Chest. 2012;142(1):1-5. doi:10.1378/chest.12-1364

In 2005, when Richard S. Irwin, MD, Master FCCP took the reins as CHEST Editor in Chief, he wrote an editorial about his goals in taking on the stewardship of the journal.1 We followed up in early 2006 with another editorial that described changes we were instituting to help CHEST continue its evolution as a clinically useful and relevant journal.2 Fast forward to 2010, Dr Irwin described the “Journal of the Future” that would include not only the cutting-edge clinical research our readers have come to expect, but also editorial cartoons and – gasp! – a poetry section to highlight the humanism of medicine.3

Chest. 2012;142(1):5-7. doi:10.1378/chest.12-1354

Editor’s Note: In an attempt to transform the health-care system in the United States to improve upon the inadequacies and deficiencies of our current model, the Robert Wood Johnson Foundation and the Institute of Medicine created a collaborative partnership to spell out what aspects of our health-care system need to be remodeled. They envisioned that “interprofessional collaboration and coordination would be the ‘norm,’”1 because no discipline functions in isolation of others, certainly not in our intensive care units. In this spirit of interdisciplinary collaboration, the American College of Chest Physicians (ACCP) and the American Association of Critical-Care Nurses (AACN)—physician and nursing societies, respectively, with combined memberships totaling more than 110,000 practicing critical care practitioners—have spoken with one voice in the editorial that follows about how and how not to address the shortage of critical care physicians. Because our critical care nurses work side by side with our intensivists, shouldn’t they have a say in how intensivists are trained? The ACCP and AACN think so, and we agree.

Chest. 2012;142(1):8-10. doi:10.1378/chest.11-3325

Pulmonary and critical care physicians are both users and abusers of antibiotics. Whether in the clinic, on the wards, or in the ICU, antibiotics represent one of our most often used tools. The amount of antibiotics given annually in the ICU alone can be measured in gross tonnage.1 Despite the frequency with which we order antibiotics, it remains fascinating how little we know about these compounds. In fact, the history of antibiotic prescribing is a story filled with hubris. The explosion in antimicrobial resistance underscores the veracity of this observation. Recent research, however, has clearly revealed that many assumptions that underlie our approach to antibiotic use are flawed and, perhaps, dangerous.

Chest. 2012;142(1):10-11. doi:10.1378/chest.12-0045

There is no doubt that the screening of health-care workers (HCWs) for latent TB infection (LTBI) and active TB should play an important role in infection control programs in hospitals and other health-care settings.1,2 TB risks appear to be particularly high in situations with ongoing exposure where inadequate infection control measures are in place.3 In their fundamental analysis of infection control measures in health-care settings from 1995, Menzies et al4 came to the conclusion that “there is an urgent need to evaluate their efficacy, feasibility, and cost effectiveness as well as their effect on the risk of transmission in various settings.”

Chest. 2012;142(1):11-13. doi:10.1378/chest.11-3162

Many patients with asthma have persistent symptoms associated with chronic inflammation despite treatment with corticosteroids. Novel approaches to the treatment of such patients include the administration of therapies targeting specific cytokines believed to be involved in persistent airway inflammation.1,2 One such candidate is thymic stromal lymphopoietin (TSLP). This cytokine upregulates the expression of OX40 ligand (OX40L) on dendritic cells, which interacts with OX40 on T cells to promote the production of TH2 cytokines such as IL-4, IL-5, and IL-13.3 TSLP has other proinflammatory effects, including the upregulation of cytokine and chemokine production from dendritic cells and mast cells.3 Animal models have implicated TSLP in allergic lung inflammation.3,4

Chest. 2012;142(1):15-17. doi:10.1378/chest.12-1085

Malignant pleural effusion (MPE) accounts for 22% of all pleural effusions, and in the United States >150,000 new cases are diagnosed annually.1 Carcinoma of any organ can metastasize to the pleura, and when malignant cells are detected in the pleural fluid or in pleural tissue they denote dissemination and poor prognosis. Median survival after the diagnosis of MPE is 4 to 6 months and is dependent on type of neoplasm.2

Chest. 2012;142(1):17-19. doi:10.1378/chest.12-1087

Malignancy is one of the most common causes of exudative pleural effusion, with approximately 200,000 cases occurring annually in the United States.1 Many patients with malignant effusions have the quality of their life diminished by shortness of breath. If the shortness of breath is relieved with a therapeutic thoracentesis, then consideration should be given to proceeding with a procedure that will prevent the accumulation of pleural fluid. If the patient is not symptomatic from the pleural effusion, no treatment is recommended. Most patients who have small effusions that do not produce symptoms never become symptomatic.2

Chest. 2012;142(1):19-20. doi:10.1378/chest.12-1086

Malignant pleural effusions (MPEs) treated with simple aspiration and intercostal tube drainage without instillation of a sclerosant are associated with high rates of recurrence. According to a survey of >800 physicians who collectively performed >8,000 pleurodesis, thoracoscopic talc poudrage (TTP) was preferred over tube talc slurry (TS).1 Cochrane database and systematic reviews have also shown better outcome with TTP than tube TS.2,3 Although overall success rates in the phase III intergroup study comparing TTP and tube TS were similar, TTP provided more comfort and safety and was more effective than slurry for breast and lung cancers, which account for 50% to 65% of MPEs.4 Moreover, Aelony and Yao5 have demonstrated better survival after talc poudrage for mesothelioma, and 90% of patients with mesothelioma will develop symptomatic MPEs during the course of disease.6 The phase III intergroup study4 excluded patients with trapped lungs because of extensive intrapleural tumor load and pleural loculations, which occur in up to 30% of MPEs and are the main cause for pleurodesis failure. Thoracoscopy facilitates lysis of adhesions, which promotes drainage of pleural loculations to allow the underlying lungs to expand and enhances success of pleurodesis.7

Chest. 2012;142(1):20-21. doi:10.1378/chest.12-1088

Patients with a malignant effusion have a mean life expectancy of only several months. It is, therefore, incumbent upon physicians caring for these patients to manage their effusions in a manner that will provide them the most high-quality days during the remainder of their lives.

Second Opinion

Chest. 2012;142(1):14. doi:10.1378/chest.142.1.14
Topics: eye contact


Chest. 2012;142(1):22-29. doi:10.1378/chest.11-3034

A millennium is 1,000 years. In little over a decade after the beginning of the new millennium in 2000, remarkable changes have occurred in health-care education and health-care delivery. A new millennial generation of students, trainees, junior faculty, and young practicing physicians has come of age. The numbers of women in medicine have vastly increased. Technology has impacted education with an array of educational content-delivery techniques vastly different from the usual broadcast method of teaching. New curricula have expanded to encompass teamwork with interprofessional education of the entire team. Outcomes of educational efforts now include not only knowledge transfer but also performance improvement. Delivery of health care is also dramatically different. The sentinel driver of the quality and patient safety moment, To Err Is Human, was published only 12 years ago, yet fundamental changes in expectations and measurement for health-care quality and safety have occurred to alter the health-care landscape. Financing health care has become a prime issue in the current state of the US economy. New themes in health-care delivery include teamwork and highly functioning teams to improve patient safety, the dramatic increase in palliative care and end-of-life care, and the expanded role of nursing in health-care delivery. Each issue emanating since the beginning of the millennium does not have a right vs wrong implication. This discussion is an apolitical “environmental scan” with the purpose of illuminating these dramatic changes and then outlining the implications for health-care education and health-care delivery in the coming years.

Topics: safety , health care

Original Research

Chest. 2012;142(1):30-39. doi:10.1378/chest.11-1671

Background:  β-Lactams are routinely used as empirical therapy in critical illness, with extended concentrations above the minimum inhibitory concentration (MIC) of the infecting organism required for effective treatment. Changes in renal function in this setting can significantly impact the probability of achieving such targets.

