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Editorials

Chest. 2005;127(6):1873-1875. doi:10.1378/chest.127.6.1873
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A relationship between cigarette smoking and postoperative pulmonary complications has long been recognized. Both smoking-associated lung diseases and smoking itself have been shown to pose an increased risk for respiratory complications in the postoperative period, as variably defined in different studies,12 but usually including some combination of pulmonary infection, atelectasis, bronchospasm, and prolonged ventilation. The development of pulmonary complications has, in turn, been associated with a higher postoperative mortality rate.3 Former smokers have a lower rate of complications than current smokers, and, while it is logical to assume that getting our patients to quit smoking before surgery would translate into a lower rate of postoperative pulmonary complications, reality proves more complex. When it comes to smoking, smoking cessation, and perioperative complications, it’s not just if you quit, but when you quit, that matters.

Chest. 2005;127(6):1875-1877. doi:10.1378/chest.127.6.1875
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Few situations elevate the BP or tighten the sphincter tone of a pulmonologist more than bleeding after transbronchial biopsy (TBB). One or two drops of blood mixed with a small volume of sputum appear through the bronchoscope to be a raging river. We all know the drill: occlude the bleeding orifice and wait. And wait. Suction a bit, but don’t disturb the forming clot. And wait.

Chest. 2005;127(6):1877-1878. doi:10.1378/chest.127.6.1877
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As physicians, we are taught early in our careers that our initial medical history and physical examination provide our most important diagnostic information. Laboratory data follow. They serve both to confirm our diagnostic impressions and to quantify the extent of the disease state. Surveys12 of asthmatic patients, however, have demonstrated that it is very difficult to ascertain the severity of a person’s illness from a verbal description of symptoms. Further observations in asthmatic subjects indicate that our patients’ personalities influence the magnitude or intensity of the symptoms they associate with their asthma. Asthmatic patients who score high on either the hypochondriasis or somatization scales, for example, report high levels of dyspnea to be associated with only mild or moderate degrees of airway dysfunction, either during an attack or when stable.34 By contrast, those patients scoring low on these scales tend to minimize the discomfort they associate with severe airway obstruction. Thus, the examining physician may gain some insight into the degree of airway dysfunction in asthmatic patients from their verbal history only if the physician is able to factor a sense of the patient’s tendency to exaggerate or minimize symptoms into the clinical assessment.

Topics: listening
Chest. 2005;127(6):1878-1879. doi:10.1378/chest.127.6.1878
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Dr. Mieno and colleagues have presented a well-written and interesting article (see page 1960) concerning other potential benefits derived from lung volume reduction surgery (LVRS) besides improvement in dyspnea and pulmonary function test results. Prior to accepting the conclusion of any study, its methodology must be critically scrutinized and questioned.

Chest. 2005;127(6):1879-1882. doi:10.1378/chest.127.6.1879
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Respiratory problems (RPs) are the main cause of death in patients with amyotrophic lateral sclerosis (ALS).12 However, nowadays many of these RPs can be successfully managed.3 Therefore, it is disturbing to see that a great number of patients are not receiving appropriate management for their RPs, with the consequences of premature death and avoidable suffering. The very interesting report by Farrero et al in this issue of CHEST (see page 2132) describes the impact on survival of patients when applying two different ways of tackling their management. The first could be called the conventional approach (which is more or less the way the patients were attended in this study from 1988 to 1997). The second way is the appropriate approach, in which the neurologists, being aware of the gravity of RPs in these patients,,3 coordinate their management with the pulmonologists (in some hospitals with the Physical Medicine and Rehabilitation Department staff) once they have a diagnosis. The pulmonologists take on the responsibility of designing a protocol for good clinical practice to prevent and treat the RPs.

Chest. 2005;127(6):1882-1885. doi:10.1378/chest.127.6.1882
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The colony-stimulating factors (CSFs) comprise a group of cytokines that are central to the hematopoiesis of blood cells, as well as to the maintenance of homeostasis and overall immune competence. This group consists of the macrophage-CSF (M-CSF), granulocyte-CSF (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and multi-CSF (interleukin [IL]-3). M-CSF and G-CSF are relatively lineage-specific, having a role in the proliferation, differentiation, and survival of macrophages, neutrophils, and their precursors. In contrast, GM-CSF and multi-CSF function at earlier stages of lineage commitment regulating the expansion and maturation of primitive hematopoietic progenitors.1 GM-CSF and G-CSF are naturally occurring cytokines that stimulate the production and antibacterial function of both neutrophils and monocytes.

Chest. 2005;127(6):1886-1888. doi:10.1378/chest.127.6.1886
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The aim is to cure and, when impossible, to prevent decline. These are measures of our success. As decline transforms into dying, harsh and inexorable, we may become discomfited. This exposes a critical deficit—the failure to see death as an opportunity to use the patient/physician relationship to improve the quality of the patient’s remaining life and the quality of the dying experience, long remembered by the survivors after the patient is gone. Instead, we commonly tiptoe away.

Chest. 2005;127(6):1888-1889. doi:10.1378/chest.127.6.1888
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Hemoptysis is not a separate disease; rather it is a manifestation of multiple pathologic processes. Despite the potentially fatal outcome of hemoptysis, the underlying disease is usually otherwise benign and treatable.13 The risk of death is particularly high when hemoptysis is massive, and some investigators46 estimate the risk of mortality with untreated massive hemoptysis to be in excess of 75%. Others78 have found the risk of death to be lower and have advocated an initially conservative approach, although there may be significant mortality from subsequent bouts of hemoptysis in these patients. Some of the variation in mortality risk is due to the lack of the common definition of the term massive. However it is defined, it is clear that massive hemoptysis represents a significant and immediate risk to these patients.

Chest. 2005;127(6):1889. doi:10.1378/chest.127.6.1889
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In this issue of CHEST (see page 2273), Kamigaki and colleagues describe a small cell lung cancer (SCLC) that presented as an intraluminal lesion in the left descending pulmonary artery. The diagnosis was based on histologic descriptions of transbronchial aspirates that were supported by immunohistochemical data (+thyroid transcription factor-1, +cytokeratin, and –leukocyte common antigen). The results of staining with both chromogranin and synaptophysin were negative, and this indeed may be the case in a small number of SCLCs. Supporting the diagnosis were elevated levels of Pro-gastrin-releasing peptide, neuron-specific enolase, and carcinoembryonic antigens. The weight of evidence suggests that the tumor is an SCLC.

Clinical Investigations

Chest. 2005;127(6):1911-1918. doi:10.1378/chest.127.6.1911
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Study objectives: The aim of this study was to examine the relationship between airway inflammation, nitrosative stress, heme-oxygenase expression, and acute severe exacerbations of COPD.

Design: We measured heme oxygenase (HO)-1, inducible nitric oxide (NO) synthase expression and nitrotyrosine formation, as well as eosinophilic cationic protein, myeloperoxidase (MPO), interleukin (IL-8), and granulocyte macrophage-colony stimulating factor levels in induced sputum samples from 12 COPD patients (mean ± SD; FEV1 40 ± 14% predicted) at the onset of an acute severe exacerbation of COPD requiring hospital admission and 16 weeks after remission.

Results: We demonstrated increased percentages (p = 0.001) and absolute numbers (p = 0.028) of total nitrotyrosine positive (+ve) inflammatory cells (ie, polymorphonuclear cells and macrophages), increased percentages (p = 0.04) and absolute numbers (p = 0.05) of total HO-1 +ve inflammatory cells, and increased MPO (p = 0.005) and IL-8 levels (p = 0.028) during severe exacerbation compared with the stable state.

Conclusions: Our results support the hypothesis of an involvement of inflammatory and nitrosative stress in severe COPD exacerbations. Future therapeutic strategies may aim at regulating inflammation and NO synthesis during COPD exacerbations.

Chest. 2005;127(6):1967-1976. doi:10.1378/chest.127.6.1967
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Objectives: To evaluate the effect of on-pump and off-pump coronary artery bypass grafting (CABG) on postoperative cognitive impairment and cerebrovascular reactivity, with attention for the perioperative high-intensity transient signals (HITS).

Design: A prospective comparative study.

Setting: Urban university hospital.

Patients: Candidates for cardiac surgery.

Methods: Measurement of HITS as a reflection of embolic load was performed in 50 patients (on-pump CABG, n = 32; off-pump CABG, n = 18). To measure cognitively induced cerebrovascular reactivity, cerebral blood flow velocity (BFV) was measured preoperatively in 66 patients, early postoperatively (after 6 days) in 63 patients, and late postoperatively (after 6 months) in 44 patients during five cognitive tasks. In the same session, seven standardized neuropsychological tests were administered.

Results: A higher embolic load was found in the on-pump group (p < 0.01). In the on-pump group, aortic cannulation was the most important HITS-prone surgical maneuver. Repeated-measures multivariate analysis of variance (using surgical technique as between-subjects factor and significant differences between both groups as covariates) on the group data revealed no significant differences in neuropsychological performance and BFV immediately after surgery or at 6 months after surgery, compared with preoperative performance. No main effect of surgery was found for neuropsychological performance and BFV. No significant correlations were found between the number of HITS and the degree of postoperative neuropsychological impairment. Individual comparisons revealed that 60% (59.4% in the on-pump group; 61.1% in the off-pump group) of the patients undergoing CABG showed evidence of cognitive impairment soon after surgery. In 24.2%, the cognitive sequelae persisted at 6 months follow-up (31.8% in the on-pump group; 9.1% in the off-pump group). The cognitive impairment index (sum of impaired neuropsychological tests) showed a significant difference after 6 months between both surgery groups with fewer neurocognitive tests that remained impaired in the off-pump group.

Conclusions: In off-pump surgery, significantly fewer HITS were observed. On an individual level, more favorable results in neuropsychological test performance were demonstrated in the off-pump group after 6 months. The number of HITS showed no correlation with degrees of early and late postoperative neuropsychological impairment.

Clinical Investigations: COPD

Chest. 2005;127(6):1890-1897. doi:10.1378/chest.127.6.1890
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Objective: To develop a comprehensive disease-specific COPD severity instrument for survey-based epidemiologic research.

Study design and setting: Using a population-based sample of 383 US adults with self-reported physician-diagnosed COPD, we developed a disease-specific COPD severity instrument. The severity score was based on structured telephone interview responses and included five overall aspects of COPD severity: respiratory symptoms, systemic corticosteroid use, other COPD medication use, previous hospitalization or intubation, and home oxygen use. We evaluated concurrent validity by examining the association between the COPD severity score and three health status domains: pulmonary function, physical health-related quality of life (HRQL), and physical disability. Pulmonary function was available for a subgroup of the sample (FEV1, n = 49; peak expiratory flow rate [PEFR], n = 93).

