Chest. 2003;124(3):775-777. doi:10.1378/chest.124.3.775

Asthma appears to be a diathesis for morbidity related to influenza infection. Children and adults with asthma are at higher risk for influenza-related adverse health outcomes, including pneumonia, hospitalization for acute respiratory disease, and death.13 Because 5 to 10% of the US population has asthma, the potential public health impact of influenza infection on this vulnerable subgroup is enormous.

Chest. 2003;124(3):777-778. doi:10.1378/chest.124.3.777

In the era of electronic ICUs, computer-assisted decision making, and robotic surgical assistants, the words of this classic American hymn are a good reminder to not forget the value of basic, simple maneuvers to improve the care of our patients. In this issue of CHEST (see page 883), Mundy and coworkers have elegantly demonstrated this approach with their study on a simple maneuver—getting patients with community-acquired pneumonia (CAP) out of bed, either into a chair or ambulating within 24 h of admission. The result was an impressive average 1.1-day decrease in the length of hospitalization. The most impressive difference in length of stay for the early ambulation group was in patients with a pneumonia severity index (PSI) class III.1 Average hospital length of stay in this group decreased from a mean of approximately 7.5 days to a mean of 5 days. The lack of benefit in the lower acuity PSI classes probably results from the primarily psychological and social reasons for hospital admission.12

Chest. 2003;124(3):778-780. doi:10.1378/chest.124.3.778

Increasingly, sleep-disordered breathing (SDB) is recognized as an important risk factor for coronary atherosclerosis and heart disease. Several large epidemiologic studies12 have demonstrated that SDB increases the risk of heart disease by approximately twofold to fourfold, independent of other risk factors. While the exact mechanisms responsible for this association are largely unknown, there is credible evidence to indicate SDB can increase systemic BP34 and sympathetic drive.5 It may also elevate circulating levels of fibrinogen6 and C-reactive protein,7 triggering a cascade of events that eventually leads to thrombus formation in the coronary vasculature. Treatment of SDB, usually with continuous positive airway pressure, leads to significant improvements in these physiologic parameters.8

Chest. 2003;124(3):780-781. doi:10.1378/chest.124.3.780

While health-related problems have a definite and identifiable effect on patients, the patients’ families are also very much affected. This may reach such a level of intensity that the patient will present to a physician because their family desires that they be evaluated and treated. Most clinicians would agree that sleep apnea is one of those conditions that stimulates familial assertion. The dynamics and repercussions of these encounters on the doctor- patient relationship and the doctor-family relationship may be staggering. The willingness and compliance of a patient with treatment may be a result of familial coercion.

Chest. 2003;124(3):781-782. doi:10.1378/chest.124.3.781

The article by Alifano et al in this issue of CHEST (see page 1004) revisits a very interesting cause of secondary spontaneous pneumothorax, that of catamenial pneumothorax. As outlined in the article, this is a pneumothorax that is usually right sided and occurs in women within 72 h of menstruation. This has been considered a rare cause of spontaneous pneumothorax but interestingly accounted for 25% of the spontaneous pneumothoraces in women in this series (8 of 32 cases). The questions raised with regard to this disorder are as follows: (1) is the true incidence higher than we previously suspected, and (2) how best should we manage it?

Clinical Investigations: ASTHMA

Asthma and Influenza Vaccination*: Findings From the 1999–2001 National Health Interview Surveys
Chest. 2003;124(3):783-789. doi:10.1378/chest.124.3.783

Study objectives: People with asthma are at high risk for complications from influenza; therefore, the Centers for Disease Control and Prevention recommends an annual influenza vaccination for people with asthma. Because little is known about such vaccination rates among adults, especially those aged 18 to 49 years and 50 to 64 years, we sought to estimate influenza vaccination rates among US adults.

Design: Cross-sectional analyses of the 1999 to 2001 National Health Interview Surveys.

Setting: US population.

Participants: Representative samples of US adults aged ≥ 18 years.

Measurements and results: Asthma status and receipt of influenza vaccination during the past 12 months were self-reported. We found that 35.1% (95% confidence interval [CI], 33.0 to 37.0%), 36.7% (95% CI, 34.7 to 38.6%), and 33.3% (95% CI, 31.6 to 35.0%) of participants with asthma reported having had an influenza vaccination in 1999 (n = 2,620), 2000 (n = 3,007), and 2001 (n = 3,582), respectively. Among participants aged 18 to 49 years, the vaccination rates were 20.9% (SE 1.2%), 22.7% (SE 1.2%), and 21.1% (SE 1.0%), respectively. Among participants aged 50 to 64 years, the vaccination rates were 46.2% (SE 2.6%), 47.8% (SE 2.3%), and 42.3% (SE 2.1%), respectively. Vaccination rates increased strongly with age and with education in each year. Associations with sex or with race or ethnicity were inconsistent during the 3 years.

Conclusions: The suboptimal vaccination rates among people with asthma aged 18 to 64 years suggest the need to increase influenza vaccination rates in this age group.

Chest. 2003;124(3):790-794. doi:10.1378/chest.124.3.790

Background: Inhaled corticosteroids (ICS) may provide benefit in the therapy of acute asthma. The purpose of this study was to test the hypothesis that ICS are as effective as oral corticosteroids (OCS) in the management of acute childhood asthma.

Methods: A randomized, masked, placebo-controlled study was conducted in children aged 6 to 16 years seeking emergent care for an acute exacerbation of asthma. Patients were randomized into one of two groups: group 1 (OCS), oral prednisone, 2 mg/kg (maximum of 60 mg/d) for 7 days, and placebo pressurized metered-dose inhaler with valved holding chamber, four inhalations bid; and group 2 (ICS), flunisolide, four inhalations (1 mg) bid for 7 days, and daily placebo tablets. Spirometry (FEV1) was performed at baseline, day 3, and day 7 of the study. A symptom diary and twice-daily peak expiratory flow were recorded.

Results: A total of 58 subjects receiving ICS (n = 27) or OCS (n = 28) were enrolled. Baseline asthma severity, race, gender, and age were balanced between the two groups. χ2 showed no significant difference in symptom severity between the two groups at any time during the study. FEV1 percentage of predicted was lower in the ICS group on day 3 (65% vs 78%, p = 0.03) and on day 7 (77% vs 95%, p = 0.002).

Conclusion: ICS were found to be useful in the management of acute asthma in children; however, spirometry data suggested a more rapid resolution of asthma with OCS.

Chest. 2003;124(3):795-802. doi:10.1378/chest.124.3.795

Study objectives: Among adults presenting to the emergency department (ED) with acute asthma, we sought to determine the prevalence of obesity, and the relation of body mass index (BMI) to asthma severity in this high-risk population.

Design: Multicenter, prospective cohort study.

Setting: Twenty-six North American EDs.

Participants: Five hundred seventy-two patients aged 18 to 54 years presenting with acute asthma.

Interventions: None.

Measurements and results: A standardized interview assessed demographic characteristics, asthma history, and details of the current asthma exacerbation. Data on ED medical management and disposition were obtained by chart review. Three of four asthmatic patients were either overweight (BMI, 25 to 29.9; 30%) or obese (BMI, ≥ 30; 44%). Normal weight/underweight, overweight, and obese patients did not differ on several markers of chronic asthma severity; obese subjects tended to rate symptoms more severely and to use more inhaled β-agonists in the 6 h hours prior to ED presentation despite a significantly higher initial percentage of predicted peak expiratory flow (PEF) [44%, 45%, and 51%, respectively; p < 0.05]. The three BMI groups responded similarly to acute therapy in the ED, with all groups demonstrating reversible airway obstruction. The sex distribution by BMI group differed markedly (p < 0.001), with women less often overweight (40% vs 24%) and more often obese (30% vs 52%). Since women were more likely have a higher initial PEF (45% vs 53%, p < 0.001), we stratified by sex to further examine the relation of BMI to asthma severity. The observed BMI-asthma associations were due largely, but not entirely, to confounding by sex.

Conclusions: Despite lingering concerns about the veracity of “asthma” among obese individuals, asthma exacerbations among obese and nonobese adults were remarkably similar. Potential differences (eg, in symptom perception, use of inhaled β-agonists before ED presentation, initial PEF rate) were due, in large part, to confounding by sex.

Acute Asthma Among Adults Presenting to the Emergency Department*: The Role of Race/Ethnicity and Socioeconomic Status
Chest. 2003;124(3):803-812. doi:10.1378/chest.124.3.803

Objectives: To investigate racial/ethnic differences in acute asthma among adults presenting to the emergency department (ED), and to determine whether observed differences are attributable to socioeconomic status (SES).

Design: Prospective cohort studies performed during 1996 to 1998 by the Multicenter Airway Research Collaboration. Using a standardized protocol, researchers provided 24-h coverage for a median duration of 2 weeks per year. Adults with acute asthma were interviewed in the ED and by telephone 2 weeks after hospital discharge.

Participants: Sixty-four North American EDs.

Results: A total of 1,847 patients were enrolled into the study. Black and Hispanic asthma patients had a history of more hospitalizations than did whites (ever-hospitalized patients: black, 66%; Hispanic, 63%; white, 54%; p < 0.001; patients hospitalized in the past year: black, 31%; Hispanic, 33%; white, 25%; p < 0.05) and more frequent ED use (median use in past year: black, three visits; Hispanic, three visits; white, one visit; p < 0.001). The mean initial peak expiratory flow rate (PEFR) was lower in blacks and Hispanics (black, 47%; Hispanic, 47%; white, 52%; p < 0.001). For most factors, ED management did not differ based on race/ethnicity. After accounting for several confounding variables, blacks and Hispanics were twice as likely to be admitted to the hospital. Blacks and Hispanics also were more likely to report continued severe symptoms 2 weeks after hospital discharge (blacks, 24%; Hispanic, 31%; white, 19%; p < 0.01). After adjusting for sociodemographic factors, the race/ethnicity differences in initial PEFR and posthospital discharge symptoms were markedly reduced.

Conclusion: Despite significant racial/ethnic differences in chronic asthma severity, initial PEFR at ED presentation, and posthospital discharge outcome, ED management during the index visit was fairly similar for all racial groups. SES appears to account for most of the observed acute asthma differences, although hospital admission rates were higher among black and Hispanic patients after adjustment for confounding factors. Despite asthma treatment advances, race/ethnicity-based deficiencies persist. Health-care providers and policymakers might specifically target the ED as a place to initiate interventions designed to reduce race-based disparities in health.

Chest. 2003;124(3):813-818. doi:10.1378/chest.124.3.813

Study objectives: During a bronchial provocation test (BPT), the performance of maximal inspiratory-expiratory maneuvers, causing abrupt and marked shifts in intrathoracic pressure, may increase the risk of cardiac arrhythmias. Moreover, the inhalation of methacholine (MCh), a cholinergic agonist agent, could favor the development of unwelcome cardiovascular events, namely, cardiac arrhythmias.

Subjects and methods: We studied the number and severity of cardiac arrhythmias by ECG-Holter monitoring before, during, and after BPTs with MCh challenge in a group of 46 consecutive nonselected subjects (28 men and 18 women) with clinical indications for BPT, without preexisting cardiovascular diseases, and not receiving arrhythmogenic drugs. The subjects performed a routine pulmonary function test (PFT), followed by BPT, during ECG-Holter monitoring. Determination of the serum potassium concentration, a baseline arterial blood gas analysis, and monitoring of oxyhemoglobin saturation also were performed.

Results: We found no significant increase in the number of supraventricular and ventricular arrhythmias during the performance of PFTs and of BPTs with MCh in the subjects, either with or without bronchial hyperresponsiveness (BHR). However, during the performance of BPTs, we observed a significant reduction in mean heart rate.

Conclusions: Our results indicate that the performance of PFTs and BPTs with MCh does not increase the cardiac arrhythmogenic risk in subjects without cardiovascular diseases, as well as in those with BHR, suggesting that these tests are safe to perform in most subjects.

Bronchial Hyperresponsiveness in Adolescents With Long-term Asthma Remission*: Importance of a Family History of Bronchial Hyperresponsiveness
Chest. 2003;124(3):819-825. doi:10.1378/chest.124.3.819

Background: The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma.

Objective: The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence.

Methods: One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) and the bronchial responsiveness (BR) index were calculated for each individual.