Methods:  Analysis was made of trough plasma drug concentrations obtained via therapeutic drug monitoring, compared with renal function, in critically ill patients receiving empirical β-lactam therapy. Drug concentrations were measured by means of high-performance liquid chromatography and corrected for protein binding. Therapeutic levels were defined as greater than or equal to MIC and greater than or equal to four times MIC (maximum bacterial eradication), respectively. Renal function was assessed by means of an 8-h creatinine clearance (CLCR).

Results:  Fifty-two concurrent trough concentrations and CLCR measures were used in analysis. Piperacillin was the most frequent β-lactam prescribed (48%), whereas empirical cover and Staphylococcus species were the most common indications for therapy (62%). Most patients were mechanically ventilated on the day of study (85%), although only 25% were receiving vasopressors. In only 58% (n = 30) was the trough drug concentration greater than or equal to MIC, falling to 31% (n = 16) when using four times MIC as the target. CLCR values ≥ 130 mL/min/1.73 m2 were associated with trough concentrations less than MIC in 82% (P < .001) and less than four times MIC in 72% (P < .001). CLCR remained a significant predictor of subtherapeutic concentrations in multivariate analysis.

Conclusion:  Elevated CLCR appears to be an important predictor of subtherapeutic β-lactam concentrations and suggests an important role in identifying such patients in the ICU.

Chest. 2012;142(1):40-47. doi:10.1378/chest.12-0310

Background:  A recent ICU telemedicine research consensus conference identified the need for reliable methods of measuring structural features and processes of critical care delivery in the domains of organizational context and characteristics of ICU teams, ICUs, hospitals, and of the communities supported by an ICU.

Methods:  The American College of Chest Physicians Critical Care Institute developed and conducted a survey of ICU telemedicine practices. A 32-item survey was delivered electronically to leaders of 311 ICUs, and 11 domains were identified using principal components analysis. Survey reliability was judged by intraclass correlation among raters, and validity was measured for items for which independent assessment was available.

Results:  Complete survey information was obtained for 170 of 311 ICUs sent invitations. Analysis of a subset of surveys from 45 ICUs with complete data from more than one rater indicated that the survey reliability was in the excellent to nearly perfect range. Coefficients for measures of external validation ranged from 0.63 to 1.0. Analyses of the survey revealed substantial variation in the practice of ICU telemedicine, including ICU telemedicine center staffing patterns; qualifications of providers; case sign-out, ICU staffing models, leadership, and governance; intensivist review for new patients; adherence to best practices; use of quality and safety information; and ICU physician sign out for their patients.

Conclusions:  The American College of Chest Physicians ICU telemedicine survey is a reliable tool for measuring variation among ICUs with regard to staffing, structure, processes of care, and ICU telemedicine practices.

Chest. 2012;142(1):48-54. doi:10.1378/chest.11-2100

Background:  Delirium evaluation in patients in the ICU requires the use of an arousal/sedation assessment tool prior to assessing consciousness. The Richmond Agitation-Sedation Scale (RASS) and the Riker Sedation-Agitation Scale (SAS) are well-validated arousal/sedation tools. We sought to assess the concordance of RASS and SAS assessments in determining eligibility of patients in the ICU for delirium screening using the confusion assessment method for the ICU (CAM-ICU).

Methods:  We performed a prospective cohort study in the adult medical, surgical, and progressive (step-down) ICUs of a tertiary care, university-affiliated, urban hospital in Indianapolis, Indiana. The cohort included 975 admissions to the ICU between January and October 2009.

Results:  The outcome measures of interest were the correlation and agreement between RASS and SAS measurements. In 2,469 RASS and SAS paired screens, the rank correlation using the Spearman correlation coefficient was 0.91, and the agreement between the two screening tools for assessing CAM-ICU eligibility as estimated by the κ coefficient was 0.93. Analysis showed that 70.1% of screens were eligible for CAM-ICU assessment using RASS (7.1% sedated [RASS −3 to −1]; 62.6% calm [0]; and 0.4% restless, agitated [+1 to +3]), compared with 72.1% using SAS (5% sedated [SAS 3]; 66.5% calm [4]; and 0.6% anxious, agitated [5, 6]). In the mechanically ventilated subgroup, RASS identified 19.1% CAM-ICU eligible patients compared with 24.6% by SAS. The correlation coefficient in this subgroup was 0.70 and the agreement was 0.81.

Conclusion:  Both SAS and RASS led to similar rates of delirium assessment using the CAM-ICU.

Chest. 2012;142(1):55-62. doi:10.1378/chest.11-0992

Background:  Clinical data with use of serial interferon-γ release assay (IGRA) testing in US health-care workers (HCWs) are limited.

Methods:  A single-center, retrospective chart review was done from 2007 to 2010 of HCWs who underwent preemployment QuantiFERON-TB Gold In-Tube testing. Demographic data, bacille Calmette-Guérin history, prior tuberculin skin test result if done, and baseline and serial IGRA values were obtained. The number of IGRA converters and reverters and their subsequent management by infectious disease physicians were reviewed. Quantitative IGRA-negative values were not available.

Results:  A total of 7,374 IGRAs were performed on newly hired HCWs. Of these tests, 486 (6.6%) were positive at baseline, 305 (4.1%) were indeterminate, and 6,583 (89.3%) were negative. From 2007 to 2010, 52 of 1,857 HCWs (2.8%) with serial IGRA tests were identified as converters, with a serial IGRA median value of 0.63 IU/mL. Seventy-one percent of HCWs with IGRA conversion had values ≤ 1 IU/mL. None of the converters had active TB or were part of an outbreak investigation.

Conclusions:  Clinical significance of most QuantiFERON-TB Gold In-Tube conversions in serial testing remains a challenging task for clinicians. The use of a single cutoff point criterion for IGRA may lead to overdiagnosis of new TB infections. Clinical assessment and evaluation may help to prevent unnecessary therapy in these cases. The criteria for defining conversions and reversions by establishing new cutoffs needs to be evaluated further, especially in HCWs.

Chest. 2012;142(1):63-75. doi:10.1378/chest.11-3157

Background:  Given the current lack of effective vaccines against TB, the accuracy of screening tests for determining or excluding latent TB infection (LTBI) is decisive in effective TB control. This meta-analysis critically appraises studies investigating the positive and the negative predictive value (PPV and NPV, respectively) from a test-determined LTBI state for progression to active TB of interferon-γ release assays (IGRAs) and the tuberculin skin test (TST).

Methods:  We searched MEDLINE, EMBASE, and Cochrane bibliographies for relevant articles. After qualitative evaluation, the PPV and NPV for progression of commercial and “in-house” IGRAs and the TST for persons not receiving preventive treatment in the context of the respective IGRA studies were pooled using both a fixed and a random-effect model. Weighted rates were calculated for all study populations and for groups solely at high risk of TB development.

Results:  The pooled PPV for progression for all studies using commercial IGRAs was 2.7% (95% CI, 2.3%-3.2%) compared with 1.5% (95% CI, 1.2%-1.7%) for the TST (P < .0001). PPV increased to 6.8% (95% CI, 5.6%-8.3%) and 2.4% (95% CI, 1.9%-2.9%) for the IGRAs and the TST, respectively, when only high-risk groups were considered (P < .0001). Pooled values of NPV for progression for both IGRAs and the TST were very high, at 99.7% (95% CI, 99.5%-99.8%) and 99.4% (95% CI, 99.2%-99.5%), respectively, although they were significantly higher for IGRAs (P < .01).

Conclusions:  Commercial IGRAs have a higher PPV and NPV for progression to active TB compared with those of the TST, especially when performed in high-risk persons.

Chest. 2012;142(1):76-85. doi:10.1378/chest.11-1782

Background:  The mast cell localization to airway smooth muscle (ASM) bundle in asthma is important in the development of disordered airway physiology. Thymic stromal lymphopoietin (TSLP) is expressed by airway structural cells. Whether it has a role in the crosstalk between these cells is uncertain. We sought to define TSLP expression in bronchial tissue across the spectrum of asthma severity and to investigate the TSLP and TSLP receptor (TSLPR) expression and function by primary ASM and mast cells alone and in coculture.