Results: The COPD severity score had high internal consistency reliability (Cronbach α = 0.80). Among the 49 subjects with FEV1 data, higher COPD severity scores were associated with poorer percentage of predicted FEV1 (r = − 0.40, p = 0.005). In the 93 subjects with available PEFR measurements, greater COPD severity was also related to worse percentage of predicted PEFR (r = − 0.35, p < 0.001). Higher COPD severity scores were strongly associated with poorer physical HRQL (r = − 0.58, p < 0.0001) and greater restricted activity attributed to a respiratory condition (r = 0.59, p < 0.0001). Higher COPD severity scores were also associated with a greater risk of difficulty with activities of daily living (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.8 to 3.0) and inability to work (OR, 4.2; 95% CI, 3.0 to 5.8).

Conclusion: The COPD severity score is a reliable and valid measure of disease severity, making it a useful research tool. The severity score, which does not require pulmonary function measurement, can be used as a study outcome or to adjust for disease severity.

Chest. 2005;127(6):1898-1903. doi:10.1378/chest.127.6.1898
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Background: COPD is often associated with changes of the structure and the function of the heart. Although functional abnormalities of the right ventricle (RV) have been well described in COPD patients with severe hypoxemia, little is known about these changes in patients with normoxia and mild hypoxemia.

Study objectives: To assess the structural and functional cardiac changes in COPD patients with normal Pao2 and without signs of RV failure.

Methods: In 25 clinically stable COPD patients (FEV1, 1.23 ± 0.51 L/s; Pao2, 82 ± 10 mm Hg [mean ± SD]) and 26 age-matched control subjects, the RV and left ventricular (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP) was estimated from right pulmonary artery distensibility.

Results: RV mass divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 ± 0.18 g/mL in the COPD group and 0.41 ± 0.09 g/mL in the control group (p < 0.01). LV and RV ejection fractions were 62 ± 14% and 53 ± 12% in the COPD patients, and 68 ± 11% and 53 ± 7% in the control subjects, respectively. PAP estimated from right pulmonary artery distensibility was not elevated in the COPD group.

Conclusion: From these results, we conclude that concentric RV hypertrophy is the earliest sign of RV pressure overload in patients with COPD. This structural adaptation of the heart does not alter RV and LV systolic function.

Chest. 2005;127(6):1904-1910. doi:10.1378/chest.127.6.1904
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Study objectives: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (Pimax), decreased maximum expiratory mouth pressure (Pemax), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well.

Methods: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender.

Results: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, Pimax, Pemax, and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pao2 affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Paco2 tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients.

Conclusion: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pao2 level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.

Clinical Investigations: ASTHMA

Chest. 2005;127(6):1919-1927. doi:10.1378/chest.127.6.1919
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Background: The rate of decline in lung function is increased in asthmatic patients, particularly in those with coexisting asthmatic mucus hypersecretion (AMH), in whom inflammation and the activity of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in serum and BAL fluid (BALF) may be increased.

Methods: Seven nonasthmatic subjects and 22 asthmatic subjects completed a questionnaire, and underwent lung function testing and bronchoscopy, during which AMH was diagnosed by the presence of mucus plugging. Subjects were classified as follows: mild/moderate asthma; severe asthma; and AMH. In BALF, we measured the differential WBC counts and MMP-9 activity by zymography. We measured total MMP-9 and TIMP-1 activity by enzyme-linked immunosorbent assay in BALF and serum.

Results: The mean (± confidence interval) FEV1 was lower in AMH patients (73 ± 13% predicted) compared with nonasthmatic subjects (95 ± 7%) and patients with mild/moderate asthma (73 ± 9%; p < 0.05), and was similar to that of patients with severe asthma (80 ± 20%). MMP-9 activity was greater in AMH patients and in patients with severe asthma compared with nonasthmatic subjects (p = 0.05 and p = 0.01, respectively), as were TIMP-1 activities (p = 0.001 and p = 0.04, respectively), but MMP-9/TIMP-1 ratios were not. MMP-9 activity increased across the four groups from nonasthmatic subjects to AMH patients (r = 0.58; p = 0.0009), but the differential and total WBC counts were similar. There were no relationships between FEV1 percent predicted and either MMP-9 activity or MMP-9/TIMP-1 ratio. There were no differences in serum MMP-9 activity, which did not correlate with MMP-9 activity in BALF.

Conclusions: AMH and severe asthma were associated with greater proteolytic enzyme activities despite similar airway inflammation, which might play a role in remodeling and accelerated the decline in lung function in these patients.

Chest. 2005;127(6):1928-1934. doi:10.1378/chest.127.6.1928
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Study objectives: Longitudinal data on adult asthma are sparse. The objectives of this study were to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period.

Design: From birth cohorts over the period 1953 to 1982 in The Danish Twin Registry, 19,349 subjects with no history of asthma, as determined by a questionnaire-based survey in 1994, answered a follow-up questionnaire in 2002. The subjects were regarded as incident asthma cases when answering “yes” to the question “Do you have, or have you ever had asthma?” in 2002, and “no” to the same question in 1994.

Results: A total of 838 cases (4.3%) of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and 6.4 per 1,000 person-years, respectively, among male and female subjects. For all ages, the probability of adult-onset asthma was greater for female subjects (odds ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in probability with increasing age. There was a positive association between increasing body mass index (BMI) and risk of adult-onset asthma applying to both sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were found between incident asthma and a history of hay fever (OR: male subjects, 4.2; female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects, 8.0; p < 0.001).

Conclusions: There is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis.

Topics: asthma
Chest. 2005;127(6):1935-1941. doi:10.1378/chest.127.6.1935
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Background: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear.

Study objectives: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms.

Design: Cross-sectional observational study.

Setting: Lung function and exercise laboratory at a university hospital.

Patients and measurements: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation.

Results: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [± SD] eosinophil count, 4.1 ± 8.5% vs 0.3 ± 0.9% vs 0%, respectively), higher NO concentrations (19 ± 10 vs 14 ± 4 vs 13 ± 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with nonhyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05).

Conclusion: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.

Clinical Investigations: PULMONARY FUNCTION

Respiratory Complaints in Chinese*: Cultural and Diagnostic Specificities
Chest. 2005;127(6):1942-1951. doi:10.1378/chest.127.6.1942
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Study objectives: We investigated the qualitative components of a wide range of Chinese descriptors of dyspnea and associated symptoms, and their relevance for clinical diagnosis.

Measurements: Sixty-one spontaneously reported descriptors were elicited in Chinese patients to make a symptom checklist, which was administered to new groups of patients with different cardiopulmonary diseases, to patients with medically unexplained dyspnea and to healthy subjects.

Results: Test-retest reliability was satisfactory for most of the descriptors. A principal component analysis on 61 descriptors yielded the following eight factors: dyspnea-effort of breathing; dyspnea-affective aspect; wheezing; anxiety; tingling; palpitation; coughing and sputum; and dying experience. Although the descriptors of dyspnea-effort of breathing resembled Western wordings and were shared by patients with a variety of diseases, the descriptors of dyspnea-affective aspect appeared to be more culturally specific and were primarily linked to the diagnosis of medically unexplained dyspnea, whereas wheezing was specifically linked to asthma.

Conclusions: Three factors of breathlessness were found in Chinese. The descriptors of dyspnea-effort of breathing and wheezing appear to be similar to Western descriptors, whereas the dyspnea-affective aspect seems to bear cultural specificity.

The Relationship Between Reduced Lung Function and Cardiovascular Mortality*: A Population-Based Study and a Systematic Review of the Literature
Chest. 2005;127(6):1952-1959. doi:10.1378/chest.127.6.1952
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Study objectives: Conditions that give rise to reduced lung function are frequently associated with low-grade systemic inflammation, which may lead to poor cardiovascular outcomes. We sought to determine the relationship between reduced FEV1 and cardiovascular mortality, independent of smoking.

Design: Longitudinal population-based study and a metaanalysis of literature.

Setting: Representative sample of the general population.

Participants: Participants of the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study who were 40 to 60 years of age at baseline assessment (n = 1,861).

Measurements and results: We compared the risk of cardiovascular mortality across quintiles of FEV1. Individuals in the lowest FEV1 quintile had the highest risk of cardiovascular mortality (relative risk [RR], 3.36; 95% confidence interval [CI], 1.54 to 7.34). Compared to FEV1 quintile 1, individuals in quintile 5 had a fivefold increase in the risk of death from ischemic heart disease (RR, 5.65; 95% CI, 2.26 to 14.13). We also performed a systematic review of large cohort studies (> 500 participants) that reported on the relationship between FEV1 and cardiovascular mortality (12 studies; n = 83,880 participants). Compared to participants in the highest FEV1 category, those with reduced FEV1 had a higher risk of cardiovascular mortality (pooled RR, 1.77; 95% CI, 1.56 to 1.97).

Conclusions: There is strong epidemiologic evidence to indicate that reduced FEV1 is a marker for cardiovascular mortality independent of age, gender, and smoking history.

Clinical Investigations: SURGERY

Chest. 2005;127(6):1960-1966. doi:10.1378/chest.127.6.1960
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Background: In patients with severe emphysema, bone mineral density (BMD) is reduced and the risk of osteoporosis is increased.

Study objectives: To identify the impact of lung volume reduction surgery on BMD.

Design: Prospective cohort study.

Setting: University hospital.

Patients and interventions: Forty emphysematous patients, all receiving oral steroid therapy, underwent bilateral lung volume reduction surgery. Thirty similar patients, who refused the operation, followed a standard respiratory rehabilitation program.

Measurements: All subjects were evaluated pretreatment and 12 months posttreatment for respiratory function, nutritional status, and bone-related biochemical parameters. BMD was assessed by dual-energy radiograph absorptiometry.

Results: After surgery, we observed significant improvements in respiratory function (FEV1, + 18.8% [p < 0.01]; residual volume [RV], −29.6% [p < 0.001]; diffusing capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones (free-testosterone, + 20.5% [p < 0.01]; parathormone, –11.2% [p < 0.01]), bone turnover markers (osteocalcin, –12.7% [p < 0.05]; bone-alkaline-phosphatase, –14.0% [p < 0.05]; β-crosslaps, −33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p < 0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01]; femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%). Nineteen patients who had undergone surgery were able to discontinue treatment with oral steroids. These subjects showed a more significant improvement in BMD (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%; femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery experienced significant improvement compared to respiratory rehabilitation subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs −0.7%, respectively [p < 0.01]; femoral, + 2.7% vs –1.1%, respectively [p < 0.05]; T-score: lumbar, + 14 vs –2.1, respectively [p < 0.01]; femoral, + 7.4 vs –2.7, respectively [p < 0.01]). The increase in lumbar BMD was correlated with the surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and fat-free mass (p = 0.01).

