivists who coordinated the care on all patients in a large community hospital. PRIMARY OUTCOME: In-hospital mortality. SECONDARY OUTCOMES: Hospital length of stay (LOS), ICU LOS, and relative costs of hospitalization. RESULTS: From January 2006 to December 2007, we identified 2602 consecutive admissions to the 2 medical ICUs. Of all patients admitted to the closed and open units, 19.2% and 24.7%, respectively, did not survive (P < 0.001, adjusted for severity). Median hospital LOS was 10 days for the closed unit and 12 days for the open unit (P < 0.001). Median ICU LOS was 2.2 days for the closed unit and 2.4 days for the open unit (P = NS). The unadjusted cost index for the open unit was 1.11 relative to the closed unit (1.0) (P < 0.001). However, after adjusting for disease severity, cost differences were not significantly different. CONCLUSIONS: We observed significant reductions in mortality and hospital LOS for patients initially admitted to a closed ICU versus an open unit. We did not observe a significant difference in ICU LOS or total cost after adjustment for severity.

CT metrics of airway disease and emphysema in severe COPD.

BACKGROUND: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. METHODS: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV(1) and percent predicted value of FEV(1) with CT scan measures of emphysema and airway disease. RESULTS: In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT (r = -0.28, p = 0.0001) and SRWA (r = -0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV(1)% predicted (R = -0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (beta = -5.2, p = 0.009; beta = -2.6, p = 0.008, respectively) and %LAA-950 (beta = -10.6, p = 0.03) with the postbronchodilator FEV(1)% predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). CONCLUSIONS: Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Inhaled and systemic corticosteroids in chronic obstructive pulmonary disease.

Systemic and local inflammation is central to the pathophysiology of chronic obstructive pulmonary disease (COPD). Increased levels of inflammation have been linked to a more progressive course in COPD and have been shown to be present during an exacerbation. Decreases in inflammatory cytokines, C-reactive protein, and inflammatory cells have been observed with corticosteroid use, suggesting a possible mechanism for a therapeutic benefit of steroids. No available data support the routine use of systemic corticosteroids in stable COPD; however, short courses during exacerbations are likely to improve length of hospitalization, lung function, and relapse rate. Inhaled corticosteroids (ICS) decrease the rate of exacerbation and may improve the response to bronchodilators and decrease dyspnea in stable COPD. No study shows that ICS reduce the loss of lung function; however, recent data suggest a possible survival benefit when combined with long-acting beta agonists. There are limited data on the use of ICS in the treatment of acute exacerbations of COPD, and its role in this setting must be more clearly defined. The empiric use of systemic corticosteroids perioperatively represents another area of uncertainty. The role of pharmacogenetics in the metabolism of corticosteroids in COPD is evolving but may be partially responsible for the observed variability in patient responsiveness. The potential benefits of systemic or inhaled corticosteroid use must be weighed against the risk of known toxicities.