Results: Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC20 < 18 mg/mL). The frequency of BHR and the BR index were significantly higher in parents (n = 138) of the BHR-persisting group (28.3% and 1.150 ± 0.103, respectively [mean ± 1 SD]) than in parents (n = 114) of BHR-nonpersisting group (16.7% [p = 0.030] and 1.124 ± 0.088 [p = 0.029], respectively). Furthermore, adolescents (n = 56) with at least one BHR-positive parent were found to have a higher frequency of BHR (66.1% vs 45.7%, p = 0.023) and a higher BR index (1.244 ± 0.090 vs 1.204 ± 0.082, p = 0.011) than adolescents (n = 70) with non-BHR parents.

Conclusion: Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.

Clinical Investigations: COPD

Chest. 2003;124(3):826-831. doi:10.1378/chest.124.3.826

Study objectives: To examine the sources of the direct medical costs of α1-antitrypsin (AAT) deficiency based on survey data from affected individuals.

Background: Prior research has reported the total cost of AAT deficiency but has not examined the specific components of the direct medical costs of affected individuals.

Methods: In order to detail the sources of the direct medical costs, we sent surveys to 688 respondents of a previous survey. We estimated the costs in three ways, which differed in the method of managing missing values. With method 1, the group mean value of cost per unit of utilization, multiplied by the occurrences of utilization, was used to replace the missing value. Two sensitivity analyses (ie, methods 2 and 3) were conducted to test the robustness of our estimate. With method 2, values of zero were entered for all missing values. With method 3, the missing values were replaced by the group mean value. The Wilcoxon test was used to test the cost differences between patients of different phenotypes. All cost data were expressed in 1998 US dollars.

Results and conclusions: Two hundred ninety-two individuals responded to the survey. The annual total health-care costs were high (mean range, $36,471 to $46,114; median range, $12,485 to $37,100 [according to the method for managing missing data]) for AAT deficiency. The total costs for individuals with the PI*ZZ phenotype exceeded those for individuals with a non-PI*ZZ phenotype. The use of IV augmentation therapy accounted for more than half of all direct medical costs for the respondents. Besides the costs for therapy with α1-proteinase inhibitor (Prolastin; Bayer; West Haven, CT), other major cost sources were prescription drugs other than α1-proteinase inhibitor, hospitalization, health insurance, and physician visits.

Chest. 2003;124(3):832-833. doi:10.1378/chest.124.3.832

Objective: To assess the role of anaerobic bacteria in acute exacerbation of chronic bronchitis (AECB).

Methods: The level of the Ig-A class to two organisms (Fusobacterium nucleatum and Prevotella intermedia) was determined in the sputum of 25 patients with AECB and 25 control patients. The presence and level of these antibodies were investigated by enzyme-linked immunosorbent assay.

Results: The median sputum antibody level for F nucleatum and P intermedia were significantly higher in patients with AECB as compared to control patients (p < 0.05). The IgA levels for F nucleatum was 3.5 times higher in patients with AECB and 3.8 times greater for P intermedia.

Conclusions: This study demonstrates for the first time an elevated sputum antibody titers in patients with AECB to F nucleatum and P intermedia.

Chest. 2003;124(3):834-843. doi:10.1378/chest.124.3.834

Study objectives: To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting β2-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD.

Design: Randomized, double-blind, multicenter, placebo-controlled study.

Setting: Seventy-six investigative sites in the United States.

Patients: Seven hundred twenty-three patients ≥ 40 years of age with COPD and a mean baseline FEV1 of 42% predicted.

Interventions: FP (250 μg), SM (50 μg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks.

Measurements: Primary efficacy measures were morning predose (ie, trough FEV1) for FSC compared with SM and 2-h postdose FEV1 for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures.

Results: At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p ≤ 0.012) increased the morning predose FEV1 (165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p ≤ 0.001) increased the 2-h postdose FEV1 (281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p ≤ 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups.

Conclusions: Treatment with FSC (FP, 250 μg, and SM, 50 μg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.

Chest. 2003;124(3):844-849. doi:10.1378/chest.124.3.844

Background: Levalbuterol, the R-isomer of albuterol, has advantages over racemic albuterol in asthma; however, the effectiveness of this β-agonist in COPD has received little attention.

Objectives: To evaluate the effectiveness of a single dose of nebulized levalbuterol in COPD.

Design: A randomized, double-blind, placebo-controlled trial comparing nebulized levalbuterol to racemic albuterol, combined racemic albuterol and ipratropium, and placebo.

Patients: Thirty patients with stable COPD (FEV1 between 45% and 70% of predicted) were studied.

Methods: After withholding usual bronchodilator medications for appropriate washout periods, patients were randomized on separate visits to receive single doses of each the following nebulized bronchodilator medications: (1) levalbuterol, 1.25 mg; (2) racemic albuterol, 2.5 mg; (3) combined racemic albuterol, 2.5 mg, and ipratropium, 0.5 mg; or (4) placebo. FEV1, FVC, pulse rate, and oxygen saturation were measured at baseline, 0.5 h following nebulization, and hourly for 6 h. Hand tremor, using a 7-point scale, was measured at baseline, 0.5 h, 1 h, and 2 h. Treatment-placebo differences were analyzed using repeated-measures analysis of variance and least-squares means.

Results: The mean age (± SD) of patients was 69 ± 15 years. Mean FEV1 was 1.15 ± 0.49 L. By 0.5 h following study drug administration, all three nebulized bronchodilator treatments led to similar, significant improvements in FEV1 compared to placebo. These effects persisted at 1 h and 2 h for all three treatments; however, by 3 h, only the combined albuterol/ipratropium group had a mean change in FEV1 significantly greater than placebo. There were no significant differences between bronchodilator groups at any time period. A mild increase in pulse rate was observed in all treatment groups. There were no significant treatment-placebo differences in oxygen saturation or hand tremor.

Conclusion: For single-dose, as-needed use in COPD, there appears to be no advantage in using levalbuterol over conventional nebulized bronchodilators.

Clinical Investigations: IPPV

Chest. 2003;124(3):850-856. doi:10.1378/chest.124.3.850

Study objectives: Ventilator users who are unable to leave the acute care setting may be transferred to a unit for chronic assisted ventilatory care (CAVC) with the goal of optimizing their level of function. In this report, we summarize the outcomes of all patients admitted to a CAVC unit between 1986 and 2001.

Patients and methods: Fifty patients (24 with neuromuscular disease [NMD], 10 with spinal cord injury [SCI], 7 with thoracic restriction [TR], 7 with COPD, and 2 with parenchymal restriction [PR]) were reviewed. Thirty-eight patients were transferred to the CAVC unit from intensive care, 5 patients were transferred from inpatient respiratory rehabilitation, 4 patients came from home, and 3 patients came from pediatric long-term care. At the time of CAVC unit admission, all patients were receiving mechanical ventilation via a tracheostomy tube.

Results: Ventilator time increased gradually in patients with COPD from 16 h (SD, 5.6) to 22.9 h (SD, 3.0) per day (p < 0.05), and in patients with TR from 18.9 h (SD, 6.1) to 22.9 h (SD, 4.5) [not significant]. Five of the 10 patients with SCI were decannulated. Functional mobility, which decreased in patients with COPD and patients with TR, remained stable in NMD and PR and improved in SCI. Eighteen patients returned home or to an attendant care facility (COPD, n = 1; NMD, n = 10; SCI, n = 5; PR, n = 2); 11 patients died in the CAVC unit (COPD, n = 6; TR, n = 3; NMD, n = 1; SCI, n = 1); and 7 patients were transferred to intensive care, where they died. The average direct cost per patient per diem increased from $252 (Canadian) in 1988 to $335 in 2001.

Conclusion: A CAVC unit can provide a safe environment for severely impaired, ventilator-dependent individuals, many of whom (36%) left for a more independent community-based environment. Better outcomes were seen among patients with SCI and NMD than in patients with COPD and TR.

Kyphoscoliotic Ventilatory Insufficiency*: Effects of Long-term Intermittent Positive-Pressure Ventilation
Chest. 2003;124(3):857-862. doi:10.1378/chest.124.3.857

Objectives: To determine the effects of long-term nocturnal intermittent positive-pressure ventilation (NIPPV) on symptoms, pulmonary function test results, sleep, and respiratory muscle performance in patients with ventilatory insufficiency due to severe kyphoscoliosis.

Design: A prospective study in which 16 severe kyphoscoliotic patients were treated with NIPPV delivered by volume-cycled and pressure-cycled ventilators, over a period of 36 months.

Interventions and measurements: At baseline, pulmonary function tests, blood gas measurements, polysomnography, and respiratory muscle strength (measured by noninvasive indexes) were obtained. Symptoms and the number of hospitalizations in the previous 6 months also were recorded. Patients then began using a ventilator for > 1 to 2 days, in order to select the type of ventilator and the appropriate interface. Patients returned for evaluation (in outpatient setting) every 6 months for a follow-up period of 3 years. At 6 months, polysomnography was repeated, and by the third year clinical and functional parameters had been reassessed.

Results: All symptoms improved significantly with NIPPV therapy, when compared with the baseline values. The mean (± SD) Pao2 and FVC values increased at 36 months compared with baseline values (62.6 ± 7.1 vs 67.8 ± 8.8 mm Hg, respectively; and 37.9 ± 7.2% vs 47.5 ± 11.9%, respectively; p < 0.05 for both). There were significant improvements in mean maximal inspiratory pressure (55.8 ± 17.4 to 78.5 ± 17.5 cm H2O), maximal expiratory pressure (53.8 ± 17.7 to 72.3 ± 11.0 cm H2O), mouth pressure (0.28 ± 0.08 to 0.22 ± 0.02 cmH2O), and pressure-time index (0.18 ± 0.05 to 0.11 ± 0.02; p < 0.05 for all comparisons). There were no significant differences in breathing pattern and ventilatory drive. After 6 months, nocturnal oxyhemoglobin saturation improved, however, there was no significant change in sleep architecture. All patients subjectively perceived a better quality of life after beginning ventilation, which persisted over the course of the study.

Conclusions: Long-term NIPPV therapy improves daytime blood gas levels, respiratory muscle performance, and hypoventilation-based symptoms in patients with severe kyphoscoliosis.

Clinical Investigations: EXERCISE

Chest. 2003;124(3):863-869. doi:10.1378/chest.124.3.863

Study objectives: To evaluate cardiac autonomic modulation in patients with COPD during peak exercise.

Methods: Fifty-three patients with COPD (mean FEV1, 35% predicted [SD, 11% predicted]; mean Pao2, 68 mm Hg [SD, 11 mm Hg]; mean Paco2, 40 mm Hg [SD, 7 mm Hg]; mean age, 61 years [SD, 10 years]; 26 women and 27 men) and 14 healthy control subjects aged 60 years (SD, 8 years) [seven women and seven men] were studied at rest and during ramped bicycle ergometry to their volitional peak. Patients were not receiving autonomic medications other than inhaled β-agonist agents and/or anticholinergic agents. Control subjects were not receiving any medications. Cardiac autonomic modulation was assessed via time-frequency analysis (Wigner-Ville) of ECG-derived heart rate variability as the power in the low-frequency (LF) band (ie, 0.04 to 0.15 Hz) and the high-frequency (HF) band (ie, > 0.15 to 0.4 Hz) averaged from > 3 min at rest and minutes 2 through 5 of their exercise period.

Results: Patients with COPD had a significantly increased mean, ln-transformed HF band from rest to peak exercise (9.9 ms2 [SD, 1.4 ms2] vs 10.7 ms2 [SD, 1.4 ms2], respectively; p < 0.01), while the HF band was unchanged for the control group (10.7 ms2 [SD, 1.5 ms2] vs 10.4 ms2 [1.3 ms2], respectively; difference not significant). The mean ln-transformed LF band was significantly increased from rest to peak exercise in patients with COPD (10.9 ms2 [SD, 1.5 ms2] vs 11.5 ms2 [SD, 1.4 ms2], respectively; p < 0.01) and in control subjects (10.9 ms2 [SD, 1.5 ms2] vs 11.5 ms2 [SD, 1.3 ms2], respectively; p < 0.01). The mean LF/HF ratio was significantly decreased from rest to peak exercise in patients with COPD (3.1 [SD, 1.5] vs 2.5 [SD, 1.0], respectively; p < 0.01) and was increased in control subjects (1.9 [SD, 0.8] vs 2.4 [1.0], respectively; p < 0.01). When expressed in normalized units ([absolute power of the components]/[total power − very low frequency power] × 100), the HF band was again significantly greater during peak exercise than at rest in the patients with COPD and was unchanged during peak exercise for the control group. Autonomic changes were not significantly correlated with age, gender, body mass index, spirometry, lung volumes, resting gas exchange, or oxygen saturation during exercise

Conclusion: These data suggest that, in contrast to control subjects, the balance of sympathetic to parasympathetic cardiac modulation decreases in patients with COPD during maximal volitional exercise.