Conclusions: Lung volume reduction surgery significantly improves BMD compared to respiratory rehabilitation therapy, even in patients requiring oral steroids. The increase in BMD correlates with RV, Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics, gas exchange, and nutritional status induces improvement in bone metabolism and mineral content.

Smoking and Timing of Cessation*: Impact on Pulmonary Complications After Thoracotomy
Chest. 2005;127(6):1977-1983. doi:10.1378/chest.127.6.1977
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Study objective: The benefit of smoking cessation just prior to surgery in preventing postoperative pulmonary complications has not been proven. Some studies actually show a paradoxical increase in complications in those quitting smoking only a few weeks or days prior to surgery. We studied the effect of smoking and the timing of smoking cessation on postoperative pulmonary complications in patients undergoing thoracotomy.

Design and setting: Prospective study conducted in a tertiary care cancer center in 300 consecutive patients with primary lung cancer or metastatic cancer to the lung who were undergoing anatomical lung resection.

Results: The groups studied were nonsmokers (21%), past quitters of > 2 months duration (62%), recent quitters of < 2 months duration (13%), and ongoing smokers (4%). Overall pulmonary complications occurred in 8%, 19%, 23%, and 23% of these groups, respectively, with a significant difference between nonsmokers and all smokers (p = 0.03) but no difference among the subgroups of smokers (p = 0.76). The risk of pneumonia was significantly lower in nonsmokers (3%) compared to all smokers (average, 11%; p < 0.05), with no difference detected among subgroups of smokers (p = 0.17). Comparing recent quitters and ongoing smokers, no differences in pulmonary complications or pneumonia were found (p = 0.67). Independent risk factors for pulmonary complications were a lower diffusing capacity of the lung for carbon monoxide (Dlco) [odds ratio [ OR] per 10% decrement, 1.41; 95% confidence interval [ CI], 1.17 to 1.70; p = 0.01) and primary lung cancer rather than metastatic disease (OR, 3.94; 95% CI, 1.34 to 11.59; p = 0.003). Among smokers, a lower Dlco percent predicted (OR per 10% decrement, 1.42; 95% CI, 1.16 to 1.75; p = 0.008) and a smoking history of > 60 pack-years (OR, 2.54; 95% CI, 1.28 to 5.04; p = 0.0008) were independently associated with overall pulmonary complications.

Conclusions: In patients undergoing thoracotomy for primary or secondary lung tumors, there is no evidence of a paradoxical increase in pulmonary complications among those who quit smoking within 2 months of undergoing surgery. Smoking cessation can safely be encouraged prior to surgery

Chest. 2005;127(6):1984-1990. doi:10.1378/chest.127.6.1984
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Objectives: To determine the morbidity, mortality, and feasibility of lung resection in patients with tumors and preoperative FEV1 < 35% predicted.

Design: Retrospective review.

Setting: A 734-bed, tertiary care, academic hospital with a dedicated general thoracic surgery unit performing > 2,000 operations per year.

Patients: One hundred consecutive patients with discrete lung tumors and with preoperative FEV1 < 35% predicted undergoing lung resection between September 1997 and May 2003. Only operations with curative intent were included. Average preoperative predicted FEV1 was 26%. Sixteen percent of the patients were oxygen dependent prior to the operation.

Results: Open and thoracoscopic wedge resections, segmentectomies, lobectomies, and combined lung resections with lung volume reduction were performed. Sixty-six of the lesions were malignant, and 57 were primary lung cancers. Only one patient left the operating room with positive margins. There was one in-hospital or 30-day mortality. Thirty-six percent of the patients had one or more complications. Twenty-two percent of the patients had prolonged air leaks requiring a chest tube for > 7 days. One patient left the hospital ventilator dependent, 3 additional patients required intubation > 48 h, and 11 patients were discharged with a new oxygen requirement. There were four pneumonias, one myocardial infarction, and two reoperations for bleeding. Male gender (p = 0.003), preoperative oxygen dependence (p = 0.03), and pack-year history (p = 0.006) were associated with a higher overall incidence of complications, while age, incision, diabetes, coronary artery disease, duration of smoking cessation, amount of lung resected, size of lesion, and preoperative percentage of predicted FEV1 did not correlate with the overall incidence of complications.

Conclusions: In a large academic center, minimally invasive surgical techniques, intensive pulmonary care, and advanced anesthetic techniques allow for curative lung tumor resections in patients with very low preoperative FEV1 with a very low mortality and very low incidence of ventilator dependence. Other serious complications such as pneumonia, myocardial infarction, and bleeding are uncommon. An extended hospital stay and a high incidence of prolonged air leak should be expected, especially in patients with preoperative FEV1 ≤ 20% predicted.

Clinical Investigations: COUGH

Chest. 2005;127(6):1991-1998. doi:10.1378/chest.127.6.1991
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Study objectives: To determine whether the health-related quality of life (HRQOL) of women and men is adversely affected by acute cough (AC), affected differently by AC, or affected differently by AC and chronic cough (CC).

Design: Analysis of consecutively and prospectively collected AC data from two time periods, and previously prospectively and consecutively collected CC data that had not been previously analyzed. When no differences were found in the two cohorts of acute coughers, as was the case in the greatest majority of comparisons, the two samples were pooled, treated as one sample of acute coughers, and compared with chronic coughers.

Settings: Primary care and cough clinics in an academic, tertiary care medical center.

Participants: Subjects prospectively seeking medical attention complaining of AC for < 3 weeks and CC for at least 8 weeks.

Measurement: All subjects completed the cough-specific quality-of-life questionnaire (CQLQ) prior to contact with a physician and medical intervention.

Results: Of 62 acute coughers, 32 were women and 30 were men (p = 0.25). Total CQLQ scores for women were 59.9, and for men they were 59.2. (There was no difference in total CQLQ scores in the two cohorts of acute coughers.) The mean (± SD) combined total CQLQ score of women and men of 59.57 ± 10.4 was higher (t90 = 11.39; p < 0.0001) than the score in an historical control group of women and men who were not complaining of cough (35.06 ± 8.40). In acute coughers, there were no gender differences in the total or six subscale scores when the two cohorts were considered separately or combined. Of 172 chronic coughers, 116 were women and 56 were men (p < 0.0001). Women with CC rated themselves significantly higher than did women with AC on the total CQLQ and on five of the six subscales. Women with AC did not rate themselves higher on any of the CQLQ subscales. Total CQLQ scores for men with AC and CC were similar. Men with CC, compared with men with AC, scored significantly higher in two of six subscales (and significantly lower in one subscale) and scored similarly in three subscales.

Conclusions: AC, like CC, adversely affected the HRQOL of women and men. Unlike CC, AC did not adversely affect the HRQOL of women more than men. The HRQOL of women is more adversely affected than the HRQOL of men, the longer a cough lasts.

Clinical Investigations: BRONCHOSCOPY

Chest. 2005;127(6):1999-2006. doi:10.1378/chest.127.6.1999
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Background: Bronchial thermoplasty is a novel procedure being developed as a potential treatment for asthma. Experience with animal studies has enabled development of appropriate reliable equipment, definition of therapeutic parameters, and descriptions of tissue effects of treatment.

Study objectives: This study was undertaken to assess the feasibility and general safety of the application of bronchial thermoplasty in the human airway, and to determine if the reduction in airway smooth muscle seen in animal studies could be replicated.

Design: A prospective study.

Setting: Academic thoracic surgery center.

Participants: Nine patients scheduled to undergo lung resection for suspected or proven lung cancer.

Interventions: Bronchial thermoplasty was performed during routine preoperative bronchoscopy up to 3 weeks prior to prescheduled lung resection. Treatment was limited to areas of the segmental bronchi within the lobe that was to be removed. Treated airways were inspected via bronchoscopy at the time of thoracotomy, and were examined histologically following surgical resection.

Results: There were no adverse clinical effects of the procedure, including no new symptoms and no unscheduled visits for medical care. Treated sites exhibited slight redness and edema of the mucosa within 2 weeks of treatment, and appeared normal at later time points. There was narrowing (visually estimated at 25 to 50%) in four airways in two subjects examined at 5 days and 13 days after treatment, with excess mucus in two of these airways. There was no bronchoscopic evidence of scarring in any of the airways examined. Histologic examination showed a reduction in airway smooth muscle, and the extent of the treatment effect was confined to the airway wall and the immediate peribronchial region.

Conclusion: Application of bronchial thermoplasty to the human airway appears to be well tolerated. Treatment resulted in significant reduction of smooth muscle mass in the airways. Bronchial thermoplasty may provide therapeutic benefit in disease states such as asthma.

Chest. 2005;127(6):2007-2014. doi:10.1378/chest.127.6.2007
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Study objectives: More than 80% of patients with lung cancer are unsuitable for curative surgical treatment. Palliative relief of symptoms, often caused by airway obstruction, is very important. Endobronchial cryosurgery is used for destruction of intraluminal tumors. This study analyzes the effects of cryosurgery on patients with obstructive endobronchial carcinoma.

Design: Retrospective analysis of data extracted from a prospective computerized database.

Setting: Tertiary referral thoracic surgical center.

Patients: Data of the 172 patients who underwent at least two sessions of endobronchial cryosurgery (group A) were compared with 157 patients who underwent one session of cryosurgery (group B) for malignant primary or metastatic obstructive lung carcinoma over a 5-year period.

Intervention: Endobronchial cryosurgery is performed under general anesthesia. A nitrous oxide cryoprobe is inserted through a rigid bronchoscope. The probe achieves a temperature of − 70°C at its tip and is applied to the tumor for two 3-min periods. Statistical analysis assessed the effects of cryosurgery on symptoms, lung function, Karnofsky performance score, and survival.

Results: Symptoms of dyspnea, cough, and hemoptysis were significantly reduced in both groups after cryosurgery (p < 0.001), although group A benefited more than group B. Lung function test results improved significantly in group A. The mean Karnofsky performance score (± SD) increased from 67 ± 9 to 74 ± 10 (group A) and from 67 ± 10 to 73 ± 11 (group B). The mean survival was 15 months (median, 11 months) for group A and 8.3 months (median, 6 months) for group B (p = 0.006). Univariate regression analysis showed that no particular patient or tumor characteristic was associated with reduction of symptoms. Patients who had cryosurgery and external beam radiotherapy showed longer survival (p < 0.01). Females and patients with stage IIIa and IIIb tumors achieved significantly improved Karnofsky scores (p < 0.02). Female sex was also a factor for increase in FEV at 1 min (p = 0.003) and FVC (p < 0.001).