Methods:  TSLP expression was assessed in bronchial tissue from 18 subjects with mild to moderate asthma, 12 with severe disease, and nine healthy control subjects. TSLP and TSLPR expression in primary mast cells and ASM was assessed by immunofluorescence, flow cytometry, and enzyme-linked immunosorbent assay, and its function was assessed by calcium imaging. The role of TSLP in mast cell and ASM proliferation, survival, differentiation, synthetic function, and contraction was examined.

Results:  TSLP expression was increased in the ASM bundle in mild-moderate disease. TSLP and TSLPR were expressed by mast cells and ASM and were functional. Mast cell activation by TSLP increased the production of a broad range of chemokines and cytokines, but did not affect mast cell or ASM proliferation, survival, or contraction.

Conclusions:  TSLP expression by the bronchial epithelium and ASM was upregulated in asthma. TSLP promoted mast cell synthetic function, but did not contribute to other functional consequences of mast cell-ASM crosstalk.

Chest. 2012;142(1):86-93. doi:10.1378/chest.11-1838

Background:  The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects.

Methods:  Adults with stable asthma (n = 152) and healthy control subjects (n = 83) underwent hypertonic saline challenge and sputum induction. Differential leukocyte counts were performed on selected sputum. Plasma high-sensitivity C-reactive protein (CRP), IL-6, and tumor necrosis factor-α levels and sputum IL-8 and neutrophil elastase levels were determined by enzyme-linked immunosorbent assay. Sputum IL-8 receptor α (IL-8RA) and IL-8 receptor β (IL-8RB) messenger RNA expression were determined by real-time polymerase chain reaction.

Results:  Subjects with asthma were classified as having nonneutrophilic asthma or neutrophilic asthma. The asthma (neutrophilic) group had increased systemic inflammation compared with the asthma (nonneutrophilic) and healthy control groups, with median (interquartile range) CRP levels of 5.0 (1.6-9.2), 1.8 (0.9-5.3), and 1.8 (0.8-4.1) mg/L (P = .011), respectively, and IL-6 levels of 2.1 (1.5-3.1), 1.4 (1.0-2.1), and 1.1 (0.8-1.5) pg/mL (P < .001), respectively. The proportion of subjects with elevated CRP and IL-6 levels was also higher in the asthma (neutrophilic) group. Sputum IL-8 and neutrophil elastase protein and IL-8RA and IL-8RB gene expression were significantly increased in the asthma (neutrophilic) group. In multiple regression analysis of subjects with asthma, sex, BMI, statin use, and percent sputum neutrophils were significant predictors of log10CRP. Sex, BMI, and %FEV1 were significant predictors of log10IL-6.

Conclusions:  Systemic inflammation is increased in patients with asthma with neutrophilic airway inflammation and associated with worse clinical outcomes. Systemic inflammation may contribute to the pathophysiology of neutrophilic asthma.

Chest. 2012;142(1):94-100. doi:10.1378/chest.11-2013

Background:  The prevalence of obstructive sleep apnea syndrome (OSAS) is higher in children with sickle cell disease (SCD) as compared with the general pediatric population. It has been speculated that overgrowth of the adenoid and tonsils is an important contributor.

Methods:  The current study used MRI to evaluate such an association. We studied 36 subjects with SCD (aged 6.9 ± 4.3 years) and 36 control subjects (aged 6.6 ± 3.4 years).

Results:  Compared with control subjects, children with SCD had a significantly smaller upper airway (2.8 ± 1.2 cm3 vs 3.7 ± 1.6 cm3, P < .01), and significantly larger adenoid (8.4 ± 4.1 cm3 vs 6.0 ± 2.2 cm3, P < .01), tonsils (7.0 ± 4.3 cm3 vs 5.1 ± 1.9 cm3, P < .01), retropharyngeal nodes (3.0 ± 1.9 cm3 vs 2.2 ± 0.9 cm3, P < .05), and deep cervical nodes (15.7 ± 5.7 cm3 vs 12.7 ± 4.0 cm3, P < .05). Polysomnography showed that 19.4% (seven of 36) of children with SCD had OSAS compared with 0% (zero of 20) of control subjects (P < .05) and that in children with SCD the apnea-hypopnea index correlated positively with upper airway lymphoid tissues size (r = 0.57, P < 001). In addition, children with SCD had lower arterial oxygen saturation nadir (84.3% ± 12.3% vs 91.2% ± 4.2%, P < .05), increased peak end-tidal CO2 (53.4 ± 8.5 mm Hg vs 42.3 ± 5.3 mm Hg, P < .001), and increased arousals (13.7 ± 4.7 events/h vs 10.8 ± 3.8 events/h, P < .05).

Conclusions:  Children with SCD have reduced upper airway size due to overgrowth of the surrounding lymphoid tissues, which may explain their predisposition to OSAS.

Chest. 2012;142(1):101-110. doi:10.1378/chest.11-2456

Background:  Esophageal pressure monitoring during polysomnography in children offers a gold-standard, “preferred” assessment for work of breathing, but is not commonly used in part because prospective data on incremental clinical utility are scarce. We compared a standard pediatric apnea/hypopnea index to quantitative esophageal pressures as predictors of apnea-related neurobehavioral morbidity and treatment response.

Methods:  Eighty-one children aged 7.8 ± 2.8 (SD) years, including 44 boys, had traditional laboratory-based pediatric polysomnography, esophageal pressure monitoring, multiple sleep latency tests, psychiatric evaluations, parental behavior rating scales, and cognitive testing, all just before clinically indicated adenotonsillectomy, and again 7.2 ± 0.8 months later. Esophageal pressures were used, along with nasal pressure monitoring and oronasal thermocouples, not only to identify respiratory events but also more quantitatively to determine the most negative esophageal pressure recorded and the percentage of sleep time spent with pressures lower than −10 cm H2O.

Results:  Both sleep-disordered breathing and neurobehavioral measures improved after surgery. At baseline, one or both quantitative esophageal pressure measures predicted a disruptive behavior disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined attention-deficit/hyperactivity disorder, conduct disorder, or oppositional defiant disorder) and more sleepiness and their future improvement after adenotonsillectomy (each P < .05). The pediatric apnea/hypopnea index did not predict these morbidities or treatment outcomes (each P > .10). The addition of respiratory effort-related arousals to the apnea/hypopnea index did not improve its predictive value. Neither the preoperative apnea/hypopnea index nor esophageal pressures predicted baseline hyperactive behavior, cognitive performance, or their improvement after surgery.

Conclusions:  Quantitative esophageal pressure monitoring may add predictive value for some, if not all, neurobehavioral outcomes of sleep-disordered breathing.

Trial registry:  ClinicalTrials.gov; No.: NCT00233194; URL: www.clinicaltrials.gov

Chest. 2012;142(1):111-118. doi:10.1378/chest.11-1563

Background:  Periodic leg movements (PLMs) may appear during nasal CPAP titration, persisting despite the elimination of hypopneas.

Methods:  Systematic recordings of expiratory abdominal muscles on the right and left sides with surface electromyographic (EMG) electrodes lateral to navel, and close from the lateral side of abdomen, were added during nasal CPAP titration for treatment of obstructive sleep apnea (OSA). Positive airway pressure was titrated during nocturnal polysomnography, based on analysis of the flow curve derived from the CPAP equipment and EEG analysis, including persistence of phases A2 and A3 of the cyclic alternating pattern (CAP). The requirement was to eliminate American Association of Sleep Medicine (AASM)-defined hypopnea and also flow limitation and abnormal EEG patterns. When CPAP reached valid results, it was lowered at the time of awakening by 2 or 3 cm H2O, and titration was performed again. Data collected during a 7-month period on adults with a prior diagnosis of OSA who had received treatment with nasal CPAP regardless of age and sex were rendered anonymous and were retrospectively rescored by a blinded investigator.