Chest. 2003;124(3):870-882. doi:10.1378/chest.124.3.870

Purpose: Uncertainty exists as to whether pectus excavatum causes true physiologic impairments to exercise performance as opposed to lack of fitness due to reluctance to exercise. The purpose of this study was to examine the effect of pectus excavatum on ventilatory and cardiovascular responses to incremental exercise in physically active patients.

Methods: Twenty-one patients with pectus excavatum (age range, 13 to 50 years; mean [± SD] age, 23.6 ± 8.9 years; severity index range, 3.7 to 8.0; mean severity index, 5.1 ± 1.2) were referred for preoperative evaluation. Eighteen of the patients (85%) had a history of performing aerobic activity ranging from 30 min to 2 h per day (mean duration, 1.0 ± 0.61 h per day) for 3 ± 1.5 days per week. Patients performed pulmonary function tests, and submaximal and maximal incremental exercise testing.

Results: On maximal exercise testing, the maximum oxygen uptake (V̇o2max), and oxygen-pulse were significantly lower than the reference values (t20 = 6.17 [p < 0.0001] and t20 = 4.52 [p < 0.0001], respectively). Furthermore, patients exhibited cardiovascular limitation, but not ventilatory limitation. Despite their high level of habitual exercise activity, the overall metabolic threshold for lactate accumulation was abnormally low (ie, 41% of the reference value for V̇o2max) especially in those with a pectus severity index (PSI) of > 4.0 (39% of the reference value of V̇o2max), which is consistent with cardiovascular impairment rather than physical deconditioning. Patients with a PSI of > 4.0 were also eight times more likely to have reduced aerobic capacity than patients who had a low severity index, despite their level of exercise participation. On submaximal testing, we found that the time constant for O2 uptake kinetics was 37.4 s for the on-transit and 41.6 s for the off-transit. The observed values for FVC, FEV1, maximum voluntary ventilation, and diffusing capacity of the lung for carbon monoxide were significantly lower than reference values, but those for total lung capacity and residual volume were not significantly lower than reference values.

Conclusions: The information derived from this study supports the opinion that pectus excavatum is associated with true physiologic impairment and reduced exercise capacity, predominantly due to impaired cardiovascular performance rather than ventilatory limitation. Furthermore, the impairment is not explained by physical deconditioning.

Clinical Investigations: INFECTION

Chest. 2003;124(3):883-889. doi:10.1378/chest.124.3.883

Study objective: To determine if early mobilization (EM) of hospitalized adults with community-acquired pneumonia (CAP) reduces hospital length of stay.

Design: Group randomized trial.

Setting: Three Midwestern hospitals.

Participants: Four hundred fifty-eight patients with CAP admitted to 17 general medical units between November 1997 and April 1998.

Intervention: EM was defined as sitting out of bed or ambulating for at least 20 min during the first 24 h of hospitalization. Progressive mobilization occurred each subsequent day during hospitalization.

Measurements and results: Intervention (n = 227) and usual-care patients (n = 231) were similar in age, gender, disease severity, door-to-drug delivery time, and IV-to-po switchover time. Hospital length of stay for EM vs usual care was significantly less (mean, 5.8 vs 6.9 days; adjusted absolute difference, 1.1 days; 95% confidence interval, 0.0 to 2.2 days). There were no differences in adverse events or other secondary outcomes between treatment groups.

Conclusions: Like patients hospitalized with acute myocardial infarction and total knee replacements, EM of hospitalized patients with CAP reduces overall hospital length of stay and institutional resources without increasing the risk of adverse outcomes.

Chest. 2003;124(3):890-892. doi:10.1378/chest.124.3.890

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. There are patients with asthma who fulfill the diagnostic criteria of ABPA by serologic evaluation (specific IgE/IgG to Aspergillus fumigatus), bronchography, CT, and or conventional linear tomography.

Objective: To identify different forms of ABPA based on various diagnostic criteria.

Methods: Eighteen patients with asthma fulfilling the criteria of ABPA were evaluated in the present study. Six patients each received a diagnosis of ABPA serologic positive (ABPA-S), ABPA with central bronchiectasis (ABPA-CB), and ABPA with central bronchiectasis and other radiologic features (ABPA-CB-ORF).

Results: The spirometric changes in the ABPA-S group (group 1) were mild, in the ABPA-CB group (group 2) were moderate, and in the ABPA-CB-ORF group (group 3) were severe. Absolute eosinophil count was raised in each group but was maximum (1,233 μL) in severe form of disease (group 3). Specific IgE against A fumigatus was raised in each group, and the maximum was 47.91 IU/mL in ABPA-CB-ORF. CT scan findings of the ABPA-S group were normal without central bronchiectasis. The exacerbation in symptoms was maximum in group 3 compared to other groups.

Conclusion: The present observations suggest that ABPA includes mild (ABPA-S), moderate (ABPA-CB), and severe (ABPA-CB-ORF) forms of disease. It is recommended, therefore, that the disease should be diagnosed early, treated at the mild form of disease (ABPA-S), and prevented from leading to ABPA-CB or ABPA-CB-ORF.

Clinical Investigations: TUBERCULOSIS

Chest. 2003;124(3):893-901. doi:10.1378/chest.124.3.893

Study objective: The purpose of this study was to examine the uptake rates of 18F-fluorodeoxyglucose (FDG) and 11C-choline in patients with lung cancer, pulmonary tuberculosis, and atypical mycobacterial infection of the lung by positron emission tomography (PET) scanning with relation to their tumor size.

Design: Ninety-seven patients with untreated lung cancer, 14 patients with untreated pulmonary tuberculosis, and 5 patients with untreated atypical mycobacterial infection were examined. The diagnosis of lung cancer was confirmed pathologically after biopsy and surgery. The diagnosis of tuberculosis and atypical mycobacterial infection was confirmed by bacterial culture. The uptake rates of FDG and 11C-choline were presented quantitatively as the standardized uptake value (SUV).

Setting: International Medical Center of Japan.

Results: In lung cancer patients, the SUV of FDG increased with increasing tumor size, whereas the SUV of 11C-choline was almost constant at around 3.5 for every tumor size. In tuberculosis patients, the SUV of FDG increased with increasing tumor size, whereas the SUV of 11C-choline was almost constant at around 2 for every tumor size. In atypical mycobacterial infection patients, the SUV of FDG and the SUV of 11C-choline were equally low at around ≤ 2.

Conclusion: The differences in the SUVs of FDG and 11C-choline in patients with lung cancer, tuberculosis, and atypical mycobacterial infection for the same tumor size (tumor size, > 1.5 cm) were distinct. In lung cancer patients, the SUVs of both FDG and 11C-choline were high. In tuberculosis patients, the SUV of FDG was high, but the SUV of 11C-choline was low. In atypical mycobacterial infection patients, the SUVs of both FDG and 11C-choline were low. It may be possible to apply this principle to make a presumptive diagnosis of a solitary pulmonary nodule if it is too small to make a definitive diagnosis pathologically and bacteriologically.

Chest. 2003;124(3):902-908. doi:10.1378/chest.124.3.902

Background: Several nucleic acid amplification (NAA) tests for Mycobacterium tuberculosis (MTB) have been licensed for the rapid diagnosis of active pulmonary tuberculosis (PTB) in respiratory secretions. There is uncertainly however regarding the practical application of these tests in clinical decision making.

Objective: To evaluate the utility of the COBAS AMPLICOR assay (Roche Diagnostics; Singapore) for MTB as applied by specialists for the rapid diagnosis of PTB in the routine clinical setting.

Design: A prospective study of consecutive patients suspected of PTB and tested with the AMPLICOR assay under the care of respiratory physicians. The final diagnosis was based on all relevant clinical information after at least 3 months of follow-up. Accuracy of the NAA test was compared with that of the initial expectant treatment. Expectant treatment was based on an integrated approach that incorporated clinical evaluation with results of direct smear and NAA tests.

Results: The incidence of PTB in 168 patients was 32%. The basis for expectant treatment of PTB was positive smear result in 47%, clinical suspicion in 26%, and positive AMPLICOR result in 23%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the AMPLICOR test were 77%, 100%, 99%, 90%, and 93%, respectively. In comparison, they were 96%, 97%, 94%, 98%, and 97%, respectively, for the integrated clinical approach.

Conclusions: In the rapid diagnosis of PTB, the clinical judgment of specialists augmented the utility of the NAA test: (1) specialists selected patients with high-to-moderate pretest probabilities, (2) they commenced treatment promptly on a positive NAA test result, and (3) they were willing to start treatment in some patients on the basis of high clinical suspicion despite negative smear and negative NAA test results.

Chest. 2003;124(3):909-914. doi:10.1378/chest.124.3.909

Study objectives: Evaluation of the combined use of polymerase chain reaction (PCR) and adenosine deaminase (ADA) activity on the diagnosis of pleural tuberculosis (pTB) in a region of high prevalence of tuberculosis.

Patients: PCR and determination of ADA activity were performed on the pleural fluid of every patient presenting with pleural effusion suspected to be associated with tuberculosis. The case definition of pTB involved parameters including the combination of clinical and radiologic findings; biochemical, microbiologic, and cytologic examination of the pleural fluid; and the histopathologic findings of pleural fragments obtained by biopsy. The diagnosis of pTB was confirmed in any patient presenting with positive culture findings of Mycobacterium tuberculosis, either on the pleural fluid or other biological material, or the presence of histopathologic findings suggestive of pTB on pleural biopsy, and also, in the absence of negative laboratory results, those patients with clinical improvement after empirical treatment.

Results: We studied 45 patients with pleural effusion. Of these, 16 patients met the diagnosis of pTB by our broad case definition. PCR findings were positive in six patients. The reaction was also positive in a patient whose diagnosis of tuberculosis could not be confirmed. ADA activity was considered positive in 11 patients with pTB. The combined use of PCR and ADA activity confirmed pTB in 14 patients; however, when analyzed in combination with the conventional methods, diagnosis of pTB was achieved in all 16 patients.

Conclusion: Our results show that, even in a highly endemic area, neither PCR nor ADA activity should be relied on as a single test that substitutes for the diagnostic methods already available, but rather they should be used as an extra tool in the diagnosis of pTB. The combined analysis of PCR and ADA activity, however, is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in the cases of pTB.

Chest. 2003;124(3):915-921. doi:10.1378/chest.124.3.915

Background and objectives: Between 1998 and 2000, approximately 525 Tibetan people previously living in the United States claimed refugee status in Canada, many of whom were referred to our centers for completion of tuberculosis (TB) screening. We reviewed TB-related outcomes in this cohort, to compare our experience with previously published work, and to assess follow-up after a stay in a low-incidence region.

Methods: We performed a retrospective study of all patients of Tibetan origin assessed at our centers (St. Michael’s Hospital and West Park Healthcare Centre, both in Toronto) for completion of TB screening, referred because of abnormal chest radiographic findings or positive tuberculin skin test (TST) result. We compared rates of active and drug-resistant TB in our cohort with local and national rates, as well as those previously published in similar groups.

Results: One hundred eighty-nine individuals were referred to us for assessment, and 181 records were available for review. The mean duration of stay in Canada prior to presentation was 2.6 months, after having spent a mean of 11 months in the United States. Thirty-two percent of patients gave a history of previous TB, and 97% were TST positive. Culture-positive TB was diagnosed in 24 patients (13%, 4,571 per 100,000), 12 patients had at least one drug resistance (50% of cases), and 4 patients were resistant to at least isoniazid and rifampin (multidrug resistant, 17% of cases).

Interpretation: People from highly TB endemic areas retain a very high risk of active TB and drug resistance, despite an intervening period in a low-prevalence country. It is important to maintain a high degree of suspicion for TB in all people from high-incidence areas. Treatment of all cases of latent TB infection or ongoing medical surveillance is likely justified in this population.

Clinical Investigations: SARCOIDOSIS

Chest. 2003;124(3):922-928. doi:10.1378/chest.124.3.922

Objectives: To identify factors associated with mortality in patients with sarcoidosis listed for lung transplantation, and to create a model for predicting intermediate-term mortality in these individuals.

Design: Retrospective cohort study of patients with sarcoidosis listed for lung transplant in the United States between 1995 and 2000. After identifying important risk factors for death, we developed a mortality prediction model based on an inception cohort of 75% of the subjects. The remaining 25% of the individuals served as a validation cohort for determining the validity of the model.