Conclusions: Cryosurgery is a safe method for palliation of endobronchial malignancies causing airway obstruction. Statistical analysis showed improvement of dyspnea, cough, and hemoptysis. Cryosurgery can be considered in patients with inoperable obstructive endobronchial carcinoma.

Transbronchial Needle Aspirates*: Comparison of Two Preparation Methods
Chest. 2005;127(6):2015-2018. doi:10.1378/chest.127.6.2015
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Study objectives: Transbronchial needle aspiration has evolved as a key bronchoscopic sampling method. Specimen handling and preparation are underrated yet crucial aspects of the technique. This study was designed to identify which of two widely practiced sample preparation methods has a higher yield.

Design: Prospective comparison of two diagnostic methods.

Setting: Tertiary academic hospital.

Patients: Consecutive patients undergoing transbronchial needle aspiration.

Interventions: Transbronchial aspirates were obtained pairwise. One specimen was placed directly onto a slide and smears were prepared on site (ie, the direct technique), and the other specimen was deposited into a vial containing 95% alcohol and further prepared in the laboratory (ie, the fluid technique). In total, 282 pairs of samples were aspirated from 145 target sites (paratracheal, 10 sites; tracheobronchial, 101 sites; hilar, 17 sites; endobronchial or peripheral, 17 sites).

Measurements and results: The measured outcome was the presence of diagnostic material at the final laboratory assessment. At least one diagnostic aspirate was obtained in 66% of 86 investigated patients (small cell lung cancer, 18 patients; non-small cell lung cancer, 47 patients; other diagnoses, 21 patients). The direct technique had a better yield overall than the fluid technique (positive aspirates, 36.2% vs 12.4%, respectively; p < 0.01), as well as after stratification for tumor type and for anatomic site.

Conclusion: The direct technique is superior to the fluid technique for the preparation of transbronchial needle aspirates.

Clinical Investigations: INTERSTITIAL LUNG DISEASE

Chest. 2005;127(6):2019-2027. doi:10.1378/chest.127.6.2019
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Study objectives: To investigate the histopathologic pattern and clinical features of patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) according to the American Thoracic Society (ATS)/European Respiratory Society consensus classification of idiopathic interstitial pneumonia.

Design: Retrospective review.

Setting: Two thousand-bed, university-affiliated, tertiary referral center.

Patients: Eighteen patients with RA who underwent surgical lung biopsy (SLBx) for suspected ILD.

Method: SLBx specimens were reviewed and reclassified by three lung pathologists according to the ATS/European Respiratory Society classification. Clinical features and follow-up courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific interstitial pneumonia (NSIP) pattern were compared.

Results: The histopathologic patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP pattern, and 2 patients with inflammatory airway disease with the organizing pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three patients, ILD preceded RA; in three patients, both conditions were diagnosed simultaneously. The majority (n = 13) of patients had a restrictive defect with or without low diffusion capacity of the lung for carbon monoxide (Dlco) on pulmonary function testing; 2 patients had only low Dlco. The UIP and NSIP groups were significantly different in their male/female ratios (8/2 vs 0/6, respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2 vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high-resolution CT features of UIP. Five patients with the UIP pattern died, whereas no deaths occurred among patients with the NSIP pattern during median follow-up durations of 4.2 years and 3.7 years, respectively.

Conclusions: The histopathologic type of RA-ILD was diverse; in our study population, the UIP pattern seemed to be more prevalent than the NSIP pattern.

Chest. 2005;127(6):2028-2033. doi:10.1378/chest.127.6.2028
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Study objective: In COPD, it has been shown that peripheral muscle dysfunction is a factor determining exercise intolerance. We examined the hypothesis that exercise capacity of patients with idiopathic pulmonary fibrosis (IPF) is, at least in part, determined by peripheral muscle dysfunction.

Methods: Maximum oxygen uptake (V̇o2max) was evaluated in 41 consecutive patients with IPF, along with potential determinants of exercise capacity, both in the lungs and in the peripheral muscles.

Results: Patients had reduced V̇o2max (893 ± 314 mL, 46.0% predicted) and reduced quadriceps force (QF) [65% predicted]. Significant correlates of V̇o2max reduction were vital capacity (VC) [r = 0.79], total lung capacity (r = 0.64), diffusion capacity (r = 0.64), QF (r = 0.62), maximum expiratory pressure (r = 0.48), and Pao2 at rest (r = 0.33). In stepwise multiple regression analysis, VC and QF were independent predictors of V̇o2max. Furthermore, in subgroup analysis, QF was a significant contributing factor for V̇o2max in patients who discontinued exercise because of dyspnea and/or leg fatigue.

Conclusions: We conclude that QF is a predictor of exercise capacity in IPF. Measures that improve muscle function might improve exercise tolerance.

Familial Idiopathic Pulmonary Fibrosis*: Clinical Features and Outcome
Chest. 2005;127(6):2034-2041. doi:10.1378/chest.127.6.2034
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Study objectives: Familial idiopathic pulmonary fibrosis (FIPF) has been defined as idiopathic pulmonary fibrosis (IPF) occurring in two or more members of a family. The clinical course of FIPF has not been fully defined. Accordingly, the current study was undertaken to establish clinical, radiologic, and histologic features, and survival in a consecutive series of patients with FIPF.

Design: Retrospective analysis of clinical, radiologic, and pathologic data from a consecutive series of patients with FIPF who were seen at Mayo Medical Center. Survival in patients with FIPF was contrasted to that of previously characterized patients with nonfamilial IPF who were evaluated at our institution.

Setting: Tertiary referral medical center.

Patients: We screened 47 patients and family members with FIPF from 15 families who were identified between the years 1992 and 2002. We further analyzed the subgroup of FIPF patients that was composed of 27 patients from 15 families in whom the complete clinical course was monitored at our institution.

Measurements: All patients exhibited clinical features that were compatible with IPF and either compatible high-resolution CT (HRCT) scan findings or histologic evidence of usual interstitial pneumonia. Clinical data, including symptoms, physical findings, HRCT scan findings, lung function test results, biopsy results, and survival were abstracted from the clinical records.

Results: Compared to patients with nonfamilial IPF, patients with FIPF did not demonstrate any notable differences in clinical, radiologic, or pathologic features. We observed that the total number of affected members in a family with FIPF was a significant risk factor for earlier mortality (p = 0.0157; hazard ratio, 1.434). Overall, however, patients with FIPF had a statistically similar outcome to those patients with nonfamilial IPF.

Conclusions: Although uncommon, FIPF represents a distinct syndrome, which has clinical features and patient survival rates that are similar to those of nonfamilial IPF.

Clinical Investigations: CARDIOLOGY

Improving Outcomes in Heart Failure in the Community*: Long-term Survival Benefit of a Disease-Management Program
Chest. 2005;127(6):2042-2048. doi:10.1378/chest.127.6.2042
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Objectives: The purpose of our current study was to determine whether our disease-management model was associated with long-term survival benefits. A secondary objective was to determine whether program involvement was associated with medication maintenance and reduced hospitalization over time compared to usual care management of heart failure.

Design: A retrospective chart review was conducted in patients who had been hospitalized for congestive heart failure between April 1999 and March 31, 2000, and had been discharged from the hospital for follow-up in the Heart Failure Clinic vs usual care.

Setting: An integrated health-care center serving a tristate area.

Patients: Patients (n = 101) were followed up for 4 years after their index hospitalization for congestive heart failure.

Measurements and results: The patients followed up in the Heart Failure Clinic comprised group 1 (n = 38), and the patients receiving usual care made up group 2 (n = 63). The mean (± SD) age of the patients in group 1 was 68 ± 16 years compared to 76 ± 11 years for the patients in group 2 (p = 0.002). The patients in group 1 were more likely to have renal failure (p = 0.035), a lower left ventricular ejection fraction (p = 0.005), and hypotension at baseline (p = 0.002). At year 2, more patients in group 1 were maintained by therapy with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) [p = 0.036]. The survival rate over 4 years was better for group 1. Univariate Cox proportional hazard ratios revealed that age, not receiving ACEIs or ARBs, and renal disease or cancer at baseline were associated with mortality. When controlling for these variables in a multivariate Cox proportional hazards ratio model, survival differences between groups remained significant (p = 0.021). Subjects in group 2 were 2.4 times more likely to die over the 4-year period than those in group 1.

Conclusions: Our study demonstrated that, after controlling for baseline variables, patients participating in a heart failure clinic enjoyed improved survival.

Warfarin Maintenance Dosing Patterns in Clinical Practice*: Implications for Safer Anticoagulation in the Elderly Population
Chest. 2005;127(6):2049-2056. doi:10.1378/chest.127.6.2049
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Background: The use of anticoagulant therapy is expanding among the elderly population, in part because of the increasing prevalence of atrial fibrillation. Published data describing the warfarin maintenance dose requirements for this age group are limited. Because warfarin therapy is often initiated in the outpatient setting where significant barriers to daily monitoring exist for this patient population, a better understanding of the factors that predict lower dose requirements may reduce the risk of unanticipated overanticoagulation and hemorrhage.

Objective: To define the effects of age and gender on the warfarin maintenance dose among ambulatory adult patients with an international normalized ratio target between 2.0 and 3.0.

Design: Prospective cohort study and retrospective cohort secondary data source.

Setting: One hundred one community-based physician practices with dedicated warfarin management systems and an academic medical center anticoagulation clinic.

Patients: A total of 4,616 patients comprised the prospective cohort, and 7,586 patients comprised the retrospective cohort. Of the 12,202 patients, 2,359 were ≥ 80 years of age.

Measurements: Median weekly and daily maintenance warfarin dose.

Results: The warfarin dose was inversely related to age and was strongly associated with gender. The median weekly dose ranged from 45 mg (6.4 mg/d) for men who were < 50 years of age to 22 mg (3.1 mg/d) for women ≥ 80 years of age. The weekly dose declined by 0.4 mg/yr (95% confidence interval [CI], 0.37 to 0.44; p < 0.001) and women required 4.5 mg less per week than men (95% CI, 3.8 to 5.3; p < 0.001). Among patients who were > 70 years of age, the often-suggested initiation dose of 5 mg/d will be excessive for 82% of women and 65% of men.

Conclusions: Warfarin dose requirements decrease greatly with age. Older women require the lowest warfarin doses. These observations suggest that, when warfarin is being initiated, the commonly employed empiric starting dose of 5 mg/d will lead to overanticoagulation for the majority of patients in the geriatric age group; lower initiation and maintenance doses should be considered for the elderly.

Chest. 2005;127(6):2057-2063. doi:10.1378/chest.127.6.2057
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Study objectives: Although inhaled β2-agonists are in widespread use, several reports question their potential arrhythmogenic effects. The purpose of this study was to evaluate the cardiac electrophysiologic effects of a single, regular dose of an inhaled β2-agonist in humans.