Results:  Eighty-one successively seen patients with PLMs during CPAP titration were investigated. Elimination of AASM-defined hypopnea was not sufficient to eliminate the PLMs observed during the titration; higher CPAP eliminated flow limitation and CAP phases A2 and A3 and persisting PLMs. PLMs were associated with simultaneous EMG bursts in expiratory abdominal muscles.

Conclusions:  The presence of PLMs during CPAP titration indicates the persistence of sleep-disordered breathing. PLMs during CPAP titration are related to the presence of abdominal expiratory muscle activity.

Chest. 2012;142(1):119-127. doi:10.1378/chest.11-2231

Background:  Vilanterol (GW642444M) (VI) is a novel, inhaled, long-acting β2 agonist with inherent 24-h activity under development as a once-daily combination therapy with an inhaled corticosteroid for COPD and asthma. This study assessed the dose response, efficacy, and safety of VI at doses of 3 to 50 μg in patients with moderate to severe COPD.

Methods:  Six hundred two patients (intent-to-treat) were randomized (double-blind) to VI 3, 6.25, 12.5, 25, or 50 μg or placebo once daily for 28 days. The primary end point was change from baseline in trough FEV1 at the end of the 28-day treatment period. Secondary end points included 0- to 24-h weighted mean FEV1 on days 1 and 28 and time to increases of ≥ 100 mL or ≥ 12% from baseline FEV1 on day 1. Safety assessments included adverse events, vital signs, ECG assessment, and clinical laboratory tests.

Results:  VI once daily for 28 days significantly improved trough FEV1 in a dose-dependent manner vs placebo. Clinically relevant treatment differences of ≥ 130 mL in trough and 0- to 24-h weighted mean FEV1 were observed with VI 25- and 50-μg doses vs placebo. All doses of VI were associated with a low incidence of treatment-related adverse events/serious adverse events, with no suggestion of effects on BP, pulse rate, QT intervals corrected for heart rate calculated by Fridericia formula, or blood glucose and potassium levels.

Conclusions:  VI 25 and 50 μg once daily provided both statistically and clinically relevant 24-h improvements in lung function in patients with COPD compared with placebo. All doses of VI had a safety and tolerability profile similar to placebo.

Trial registry:  ClinicalTrials.gov; No.: NCT00606684; URL: www.clinicaltrials.gov

Chest. 2012;142(1):128-133. doi:10.1378/chest.11-2222

Background:  Despite strong preferences for discussions about end-of-life care, patients with COPD do not often have these discussions with their providers. Our objective was to determine whether patients who reported having end-of-life discussions also reported higher perceived markers of quality of care and health status.

Methods:  A cross-sectional study of data collected at baseline for a trial to improve the occurrence and quality of end-of-life communication in patients with COPD was conducted. The primary exposure was self-reported acknowledgment of having discussions about end-of-life planning with their physicians. The primary outcome measures were patient-reported quality of care and satisfaction with care, which were dichotomized as best imaginable quality of care vs other ratings of quality and highest satisfaction vs other ratings of satisfaction. We adjusted for confounding factors, including patient and provider characteristics, using logistic regression clustered by provider.

Results:  Three hundred seventy-six patients were enrolled, of whom 55 (14.6%) reported having end-of-life discussions. Individuals who reported having end-of-life discussions with their physicians were significantly more likely to rate their quality of care as the best imaginable (OR, 2.07; 95% CI, 1.05-4.09) and to be very satisfied with their medical care (OR, 1.98; 95% CI, 1.10-3.55). Discussions were more likely to have occurred among patients with worse health status as measured by St. George Respiratory Questionnaire total and impact scores.

Conclusions:  Patients who reported having end-of-life care discussions with their physicians had higher perceived quality of care and satisfaction with their physicians. Discussing end-of-life care with patients who have COPD may improve their perceived overall quality of and satisfaction with care.

Chest. 2012;142(1):134-140. doi:10.1378/chest.11-0309

Background:  The COPD Assessment Test (CAT) is an eight-item questionnaire suitable for routine clinical use that shows reliability and validity in stable and exacerbating COPD.

Methods:  Study 1 assessed CAT responsiveness to changes in health status in 67 patients during an exacerbation (days 1-14). Study 2 assessed CAT responsiveness in 64 patients undergoing pulmonary rehabilitation (days 1-42). Correlations between CAT and other outcome measures were examined.

Results:  In study 1, mean 14-day improvement in CAT score was −1.4 ± 5.3 units (P = .03). In patients judged to be responders (clinician defined) change in score was −2.6 ± 4.4; in nonresponders it was −0.2 ± 5.9. In study 2, the mean improvement in CAT score was −2.2 ± 5.3 (P = .002); the effect size for the change was −0.33. Effect size for changes in the Chronic Respiratory Questionnaire—Self Administered Standardized (CRQ-SAS) form domain scores ranged from −0.02 to 0.34. Change in 6-min walk distance (6MWD) was 41 ± 55 m. CAT and CRQ-SAS domain scores correlated at baseline (r = −0.54 to −0.69, P < .0001) and in terms of change following pulmonary rehabilitation (r = −0.39 to −0.63, P < .01). Correlations were less strong between change in the CAT and St. George Respiratory Questionnaire for COPD in study 1 (r < 0.24) and for 6MWD (r < 0.11) in study 2.

Conclusions:  These studies indicate that the CAT is sensitive to changes in health status following exacerbations and is as responsive to pulmonary rehabilitation as more complex COPD health status measures.

Chest. 2012;142(1):141-150. doi:10.1378/chest.11-2552

Objective:  Visceral pleural invasion (VPI) has been defined as invasion of the tumor beyond the elastic layer (PL1), including invasion to the visceral pleural surface (PL2). The aim of this study was to evaluate the prognostic factors and patterns of recurrence in resected node-negative non-small cell lung cancer (NSCLC) with VPI.

Methods:  We retrospectively reviewed the clinicopathologic characteristics of 355 patients with resected node-negative NSCLC with VPI at Taipei Veterans General Hospital between 1990 and 2006. The prognostic value and patterns of recurrence were analyzed and compared between PL1 and PL2 groups.

Results:  The median follow-up time was 54.2 months. The 5-year overall survival rate and probability of freedom from recurrence were 61.9% and 66.2%, respectively. The extent of VPI was PL1 in 300 patients (84.5%) and PL2 in 55 (15.5%). During follow-up, 107 patients (30.1%) developed recurrence. The patterns of recurrence included local recurrence only in 20 patients (18.7%), distant metastasis only in 59 (55.1%), and both local recurrence and distant metastasis in 28 (26.2%). Thirteen of the 107 patients (12.1%) with recurrence developed malignant pleural effusion. The percentage of malignant pleural effusion in the PL2 group was significantly higher than that in the PL1 group (P = .006). Patients with PL2 had significantly worse overall survival (P = .046) and lower probability of freedom from recurrence (P = .028) in multivariate analysis.

Conclusions:  PL2 was a significant prognostic factor for recurrence and worse overall survival in node-negative NSCLC with VPI. This information is important for further design of clinical trials for aggressive adjuvant therapy.

Chest. 2012;142(1):151-158. doi:10.1378/chest.11-2458

Background:  The tumor microenvironment, of which cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are the major cellular components, plays an important role in tumor progression. This study evaluated the significance of podoplanin-positive CAFs and CD204-positive TAMs, which may reflect tumor-promoting CAFs and TAMs, as risk factors for recurrence in patients with stage I lung adenocarcinoma.

Methods:  The expression of podoplanin in CAFs and CD204 in TAMs was analyzed by immunohistochemistry in 304 patients with stage I lung adenocarcinoma who underwent surgical resection between September 1992 and July 2004. The recurrence-free proportion (RFP) was estimated using the Kaplan-Meier method.