Setting and patients: All patients with sarcoidosis in the United States irrespective of referral center listed for lung transplantation between 1995 and 2000.

Measurements and main results: Adequate follow-up data were available for 405 patients, and 111 patients (27.4%) died while awaiting lung transplantation. Neither patient age nor gender correlated with mortality. Survivors and nonsurvivors did not differ based on the results of spirometric testing. African Americans faced a significantly increased risk of death, which persisted after controlling for other confounders (odds ratio, 2.5). The amount of supplemental oxygen used and the mean pulmonary artery pressure were the only other variables predictive of mortality. The mean (± SD) pulmonary artery pressure in those who survived was 31.7 ± 11.5 mm Hg, compared to 41.4 ± 14.4 mm Hg in nonsurvivors (p < 0.01). Survivors required 2.2 ± 2.0 L/min of oxygen vs 2.9 ± 1.7 L/min in those who died awaiting transplant (p < 0.01). Differences in pulmonary artery pressures did not reflect differences in cardiac status, as the pulmonary capillary wedge pressure and the cardiac index were similar in survivors and nonsurvivors. The final mortality prediction model included three variables: race, amount of supplemental oxygen needed, and mean pulmonary artery pressure. Based on the validation cohort, the concordance of the model for death within 2 years of listing was 0.61 (95% confidence interval, 0.47 to 0.76), indicating only moderate explanatory power.

Conclusions: Race, pulmonary hypertension, and oxygen use are important factors indicative of mortality in this population. Specific guidelines for determining time of referral for transplantation in advanced sarcoidosis should be developed. Recommendations extrapolated from data for other types of interstitial lung disease may not be applicable in sarcoidosis. The independent effect of race on outcome is troubling.

Sarcoidosis Following HIV Infection*: Evidence for CD4+ Lymphocyte Dependence
Chest. 2003;124(3):929-935. doi:10.1378/chest.124.3.929

Background: The chronic granulomatous inflammation of sarcoidosis has been hypothesized to depend on the CD4+ T-helper lymphocyte. HIV infection, which depletes these cells, has been reported to attenuate the manifestations of sarcoidosis.

Study objectives: We asked whether the development of symptomatic sarcoidosis in the context of preexisting HIV infection was dependent on the CD4+ lymphocyte count.

Design: We performed a retrospective standardized chart review of all patients who developed granulomatous inflammation following HIV infection at an urban academic referral center.

Measurements: We identified seven patients with sarcoidosis within this cohort and compared their CD4+ lymphocyte count to that in a cohort of 16 patients in whom similar granulomatous inflammation was found but who did not have sarcoidosis. We then compared our cases to all reported cases using a systematic literature review.

Results: The CD4+ lymphocyte count was > 200 cells/μL in all of our patients with HIV infection when they developed subsequent sarcoidosis. In contrast, specific etiologies for granulomatous inflammation were found in all 10 HIV-infected patients who presented with granulomatous inflammation and a CD4+ lymphocyte count of < 200 cells/μL, with infectious etiologies found in 8 patients. Similarly, there was relative preservation of the CD4+ lymphocyte count in previously reported cases, with 14 of 19 patients (74%) having an absolute CD4+ lymphocyte count of > 200 cells/μL.

Conclusions: We conclude that the development of the chronic granulomatous inflammation of sarcoidosis appears to depend on the preservation or restoration of the peripheral CD4+ lymphocyte count and that in most cases the CD4+ lymphocyte count exceeds 200 cells/μL. Furthermore, alternative specific etiologies of granulomatous inflammation are generally identifiable in HIV-infected patients with peripheral CD4+ lymphocyte counts of < 200 cells/μL.

Clinical Investigations: SLEEP AND BREATHING

Chest. 2003;124(3):936-941. doi:10.1378/chest.124.3.936

Study objectives: It has been suggested that sleep-disordered breathing (SDB) is a risk factor for ischemic heart disease, and may be associated with increased morbidity and mortality due to cardiovascular disease. The aim of this study was to examine the relation between nocturnal oxygen desaturation (NOD) due to SDB and the Gensini score, which is given to define the severity of coronary atherosclerosis, based on coronary angiograms findings, in patients with coronary artery disease.

Design: We examined the NOD index (ODI) (desaturation of > 3%/events per hour) using pulse oximetry in 59 consecutive patients with coronary artery disease (ejection fraction, > 40%) that was diagnosed by coronary angiography, 30 patients with angina pectoris and 29 patients with old myocardial infarction. The Gensini score was calculated for each patient from the coronary arteriogram. The patients were classified into the following three groups according to the severity of oxygen desaturation: ODI of < 5 events per hour (group N; 16 patients); ODI of ≧ 5 but < 15 events per hour (group A; 27 patients); and ODI of ≧ 15 events per hour (group B; 16 patients). The groups then were examined for the relation between the ODI and the Gensini score.

Results: Of the total number of patients, 72.9% had a nocturnal ODI of more than five events per hour. The Gensini score was significantly higher in groups A and B than in group N, and showed a significant positive correlation with the ODI (R = 0.45; p = 0.01) in all patients. Multiple regression analysis showed that the ODI was the most significant, independent determinant of the Gensini score among the coronary risk factors tested, and that it explained 13.4% of the variance.

Conclusion: These findings suggest that NOD due to SDB may be an important contributor to coronary atherosclerosis in the patients with cardiovascular disease.

Chest. 2003;124(3):942-947. doi:10.1378/chest.124.3.942

Objective: Obstructive sleep apnea (OSA) has been shown to affect the quality of life (QOL) in patients, and QOL improves after treatment with nasal continuous positive airway pressure (CPAP). However, the effects on the bed partner of the patient with OSA have received little attention. We studied QOL in patients with OSA and their bed partners, and the effect of CPAP therapy on QOL.

Design: Fifty-four patients and their bed partners who had been seen for evaluation of OSA, had undergone polysomnography, and subsequently had received treatment with CPAP. Patients and bed partners completed the Epworth sleepiness scale (ESS) and QOL questionnaires before and after the patients’ therapy.

Setting: Sleep disorders center in an academic medical center.

Participants: Patients with documented OSA and regular bed partners.

Interventions: Both individuals completed the 36-item short-form health survey (SF-36), the ESS, and the Calgary sleep apnea quality of life index (SAQLI). At about 6 weeks after CPAP therapy, patients and their bed partners completed the same set of questionnaires again.

Results: Of the 54 subjects who completed the study, the mean (± SD) apnea-hypopnea index was 48.4 ± 33.3. For the subjects, the mean ESS decreased from 12.9 ± 4.4 to 7.3 ± 4.0 (p < 0.001) after treatment with CPAP. For the bed partners, the mean ESS decreased from 7.4 ± 6.1 to 5.8 ± 4.7 (p = 0.02). The mean scores on the SAQLI were 4.1 ± 1.0 for the subjects and 4.5 ± 1.3 for the bed partners. Following CPAP therapy, the SAQLI increased in the subjects to 4.9 ± 1.2 (p < 0.001), and in the bed partners to 5.1 ± 0.9 (p = 0.002). The SF-36 showed positive changes in both the subjects and the bed partners. Significant improvements were observed in the subjects in role-physical, vitality, social functioning, role-emotional, and mental health domains. In the bed partners, significant changes in the SF-36 were observed in role-physical, vitality, social functioning, and mental health domains.

Conclusion: OSA results in impaired QOL in both the patients and their bed partners. Treatment with CPAP improves QOL, as measured by the SF-36 and the SAQLI.

Chest. 2003;124(3):948-953. doi:10.1378/chest.124.3.948

Objective: To compare the effect of adenotonsillectomy on rapid eye movement (REM)- and non-REM–related respiratory and sleep architecture characteristics in children with obstructive sleep apnea syndrome (OSAS).

Study design: This prospective study evaluated 36 children (median age, 6.9 years; range, 1.8 to 12.6 years) with OSAS using polysomnography before and a few months after adenotonsillectomy. Primary outcomes included the number of obstructive apnea and hypopnea and arousals per hour of sleep.

Results: At 4.6 months (range, 1 to 16 months) after adenotonsillectomy, there was a significant improvement of all respiratory parameters. The median respiratory disturbance index (RDI) decreased from 4.1/h (range, 0 to 85/h) to 0.9/h (range, 0 to 13/h) after adenotonsillectomy (p < 0.0001). The median non-REM RDI decreased from 3.0/h (range, 0 to 89/h) to 0.4/h (range, 0 to 13/h) [p < 0.001] as compared with REM RDI, which decreased from 7.8/h (range, 0 to 69/h) to 2.3/h (range, 0 to 54/h) after adenotonsillectomy (p < 0.01). Median arousal index decreased following adenotonsillectomy from 17.5/h (range, 7 to 57/h) to 14.0/h (range, 6 to 47/h) [p < 0.03].

Conclusions: Adenotonsillectomy resulted in a greater improvement in non-REM RDI as compared with REM-RDI, and a decrease in the number of arousals.

Clinical Investigations: CARDIOLOGY

Chest. 2003;124(3):954-961. doi:10.1378/chest.124.3.954

Background and objectives: The effects of β-blocking agents on exercise tolerance in cardiopulmonary exercise testing (CPX) have not been fully identified. Because the negative chronotropic effects of these agents produce a sluggish increase in heart rate (HR) during CPX, exercise capacity is actually underestimated by methods that depend on HR-related variables such as peak oxygen uptake (V̇o2) and anaerobic threshold (AT). The aim of this study was to clarify the efficacy of β-blocking agents by means of V̇o2 kinetics, a parameter independent of HR, in patients with dilated cardiomyopathy (DCM).

Design and patients: The exercise capacity of 12 patients (9 men and 3 women; mean ± SD age, 54 ± 12 years; New York Heart Association class I [n = 1], NYHA class 2 [n = 4], and NYHA class III [n = 6]) with DCM, who were treated with β-blocking agents, was evaluated by CPX. V̇o2 was calculated from respiratory gas analysis on a breath-by-breath basis. Nine patients were treated with metoprolol (30 mg or 60 mg), two with carteolol (10 mg or 20 mg), and one patient with atenolol (25 mg).

Results: All patients showed a significantly favorable results (ie, improvement in symptoms of congestive heart failure). Peak V̇o2 (20.4 ± 5.1 to 18.8 ± 5.8 mL/min/kg), AT (12.7 ± 3.5 to 12.1 ± 2.1 mL/min/kg), and exercise time (4.8 ± 2.2 to 4.5 ± 2.1 s) were unchanged. The time constant of V̇o2 kinetics (τ) on response to constant low-dose work loading (warm up) decreased significantly (64 ± 30 to 44 ± 24 s; p < 0.01) and ejection fraction increased (30 ± 14 to 44 ± 15%, p < 0.01) significantly following treatment with β-blocking agents. In spite of excluding two NYHA I patients, these changes were also statistically correlated.

Conclusion: In the low level of exercise, τ was prolonged in patients with DCM. Although indexes of total exercise time and AT were not useful markers for clinical improvement in cardiac performance as assessed by echocardiography, measuring can validly assess the beneficial effects in heart failure treated with β-blocking agents.

Chest. 2003;124(3):962-968. doi:10.1378/chest.124.3.962

Background: Recently, we demonstrated that angiographic morphologic features of high-burden thrombus formation are independent predictors of combined slow flow (ie, Thrombolysis in Myocardial Infarction [TIMI] grade 2) and no reflow (ie, ≤ TIMI grade 1) in the infarct-related artery (IRA) after direct percutaneous coronary intervention (d-PCI) for the treatment of acute myocardial infarction (AMI). Current data have demonstrated that when administered in conjunction with PCI for acute coronary syndrome, platelet glycoprotein IIb/IIIa inhibitors can provide additional clinical benefits. Thus, we hypothesized that after pretreatment with tirofiban, angiographic morphologic features of high-burden thrombus formation would no longer be independent predictors of combined slow flow and no reflow after treatment with d-PCI.