Design: Prospective study.

Setting: Tertiary referral center.

Patients: Six patients with bronchial asthma and 12 patients with mild COPD.

Interventions: All patients underwent an electrophysiologic study before and after the administration of salbutamol solution (5 mg in a single dose).

Measurements and results: Sinus cycle length, sinus node recovery time (SNRT), interval from the earliest reproducible rapid deflection of the atrial electrogram in the His bundle recording to the onset of the His deflection (AH), interval from the His deflection to the onset of ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective refractory period (AERP), and ventricular effective refractory period (VERP) were evaluated just before and 30 min after the scheduled intervention. Salbutamol, a selective β2-agonist, administered by nebulizer had significant electrophysiologic effects on the atrium, nodes, and ventricle. The AH length decreased from 86.1 ± 19.5 ms at baseline to 78.8 ± 18.4 ms (p < 0.001), and the WCL decreased from 354.4 ± 44.2 to 336.6 ± 41.7 ms (p = 0.001). Salbutamol significantly decreased the AERP and VERP too while leaving the HV unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 ± 12.8 beats/min at baseline to 93.1 ± 16 beats/min, p < 0.001) and shortened the SNRT (from 1,073.5 ± 178.7 to 925.2 ± 204.9 ms, p = 0.001).

Conclusion: Inhaled salbutamol results in significant changes of cardiac electrophysiologic properties. Salbutamol enhances atrioventricular (AV) nodal conduction and decreases AV nodal, atrial, and ventricular refractoriness in addition to its positive chronotropic effects. These alterations could contribute to the generation of spontaneous arrhythmias.

Topics: albuterol

Clinical Investigations: AIRWAYS

Zinc Chloride (Smoke Bomb) Inhalation Lung Injury*: Clinical Presentations, High-Resolution CT Findings, and Pulmonary Function Test Results
Chest. 2005;127(6):2064-2071. doi:10.1378/chest.127.6.2064
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Study objectives: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and has been rarely described in previous studies. We hypothesized that structural changes of the lung might correlate with pulmonary function. To answer this question, we correlated findings from high-resolution CT (HRCT) scan and the results of pulmonary function tests (PFTs) in patients with ZCSII.

Design: Retrospective cohort study.

Setting: University hospital.

Patients: Twenty patients who had been hospitalized with ZCSII-related conditions.

Measurements: The study included HRCT scan scores (0 to 100), static and dynamic lung volumes, and diffusing capacity of the lung for carbon monoxide (Dlco).

Results: HRCT scans and PFTs were performed initially after injury (range, 3 to 21 days) in all patients and during the follow-up period (range, 27 to 66 days) in 10 patients. The predominant CT scan findings were patchy or diffuse ground-glass opacities with or without consolidation. The majority of patients showed a significant reduction of FVC, FEV1, total lung capacity, and Dlco, but normal FEV1/FVC ratio values. Changes of functional parameters correlated well with HRCT scan scores. Substantial improvements in CT scan abnormalities and pulmonary function were observed at follow-up.

Conclusions: The majority of our patients with ZCSII presented with a predominant parenchymal injury of the lung that was consistent with a restrictive type of functional impairment and a reduction in Dlco rather than with obstructive disease. Our results suggest that HRCT scanning and pulmonary function testing may reliably predict the severity of ZCSII.

Chest. 2005;127(6):2072-2075. doi:10.1378/chest.127.6.2072
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Background: Active smoking and passive exposure to cigarette smoke are associated with colonization by some potentially pathogenic species of bacteria and an increased risk of respiratory tract infection in both adults and children. In an attempt to explain these observations, this study compared the frequency of isolation of potential pathogens, and aerobic and anaerobic bacteria that possess interfering capabilities (ie, interfering with the in vitro growth of potential pathogens) in the nasopharynx of smokers to their recovery in nonsmokers.

Methods: Nasopharyngeal specimens for cultures were taken from 20 smokers and 20 nonsmokers. Potential pathogens, and aerobic and anaerobic bacteria with interfering capabilities against these organisms were identified.

Results: Fourteen potential pathogens (0.7 per patient) were isolated from nasopharyngeal cultures obtained from 11 of the 20 smokers, and 4 (0.2 per patient) were recovered from 3 of the 20 nonsmokers (p < 0.01). In vitro bacterial interference between two aerobic (α-hemolytic and nonhemolytic streptococci) and two anaerobic species (Prevotella and Peptostreptococcus species), and four potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae [non-type b], Moraxella catarrhalis, and Streptococcus pyogenes) was observed. Bacterial interference was noted in 61 instances against the four potential pathogens by 22 normal flora isolates that were recovered from the group of smokers, and in 155 instances by 50 isolates from the group of nonsmokers (p < 0.01).

Conclusions: These findings illustrate for the first time that the nasopharyngeal flora of smokers contains fewer aerobic and anaerobic organisms with interfering capabilities and more potential pathogens compared with those of nonsmokers.

Clinical Investigations: CPAP

Chest. 2005;127(6):2076-2084. doi:10.1378/chest.127.6.2076
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Background: Obstructive sleep apnea syndrome (OSAS) has been associated with increased morbidity and mortality, principally from cardiovascular disease, but the impact of nasal continuous positive airway pressure (CPAP) therapy is unclear.

Methods: We performed a long-term follow-up study of 168 patients with OSAS who had begun receiving CPAP therapy at least 5 years previously, most of whom had been prospectively followed up, having been the subject of an earlier report on cardiovascular risk factors in OSAS patients. The average follow-up period was 7.5 years. We compared the cardiovascular outcomes of those patients who were intolerant of CPAP (untreated group, 61 patients) with those continuing CPAP therapy (107 patients).

Results: CPAP-treated patients had a higher median apnea-hypopnea index score than the untreated group (48.3 [interquartile range (IQR), 33.6 to 66.4] vs 36.7 [IQR, 27.4 to 55], respectively; p = 0.02), but age, body mass index, and time since diagnosis were similar. Deaths from cardiovascular disease were more common in the untreated group than in the CPAP-treated group during follow-up (14.8% vs 1.9%, respectively; p = 0.009 [log rank test]), but no significant differences were found in the development of new cases of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie, death and new cardiovascular disease combined) were more common in the untreated group than in the CPAP-treated group (31% vs 18%, respectively; p < 0.05).

Conclusions: The data support a protective effect of CPAP therapy against death from cardiovascular disease in patients with OSAS.

Chest. 2005;127(6):2085-2093. doi:10.1378/chest.127.6.2085
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Study objectives: To compare adherence and clinical outcomes between flexible positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and standard PAP therapy (ie, continuous positive airway pressure [CPAP]).

Design and setting: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex device in participants with moderate-to-severe obstructive sleep apnea. Participants were recruited from and followed up through an academic sleep disorders center.

Participants: Eighty-nine participants were recruited into the study after they had undergone complete in-laboratory polysomnography and before initiating therapy. Participants received either therapy with CPAP (n = 41) or with the C-Flex device (n = 48), depending on the available treatment at the time of recruitment, with those recruited earlier receiving CPAP therapy and those recruited later receiving therapy with the C-Flex device. Follow-up assessments were conducted at 3 months.

Measurements and results: The groups were similar demographically. The mean (± SD) treatment adherence over the 3-month follow-up period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4, 4.2 ± 2.4 vs 3.5 ± 2.8, respectively; weeks 9 to 12, 4.8 ± 2.4 vs 3.1 ± 2.8, respectively). Clinical outcomes and attitudes toward treatment (self-efficacy) were also measured. Change in subjective sleepiness and functional outcomes associated with sleep did not improve more in one group over the other. Self-efficacy showed a trend toward being higher at the follow-up in those patients who had been treated with the C-Flex device compared to CPAP treatment.

Conclusions: Therapy with the C-Flex device may improve overall adherence over 3 months compared to standard therapy with CPAP. Clinical outcomes do not improve consistently, but C-Flex users may be more confident about their ability to adhere to treatment. Randomized clinical trials are needed to replicate these findings.

Clinical Investigations: PLEURAL

Chest. 2005;127(6):2094-2100. doi:10.1378/chest.127.6.2094
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Objectives: The primary aim of this study was to examine the association between pleural fluid (PF) eosinophilia, and the PF and serum levels of interleukin (IL)-5, eotaxin-2, eotaxin-3, and vascular cell adhesion molecule (VCAM)-1 in patients with post-coronary artery bypass grafting (CABG) pleural effusions.

Design: A prospective observational study.

Setting: A tertiary teaching hospital.

Patients and methods: Thirty-eight patients with post-CABG pleural effusions were recruited into the study. An effusion that contained at least 10% eosinophils was called “eosinophilic.” The PF and serum levels of the cytokines and VCAM-1 were measured using an enzyme-linked immunosorbent assay.

Results: (1) The number of PF eosinophils significantly correlated with the number of blood eosinophils. (2) PF IL-5 levels were significantly higher than the corresponding serum levels, and there was a significant correlation between the PF and serum IL-5 levels. PF IL-5 levels significantly correlated with the PF eosinophil count, and serum IL-5 levels significantly correlated with the number of blood eosinophils. (3) PF eotaxin-3 levels were significantly higher than serum levels, and PF eotaxin-3 levels significantly correlated with the PF eosinophil count. (4) PF VCAM-1 levels were significantly lower than the corresponding serum levels, and PF VCAM-1 levels were significantly higher in eosinophilic pleural effusions (EPEs) than in non-EPEs.

Conclusion: In patients with post-CABG pleural effusions, IL-5 and eotaxin-3 are produced preferentially in the pleural cavity, and they are strongly associated with PF eosinophilia.

Chest. 2005;127(6):2101-2105. doi:10.1378/chest.127.6.2101
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Background: Pleural effusions occur in patients with hematologic malignancies, particularly during periods of hospitalization. Thoracentesis is often performed to diagnose infection and to exclude the presence of complicated parapneumonic effusions. The efficacy and safety of thoracentesis in this setting has not been well-studied.

Design: Retrospective chart review of hospitalized patients with hematologic malignancies undergoing thoracentesis. The aim of this study was to assess the role of thoracentesis in establishing a diagnosis of infection in this population and to determine the risk of complications.

Results: A total of 100 thoracentesis findings were analyzed in patients with lymphoma (52 patients) and leukemia (27 patients), and in patients who had undergone bone marrow or stem cell transplantation (21 patients). The indication for performing thoracentesis was to exclude infection in 69% of cases. Fever was present in 59% of the patients, and a concomitant lung parenchymal abnormality was present in 69% of cases. Effusions were moderate to large in size (87% of cases), and were both bilateral (62%) and unilateral (38%). Exudates were documented in 83%of the cases. A specific diagnosis was found in 21 patients and was more frequently established in those with lymphoma (31%) compared to the other groups of patients. Diagnoses found included malignancy in 14 cases, chylous effusions in 6 cases, and infection in 1 case. The one patient in whom empyema was found required drainage. The criteria for a parapneumonic effusion were not found in any other patients. The complication rate of 9% (pneumothorax, seven patients; hemothorax, two patients) was comparable to that in other populations of patients.