Results:  The presence of podoplanin-positive CAFs and the higher number of CD204-positive TAMs were associated with a lower 5-year RFP (P < .001 and P = .001, respectively). Podoplanin-positive CAFs were an independently statistically significant risk factor for recurrence with the highest hazard ratio (3.474, P = .029, by multivariate Cox proportional hazards model). According to subgroup analyses combining podoplanin-positive CAFs and other independent risk factors (visceral pleural invasion and intratumoral vascular invasion), the 5-year RFPs were 95.6%, 92.3%, 80.5%, and 30.3% (P = .294, P = .067, and P < .001) for patients with zero, one, two, or three risk factors, respectively.

Conclusions:  Podoplanin-positive CAFs were the most powerful independent risk factor for recurrence in patients with stage I lung adenocarcinoma. Podoplanin-positive CAFs may be useful for identifying patients with a high risk of recurrence who might benefit from adjuvant chemotherapy.

Chest. 2012;142(1):159-167. doi:10.1378/chest.11-1024

Background:  Previous studies of patients with bronchiectasis have found that the cause is idiopathic in the majority of cases, but these studies were done in homogeneous populations. We hypothesized that the etiology of bronchiectasis can be determined in a higher percentage of patients in a diverse US population and will differ significantly based on ethnicity.

Methods:  One hundred twelve patients with bronchiectasis confirmed by chest CT scan entered the study. Data from 106 patients were available for full evaluation. Clinical questionnaire, pulmonary function tests, sputum microbiology, laboratory data, and immune function testing were done. Results were analyzed by ethnicity and etiology.

Results:  Patients were 61.6% European American (EA), 26.8% African American (AA), 8.9% Hispanic American (HA), and 2.7% Asian American. A cause of bronchiectasis was determined in 93.3% of patients. In 63.2% of patients, bronchiectasis was caused by immune dysregulation, including deficiency (n = 18 [17%]), autoimmune disease (n = 33 [31.1%]), hematologic malignancy (n = 15 [14.2%]), and allergic bronchopulmonary aspergillosis (n = 1 [0.9%]). Rheumatoid arthritis was the cause of bronchiectasis in 28.6% of AA patients vs 6.2% of EA patients (P < .05). Hematologic malignancy was the etiology in 20.0% of the EA patients vs none of the AA patients (P = .02). A significantly higher percentage of HA patients had Pseudomonas aeruginosa in their sputum compared with AA and EA patients (P = .01).

Conclusions:  The etiology of bronchiectasis can be determined in the majority of patients in a heterogeneous US population and is most often due to immune dysregulation. Rheumatoid arthritis is more likely in AA patients than EA patients. HA patients are more likely to have P aeruginosa in their sputum.

Chest. 2012;142(1):168-174. doi:10.1378/chest.11-2361

Background:  A recent estimate for the normal range of forced expiratory tracheal collapse differs substantially from that in an earlier study performed with comparable measurement methods. Given differences in subject characteristics between the two samples, we hypothesized that these discrepant findings may reflect a heretofore unrecognized association between forced expiratory tracheal collapse and age or sex.

Methods:  We enrolled 40 female and 41 male healthy volunteers between 25 and 75 years of age who were without respiratory symptoms or known risk factors for tracheomalacia. Subjects underwent low-dose CT scanning at total lung capacity (TLC) and during forced exhalation (Expdyn) with spirometric monitoring and coaching. Percentage forced expiratory collapse was regressed on age for the total sample and separately within sex.

Results:  Mean tracheal cross-sectional area (CSA) was 2.54 cm2 ± 0.57 cm2 at TLC and 1.15 cm2 ± 0.53 cm2 at Expdyn. Mean percentage forced expiratory collapse (%collapse) was 54% ± 20%. Men aged 24 to 31 years (n = 12) had mean %collapse of 36% ± 19%, comparable to results previously reported for similarly aged men (35% ± 18%). Men, but not women, showed a significant positive correlation (R2 = 0.40, P < .001) between %collapse and age. Older men had both greater CSA at TLC (P = .02) and smaller CSA at Expdyn (P = .001) than younger men.

Conclusions:  Men exhibit positive age dependence of forced expiratory tracheal collapse. The influence of age and sex on forced expiratory tracheal collapse should be considered in the diagnostic evaluation of expiratory dynamic airway collapse and/or tracheomalacia.

Chest. 2012;142(1):175-184. doi:10.1378/chest.11-2021

Background:  In senior subjects, diffusing capacity of the lung for carbon monoxide (Dlco) is interpreted using prediction equations derived from primarily younger adult populations. Our objectives were to provide reference equations for single-breath Dlco for a cohort of healthy, never-smoking, white, European adults between 65 and 85 years of age and to compare the predicted values of this sample with those from other studies involving middle-aged adults.

Methods:  Reference equations were derived from a randomly selected sample from the general population of 431 healthy never smoker subjects aged 65 to 85 years (262 women and 169 men). Spirometry, lung volume determinations by plethysmography, and single-breath Dlco (corrected for hemoglobin) were performed following the American Thoracic Society/European Respiratory Society guidelines. Reference values and lower and upper limits of normal were derived using a piecewise polynomial model.

Results:  In addition to age, our reference equations confirmed the height and body size dependence of Dlco and diffusing capacity for alveolar volume (Dlco/Va) in older subjects. Practically all of the reference values obtained by extrapolating reference equations of middle-aged adults underestimated the true diffusing capacity of the healthy elderly volunteers. Middle-aged reference equations underestimated Dlco by 2.1% to 22.3% in women and 2.8% to 37.8% in men. In addition, Dlco/Va was overestimated up to 18% and 39.8% in women and men, respectively, whereas other equations underestimated Dlco/Va up to 22.2% and 11.9% in women and men, respectively.

Conclusions:  These results underscore the importance of using prediction equations appropriate to the origin and age characteristics of the subjects being studied.

Chest. 2012;142(1):185-191. doi:10.1378/chest.11-1926

Background:  Cystic fibrosis (CF) is one of the leading indications for lung transplantation. The incidence and pre-lung transplant risk factors for posttransplant renal dysfunction in the CF population remain undefined.

Methods:  We conducted a cohort study using adults (≥ 18 years old) in the CF Foundation Patient Registry from 2000 to 2008 to determine the incidence of post-lung transplant renal dysfunction, defined by an estimated glomerular filtration rate of < 60 mL/min/1.73 m2. Multivariable Cox proportional hazards modeling was used to identify independent pretransplant risk factors for post-lung transplant renal dysfunction.

Results:  The study cohort included 993 adult lung transplant recipients with CF, with a median follow-up of 2 years. During the study period, 311 individuals developed renal dysfunction, with a 2-year risk of 35% (95% CI, 32%-39%). Risk of posttransplant renal dysfunction increased substantially with increasing age (25 to < 35 years vs 18 to < 25 years: hazard ratio [HR], 1.60; 95% CI, 1.15-2.23; vs ≥ 35 years: HR, 2.45; 95% CI, 1.73-3.47) and female sex (HR, 1.56; 95% CI, 1.22-1.99). CF-related diabetes requiring insulin therapy (HR, 1.30; 95% CI, 1.02-1.67) and pretransplant renal function impairment (estimated glomerular filtration rate, 60-90 mL/min/m2 vs > 90 mL/min/m2: HR, 1.58; 95% CI, 1.19-2.12) also increased the risk of posttransplant renal dysfunction.

Conclusions:  Renal dysfunction is common following lung transplant in the adult CF population. Increased age, female sex, CF-related diabetes requiring insulin, and pretransplant renal impairment are significant risk factors.

Chest. 2012;142(1):192-199. doi:10.1378/chest.11-0647

Background:  There is no consensus at the present time about the effect of welding on lung function decline. This study compared lung function decline between blue-collar workers exposed and not exposed to welding fumes in a French longitudinal cohort of 21,238 subjects aged 37 to 52 years at inclusion.

Methods:  Medical data, occupation, sector of activity, and spirometry were recorded twice by occupational physicians in 1990 and 1995. A job-exposure matrix was used to identify 503 male blue-collar workers exposed to welding fumes and 709 control subjects and to define the weekly duration of exposure to welding fumes.