Methods and results: Between January 2001 and April 2002, tirofiban was administered to 210 consecutive patients with ST-segment elevated AMI before coronary angiography was performed, and 84 patients (40.0%) were found to have high-burden thrombus formation in the IRA. The TIMI flow grade of the IRA was assessed immediately after the performance of d-PCI, and the 30-day clinical outcomes were evaluated prospectively. The incidence of restoration of normal coronary flow in the IRA was 83.6%. Three baseline angiographic morphologic features indicating high-burden thrombus formation, including (1) the cutoff pattern of occlusion in the IRA (p = 0.0001), (2) the accumulated thrombus proximal to the occlusion (p = 0.0001), and (3) a reference lumen diameter of the IRA of ≥ 4.0 mm (p = 0.001), were independent predictors of combined slow flow and no reflow. In stratified analysis, the rates of slow flow and no reflow after d-PCI rose rapidly as the number of independent predictors increased (0 predictors, 3.8%; 1 predictor, 29.0%; and 2 predictors, 70.6%). The overall 30-day mortality rate was 6.7%. The mortality rate was significantly higher in patients with TIMI flow lower than or equal to grade 2 than in those with TIMI grade 3 flow (15% vs 1.3%, respectively; p = 0.003).

Conclusions: Tirofiban did not provide additional clinical benefits when administered in conjunction with d-PCI for AMI, even in the subgroup of patients with a high-burden thrombus. Those distinct angiographic morphologic features of high-burden thrombus formation remained as independent predictors of combined slow flow and no reflow after d-PCI, and were independent of the use of tirofiban.

Clinical Investigations: PLEURA

Chest. 2003;124(3):969-977. doi:10.1378/chest.124.3.969

Background: Restrictive cardiomyopathy frequently complicates primary systemic amyloidosis (AL), yet only a small number of these patients develop large pleural effusions refractory to diuretic therapy and thoracentesis. We hypothesized that disruption of pleural function by amyloid deposits underlies persistent pleural effusions (PPEs) in patients with AL disease.

Methods: We performed a retrospective study of AL patients with and without PPEs who had been referred to Boston University between 1994 and 2001. The presence of PPEs was defined by a failure to resolve the condition with thoracentesis and aggressive diuresis. AL cardiomyopathy patients without pleural effusions constituted the control (cardiac) group. Indexes of plasma cell dyscrasia, nephrotic syndrome, thyroid function, and echocardiographic measures of left and right ventricle performance were compared between groups. When available, closed needle biopsies and autopsy specimens of parietal pleura were examined for amyloid deposits.

Results: Among 636 patients with AL, 35 PPE patients underwent a median of three thoracenteses each. No statistical differences were found between the PPE and cardiac groups in echocardiographic measures of septal thickness, left ventricular systolic function, or diastolic compliance. Right ventricular (RV) hypokinesis occurred more often in PPE patients; however, nearly half of this group had normal RV systolic function. Renal function, plasma protein levels, and thyroid function were the same between groups. Nephrotic range proteinuria (ie, > 3 g/d) was more prevalent in the cardiac group than in the PPE group (44% vs 26%, respectively; p = 0.057). All pleural biopsies in the PPE group (six biopsies) revealed amyloid deposits. Autopsy samples of parietal pleura were negative for disease in two cardiac patients. Eighteen patients had chest tubes placed, and 11 underwent pleurodesis. PPE signaled limited survival among patients who were ineligible for treatment. Untreated PPE patients lived a median 1.8 months vs 6 months for untreated cardiac patients (p = 0.031). Survival after intensive chemotherapy and autologous stem cell transplantation was comparable in the PPE and cardiac groups (21.8 vs 15.6 months, respectively; p = 0.405).

Conclusion: In AL patients with cardiac amyloid, neither echocardiographic measures of ventricular function nor the degree of nephrosis distinguished those patients with PPEs. We conclude that pleural amyloid infiltration plays a central role in the creation and persistence of pleural effusions among patients with AL.

Chest. 2003;124(3):978-983. doi:10.1378/chest.124.3.978

Study objective: To report the etiology of large and massive pleural effusions, and to compare their biochemical fluid characteristics with those of smaller size, and between malignant and nonmalignant conditions.

Design: Retrospective chart review of all patients undergoing thoracentesis at an academic medical center in Lleida, Spain, during a 10-year period.

Patients: Posteroanterior chest radiographs were available in 766 patients during the study period. Large pleural effusions (ie, two thirds or more of the hemithorax without its complete obliteration) were identified in 70 patients (9%), and massive pleural effusions (ie, hemithorax was completely opacified) were identified in 93 patients (12%).

Results: A similar etiologic spectrum between large and massive pleural effusions was observed. The most frequent cause of these pleural effusions was malignancy (89 patients; 55%), followed by complicated parapneumonic or empyema (36 patients; 22%), and tuberculosis (19 patients; 12%). Compared with nonmalignant pleural effusions, patients with large or massive malignant pleural effusions were more likely to have pleural fluids with higher RBC counts (18.0 × 109 cells/L vs 2.7 × 109 cells/L, respectively; p < 0.001) and lower adenosine deaminase (ADA) activity (11.5 vs 31.5 U/L, respectively; p < 0.001), which were the two parameters that were selected by a stepwise logistic-regression model as independent predictors of malignancy. In addition, large/massive malignant pleural effusions showed higher median RBC counts (18.0 × 109 cells/L vs 4.3 × 109 cells/L, respectively; p < 0.001), higher lactate dehydrogenase levels (641 vs 409 U/L, respectively; p = 0.001), lower pH (7.39 vs 7.42, respectively; p = 0.006) content, but similar cytologic yield (63% vs 53%, respectively; p = 0.171) than smaller malignant pleural effusions.

Conclusions: The presence of a large or massive pleural effusion enables the clinician to narrow the differential diagnosis of pleurisy, since most effusions are secondary to malignancy or infections (either bacterial or mycobacterial). Bloody pleural fluid with low ADA content favors a malignant condition.

Clinical Investigations: SURGERY

Chest. 2003;124(3):984-988. doi:10.1378/chest.124.3.984

Study objectives: The aim of this study was to evaluate the early and long-term outcomes in patients undergoing aortic root replacement (ARR) with the Bentall procedure.

Design: Retrospective study.

Setting: Cardiothoracic surgery unit.

Patients and methods: Between January 1986 and January 2002, 72 patients (mean age 58.3 ± 12.4 years, 81.9% males) underwent ARR by means of a Bentall operation. Annuloaortic ectasia was the most frequent cause of aortic disease in this series of patients (31 patients; 43.1%), followed by type A dissection (19 patients; 26.3%), atherosclerotic aneurysm (18 patients; 25.1%), and poststenotic dilatation (4 patients; 5.5%). Nine patients (12.5%) had Marfan syndrome, and 10 patients (13.8%) underwent a concomitant replacement of the aortic arch. Follow-up ranged from 2 to 192 months (mean [± SD], 86.6 ± 23.8 months).

Results: The mean 30-day mortality rate was 5.5 ± 2%. The mean early mortality rate was 21 ± 4% and 0% (p < 0.001), respectively, in patients with and without dissecting aortic aneurysms. There were two late deaths that were due to a pulmonary neoplasm and a cerebrovascular accident. The mean 16-year survival rate was 91.7 ± 3.2%. The mean hazard of freedom from death was constant beyond 3 years (8.5 ± 3.5%). No patient required reoperation. Furthermore, the long-term clinical follow-up was marked by a complete absence of endocarditis, anticoagulant-related hemorrhage, valve thrombosis, and prosthesis failure. Finally, patients showed a significant improvement in mean New York Heart Association functional status (1.3 ± 0.1; p < 0.001 [postoperatively vs preoperatively]).

Conclusions: In our experience, the late results of the Bentall operation were satisfactory. Our findings confirm that this technique still represents the procedure of choice for ARR with coronary reimplantation.

Chest. 2003;124(3):989-995. doi:10.1378/chest.124.3.989

Background: After surgery to repair a type A aortic dissection, most late complications and mortality result from descending aorta-related problems. This study was performed to determine the risk factors leading to descending aortic aneurysm formation and late mortality in patients undergoing the type A aortic dissection operation.

Methods: The medical records of patients who survived the operation for type A aortic dissection between 1984 and 1998 were reviewed. There were 144 patients (95 men and 49 women), ranging in age from 24 to 78 years (mean age, 52 years). Most patients were acutely ill, 15 patients were in shock, and 54 patients had cardiac tamponade at the time of the surgical procedure. One hundred thirty-seven patients had ascending aortic replacement only, and of the other 6 patients 2 had hemiarch and 4 had total arch replacement using the elephant trunk technique. The aortic valve was replaced in 23 patients, resuspended in 100, and untouched in 21. Twenty-four risk factors were evaluated in statistical analyses for the prediction of descending aortic aneurysm formation and 3-year mortality. Risk factors were investigated using univariate and multiple logistic regression and survival analyses.

Results: The 3-year, 5-year, and 8-year cumulative survival rates were 96.2%, 89.1%, and 80.0%, respectively. The 3-year, 5-year, and 8-year cumulative survival rates, free from descending aortic aneurysm formation or descending aorta operation, were 74.7%, 58.6%, and 43.0%, respectively. Multivariate analysis confirmed that patent false lumen and initial descending aortic diameter were statistically significant risk factors for descending aortic aneurysm formation.

Conclusions: The medium-term survival rate of patients who received operations for type A aortic dissection was satisfactory, despite the high incidence of descending aortic aneurysm formation. The intimal entry site over the aortic arch that was resected during the first operation could decrease the patency rate of a false lumen over the descending aorta. In the absence of a patent false lumen over the descending aorta, the chance of descending aortic aneurysm formation or operation is lessened, and the late survival rate is increased.

Surgical Treatment of Superior Sulcus Tumors*: Results and Prognostic Factors
Chest. 2003;124(3):996-1003. doi:10.1378/chest.124.3.996

Objectives: To study the clinical characteristics, treatment modalities, and outcome of patients with superior sulcus tumors who underwent surgery over a 15-year period.

Design: Retrospective clinical study.

Methods: Clinical records of all patients operated on for superior sulcus tumors by the same surgical team between 1988 and 2002 were reviewed retrospectively.

Results: Sixty-seven patients were operated on in this period. All the patients underwent en bloc lung and chest wall resection. Surgical approaches were as follows: posterolateral thoracotomy according to Paulson (n = 33), combined transcervical and transthoracic approach (n = 33), and isolated transcervical approach (n = 1). Types of pulmonary resection included lobectomies (n = 59), pneumonectomies (n = 2), and wedge resections (n = 6). Pathologic stages were IIB, IIIA, and IIIB in 49 cases, 12 cases, and 6 cases, respectively. Resection was complete in 55 patients (82%). Operative mortality was 8.9% (n = 6). Postoperative treatment was administered in 53 patients (radiotherapy, n = 42; chemoradiotherapy, n = 9; and chemotherapy, n = 2). Overall 2-year and 5-year survival rates were 54.2% and 36.2%, respectively. Five-year survival was significantly higher after complete resection than after incomplete resection (44.9% vs 0%, p = 0.000065). The presence of associated major illness negatively affected the outcome (5-year survival, 16.9% vs 52%; p = 0.043). Age, weight loss, respiratory impairment, tumor size, presence of nodal disease, and histologic type did not influence the long-term outcome. At multivariate analysis, only the completeness of resection and the absence of associated major comorbidities had an independent positive prognostic value.

Conclusions: Superior sulcus tumor remains an extremely severe condition, but long-term survivals may be achieved in a large percentage of cases. The presence of associated major illness and the completeness of resection are the two most important factors affecting the long-term outcome.

Clinical Investigations: Miscellaneous

Catamenial Pneumothorax*: A Prospective Study
Chest. 2003;124(3):1004-1008. doi:10.1378/chest.124.3.1004

Objectives: To evaluate the incidence of catamenial pneumothorax (CP) among women who have been referred for the surgical treatment of spontaneous pneumothorax (SP) and to study its pathogenic mechanisms.

Design: A prospective study of women of reproductive age who have been referred to our center for the surgical treatment of SP. Patients with pneumothorax secondary to a known lung disease were excluded.

Setting: A university hospital.

Methods: At the preoperative evaluation, special attention was given to the investigation of a possible temporal relationship between pneumothorax and menses. Video-assisted thoracoscopy constituted the operative technique of choice. The lung was inspected to identify blebs or bullae and the origin of possible air leaks. Signs of thoracic endometriosis were also carefully searched for. The diaphragm was systematically inspected to search for holes and/or endometrial implants. When limited diaphragmatic abnormalities were found, a partial diaphragmatic resection was carried out using an endoscopic stapler. In case of lesions that were not accessible by a purely endoscopic approach, a utility minithoracotomy was used.