Conclusions: Despite a high propensity for developing pulmonary infections, hospitalized patients with hematologic malignancies rarely developed complex parapneumonic effusions. The etiology of many of the effusions that occurred in this setting was unclear.

Bronchoscopy

Chest. 2005;127(6):2106-2112. doi:10.1378/chest.127.6.2106
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Background: Complications of metallic airway stents include granulation tissue formation, fracture of struts, migration, and mucous plugging. When these complications result in airway injury or obstruction, it may become necessary to remove the stent. There have been few reports detailing techniques and complications associated with endoscopic removal of metallic airway stents. We report our experience with endoscopic removal of 30 such stents over a 3-year period.

Methods: We conducted a retrospective review of 25 patients who underwent endoscopic stent removal from March 2001 to April 2004. The patients ranged in age from 17 to 80 years (mean, 56.3 years). There were 10 male and 15 female patients. The stents had been placed for nonmalignant disease in 20 patients (80%) and malignant disease in 5 patients (20%). All procedures were done under general anesthesia with a rigid bronchoscope. Special attention was focused on the technique of stent removal and postoperative complications.

Results: Thirty metallic airway stents were successfully removed from 25 consecutive patients over a 3-year period. The basic method of removal involved the steady application of traction to the stent with alligator forceps. In all cases, an instrument such as the barrel of the rigid bronchoscope or a Jackson dilator was employed to help separate the stent from the airway wall before removal was attempted. In some instances, the airway wall was pretreated with thermal energy prior to stent removal. Complications were as follows: retained stent pieces (n = 7), mucosal tear with bleeding (n = 4), reobstruction requiring temporary silicone stent placement (n = 14), need for postoperative mechanical ventilation (n = 6), and tension pneumothorax (n = 1).

Conclusions: Although metallic stents may be safely removed endoscopically, complications are common and must be anticipated. Other investigators have described airway obstruction and death as a result of attempted stent removal. Placement and removal of metallic airway stents should only be performed at centers that are prepared to deal with the potentially life-threatening complications.

Chest. 2005;127(6):2113-2118. doi:10.1378/chest.127.6.2113
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Study objectives: Massive hemoptysis is a life-threatening condition. Therapeutic strategies such as interventional angiography, surgery, and/or bronchoscopy have been applied in the clinical setting with variable results. We investigated the efficacy of bronchoscopy-guided topical hemostatic tamponade therapy (THT) using oxidized regenerated cellulose (ORC) mesh in the management of life-threatening hemoptysis.

Design: Seventy-six consecutive patients underwent emergency bronchoscopy for massive hemoptysis. Fifty-seven patients (75%) had persistent endobronchial bleeding despite bronchoscopic wedging technique, cold saline solution lavage, and instillation of regional vasoconstrictors. These patients subsequently underwent THT according to the same procedure.

Setting: Teaching hospital, bronchoscopy unit of a 300-bed tertiary pulmonary referral center.

Results: THT with ORC was successfully performed on 56 of 57 patients (98%) with an immediate arrest of hemoptysis. All patients successfully treated with THT remained free of hemoptysis for the first 48 h. None required intensive care support or immediate surgery. Mean procedure time (± SD) of THT was 11.5 ± 4.2 min. Recurrence of hemoptysis that was characterized as being mild (< 30 mL) to moderate (30 to 100 mL) developed in six patients (10.5%) 3 to 6 days after THT. Postobstructive pneumonia developed in five subjects (9%) after endoscopic THT. A subgroup of patients (n = 14) underwent bronchoscopic follow-up 4 weeks after discharge. The ORC mesh was absorbed in all of these patients without signs of foreign body reaction.

Conclusions: Endobronchial THT using ORC is a safe and practicable technique in the management of life-threatening hemoptysis with a high success and a relatively low complication rate.

Clinical Investigations in Critical Care

Chest. 2005;127(6):2119-2124. doi:10.1378/chest.127.6.2119
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Objectives: To follow-up on the changes in lung function and lung radiographic pictures of severe acute respiratory syndrome (SARS) patients discharged from Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to analyze retrospectively the treatment strategy in these patients.

Methods: Surviving SARS patients were seen at least twice within 3 months after discharge and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing, pulmonary function testing, and chest radiography and/or high-resolution CT (HRCT) examinations at Chinese PLA General Hospital. The treatments received at Xiaotangshan Hospital were analyzed retrospectively and were correlated to later status.

Results: Positive SARS-Co virus IgG antibody results were seen in 208 of 258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion abnormality (Dlco < 80% of predicted). By comparing the 155 survivors with positive SARS-CoV IgG antibody results and Dlco ≥ 80% predicted with the 50 patients with negative SARS-CoV IgG results, we found that 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much longer course of fever and received larger doses of glucocorticoid, as well as higher ratios of oxygen inhalation and noninvasive ventilation treatment. For these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung diffusion abnormality underwent pulmonary function testing after approximately 1 month. Dlco improved in 80.4% of patients (41 of 51 patients). Of the patients with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes in the lung image examination and 22 patients (55%) showed improvement in lung fibrotic changes 1 month later.

Conclusion: These findings suggest that lung fibrotic changes caused by SARS disease occurred mostly in severely sick patients and may be self-rehabilitated. Dlco scores might be more sensitive than HRCT when evaluating lung fibrotic changes.

Chest. 2005;127(6):2125-2131. doi:10.1378/chest.127.6.2125
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Study objectives: To examine the effect of patient body mass index (BMI) on outcome in intensive care.

Design: In a prospective study, the patients were classified into groups based on the calculated BMI, as follows: BMI < 19.0 (n = 350), ≥ 19.0 and < 25.0 (n = 663), ≥ 25.0 and < 29.9 (n = 585), ≥ 30.0 and < 40.0 (n = 396), and ≥ 40.0 (n = 154). Groups were compared by age, APACHE (acute physiology and chronic health evaluation) II score, mortality, ICU length of stay (LOS), hospital LOS, number receiving ventilation, and ventilator-days. Adverse events including nosocomial pneumonia, ventilator-days per patient, failed extubations, and line-related complications were recorded.

Setting: The study was conducted in a 9-bed medical ICU of a 650-bed tertiary care hospital.

Measurements: Height and weight were prospectively recorded for the first ICU admission during a hospital stay.

Results: Between January 1, 1997, and August 1, 2001, 2,148 of 2,806 patients admitted to the ICU had height and weight recorded. There were no differences in APACHE II score, mortality, ICU LOS, hospital LOS, number receiving ventilation, ventilator-days, average total cost, or average variable cost among the five groups. However, the severely obese patients were more frequently female and younger than those who were overweight and obese (p < 0.001). Adverse events were infrequent, but there were no differences between the obese/very obese compared with others.

Conclusion: BMI has minimal effects on ICU outcome after patients are admitted to a critical care unit.

Survival in Amyotrophic Lateral Sclerosis With Home Mechanical Ventilation*: The Impact of Systematic Respiratory Assessment and Bulbar Involvement
Chest. 2005;127(6):2132-2138. doi:10.1378/chest.127.6.2132
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Study objectives: To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV).

Design and setting: Retrospective study in a tertiary care referral center.

Patients: HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B).

Results: In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002).

Conclusions: Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

Chest. 2005;127(6):2139-2150. doi:10.1378/chest.127.6.2139
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Study objective: Impaired leukocyte function in patients with serious infections may increase mortality. Granulocyte-monocyte colony-stimulating factor (GM-CSF) broadly activates peripheral monocytes and neutrophils. We performed a clinical trial of GM-CSF in septic, hemodynamically stable patients to see whether GM-CSF treatment improved leukocyte function and mortality.

Design: Randomized, unblinded, placebo-controlled, prospective study.

Setting: A 600-bed academic tertiary care center with a 120-bed ICU census with a high proportion of immunocompromised, solid-organ transplant recipients.

Patients: Forty adult patients with infections meeting the criteria for the systemic inflammatory response syndrome but without hemodynamic instability or shock.

Interventions: Patients with sepsis and a documented infection were randomized to a 72-h infusion of GM-CSF (125 μg/m2) or placebo.

Measurements and main results: GM-CSF infusion caused the up-regulation of the β2-integrin adhesion molecule CD11b and the appearance of the activated (“sticky” or “avid”) form of the molecule on circulating neutrophils and monocytes. CD11b density and avidity increases in response to the administration of tumor necrosis factor-α were blunted prior to treatment in these patients with serious infection. GM-CSF partially repaired this blunted response on both monocytes and neutrophils. It also caused the down-regulation of the adhesion molecule L-selectin on neutrophils and the up-regulation of human leukocyte antigen on monocytes. These changes were consistent with a broad activation of the circulating leukocyte pool. Although mortality and organ failure scores were similar in both groups, infection resolved significantly more often in patients receiving GM-CSF.

Conclusions: GM-CSF infusion up-regulated the functional markers of inflammation on circulating neutrophils and monocytes and was associated with both the clinical and microbiological resolution of infection. There was no detectable exacerbation of sepsis-related organ failure or other deleterious side effects with the administration of this proinflammatory agent to patients with serious infections.

Critical Care Reviews

Chest. 2005;127(6):2151-2164. doi:10.1378/chest.127.6.2151
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ICUs are a vital component of modern health care. Improving ICU performance requires that we shift from a paradigm that concentrates on individual performance to a different paradigm that emphasizes the need to assess and improve ICU systems and processes. This is the first part of a two-part treatise. It discusses existing problems in ICU care, and the methods for defining and measuring ICU performance.

Chest. 2005;127(6):2165-2179. doi:10.1378/chest.127.6.2165
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ICUs are a vital but troubled component of modern health-care systems. Improving ICU performance requires that we shift from a paradigm that concentrates on individual performance, to a systems-oriented approach that emphasizes the need to assess and improve the ICU systems and processes that hinder the ability of individuals to perform their jobs well. This second part of a two-part treatise establishes a practical framework for performance improvement and examines specific strategies to improve ICU performance, including the use of information systems.

Ethics in Cardiopulmonary Medicine

Chest. 2005;127(6):2180-2187. doi:10.1378/chest.127.6.2180
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Context: Homeless people are at increased risk of critical illness and are less likely to have surrogate decision makers when critically ill. Consequently, clinicians must make decisions independently or with input from others such as ethics committees or guardians. No prior studies have examined treatment preferences of homeless to guide such decision makers.