Results:  Baseline lung function parameters were higher in workers exposed to welding fumes than in control subjects. After a 5-year follow-up, welding-fume exposure was associated with a nonsignificant decline in FVC (P = .06) and FEV1 (P = .07) after adjustment for age, pack-years, BMI, and baseline value of the parameter. A significant accelerated decline in FEV1 (P = .046) was also observed in never smokers exposed to welding fumes. An “exposure-response” relationship was observed between FEV1 decline and weekly duration of exposure to welding fumes in nonsmokers but not in smokers.

Conclusions:  Blue-collar workers exposed to welding fumes showed accelerated decline in lung function, which, in nonsmokers, was related to weekly duration of exposure.

Translating Basic Research Into Clinical Practice

Chest. 2012;142(1):200-207. doi:10.1378/chest.11-1962

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually fatal disease, based on a multifaceted and incompletely understood pathogenesis. Some of the cellular and molecular mechanisms of vascular remodeling have been experimentally explored, and it is obvious that alterations of microvessels are involved in IPF. These can, among others, lead to the development of pulmonary hypertension. In order to understand the process of vascular integrity and repair, it is necessary to identify the factors associated with angiogenesis in IPF. A delicate balance of angiogenic and angiostatic factors regulates vessel homeostasis in normal physiologic conditions in the lungs. Although earlier studies have proposed that IPF is associated with an increase of angiogenesis, there is some more recent evidence that angiogenesis in fibrotic lungs may actually be decreased, causing some controversy in the literature in this area. This review, therefore, discusses the concept of angiogenesis in pulmonary fibrosis and speculates on how the spatial and temporal heterogeneity of IPF might explain the controversial findings about vessel density in fibrotic lungs.

Recent Advances in Chest Medicine

Chest. 2012;142(1):208-217. doi:10.1378/chest.11-2479

Hypersensitivity pneumonitis (HP) is a pulmonary disease with symptoms of dyspnea and cough resulting from the inhalation of an allergen to which the subject has been previously sensitized. The diagnosis of HP most often relies on an array of nonspecific clinical symptoms and signs developed in an appropriate setting, with the demonstration of interstitial markings on chest radiographs, serum precipitating antibodies against offending antigens, a lymphocytic alveolitis on BAL, and/or a granulomatous reaction on lung biopsies. The current classification of HP in acute, subacute, and chronic phases is now challenged, and a set of clinical predictors has been proposed. Nonspecific interstitial pneumonitis, usual interstitial pneumonia, and bronchiolitis obliterans organizing pneumonia may be the sole histologic expression of the disease. Presumably, like in idiopathic interstitial pneumonia, acute exacerbations of chronic HP may occur without further exposure to the offending antigen. New offending antigens, such as mycobacteria causing hot tub lung and metalworking fluid HP, have recently been identified and have stimulated further research in HP.

Medical Ethics

Chest. 2012;142(1):218-224. doi:10.1378/chest.12-0046

Patients approaching death because of terminal illness may find themselves trapped in a dying process they find unbearable, even with excellent pain and symptom management. Some will want the option of aid in dying. Aid in dying is the practice of a physician writing a prescription for medication for a mentally competent, terminally ill patient that the patient may ingest to bring about a peaceful death. The practice is increasingly accepted by physicians, and it is likely that a growing population of patients will inquire about it. Data from states that give terminally ill patients a statutory right to aid in dying demonstrate that the practice improves end-of-life care. Therefore, it is timely for clinical practice guidelines to emerge to offer guidance to physicians willing to provide aid in dying.

Selected Reports

Chest. 2012;142(1):225-227. doi:10.1378/chest.11-1857

We describe the case of a 40-year-old female patient who developed severe pulmonary hypertension and life-threatening right-sided heart failure in association with dietary scurvy and iron deficiency. Supplementation with oral vitamin C and iron very likely contributed to her complete cure. Scurvy-associated pulmonary arterial hypertension could result from impaired availability of endothelial nitric oxide, but inappropriate activation of the hypoxia-inducible family (HIF) of transcription factors could play an even more important role. HIF coordinates the body’s responses to hypoxia, and its activity is regulated by oxygen-dependent prolyl hydroxylases, which need vitamin C and iron as cofactors. Deficiency of these cofactors could lead to uncontrolled HIF activity and pulmonary vasoconstriction responsive to vitamin C and iron administration.

Chest. 2012;142(1):228-230. doi:10.1378/chest.11-1858

The 2008 American Thoracic Society Project concluded that idiopathic nonspecific interstitial pneumonia (NSIP), once regarded as a “provisional” diagnosis, can be considered a distinct clinical entity. However, an increasing number of recent reports have shown a likely link between the entity of idiopathic NSIP and autoimmune diseases. Similarly, IgG4-related disease is being increasingly reported, and some of the lung lesions, at least radiologically, look like NSIP. A case of IgG4-related interstitial lung disease without other systemic manifestations of IgG4-related disease is reported. The existence of IgG4-related disease should, therefore, be taken into consideration as a possible differential diagnosis from NSIP. The cause of IgG4-related disease remains unknown, but we emphasize the importance of a clinically novel interstitial lung disease.

Postgraduate Education Corner

Chest. 2012;142(1):231-238. doi:10.1378/chest.11-2420

Ventilator-associated pneumonia (VAP) is associated with high morbidity, mortality, and costs. Interventions to prevent VAP are a high priority in the care of critically ill patients requiring mechanical ventilation (MV). Multiple interventions are recommended by evidence-based practice guidelines to prevent VAP, but there is a growing interest in those related to the endotracheal tube (ETT) as the main target linked to VAP. Microaspiration and biofilm formation are the two most important mechanisms implicated in the colonization of the tracheal bronchial tree and the development of VAP. Microaspiration occurs when there is distal migration of microorganisms present in the secretions accumulated above the ETT cuff. Biofilm formation has been described as the development of a network of secretions and attached microorganisms that migrate along the ETT cuff polymer and inside the lumen, facilitating the transfer to the sterile bronchial tree. Therefore, our objective was to review the literature related to recent advances in ETT technologies regarding their impact on the control of microaspiration and biofilm formation in patients on MV, and the subsequent impact on VAP.

Chest. 2012;142(1):239-245. doi:10.1378/chest.11-2322

Obstructive sleep apnea (OSA) is a condition of repetitive upper airway collapse, which occurs during sleep. Recent literature has emphasized the role of OSA in contributing to glucose intolerance, dyslipidemia, and hypertension. OSA is associated with the development of cardiovascular disease, although definitive data are sparse with regard to the prevention of cardiovascular disease and CPAP therapy. CPAP provides effective treatment for OSA, but patient adherence remains challenging. Aside from daytime symptom improvement, it is difficult to monitor the adequacy of treatment response. Thus, the search for a biomarker becomes critical. The discovery of an ideal biomarker for OSA has the potential to provide information related to diagnosis, severity, prognosis, and response to treatment. In addition, because large-scale randomized controlled trials are both ethically and logistically challenging in assessing hard cardiovascular outcomes, certain biomarkers may be reasonable surrogate outcome measures. This article reviews the literature related to potential biomarkers of OSA with the recognition that an ideal biomarker does not exist at this time.