Results: In an 18-month period, 32 women with SP were referred for surgery. In eight cases, the catamenial character of the pneumothorax was recognized by clinical history. In all these patients, the following diaphragmatic abnormalities were found at surgery: holes (one patient); endometrial implants (three patients); and both (four patients). Visceral pleural endometriosis was found in one patient. During pathologic examination, diaphragmatic endometriosis was confirmed in seven of the eight cases. In one patient, it was associated with pulmonary and pleural endometriosis. In only one patient (with multiple diaphragmatic holes and a pulmonary nodular brown lesion), endometriosis could not be confirmed at histology, but signs of parenchymal focal hemorrhages were found.

Conclusions: Our experience shows that (1) CP is more frequent than expected and (2) diaphragmatic abnormalities seem to play a fundamental role in its pathogenesis.

Chest. 2003;124(3):1009-1015. doi:10.1378/chest.124.3.1009

Study objectives: Aspiration pneumonia, a leading cause of death in patients with Parkinson disease (PD), usually occurs at the advanced stages of the disease. We investigated both motor and sensory components of cough and induced-sputum substance P (SP) concentrations in patients with early and advanced stages of PD to assess whether cough efficacy is impaired in PD.

Subjects: Fifteen female patients with early stages of PD (Hoehn and Yahr stage II-III), 10 patients with advanced stages of PD (Hoehn and Yahr stage IV), and 15 age-matched female control subjects were investigated.

Measurements: The motor component of cough efficacy was assessed by monitoring voluntary maximal cough peak flow. The sensory component of cough efficacy was assessed by measuring cough reflex sensitivity to citric acid inhalation. Sputum SP concentrations were measured in sputum induced by hypertonic saline solution inhalation.

Results: The mean (± SD) cough peak flow rates in patients with both early PD (230 ± 74 L/min; p < 0.005) and advanced PD (186 ± 60 L/min; p < 0.0001) were significantly weaker than that in control subjects (316 ± 70 L/min). Cough reflex sensitivity in patients with advanced PD (46.7 ± 49.3 g/L) was significantly lower compared to control subjects (14.5 ± 16.6 g/L; p < 0.01) and patients with early PD (11.2 ± 14.8 g/L; p < 0.005). The sputum SP concentration was significantly lower in patients with advanced PD (11.2 ± 8.4 pg/mL) compared to that in control subjects (35.6 ± 15.4 pg/mL) and patients with early PD (28.5 ± 16.4 pg/mL).

Conclusion: In the early stages of the disease, mainly the motor component of cough was impaired. In advanced stages of the disease, both the motor and sensory components of cough were impaired. Sputum SP concentration significantly declined in patients with advanced PD. The results suggest that the combination of impaired motor and sensory components of cough may play an important role in the development of aspiration pneumonia in PD.

Clinical Investigations in Critical Care

Cirrhosis as a Risk Factor for Sepsis and Death*: Analysis of the National Hospital Discharge Survey
Chest. 2003;124(3):1016-1020. doi:10.1378/chest.124.3.1016

Study objectives: The unfavorable influence of cirrhosis on survival in the critically ill has been supported by several single-center reports. Variations in case mix, the technological capabilities of individual facilities, and differences in organizational staffing and structure could limit the extrapolation and generalization of these data to other institutions. To assess the impact of a diagnosis of cirrhosis on outcomes of sepsis, sepsis-related mortality, and respiratory failure in hospitalized patients, we analyzed data from the National Hospital Discharge Survey (NHDS) from 1995 to 1999 to determine its national consequence.

Design: Secondary analysis of an existing national database.

Patients or participants: Based on NHDS estimates, 175 million hospital discharges occurred during the 5-year period of study. One percent (1.7 million) of these hospitalizations involved a diagnosis of cirrhosis.

Interventions: None.

Measurements and results:After adjustments for age, race, and gender, cirrhotic individuals are significantly more likely to die while hospitalized (adjusted risk ratio [RR], 2.7; 95% confidence interval [CI], 2.3 to 3.1), to have hospitalizations associated with sepsis (adjusted RR, 2.6; 95% CI, 1.9 to 3.3), and to die from sepsis (adjusted RR, 2.0; 95% CI, 1.3 to 2.6). Additionally, cirrhosis is associated with an increased RR for acute respiratory failure (adjusted RR, 1.4; 95% CI, 1.1 to 1.8) and death from acute respiratory failure (adjusted RR, 2.6; 95% CI, 1.5 to 3.6).

Conclusions: In this national database of hospital discharge information, a diagnosis of cirrhosis is strongly associated with an increased risk of sepsis, acute respiratory failure, sepsis-related mortality, and acute respiratory failure-related mortality.

Chest. 2003;124(3):1021-1029. doi:10.1378/chest.124.3.1021

Objective: To determine the influence of microbiologically confirmed infection on hospital mortality among patients requiring intensive care for > 48 h.

Design: Prospective cohort study.

Setting: Medical ICU of the Barnes-Jewish Hospital, an urban teaching hospital.

Patients: A total of 893 patients requiring intensive care for > 48 h.

Interventions: Prospective patient surveillance and data collection.

Measurements and main results: Three hundred seventy-two patients (41.7%) requiring intensive care for > 48 h had a microbiologically confirmed infection. Only six patients (0.7% [1.6% of patients with microbiologically confirmed infections]) received inadequate antimicrobial therapy during the first 24 h of treatment, and 248 patients (27.8%) died during hospitalization. Compared to hospital survivors, hospital nonsurvivors were significantly more likely to have a microbiologically confirmed infection (53.2% vs 37.2%, respectively; p < 0.001) and to develop severe sepsis (45.6% vs 28.7%, respectively; p < 0.001). Cirrhosis and the requirement for vasopressors were the only variables identified by multiple logistic regression analysis as independent risk factors for hospital mortality in all patient groupings of severity of illness. Multiple logistic regression analysis also demonstrated that underlying malignancy (adjusted odds ratio [AOR], 1.98; 95% CI, 1.55 to 2.53), chronic renal insufficiency (AOR, 1.57; 95% CI, 1.31 to 1.87), cirrhosis (AOR, 1.94; 95% CI, 1.48 to 2.53), temperature > 38.3°C (AOR, 1.72; 95% CI, 1.47 to 2.02), severe sepsis (AOR, 2.78; 95% CI, 1.94 to 3.98), positive culture for vancomycin-resistant enterococci (AOR, 1.78; 95% CI, 1.51 to 2.09), and the presence of multiple infections (AOR, 1.65; 95% CI, 1.28 to 2.14) were independently associated with the requirement for therapy with vasopressors.

Conclusions: Microbiologically confirmed infections are common among patients requiring medical intensive care for > 48 h. Despite the administration of adequate antimicrobial therapy, microbiologically confirmed infections appear to be an important cause of hemodynamic instability and increased hospital mortality. These data suggest that clinical efforts aimed at the prevention of infections and improvements in the medical management of patients with severe infections, especially those associated with hemodynamic instability and the need for vasopressors, are required to achieve further improvements in patient outcomes.

Chest. 2003;124(3):1030-1038. doi:10.1378/chest.124.3.1030

Objective: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU.

Design: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999).

Setting: ICUs of a tertiary care hospital in Houston, TX.

Patients: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU).

Interventions: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999.

Measurements and main results:The rates of nosocomial BSIs and other patients’ characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients’ characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999.

Conclusions: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Chest. 2003;124(3):1039-1045. doi:10.1378/chest.124.3.1039

Objective: The past decade has witnessed growth in the long-term acute care (LTAC) hospital industry. There are no reliable risk assessment models that can adjust outcomes across such facilities with different criteria for admitting patients. Variation in reported outcomes makes it difficult to determine whether a patient, or group of patients, may benefit from such care. This study sought to determine the extent to which survival in the LTAC setting is associated with age, race, residual organ system failures (OSFs), or APACHE (acute physiology and chronic health evaluation) III scores at the time of admission to LTAC.

Design: Retrospective medical record review.

Setting: Four freestanding facilities of a LTAC hospital.

Patients: A sample of 300 hospital admissions weighted to represent the study hospital population.

Measurements: Inpatient survival modeled as a function of age, APACHE III score calculated within 72 h prior to LTAC admission, and residual OSFs present on admission to LTAC.

Results: Logistic regression analysis shows age and OSF were most predictive of inpatient survival (receiver operating characteristic curve area = 0.81). APACHE III score was not predictive of survival in the multivariate model.

Conclusions: Survival in LTAC is primarily associated with age and OSFs, which should be used to adjust for patient populations among LTAC settings when comparing outcomes. Our model identifies a group of patients with the poorest likelihood of survival in the LTAC setting, and may be used to facilitate dialogue with patients and family in cases where continued aggressive care is least effective.

Chest. 2003;124(3):1046-1052. doi:10.1378/chest.124.3.1046

Study objective: Mechanical ventilation may damage the lung. Low tidal volume (Vt) is protective, but Vt is scaled to body weight (BW) and may be high in functionally small ARDS lungs. We hypothesized that exhaled breath condensate (EBC) nitrite (NO2) concentration may increase with lung distension.

Design: Prospective, noncontrolled study.

Setting: University hospital and medical ICU.

Patients: Thirty-five ICU patients requiring mechanical ventilation (severe pneumonia, n = 31; exacerbated COPD, n = 4). Patients were scored according to American and European Consensus Conference on ARDS criteria (AECC) [no lung injury, n = 7; acute lung injury, n = 13; ARDS, n = 15], as well as the Murray lung injury severity score (LISS) [score 0, n = 3; score 0.1 to 2.5, n = 19; score > 2.5, n = 13].

Interventions: EBC was collected and analyzed for NO2, interleukin (IL)-6, and IL-8. Serum was analyzed for IL-6, IL-8, and procalcitonin.

Results and measurements: EBC NO2 correlated well with Vt (milliliters per kilogram of BW; r = 0.79, p < 0.0001) and expiratory minute volume (r = 0.60, p < 0.0001) but not with other ventilatory parameters or parameters of pulmonary (EBC IL-6, EBC IL-8) or systemic (serum IL-6, IL-8, and procalcitonin) inflammation. The ratio of EBC NO2 and the size of the Vt correlated directly with lung injury (AECC, r = 0.66, p < 0.0001; LISS, r = 0.84, p < 0.0001).

Conclusion: EBC NO2 increased linearly with Vt. The ratio of EBC NO2 to Vt is assumed to reflect NO2 release at a given Vt. An increase in this ratio indicates an inappropriate increase of NO2 production most likely due to mechanical stress of the remaining open lung units in injured lungs. We conclude that the EBC NO2/vt ratio may help to identify situations of critical mechanical stress.

Laboratory and Animal Investigations

Chest. 2003;124(3):1053-1059. doi:10.1378/chest.124.3.1053

Objectives: To develop a nonlethal model of hyperdynamic sepsis, and to measure vital organ blood flows in this setting.

Design: Randomized crossover animal study.

Setting: Animal laboratory of university-affiliated physiology institute.

Subjects: Seven Merino cross sheep.

Interventions: Surgical implantation of transit-time flow probes around sagittal sinus and circumflex coronary, superior mesenteric, and left renal arteries, and of an electromagnetic flow probe around the ascending aorta. After recovery, randomization to either 6 h of observation under normal conditions (control) or 6 h of observation after the induction of hyperdynamic nonlethal sepsis (sepsis), with each animal crossing over to the other treatment after a 2-week interval.

Measurements and main results: Injection of Escherichia coli induced nonlethal hyperdynamic sepsis within 5 to 6 h with hypotension (mean arterial pressure [± SD], 85 ± 7 mm Hg vs 69 ± 8 mm Hg), increased cardiac output (4.0 ± 0.9 L/min vs 7.2 ± 1.2 L/min), tachycardia (60 ± 10 beats/min vs 160 ± 15 beats/min), fever, oliguria, and tachypnea. Compared to control animals, hyperdynamic sepsis increased renal (330 ± 101 mL/min vs 214 ± 75 mL/min), mesenteric (773 ± 370 mL/min vs 516 ± 221 mL/min), and coronary (54 ± 24 mL/min vs 23 ± 10 mL/min) blood flow (p < 0.05). There was no significant change in sagittal sinus flow. Despite increased coronary flow, myocardial contractility decreased (800 ± 150 L/min/s vs 990 ± 150 L/min/s). Despite increased mesenteric and renal blood flow, there was hyperlactatemia (0.5 ± 0.1 mmol/L vs 1.9 ± 0.3 mmol/L); despite increased renal blood flow, all experimental animals acquired oliguria (160 ± 75.3 mL/2 h vs 50.2 ± 13.1 mL/2 h) and increased serum creatinine levels (0.07 ± 0.02 mmol/L vs 0.11 ± 0.02 mmol/L).