Design: Interviewer-administered, cross-sectional survey of homeless persons.

Setting: Homeless shelters in Seattle, WA.

Participants: Two hundred twenty-nine homeless individuals with two comparison groups: 236 physicians practicing in settings where they are likely to provide care for homeless persons and 111 patients with oxygen-dependent COPD.

Measurements: Participants were asked whether they would want intubation with mechanical ventilation or cardiopulmonary resuscitation in their current health, if they were in a permanent coma, if they had severe dementia, or if they were confined to bed and dependent on others for all care.

Results: Homeless men were more likely to want resuscitation than homeless women (p < 0.002) in coma and dementia scenarios. Homeless men and women were both more likely to want resuscitation in these scenarios than physicians (p < 0.001). Nonwhite homeless were more likely to want resuscitation than white homeless people (p < 0.033), and both were more likely to want resuscitation than physicians (p < 0.001). Homeless are also more likely to want resuscitation than patients with COPD. The majority (80%) of homeless who reported not having family or not wanting family to make medical decisions prefer a physician make decisions rather than a court-appointed guardian.

Conclusions: Homeless persons are more likely to prefer resuscitation than physicians and patients with severe COPD. Since physicians may be in the position of making medical decisions for homeless patients and since physicians are influenced by their own preferences when making decisions for others, physicians should be aware that, on average, homeless persons prefer more aggressive care than physicians. Hospitals serving homeless individuals should consider developing policies to address this issue.

Chest. 2005;127(6):2188-2196. doi:10.1378/chest.127.6.2188
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Objective: Patients with COPD frequently do not discuss end-of-life care with physicians; therefore, we sought to identify the barriers and facilitators to this communication as a first step to overcoming barriers and capitalizing on facilitators.

Design: Fifteen barriers and 11 facilitators to patient-physician communication about end-of-life care were generated from focus groups of patients with COPD. We subsequently conducted a cross-sectional study of 115 patients with oxygen-dependent COPD and their physicians to identify the common barriers and facilitators and examine the association of these barriers and facilitators with communication about end-of-life care.

Participants and setting: Patients with oxygen-dependent COPD were recruited from clinics at a university, county, and Veterans Affairs teaching hospital, and an oxygen delivery company. We also recruited the physician identified by each patient as the doctor primarily responsible for their lung disease.

Measurements and results: Patients were interviewed by trained research interviewers. Physician data collection was completed by mail survey. Participation rates were 40% for patients and 86% for physicians. Only 32% of patients reported having a discussion about end-of-life care with their physician. Two of 15 barriers and 8 of 11 facilitators were endorsed by > 50% of patients. The most commonly endorsed barriers were “I’d rather concentrate on staying alive,” and “I’m not sure which doctor will be taking care of me.” Two barriers were significantly associated with lack of communication, as follows: “I don’t know what kind of care I want,” and “I’m not sure which doctor will be taking care of me.” The greater the number of barriers endorsed by patients, the less likely they were to have discussed end-of-life care with physicians (p < 0.01), suggesting the validity of these barriers. Conversely, the more facilitators, the more likely patients were to report having had end-of-life discussions with their physicians (p < 0.001).

Conclusion: Although patients endorsed many barriers and facilitators, few barriers were endorsed by most patients. Barriers and facilitators associated with communication are targets for interventions to improve end-of-life care, but such interventions will likely need to address the specific barriers relevant to individual patient-physician pairs.

Exercise and the Heart

Chest. 2005;127(6):2197-2203. doi:10.1378/chest.127.6.2197
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Background: We are in the midst of an obesity pandemic. Morbid obesity is associated with dyspnea on exertion and higher overall mortality rates. The relations between measures of cardiorespiratory fitness in morbidly obese persons compared to those with heart failure are unknown.

Methods: We compared cardiorespiratory fitness in patients with morbid obesity (n = 43) and established systolic dysfunction heart failure (n = 235), and in age-matched medical control subjects (n = 222) who had been referred for diagnostic exercise testing with simultaneous metabolic measurements. Only patients who completed an adequate test for maximum exertion manifested by a respiratory exchange ratio of ≥ 1.10 were included in the study.

Results: The mean (± SD) body mass index (BMI) values for the three groups were 47.8 ± 5.1, 30.1 ± 5.7, and 33.8 ± 9.0, respectively (p < 0.0001 for comparisons between morbidly obese patients and each comparator). The mean left ventricular ejection fraction for the heart failure group was 21.5 ± 8.4%. Despite achieving higher peak heart rate and BP values, the morbidly obese patients had a mean maximum oxygen uptake (V̇o2max) that was similar to that of those with heart failure (17.8 ± 3.6 vs 16.5 ± 5.6 mL/kg/min, respectively; p = 0.14) and was considerably lower than that of the control group (17.8 ± 3.6 vs 21.3 ± 8.2 mL/kg/min, respectively; p = 0.007). In addition, among subjects in the control group, there was a graded inverse relation between BMI and V̇o2max.

Conclusions: Morbidly obese individuals have severely reduced cardiorespiratory fitness that is similar to those with established systolic dysfunction heart failure. In addition, in those persons who are referred for stress testing for medical reasons, there is an inverse graded relationship between BMI and cardiorespiratory fitness. These data suggest that the impairment in V̇o2max in morbidly obese persons is related to BMI and possibly to other factors that impair peak cardiac performance. These findings are consistent with overall higher expected mortality in morbidly obese persons.

Laboratory and Animal Investigations

Chest. 2005;127(6):2204-2210. doi:10.1378/chest.127.6.2204
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Study objective: Mechanical ventilation (MV) is used clinically to treat patients who are incapable of maintaining adequate alveolar ventilation. Prolonged MV is associated with diaphragmatic atrophy and a decrement in maximal specific force production (Po). Collectively, these alterations may predispose the diaphragm to injury on the return to spontaneous breathing (ie, reloading). Therefore, these experiments tested the hypothesis that reloading the diaphragm following MV exacerbates MV-induced diaphragmatic contractile dysfunction, while causing muscle fiber membrane damage and inflammation.

Methods: To test this postulate, Sprague-Dawley rats were randomly assigned to the following groups: (1) control; (2) 24 h of controlled MV; and (3) 24 h of controlled MV followed by 2 h of anesthetized spontaneous breathing. Controls were anesthetized in the short term but were not exposed to MV, whereas MV animals were anesthetized, tracheostomized, and ventilated. Reloaded animals remained under anesthesia, but were removed from MV and returned to spontaneous breathing for 2 h.

Results: Compared to the situation with control animals, MV resulted in a 26% decrement in diaphragmatic specific Po without muscle fiber membrane damage, as measured by an increase in membrane permeability (using the procion orange technique). Further, there were no increases in neutrophil or macrophage influx. Two hours of reloading did not exacerbate MV-induced diaphragmatic contractile dysfunction or cause fiber membrane damage, but increased neutrophil infiltration, myeloperoxidase activity, and muscle edema.

Conclusion: We conclude that the return to spontaneous breathing following 24 h of controlled MV does not exacerbate MV-induced diaphragm contractile dysfunction or result in fiber membrane damage, but increases neutrophil infiltration.

Chest. 2005;127(6):2211-2221. doi:10.1378/chest.127.6.2211
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Background: A pleural drainage system must be capable of efficiently evacuating the air or fluids from the pleural cavity so that adequate lung reexpansion can take place. The air flow and negative pressure of the system will depend on the particular design of each model. This experimental study analyzes the specifications and performance of the pleural drainage systems currently on the market.

Methods: Thirteen models of pleural drainage systems connected to wall suction were examined. The models were classified into the following three groups: dry systems; wet systems; and single-chamber systems. We determined the ambient air flow and the negative pressure generated according to the suction level. The components of each model are also described.

Results: Under normal conditions, dry (except for the Sentinel Seal; Sherwood Medical; Tullamore, Ireland), wet, and single-chamber systems reach similar air flow rates (17 to 30, 24 to 27, and 22 to 28 L/min, respectively). With higher wall suction levels, wet systems increase the air flow (26 to 49 L/min) but the negative pressure becomes unstable because of the water loss phenomenon, dry systems increase the air flow (29 to 50 L/min) without modifying the regulator pressure, and single-chamber systems also raise the air flow (45 to 51 L/min) but increase the negative pressure. When there is an air leak, dry systems (except for the Sentinel Seal) lose less negative pressure than the other systems.

Conclusions: The functioning of these systems can be optimized only by applying a suitable wall suction level adjusted to each case. Although the three types of systems are capable of evacuating adequate air flow rates, the negative pressure and the capacity to maintain it in the presence of an air leak are different in each system. Being fitted with valves and not water compartments makes the dry systems the safest and the ideal for use when the patient has to be moved.

Chest. 2005;127(6):2222-2225. doi:10.1378/chest.127.6.2222
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Rationale: Airway hyperresponsiveness to adenosine monophosphate (AMP) has been validated as a surrogate marker for airway inflammation. We wished to know whether an abbreviated challenge at the final threshold dose would produce the same fall in FEV1 as a full, conventional dose-response challenge.

Methods: Seventeen patients with mild-to-moderate asthma (mean FEV1, 75.5% predicted) attended for a full dose-response protocol, where the highest concentration of AMP to produce > 20% fall in FEV1 was noted, along with the maximum percentage fall and recovery time. Patients returned within 2 days for a further challenge, when they received only the highest concentration (as a single bolus) reached on the previous visit.

Results: The mean (± SEM) percentage fall in FEV1 after the full challenge was 25.5 ± 1.3%, and after the abbreviated challenge was 9.4 ± 2.4%. The mean recovery after the full challenge was 28.13 ± 4.65 min, and after the abbreviated test was 10.81 ± 4.27 min.

Conclusion: An abbreviated challenge using a single bolus dose of AMP grossly underestimates bronchial hyperresponsiveness. Although the pharmacologic half-life of AMP is short (90 s), the lesser response and shortened recovery with the abbreviated challenge suggest a more prolonged physiologic half-life, which in turn may have implications for abbreviated challenge protocols

Minimally Invasive Techniques

Video-Assisted Thoracoscopic Surgery for Primary Spontaneous Pneumothorax*: Evaluation of Indications and Long-term Outcome Compared With Conservative Treatment and Open Thoracotomy
Chest. 2005;127(6):2226-2230. doi:10.1378/chest.127.6.2226
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Study objectives: Video-assisted thoracoscopic surgery (VATS) is effective for primary spontaneous pneumothorax. We sought to evaluate the outcome of VATS compared to conservative treatment and open thoracotomy, and to discuss the indications for VATS in primary spontaneous pneumothorax.

Design: Retrospective study.