Chest. 2012;142(1):246-251. doi:10.1378/chest.11-2126

1.FishbackNFTravisWDMoranCAGuineeDGJrMcCarthyWFKossMN. Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases. Cancer. 1994;73(12):2936-2945.2.RossiGCavazzaASturmN. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol. 2003;27(3):311-324.3.TravisWD. Sarcomatoid neoplasms of the lung and pleura. Arch Pathol Lab Med. 2010;134(11):1645-1658.4.PelosiGSonzogniADe PasT. Review article: pulmonary sarcomatoid carcinomas: a practical overview. Int J Surg Pathol. 2010;18(2):103-120.5.MorimotoMOsakiTKodateMNagaieTYamamotoHOyaM. Spindle cell carcinoma of the lung. Gen Thorac Cardiovasc Surg. 2011;59(2):129-132.6.ZagrodnikDFIIKlineAL. Horner’s syndrome: a delayed complication after thoracostomy tube removal. Curr Surg. 2002;59(1):96-98.7.KongYXWrightGPesudovsKO’DayJWainerZWeisingerHS. Horner syndrome. Clin Exp Optom. 2007;90(5):336-344.8.GeorgeAHaydarAAAdamsWM. Imaging of Horner’s syndrome. Clin Radiol. 2008;63(5):499-505.9.ChangYLLeeYCShihJYWuCT. Pulmonary pleomorphic (spindle) cell carcinoma: peculiar clinicopathologic manifestations different from ordinary non-small cell carcinoma. Lung Cancer. 2001;34(1):91-97.10.SculierJPMoro-SibilotD. First- and second-line therapy for advanced nonsmall cell lung cancer. Eur Respir J. 2009;33(4):915-930.11.MochizukiTIshiiGNagaiK. Pleomorphic carcinoma of the lung: clinicopathologic characteristics of 70 cases. Am J Surg Pathol. 2008;32(11):1727-1735.12.YamamotoSHamatakeDUenoT. Clinicopathological investigation of pulmonary pleomorphic carcinoma. Eur J Cardiothorac Surg. 2007;32(6):873-876.13.YukiTSakumaTOhbayashiC. Pleomorphic carcinoma of the lung: a surgical outcome. J Thorac Cardiovasc Surg. 2007;134(2):399-404.14.HongJYChoiMKUhmJE. The role of palliative chemotherapy for advanced pulmonary pleomorphic carcinoma. Med Oncol. 2009;26(3):287-291.15.BaeHMMinHSLeeSH. Palliative chemotherapy for pulmonary pleomorphic carcinoma. Lung Cancer. 2007;58(1):112-115.16.ChangYLWuCTShihJYLeeYC. EGFR and p53 status of pulmonary pleomorphic carcinoma: implications for EGFR tyrosine kinase inhibitors therapy of an aggressive lung malignancy. Ann Surg Oncol. 2011;18(10):2952-2960.17.MainwaringMGPoorCZanderDSHarmanE. Complete remission of pulmonary spindle cell carcinoma after treatment with oral germanium sesquioxide. Chest. 2000;117(2):591-593.18.GuptaP. The Golden S sign. Radiology. 2004;233(3):790-791.19.KimTHKimSJRyuYH. Pleomorphic carcinoma of lung: comparison of CT features and pathologic findings. Radiology. 2004;232(2):554-559.20.KimTSHanJLeeKS. CT findings of surgically resected pleomorphic carcinoma of the lung in 30 patients. AJR Am J Roentgenol. 2005;185(1):120-125.21.KairaKHorieYAyabeE. Pulmonary pleomorphic carcinoma: a clinicopathological study including EGFR mutation analysis. J Thorac Oncol. 2010;5(4):460-465.22.ZafarNJohnsCD. Pleomorphic (sarcomatoid) carcinoma of lung—cytohistologic and immunohistochemical features. Diagn Cytopathol. 2011;39(2):115-116.23.MatsuiKKitagawaM. Spindle cell carcinoma of the lung. A clinicopathologic study of three cases. Cancer. 1991;67(9):2361-2367.24.PelosiGFraggettaFNappiO. Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases. Am J Surg Pathol. 2003;27(9):1203-1215.25.UshikiAKoizumiTKobayashiN. Genetic heterogeneity of EGFR mutation in pleomorphic carcinoma of the lung: response to gefitinib and clinical outcome. Jpn J Clin Oncol. 2009;39(4):267-270.

Chest. 2012;142(1):256-259. doi:10.1378/chest.11-2223

Postgraduate Education Corner: Pulmonary and Critical Care Pearls

Chest. 2012;142(1):252-255. doi:10.1378/chest.11-2437


Chest. 2012;142(1):260. doi:10.1378/chest.11-2375

I regret knowing, the way it changes
everything and nothing. I regret
cell death and its absence. I regret I am
the person you think I am. I regret
the days turned years waiting
and the luminous arriving
always eclipsed. I regret having
no sense of humor, feeling like Haiti
when I’m Liechtenstein, just as tiny but,
thanks for asking, fine. I regret
showing you what I am unable to see,
my wattled profile, baldly appraising gaze.
I regret leaving the back door open
and I regret closing it. I regret the odor
of obligation, being the small hair
that will not budge and the tongue
that must protest it. I regret
the tumor’s intelligence, the way
it dodges the needle, pretends
to swallow poison. I regret this broken
mask and I regret your looking.
I regret waiting until now
to wait on you, not anointing your feet
with oil sooner. I regret the raspberries
I failed to feed you with a spoon.
I regret that after our meal
I will be left to clear the table.

Chest. 2012;142(1):260. doi:10.1378/chest.11-2392

I choose general anesthesia again
for need of its oblivion, its power to kill.
Now rolling toward the cold lights
I pull my husband to me:
half my ashes on our Lake Michigan beach,
half on the rocks above the Mississippi,
where the blazing stars bloom in May,
but a Christian service before the burning.
Then one second later someone is calling my name.
It’s never wake up but always your name,
that word chosen at birth, for me anointed at baptism,
my name calling me back, with tubes sprouting
from my nose, arms, hands, smothered by a hot blanket
under which I sink to the bottom of Lake Michigan,
rise to beige noises, red voices demanding answers:
Are you in pain? Can you breathe?
OK, not in pain. OK, breathing.
Just let me sink one more time
to the sleep I always wanted.

Chest. 2012;142(1):261. doi:10.1378/chest.11-2450

Beneath the jaundiced gaze
of the moth-covered porch light,
my father tells me
mother has made a
“unilateral decision”
to stop all
extraordinary medical treatment.
Why does he use
these cold, military terms?
His face twists and cracks
releasing meager tears
like water wrung
from parched rocks.

Chest. 2012;142(1):261. doi:10.1378/chest.11-2394

Copper, his life given for this
shine. Now he goes even deeper
into the wet collapse of lungs,
hunting, desperate, for any vein of air.
The miner, retired, slumps over his
coffee mug, gasping like the rainbow trout
he cast on Montana’s riverbanks.
She is at the range, stirring, watching
sideways, her air wrinkling
into his, so that as she forces out
breath, she panics and calls it back.
She packed his lunch for thirty-five years,
worrying while he headed for shafts
where, beyond daylight, he harvested the stuff of
wire, bullets and pennies.
He is coughing again, shaking the table,
sloshing coffee, hot, onto his hands.
She moves across the kitchen, then,
knowing he is ready.
“May I lay upon you one more time my husband?”
Weary as habit, he follows her up
impossible stairs, stopping on every other one
to wheeze and pant, collect enough
wind for one more tread
toward the room where he hasn’t slept for years.
The ceiling sighs, the bedsprings creak
once, then again, as she drapes her body
over his, presses down, breasts to chest,
so that no amount of will can make
it rise. Silence, then weeping. An old
remedy. A kindness, really.


Chest. 2012;142(1):262. doi:10.1378/chest.12-0275

1.KidoTYateraKNoguchiS. Detection of MALT1 gene rearrangements in BAL fluid cells for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma. Chest. 2012;141(1):176-182.2.BorieRWislezMAntoineM. Clonality and phenotyping analysis of alveolar lymphocytes is suggestive of pulmonary MALT lymphoma. Respir Med. 2011;105(8):1231-1237.3.ZompiSCoudercLJCadranelJ. Clonality analysis of alveolar B lymphocytes contributes to the diagnostic strategy in clinical suspicion of pulmonary lymphoma. Blood. 2004;103(8):3208-3215.4.BorieRWislezMThabutG. Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. Eur Respir J. 2009;34(6):1408-1416.