Conclusions: Injection of E coli induced hyperdynamic nonlethal sepsis. During such hyperdynamic sepsis, blood flow to heart, gut, and kidney was markedly increased; however, organ dysfunction developed. We speculate that global ischemia may not be the principal mechanism of vital organ dysfunction in hyperdynamic sepsis.

Chest. 2003;124(3):1060-1066. doi:10.1378/chest.124.3.1060

Background: Induced sputum (IS) using the cytospin technique has been extensively employed to characterize inflammatory airway diseases; however, procedures of cell enrichment based on cytospin increase the analytical costs and require slide processing within a short period of time after sampling.

Study objectives: To compare three different techniques for cytologic analysis of IS, and to determine the time required by each method and the costs involved.

Design: Cross-sectional study.

Setting: Tertiary-care university hospital.

Patients and measurements: Eighty-nine patients with asthma and 11 subjects without asthma were submitted to increasing hypertonic saline solution concentrations of 2, 3, 4, and 5% for 7 min for sputum induction. Samples were smeared without treatment with 0.1% dithiothreitol (DTT) [technique A], after treatment with DTT (technique B), and after treatment with DTT and cytospin (technique C). All slides were air-dried and stained with Leishman stain. Two independent observers counted at least 200 inflammatory cells on each slide.

Results: Eighty percent of the slides processed by techniques A and B and 65% of the slides processed by technique C represented sputum samples of acceptable quality. The eosinophil percentages in sputum obtained by techniques A and C were closely correlated, as also were those obtained by techniques B and C (r = 0.64 and r = 0.63, respectively; p < 0.01). There was a positive correlation for eosinophils when we compared techniques A and B (r = 0.57, p < 0.01). The neutrophil correlation was significant when the three techniques were compared (technique A vs technique B, r = 0.66; technique A vs technique C, r = 0.51; and technique B vs technique C, r = 0.57; p < 0.01). Bland-Altman analysis showed a good agreement for eosinophil and neutrophil counts when techniques A and B were compared to technique C.

Conclusions: The three techniques are good indicators of lung inflammation. Techniques A and B are less time consuming and are of lower cost.

Topics: cell count , sputum , asthma
Chest. 2003;124(3):1067-1072. doi:10.1378/chest.124.3.1067

Background: Both vasoactive intestinal peptide (VIP) and nitric oxide (NO) relax airway smooth muscle and are potential co-transmitters of neurogenic airway relaxation. The availability of neuronal NO synthase (nNOS) knockout mice (nNOS−/−) provides a unique opportunity for evaluating NO.

Objective: To evaluate the relative importance of NO, especially that generated by nNOS, and VIP as transmitters of the inhibitory nonadrenergic, noncholinergic (NANC) system.

Study design: In this study, we compared the neurogenic (tetrodotoxin-sensitive) NANC relaxation of tracheal segments from nNOS−/− mice and control wild-type mice (nNOS+/+), induced by electrical field stimulation (EFS). We also examined the tracheal contractile response to methacholine and its relaxant response to VIP.

Results: EFS (at 60 V for 2 ms, at 10, 15, or 20 Hz) dose-dependently reduced tracheal tension, and the relaxations were consistently smaller (approximately 40%) in trachea from nNOS−/− mice than from control wild-type mice (p < 0.001). VIP (10− 8 to 10−6 mol/L) induced concentration-dependent relaxations that were approximately 50% smaller in nNOS−/− tracheas than in control tracheas. Methacholine induced concentration-dependent contractions that were consistently higher in the nNOS−/− tracheas relative to wild-type mice tracheas (p > 0.05).

Conclusion: Our data suggest that, in mouse trachea, NO is probably responsible for mediating a large (approximately 60%) component of neurogenic NANC relaxation, and a similar (approximately 50%) component of the relaxant effect of VIP. The results imply that NO contributes significantly to neurogenic relaxation of mouse airway smooth muscle, whether due to neurogenic stimulation or to the neuropeptide VIP.

Preliminary Report

Chest. 2003;124(3):1073-1080. doi:10.1378/chest.124.3.1073

Study objectives: Significant morbidity and mortality offset the benefits of lung volume reduction surgery (LVRS) for emphysema. By contributing to distal lung collapse, bronchoscopic placement of valved prostheses has the potential to noninvasively replicate the beneficial effects of LVRS. The purpose of this study was to investigate the safety and feasibility of placing valves in segmental airways of patients with emphysema.

Design: Case series.

Setting: Tertiary hospital, severe airways disease clinic.

Patients: Ten patients aged 51 to 69 years with apical emphysema and hyperinflation, otherwise suitable for standard LVRS. Mean preoperative FEV1 was 0.72 L (19 to 46% predicted), and 6-min walk distance was 340 m (range, 245 to 425 m).

Intervention: Apical, bronchoscopic, segmental airway placement of one-way valves (silicone-based Nitinol bronchial stent; Emphasys Medical; Redwood City, CA) under general anesthesia. Placement was over a guidewire under bronchoscopic and fluoroscopic control.

Results: Four to 11 prostheses per patient took 52 to 137 min to obstruct upper-lobe segments bilaterally. Inpatient stay was 1 to 8 days. No major complications were seen in the 30-day study period. Minor complications included exacerbation of COPD (n = 3), asymptomatic localized pneumothorax (n = 1), and lower-lobe pneumonia (day 37; n = 1). Symptomatic improvement was noted in four patients. No major change in radiologic findings, lung function, or 6-min walk distance was evident at 1 month, although gas transfer improved from 7.47 ± 2.0 to 8.26 ± 2.6 mL/min/mm Hg (p = 0.04) and nuclear upper-lobe perfusion fell from 32 ± 10 to 27 ± 9% (mean ± SD) [p = 0.02].

Conclusion: Bronchoscopic prostheses can be safely and reliably placed into the human lung. Further study is needed to explore patient characteristics that determine symptomatic efficacy in a larger patient cohort.


Chest. 2003;124(3):1081-1089. doi:10.1378/chest.124.3.1081

Transesophageal echocardiography (TEE) is a growing technology that is frequently utilized in the critical care setting by intensivists, surgeons, anesthesiologists as well as specialists in cardiovascular diseases. The clinical application of TEE continues to emerge, and the indications and diagnostic utility of this technology as currently available are summarized in this review.

Alveolar-Capillary Membrane Dysfunction in Heart Failure*: Evidence of a Pathophysiologic Role
Chest. 2003;124(3):1090-1102. doi:10.1378/chest.124.3.1090

Chronic heart failure (CHF) increases the resistance to gas transfer across the alveolar-capillary interface. Recent reports highlight the pathophysiologic relevance of changes in the lung leading to impaired fluid and gas exchange in the distal airway spaces. Under experimental conditions, an acute pressure or volume overload can injure the alveolar blood-gas barrier. This may disrupt its anatomic configuration, cause the loss of regulation of fluid-flux, and thereby affect alveolar gas conductance properties. These ultrastructural changes have been identified under the term of stress failure of the alveolar-capillary membrane. In the short term, these alterations are reversible due to the reparative properties of the alveolar surface. However, when the alveolar-capillary membrane is chronically challenged, for instance in patients with CHF, by noxious stimuli, such as humoral, cytotoxic, and genetic factors other than by mechanical trauma, remodeling of pathophysiologic and clinical importance may take place. These changes in some respects resemble the remodeling process in the heart. Emerging findings support the view that, in patients with CHF, alveolar-capillary membrane dysfunction may contribute to symptom exacerbation and exercise intolerance, and may be an independent prognosticator of clinical course. Angiotensin-converting enzyme inhibitors ameliorate the alveolar membrane gas conductance abnormality, reflecting improvement in the remodeling process. This article reviews the putative mechanisms involved in the impairment in gas diffusion in CHF patients and provides a link between physiologic changes and clinical findings.

Critical Care Reviews

Genetic Polymorphisms in Sepsis and Septic Shock*: Role in Prognosis and Potential for Therapy
Chest. 2003;124(3):1103-1115. doi:10.1378/chest.124.3.1103

Genetic epidemiologic studies suggest a strong genetic influence on the outcome from sepsis, and genetics may explain the wide variation in the individual response to infection that has long puzzled clinicians. Several candidate genes have been identified as important in the inflammatory response and investigated in case-controlled studies, including the tumor necrosis factor (TNF)-α and TNF-β genes, positioned next to each other within the cluster of human leukocyte antigen class III genes on chromosome 6. Other candidate genes for sepsis and septic shock include the interleukin (IL)-1 receptor antagonist gene, the heat shock protein gene, the IL-6 gene, the IL-10 gene, the CD-14 gene, the Toll-like receptor (TLR)-4 gene, and the TLR-2 gene, to name a few. In this review, we summarize the evidence for a genetic susceptibility to development of sepsis and death from sepsis, discuss design of clinical genetics studies relevant to the study of complex disorders, consider the candidate genes likely to be involved in the pathogenesis of sepsis, and discuss the potential for targeted therapy of sepsis and septic shock based on genetic variability.


Chest. 2003;124(3):1116-1119. doi:10.1378/chest.124.3.1116

Improved access to noninvasive investigation and a declining tolerance for diagnostic uncertainty has resulted in increasing numbers of patients who are referred with suspected venous thromboembolism (VTE), all of whom require objective testing to confirm or exclude the diagnosis. Hence, the proportion of patients with suspected VTE in whom the diagnosis is confirmed has fallen progressively from 30 to 35% in the 1970s and 1980s,13 to around 15 to 25% in the last decade.46 Indeed, prevalences of < 10% have been reported.7 This trend is not inappropriate for a potentially fatal disorder that can be effectively treated, but it has important resource implications.

Chest. 2003;124(3):1120-1128. doi:10.1378/chest.124.3.1120

Asbestosis can cause significant impairment and even death. It is also a well-recognized risk factor for the development of lung cancer. However, asbestosis is usually diagnosed on clinical grounds without the aid of pathology. Many physicians and researchers believe that in asbestos-exposed individuals with adequate latency, chest radiographic findings that are compatible with asbestosis are sufficient for the diagnosis. In order to determine whether this approach is reasonable, the positive predictive value of the chest radiograph for the diagnosis of pathologic asbestosis must be determined. This requires information about the prevalence of asbestosis, and the sensitivity and specificity of the chest radiograph in its diagnosis. In this article, the sensitivity and specificity of the chest radiograph in diagnosing asbestosis is determined from a literature analysis. The prevalence of asbestosis among present-day cohorts, such as construction workers and petrochemical workers, is assessed based on the relative risk of lung cancer in patients with asbestosis and the overall relative risk of lung cancer in these occupationally asbestos-exposed cohorts. The results indicate a positive predictive value for abnormal chest radiograph findings alone to be significantly < 50%. Therefore, the chest radiograph is inadequate as the sole clinical tool to be used to diagnose asbestosis in these cohorts. However, when rales and a low diffusing capacity of the lung for carbon monoxide are also present, the diagnosis of asbestosis on clinical grounds can be made with reasonable confidence.

Chest. 2003;124(3):1129-1132. doi:10.1378/chest.124.3.1129

Approximately 50% of patients who are admitted to the hospital with community-acquired pneumonia will develop a pleural effusion.12 While most parapneumonic effusions will resolve without specific therapy, approximately 10% will become complicated or progress to empyema.3 Because delays in the drainage of these clinically significant effusions have been associated with increased morbidity and mortality,4 prompt detection and accurate characterization of a parapneumonic effusion are important. Guidelines5 based on a consensus conference have comprehensively summarized the literature regarding parapneumonic effusions and have made specific recommendations for their management. Although this document reflects the “state of the art,” as the authors noted, most studies of parapneumonic effusions have been observational, often with a limited numbers of patients.

Special Report

Taft and Pickwick*: Sleep Apnea in the White House
Chest. 2003;124(3):1133-1142. doi:10.1378/chest.124.3.1133

As President of the United States from 1909 to 1913, William Howard Taft’s minimum body mass index was 42 kg/m2. This article presents evidence that he suffered from obstructive sleep apnea, manifested by excessive daytime somnolence, snoring, systemic hypertension and, perhaps, cognitive and psychosocial impairment. As president, Taft’s hypersomnolence was severe and obvious, but never prompted official discussion of his fitness to govern. Within 12 months of leaving office, Taft permanently lost over 60 pounds. His somnolence resolved. As Chief Justice of the United States from 1921 to 1930, he was not somnolent. President Taft’s case illuminates historical puzzles of his performance as President, raises public awareness of sleep apnea, and informs discussions of presidential disability and the 25th Amendment to the Constitution of the United States.