Patients and interventions: Primary spontaneous pneumothorax was diagnosed in 281 consecutive patients between January 1989 and April 2001. Mean age was 29.1 years. Mean follow-up period was 78.3 months (range, 13 to 163 months). For these patients, conservative treatment, open thoracotomy, or VATS were performed, and the outcomes of the three treatments were evaluated. If recurrence occurred, outcome of treatment for the recurrence was also evaluated according to the number of times of recurrence.

Results: Recurrences were observed in 109 of 281 patients (38.8%). Forty-three patients (15.3%) had repeat recurrences. Regarding the outcome of the first episode, recurrence rates were 54.7% for conservative treatment, 7.7% for open thoracotomy, and 10.3% for VATS. Recurrence rates after the second episode were 60.3% for conservative treatment, 0% for open thoracotomy, and 18.6% for VATS. Overall recurrence rates of each treatment were 56.4%, 3.0%, and 11.7%, respectively. There was no statistical difference between the open thoracotomy and VATS groups (p = 0.15). Hospital stays from operation until discharge were 11.5 days for open thoracotomy and 4.1 days for VATS (p < 0.001).

Conclusion: The outcomes of VATS were very good compared to conservative treatment and equal to those of the open thoracotomy, not only for the first episode but also for the case of recurrence. In terms of low morbidity, low invasiveness, and cosmetic issues, VATS is superior to open thoracotomy. VATS is standard in cases of recurrence and should be considered for treatment at the first episode.

Opinions/Hypotheses

Chest. 2005;127(6):2231-2236. doi:10.1378/chest.127.6.2231
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Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.

Preliminary Reports

Chest. 2005;127(6):2237-2242. doi:10.1378/chest.127.6.2237
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Purpose: To assess the safety of CT-guided brachytherapy of lung malignancies and to evaluate the initial therapeutic response.

Patients and methods: Fifteen patients with 30 lung malignancies were included in this prospective phase I trial (metastases, 28; non-small cell lung cancers, 2). Preinterventionally two patients had a vital capacity of < 80% (39% and 63%). These two patients, and one other, had FEV1 values of < 80% predicted (17%, 48%, and 64%). Tumors with a maximum diameter of 4 cm were treated with a single brachytherapy catheter that was positioned under CT-fluoroscopy. In two tumors with tumor diameters of 5.5 and 6.5 cm, two applicators were used. In one patient with an 11-cm irregularly shaped tumor, nine catheters were inserted. Treatment planning for 192Ir brachytherapy was performed using three-dimensional CT data that were acquired after percutaneous applicator positioning. All procedures were performed under local anesthesia. A follow-up CT was performed 6 weeks later and every 3 months postintervention.

Results: The mean diameter of the 30 lung tumors was 2 cm (range, 0.6 to 11 cm; median diameter, 1.5 cm). The minimal dose within the tumor margin was 20 Gy in all 30 tumors treated. Except for nausea in one patient and focal hemorrhage detected on CT in two patients, no acute adverse events were recorded. One patient developed an abscess at the previous tumor location 9 months after treatment, which proved to be a local tumor recurrence. The median follow-up period was 5+ months with a local tumor control of 97%.

Conclusion: The novel technique of CT-guided interstitial brachytherapy was safe for the treatment of lung tumors and yielded a very low complication rate. The initial data on therapeutic response are promising.

Reviews

Chest. 2005;127(6):2243-2253. doi:10.1378/chest.127.6.2243
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Study objectives: The aims of this study were to investigate the frequency of pulmonary problems in Behçet disease (BD), and to discuss lesser-known features of pulmonary BD such as clinical characteristics, analysis of prognosis, and evaluation of treatment options with respect to the previously published cases.

Design: We conducted a comprehensive review of the literature to analyze cumulated data about pulmonary involvement in BD.

Setting: We found 159 articles regarding pulmonary disease associated with BD in May 2003.

Patients: The evaluation of these articles demonstrated 598 pulmonary problems in 585 cases.

Results: Pulmonary artery aneurysms (PAAs) are the most common pulmonary lesion in BD, and these are almost always associated with hemoptysis. Seventy-eight percent of patients with aneurysms have concomitant extrapulmonary venous thrombi or thrombophlebitis. Other pulmonary problems are reported in BD, and these are principally related to vascular lesions and radiologic abnormalities.

Conclusions: Pulmonary vascular problems, either PAA or involvement of small-sized vessels, are the main pulmonary disorders in BD. Immunopathologic findings indicate that the underlying pathogenesis is pulmonary vasculitis, which may result in thrombosis, infarction, hemorrhage, and PAA formation. Patients with small nonspecific radiologic abnormalities should be followed up closely since early diagnosis of vascular lesions may be life-saving. Immunosuppression is the main therapy for the treatment of a vasculitis. It is important that pulmonary angiitis is not mistaken for pulmonary thromboembolic disease since fatalities have occurred in BD shortly after initiation of anticoagulation/thrombolytic treatment.

Flow-Mediated Vasodilation*: A Diagnostic Instrument, or an Experimental Tool?
Chest. 2005;127(6):2254-2263. doi:10.1378/chest.127.6.2254
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Brachial arterial flow-mediated dilation (FMD), assessed by high-resolution ultrasonography, reflects endothelium-dependent vasodilator function. FMD is diminished in patients with atherosclerosis and with coronary risk factors, and improves with risk-reduction therapy. Therefore, the measurement of FMD can be a good prognostic instrument in preventive cardiology, is useful to predict short-term postoperative cardiovascular events in a high-risk population and to assess long-term cardiovascular risk in a lower risk population, and is an excellent experimental tool to detect changes in endothelial function after new therapeutic interventions. In this review article, the pathophysiology of FMD, based on reactive hyperemia, is extensively discussed. Furthermore, an overview is given of the actual clinical indications of FMD measurement.

Roentgenogram of the Month

Chest. 2005;127(6):2264-2265. doi:10.1378/chest.127.6.2264
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A 63-year-old woman presented with a short history (a few months) of persistent cough and mild shortness of breath. On further enquiry, she admitted to having a poor appetite, with an associated weight loss of approximately 4 kg over a period of 6 months. Clinical examination was unremarkable and did not reveal any signs of lung malignancy. A chest roentgenogram showed bilateral multiple pulmonary nodules (Fig 1 ). Blood tests for angiotensin-converting enzyme levels, systemic vasculitic screen, antineutrophil cytoplasmic antibody, and rheumatoid factor were normal. The C-reactive protein was mildly elevated at 52 mg/L.

Pulmonary and Critical Care Pearls

Chest. 2005;127(6):2266-2270. doi:10.1378/chest.127.6.2266
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A 55-year-old African-American man presented with a week-long history of cough with blood-streaked sputum. He denied fevers, night sweats, weight change, and sinus symptoms. He was physically active and had no dyspnea on exertion. He reported gastroesophageal reflux symptoms but denied any other complaints. His medical history included diverticulosis and depression. He took no medications. He was an active smoker with a 60-pack-year smoking history. In addition, he smoked crack cocaine with reported use 3 months prior. He denied alcohol or IV drug use. He had no significant travel, occupational, or exposure history.

Selected Reports

Chest. 2005;127(6):2271-2273. doi:10.1378/chest.127.6.2271
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Recently, ultrathin bronchoscopes with a thinner external diameter, greater visual range, improved visibility, and a larger working channel have been developed. The utility of a 2.8-mm diameter ultrathin bronchoscope in diagnosing peripheral pulmonary nodules has been reported by some authors. While the feasibility of approaching peripheral pulmonary lesions is attractive, peculiar complications that have not been experienced with standard bronchoscopy may occur. We report two cases in which pneumothoraces occurred because their visceral pleuras were perforated with an ultrathin bronchoscope during the procedure. The peculiar mechanism of pneumothorax in relation to ultrathin bronchoscopy is discussed.

Topics: bronchoscopy , pleura
Chest. 2005;127(6):2273-2276. doi:10.1378/chest.127.6.2273
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We encountered a 69-year-old woman displaying a filling defect within the left descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A subsequent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination of transbronchial needle aspiration specimens revealed small cell carcinoma. The patient underwent concurrent radiation therapy and chemotherapy with cisplatin and etoposide, resulting in tumor shrinkage and recanalization of the involved PA. This is the first case of small cell carcinoma localized exclusively within the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.

Chest. 2005;127(6):2276-2281. doi:10.1378/chest.127.6.2276
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Liquid silicone is an inert material that is utilized for cosmetic procedures by physicians as well as illegally by nonmedical personnel. We present a case report and collated clinical findings of 32 other patients who were hospitalized after illegal silicone injections. Symptoms and signs of the “silicone syndrome” included dyspnea, fever, cough, hemoptysis, chest pain, hypoxia, alveolar hemorrhage, and altered consciousness. Bilateral patchy alveolar infiltrates were present on the chest radiographs, and silicone pulmonary emboli were detected in all the patients. The patients could be divided into two groups based on the initial presentation and clinical outcome. Twenty-seven patients in group 1 presented predominantly with respiratory symptoms, and 93% of patients were discharged home within 3 weeks. Six patients (group 2) presented with severe neurologic findings, and experienced rapid deterioration and 100% mortality. The clinical findings after silicone embolism are very similar to the published reports of fat embolism, including hypoxemia in 92% of patients with silicone embolism (patients with fat embolism, 56 to 96%), dyspnea in 88% of patients (patients with fat embolism, 56 to 75%), fever in 70% of patients (patients with fat embolism, 23 to 67%), alveolar hemorrhage in 64% of patients (patients with fat embolism, 66%), neurologic symptoms in 33% of patients (patients with fat embolism, 22 to 86%), petechiae in 18% of patients (patients with fat embolism, 20 to 50%), chest pain in 15% of patients (patients with fat embolism, 26%), and mortality in 24% of patients (patients with fat embolism, 5 to 20%). The similarities among the mode of injury to the lung, the clinical findings, and the high incidence of alveolar hemorrhage suggest a common pathogenesis of silicone and fat embolism syndromes. We discuss the possibility that the activation of the coagulation system may be important in the development of these clinical syndromes.

Communications to the Editor

Chest. 2005;127(6):2282-2283. doi:10.1378/chest.127.6.2282
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Chest. 2005;127(6):2302-2303. doi:10.1378/chest.127.6.2302
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By Nicholas N. Kipshidze and Patrick W. Serruys, eds. London, UK: Martin Dunitz, an imprint of the Taylor & Francis Group, 2004; 448 pp; $136

Chest. 2005;127(6):2303-2304. doi:10.1378/chest.127.6.2303
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By Larry R. Kaiser, MD, and Sunil Singhal, MD, eds. Philadelphia, PA: Elsevier Mosby, 2004; 366 pp; $79.00

Erratum

Chest. 2005;127(6):2304. doi:10.1378/chest.127.6.2304
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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543