Chest. 2012;142(1):262-263. doi:10.1378/chest.12-0543

1.KidoTYateraKNoguchiS. Detection of MALT1 gene rearrangements in BAL fluid cells for the diagnosis of pulmonary mucosa-associated lymphoid tissue lymphoma. Chest. 2012;141(1):176-182.2.BorieRWislezMAntoineM. Clonality and phenotyping analysis of alveolar lymphocytes is suggestive of pulmonary MALT lymphoma. Respir Med. 2011;105(8):1231-1237.

Chest. 2012;142(1):263. doi:10.1378/chest.12-0378

1.YamauchiYIzumiYYashiroH. Percutaneous cryoablation for pulmonary nodules in the residual lung after pneumonectomy: report of two cases. Chest. 2011;140(6):1633-1637.2.HaasbeekCJLagerwaardFJde JaegerKSlotmanBJSenanS. Outcomes of stereotactic radiotherapy for a new clinical stage I lung cancer arising postpneumonectomy. Cancer. 2009;115(3):587-594.3.PalmaDSenanS. Stereotactic radiation therapy: changing treatment paradigms for stage I nonsmall cell lung cancer. Curr Opin Oncol. 2011;23(2):133-139.4.InoueMNakatsukaSYashiroH. Percutaneous cryoablation of lung tumors: feasibility and safety. J Vasc Interv Radiol. 2012;23(3):295-302.5.WienerRSSchwartzLMWoloshinSWelchHG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med. 2011;155(3):137-144.

Chest. 2012;142(1):264. doi:10.1378/chest.12-0719

1.YamauchiYIzumiYYashiroH. Percutaneous cryoablation for pulmonary nodules in the residual lung after pneumonectomy: report of two cases. Chest. 2011;140(6):1633-1637.2.HaasbeekCJLagerwaardFJde JaegerKSlotmanBJSenanS. Outcomes of stereotactic radiotherapy for a new clinical stage I lung cancer arising postpneumonectomy. Cancer. 2009;115(3):587-594.3.TakedaAKuniedaEOhashiT. Severe COPD is correlated with mild radiation pneumonitis following stereotactic body radiotherapy. Chest. 2012;141(4):858-866.4.BaumannPNymanJHoyerM. Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer–a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study. Radiother Oncol. 2008;88(3):359-367.5.OnishiHShiratoHNagataY. Stereotactic body radiotherapy (SBRT) for operable stage I non-small-cell lung cancer: can SBRT be comparable to surgery?Int J Radiat Oncol Biol Phys. 2011;81(5):1352-1358.

Chest. 2012;142(1):264. doi:10.1378/chest.12-0392

1.NowakABreidthardtTChrist-CrainM. Direct comparison of three natriuretic peptides for prediction of short- and long-term mortality in patients with community-acquired pneumonia. Chest. 2012;141(4):974-982.2.Christ-CrainMBreidthardtTStolzD. Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia. J Intern Med. 2008;264(2):166-176.3.MüellerCLaule-KilianKScholerAPerruchoudAP. B-type natriuretic peptide for risk stratification in community-acquired pneumonia. J Intern Med. 2005;258(4):391-393.4.Christ-CrainMStolzDBingisserR. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93.

Chest. 2012;142(1):265. doi:10.1378/chest.12-0516

1.NovakABreidthardtTChrist-CrainM. Direct comparison of three natriuretic peptides for prediction of short- and long-term mortality in patients with community acquired pneumonia. Chest. 2012;141(4):974-982.2.Christ-CrainMBreidthardtTStolzD. Use of B-type natriuretic peptide in the risk stratification of community-acquired pneumonia. J Intern Med. 2008;264(2):166-176.3.MüellerCLaule-KilianKScholerAPerruchoudAP. B-type natriuretic peptide for risk stratification in community-acquired pneumonia. J Intern Med. 2005;258(4):391-393.4.Christ-CrainMStolzDBingisserR. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84-93.

Chest. 2012;142(1):265-266. doi:10.1378/chest.12-0423

1.KahnSRLimWDunnAS. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(suppl):e195S-e226S.2.AmirESerugaBNiraulaSCarlssonLOcañaA. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299-1309.3.HurwitzHISaltzLBVan CutsemE. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol. 2011;29(13):1757-1764.4.KhoranaAA. Risk assessment and prophylaxis for VTE in cancer patients. J Natl Compr Canc Netw. 2011;9(7):789-797.5.GrahamRMancherMWolmanDMGreenfieldSSteinbergE, eds; Committee on Standards for Developing Trustworthy Clinical Practice Guidelines; Board on Health Care Services; Institute of Medicine of the National Academies. Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011.

Chest. 2012;142(1):266-267. doi:10.1378/chest.12-0702

1.KahnSRLimWDunnAS. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl)e195S-e226S.2.GuyattGHOxmanADKunzRGRADE Working Group. Going from evidence to recommendations. BMJ. 2008;336(7652):1049-1051.3.GuyattGHNorrisSLSchulmanS. Methodology for the development of antithrombotic therapy and prevention of thrombosis guidelines: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2)(suppl):53S-70S.4.AklEAGunukulaSBarbaM. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. 2011:CD006652.5.AgnelliGGeorgeDJKakkarAKSAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med. 2012;366(7):601-609.6.van DoormaalFFDi NisioMOttenHM. Randomized trial of the effect of the low molecular weight heparin nadroparin on survival in patients with cancer. J Clin Oncol. 2011;29(15):2071-2076.7.AklEASchünemannHJ. Routine heparin for patients with cancer? One answer, more questions. N Engl J Med. 2012;366(7):661-662.8.KhoranaAAKudererNMCulakovaELymanGHFrancisCW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111(10):4902-4907.

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1.GOLD Committee. Global strategy for the diagnosis, management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Initiative for Chronic Obstructive Lung Disease website. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html. Updated December 2011. Accessed February 20, 2012.2.JonesPWHardingGWiklundI. Tests of the responsiveness of the COPD Assessment Test following acute exacerbation and pulmonary rehabilitation. Chest. 2012;142(1):134-140.3.KocksJWHTuinengaMGUilSMvan den BergJWKStåhlEvan der MolenT. Health status measurement in COPD: the minimal clinically important difference of the clinical COPD questionnaire. Respir Res. 2006;7:62.4.TsiligianniIGvan der MolenTMoraitakiD. Assessing health status in COPD. A head-to-head comparison between the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) [published online ahead of print May 20, 2012]. BMC Pulm Med. In press. doi:10.1186/1471-2466-12-20.5.JonesPW. St. George’s Respiratory Questionnaire: MCID. COPD. 2005;2(1):75-79.6.DoddJWHoggLNolanJ. The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study. Thorax. 2011;66(5):425-429.

Chest. 2012;142(1):268-269. doi:10.1378/chest.12-0838

I appreciate the questions posed by Dr Kocks and colleagues following our article in CHEST1 concerning the responsiveness of the minimal clinically important difference (MCID) for the COPD Assessment Test (CAT). They discuss two methods for estimating the MCID: one that is clinical (anchor based) and the other statistical (distribution based).

Chest. 2012;142(1):269. doi:10.1378/chest.12-0582

1.WalkeyAJO’DonnellMRWienerRS. Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials . Chest. 2011;139(5):1148-1155. 2.WunderinkRGNiedermanMSKollefMH. Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study . Clin Infect Dis. 2012;54(5):621-629. 3.StevensDLHerrDLampirisHHuntJLBattsDHHafkinB. Linezolid versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus infections . Clin Infect Dis. 2002;34(11):1481-1490. 4.WunderinkRGCammarataSKOliphantTHKollefMH. Linezolid Nosocomial Pneumonia Study Group. Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia. Clin Ther. 2003;25(3):980-992. 5.CepedaJAWhitehouseTCooperB. Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study. J Antimicrob Chemother. 2004;53(2):345-355. 6.KohnoSYamaguchiKAikawaN. Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan . J Antimicrob Chemother. 2007;60(6):1361-1369. 7.WunderinkRGMendelsonMHSomeroMS. Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus. Chest. 2008;134(6):1200-1207.

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  • CHEST Journal
    Print ISSN: 0012-3692
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