Roentgenogram of the Month

Chest. 2003;124(3):1143-1144. doi:10.1378/chest.124.3.1143

A 55-year-old man presented to the hospital on several occasions with “atypical” chest pain sometimes consistent with angina, with normal ECG findings and cardiac enzyme levels. The only risk factor for ischemic heart disease was smoking 10 to 20 cigarettes a day. His medical history included hematuria, with normal IV urogram and cystoscopic findings. He was unable to perform an exercise test due to severe diffuse “arthritis” (previous radiographic confirmation of lumbar and cervical osteoarthritis), and results of a subsequent dipyridamole myocardial perfusion scan suggested mild ischemic heart disease. He was started on treatment with aspirin, atenolol, and glyceryl trinitrate spray. A chest radiograph (Fig 1 ) was performed that revealed a new hazy opacity in the right upper zone, and referral to a chest physician was made. Subsequent bronchoscopy did not show any endobronchial lesion, and test findings of BAL fluid for cytology, bacteria, mycobacteria, fungi, viruses, and Pneumocystis carinii were negative. CT of the thorax showed no evidence of a lung mass, and he was assumed to have had a transient area of infective consolidation. However, another chest radiograph revealed persistent unchanged right-upper-zone opacification.

Occupational and Environmental Lung Disease

Suberosis*: Clinical Study and New Etiologic Agents in a Series of Eight Patients
Chest. 2003;124(3):1145-1152. doi:10.1378/chest.124.3.1145

Background: Penicillium frequentans is considered to be the causal agent of suberosis, hypersensitivity pneumonitis due to cork dust inhalation. Nevertheless, other fungi can colonize cork during its storage period in humid conditions. The aims of the study were to assess the etiologic role of several fungi and cork itself in the genesis of suberosis, and to review the clinical characteristics of patients with this disease.

Methods: Eight patients with suberosis were studied. Chest radiography, high-resolution chest CT, pulmonary function testing, bronchofibroscopy with BAL and transbronchial biopsy, and delayed cutaneous hypersensitivity tests were performed. Fungal and suberin (cork that is culture negative for fungi) antigens were used for serum determination of specific IgG antibodies, immediate hypersensitivity specific skin tests, and specific bronchial challenge tests.

Results: Serum specific IgG antibody determinations and specific skin tests against Aspergillus fumigatus and suberin demonstrated the capacity of both these antigenic extracts to induce an immunologic response. Positive specific bronchial challenge tests performed not only with P frequentans but also with A fumigatus, and cork itself were recorded in some patients for the first time in this disease. Dyspnea and cough were the most frequent symptoms. Clinical and functional improvement occurred after antigen avoidance.

Conclusions: In addition to P frequentans, A fumigatus and cork dust itself may contribute to the development of suberosis.

Chest. 2003;124(3):1153-1159. doi:10.1378/chest.124.3.1153

Background: Work-related symptoms and disability due to respiratory disease are common and costly among working-age adults. To investigate this problem, we analyzed data on respiratory symptoms related to the workplace and occupational disability from the European Community Respiratory Health Survey (ECRHS).

Methods: The ECRHS is a population-based sample of adults aged 20 to 44, with oversampling of subjects with symptoms that are consistent with respiratory disease. We analyzed structured interviews from 17,567 subjects, of whom 15,039 were from a general random population sample and 2,528 were from the respiratory symptom oversample. We defined work-related respiratory symptoms as self-reported wheeze or chest tightness at work, and work-related respiratory disability as reported job change due to breathing difficulties at work. We used binary generalized linear modeling with a log link to estimate the risk of symptoms and disability.

Findings: Wheeze at work was reported in the general population sample by 1,552 subject (10%), ranging from 4 to 15% among the 16 countries analyzed. Work-related respiratory disability was reported by 540 subjects (4%), ranging from 1 to 8%. Reported workplace exposure to vapors, gases, dust, or fumes was associated with increased risk of respiratory symptoms at work (prevalence ratio [PR], 2.1; 95% CI 1.8–2.4) and work-related respiratory disability (PR, 3.4; 95% confidence interval [CI], 2.0 to 5.1). Workplace environmental tobacco smoke exposure was associated with symptoms (PR, 1.3; 95% CI, 1.2 to 1.5) but not with disability (PR, 1.1; 95% CI, 0.9 to 1.4).

Interpretation: These data indicated that work-related respiratory symptoms and disability vary widely in this international sample but, nonetheless, are associated with workplace exposures that could be addressed through preventive measures.

Pulmonary and Critical Care Pearls

Chest. 2003;124(3):1160-1163. doi:10.1378/chest.124.3.1160

A 77-year-old woman presented to the walk-in clinic with a 1-week history of increasing dyspnea and wheezing. She had a history of frequent episodes of shortness of breath triggered by various irritants such as dust and fumes, and asthma was diagnosed 12 years earlier. Recent pulmonary function studies showed a reduced FEV1 and FVC but a preserved ratio. Lung volumes showed a normal total lung capacity but elevated residual volume/total lung capacity ratio consistent with airtrapping; specific airway conductance was normal and a methacholine challenge test had not been done.

Selected Reports

Chest. 2003;124(3):1164-1168. doi:10.1378/chest.124.3.1164

Prolonged open sternotomy is a well-known phenomenon in the pediatric and adult cardiac surgery literature. It is usually an adjuvant in the treatment of a severely compromised heart. We present a case of thoracic compartment syndrome that developed postoperatively from a noncardiac thoracic procedure. Management, diagnosis, and literature review are presented.

Chest. 2003;124(3):1168-1170. doi:10.1378/chest.124.3.1168

Catamenial hemoptysis is a rare condition that is associated with the presence of intrapulmonary or endobronchial endometrial tissue. Diagnosis of and therapy for this condition are still a matter of debate. We describe a case of endobronchial endometriosis with catamenial hemoptysis. An endobronchial lesion was diagnosed by spiral CT scan, taken at the onset of the menses, and confirmed with flexible bronchoscopy. The patient was successfully treated with endoscopic Nd-YAG laser therapy with a 1-day in-hospital procedure. We suggest that endoscopic laser treatment should be the first line of therapy for central airway endometriosis, provided that the source of bleeding has been conclusively located and all of the lesions can be reached with the bronchoscope.

Chest. 2003;124(3):1170-1173. doi:10.1378/chest.124.3.1170

Pregnancy in the setting of pulmonary hypertension and Eisenmenger physiology is associated with a substantial maternal and fetal risk. Such patients are advised against pregnancy. We report a case of a woman with an Eisenmenger atrial septal defect diagnosed during the last trimester of pregnancy. On presentation, she was critically ill and there was evidence of fetal distress. She was emergently treated with IV epoprostenol, and her status improved. She underwent cesarean section and delivered a male infant with Apgar scores of 8 and 9. Her dyspnea improved, and she was characterized as World Health Organization functional class II on a subsequent clinical visit. Although pregnancy should be discouraged in women with Eisenmenger syndrome, we have demonstrated that IV epoprostenol successfully treated a woman with Eisenmenger syndrome diagnosed in the third trimester.

Communications to the Editor

Chest. 2003;124(3):1174-1175. doi:10.1378/chest.124.3.1174

1Peno-Green, L, Lluberas, G, Kingsley, T, et al (2002) Lung injury linked to etanercept therapy.Chest122,1858-18602Embil, J, Warren, P, Yarkus, M, et al Pulmonary illness associated with exposure toMycobacterium aviumcomplex in hot tub water: hypersensitivity pneumonitis or infection?Chest1997;111,813-8163Keane, J, Gershon, S, Wise, RP, et al Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent.N Engl J Med2001;345,1098-11044Day, R Adverse reactions to TNF-alpha inhibitors in rheumatoid arthritis.Lancet2002;359,540-5415Cush, JJ, Matteson, EL FDA advisory committee reviews safety of TNF inhibitors: ACR Hotline.2001 American College of Rheumatology. Atlanta, GA:

Chest. 2003;124(3):1175-1176. doi:10.1378/chest.124.3.1175

1Truitt, T, Witko, J, Halpern, M (2003) Levalbuterol compared to racemic albuterol: efficacy and outcomes in patients hospitalized with COPD or asthma.Chest123,128-135

Chest. 2003;124(3):1176. doi:10.1378/chest.124.3.1176

1Truitt, T, Witko, J, Halpern, M (2003) Levalbuterol compared to racemic albuterol; efficacy and outcomes in patients hospitalized with COPD and asthma.Chest123,128-1352Medical Economics Inc.. 2001 drug topics red book2001,170 Medical Economics Inc. Montvale, NJ: 571

Chest. 2003;124(3):1178-1179. doi:10.1378/chest.124.3.1178

1Dalen, JE (2002) Pulmonary embolism: what have we learned since Virchow?Chest122,1801-18172Barritt, DW, Jordan, SC Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.Lancet1960;1,1309-13123Wolfe, TR, Hartsell, SC Pulmonary embolism: making sense of the diagnostic evaluation.Ann Emerg Med2001;37,504-514

Chest. 2003;124(3):1179. doi:10.1378/chest.124.3.1179

1Girish, M, Trayner, E, Damman, O, et al (2001) Symptom-limited stair climbing as a predictor of postoperative cardiopulmonary complications after high-risk surgery.Chest120,1147-11512Brunelli, A, Al Refai, M, Monteverde, M, et al Stair climbing test predicts cardiopulmonary complications after lung resection.Chest2002;121,1106-1110

Chest. 2003;124(3):1179-1180. doi:10.1378/chest.124.3.1179-a

1Rello, J, Bodi, M, Mariscal, D, et al (2003) Microbiological resting and outcome of patients with severe community-acquired pneumonia.Chest123,174-1802Höffken, G, Niederman, MS Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU.Chest2002;122,2183-21963Ruiz, M, Ewig, S, Torres, A, et al Severe community-acquired pneumonia: risk factors and follow-up epidemiology.Am J Respir Crit Care Med1999;160,923-9294Gleason, PP, Meehan, TP, Fine, JM, et al Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia.Arch Intern Med1999;159,2562-25725Houck, PM, MacLehose, RF, Niederman, MS, et al Empiric antibiotic therapy and mortality among Medicare pneumonia inpatients in 10 western states: 1993, 1995, and 1997.Chest2001;119,1420-14266Pachon, J, Prados, MD, Capote, F, et al Severe community-acquired pneumonia: etiology, prognosis, and treatment.Am Rev Respir Dis1990;142,369-3737Leroy, O, Santré, C, Beuscart, C, et al A five-year study of severe community-acquired pneumonia with emphasis on prognosis in patients admitted to an intensive care unit.Intensive Care Med1995;21,24-318Moine, P, Vercken, JB, Chevret, S, et al Severe community-acquired pneumonia: etiology, epidemiology, and prognosis factors.Chest1994;105,1487-1495

Chest. 2003;124(3):1181. doi:10.1378/chest.124.3.1181

1Caldera, A, Mora, J, Kotler, M, et al (2002) Pulmonary embolism in a patient with pernicious anemia and hyperhomocysteinemia.Chest122,1487-14882Andrès, E, Pflumio, F, Knab, MC, et al Splenic thrombosis and celiac disease: a fortuitous association?Presse Med2000;29,1933-19343Andrès, E, Goichot, B, Schlienger, JL Food-cobalamin malabsorption: a usual cause of vitamin B12 deficiency.Arch Intern Med2000;160,2061-20624Andrès, E, Perrin, AE, Vinzio, S, et al L’hyperhomocystéinémie modérée liée à une carence en vitamine B12 est-elle un facteur de thrombophilie? Etude rétrospective de 120 observations.Rev Med Interne2001;22(suppl 4),522s


Chest. 2003;124(3):1181. doi:10.1378/chest.124.3.1181-a

In the July 2003 issue, the article, “What Is Sarcoidosis” (CHEST 2003; 124:367–371) by Jerome Reich, contained an error introduced during production. On page 368, the last sentence in the left column should read as follows: “In the remaining 12, a more gradual response developed, characterized by close associations of phagocytic macrophages and helper T cells, some of which were also Tac+; dendritic Langerhans cells were not seen.”


Chest. 2003;124(3):1182-1183. doi:10.1378/chest.124.3.1182

By Paolo Gresele, Clive P. Page, Valentin Fuster, and Jos Vermylen, eds. Cambridge, UK: Cambridge University Press, 2002; 1124 pp; $300

Chest. 2003;124(3):1183. doi:10.1378/chest.124.3.1183

By J. M. B. Hughes and N. W. Morrell. London, UK: Imperial College Press, 2001; 320 pp; $58 (hardbound), $32 (paperback)

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