Current Issue


Chest. 2014;146(6):1423-1424. doi:10.1378/chest.14-1249

In a famous paper from the late 1970s, Robin1 postulated his concerns about overdiagnosis and overtreatment of pulmonary embolism (PE), stating that “the emperor of embolism may have no clothes.” He was mainly concerned about overdiagnosing PE in previously healthy young women, arguing that the prior probability of PE is low in these patients, and this subsequently results in a lower positive predictive value of perfusion scans (following Bayes’ theorem). Today, concerns about overdiagnosing PE still remain highly relevant.2 However, in addition to concerns about overdiagnosing PE in young adults, current research also focuses on referring (thus, also overdiagnosing) frail elderly patients too often or too soon for suspected PE: The naked emperor of embolism is aging. The main reason behind this problem comes from the fact that D-dimer testing yields more false-positive results in the elderly as compared with a non-aged population. Thus, many patients need to be referred, and typically only 10% to 15% of these patients have confirmed PE. The use of an age-adjusted cutoff for D-dimer testing (age × 10 in those aged > 50 years) has been proposed, aiming to reduce this number of false-positive results and, thus, the number of patients for whom imaging (CT pulmonary angiography [CTPA]) is required to confirm or refute the diagnosis.3

Chest. 2014;146(6):1425-1426. doi:10.1378/chest.14-1442

The roots of modern robotic surgery can be traced back to US Department of Defense-funded research focused on applications for battlefield telesurgery. Following a period of commercial development, legal battles, and industry consolidation, robotic surgery has matured and expanded across a variety of disciplines. Yet there is still uncertainty regarding the value generated by this proliferation. In this issue of CHEST (see page 1505), Paul and colleagues1 add to the growing literature on robotic technology in thoracic surgery. They identify several important findings. First, robotic lobectomy volume increased substantially over their study period. Second, when compared with an established minimally invasive platform, video-assisted thoracoscopic surgery (VATS), robotic lobectomy was associated with more intraoperative hemorrhage and iatrogenic injury and cost, yet offered no clinical benefit.

Chest. 2014;146(6):1426-1428. doi:10.1378/chest.14-1308

Overweight and obesity are major public health problems around the world. Despite global efforts and actions for their prevention and control, the prevalence of these conditions is rising and expected to increase even further in the next decades. Data from the Global Burden of Disease Study 2013 indicated that the number of adults with a BMI ≥ 25 kg/m2 increased from 857 million in 1980 to 2.1 billion in 2013,1 corresponding with 37% of adult men and 38% of adult women. In 2010, high BMI was ranked sixth in the risk factors for global burden of disease, accounting for almost 3.5 million deaths per year.2

Chest. 2014;146(6):1428-1430. doi:10.1378/chest.14-2024

Bronchiolitis is the most common cause of hospitalization of very young children.1 Although the mortality associated with bronchiolitis is low in affluent countries, the related cost and morbidity are high,2 especially in some minority groups, such as indigenous children.3 Despite the burden of illness, there is a relative paucity of evidence-based guidelines on the management of bronchiolitis in and out of hospitals. Prior to the updated bronchiolitis guideline from the American Academy of Pediatrics (AAP),1 the latest most comprehensive collation of evidence for the management of bronchiolitis was that from the Scottish Intercollegiate Guidelines Network (SIGN) guideline from the United Kingdom,2 where the latest search date was 2005. Thus, the updated AAP bronchiolitis guideline,1 which has incorporated relevant data from the past 10 years, should be a welcomed document by clinicians worldwide.

Point and Counterpoint

Chest. 2014;146(6):1431-1433. doi:10.1378/chest.14-2223

With the release of updated guidelines for the treatment of cholesterol, an additional 13 million Americans may be eligible for or prescribed statin therapy, possibly bringing the overall total to 56 million.1,2 Already, as many as 30% of acute hospital admissions are prescribed statins.3 More patients than ever before are likely to present to the hospital receiving statins prior to admission, making the decision to continue a patient’s home statin regimen an almost daily occurrence for practicing critical care physicians. Unintentional discontinuation of medications for chronic disease is a risk with hospitalization and an even greater risk with ICU admission.4 As such, the clinical question related to continued statin therapy in the ICU provides an opportunity to influence both short- and long-term outcomes from critical illness.

Chest. 2014;146(6):1433-1435. doi:10.1378/chest.14-2225

For every patient admitted to an ICU, providers must make crucial decisions regarding which medications to use to enhance the patient’s likelihood of survival and long-term recovery. Sometimes the decision is only regarding which medications to initiate in the ICU. However, we often must decide which outpatient medications are crucial or desirable to continue in the ICU and which are either not helpful or detrimental to the patient’s current condition. Among the most common drugs that force this decision are the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, commonly known as statins. Statins are the best selling and most widely used agents in the history of the pharmaceutical industry, and many patients admitted to the ICU with a critical illness have been taking these drugs as outpatients.1 We believe that for most critical illnesses, there is insufficient evidence to warrant continuation of treatment with statins in the ICU setting. To address this issue as a risk analysis proposition, we pose a series of important questions.

Chest. 2014;146(6):1435-1436. doi:10.1378/chest.14-2224

It is true that no definitive answer exists to this question within the current literature, but we would disagree with the assertion by Drs Mermis and Simpson1 that continued statin use in the ICU is both unsafe and ineffective. Although the randomized trials to date have not consistently shown an improved outcome, multiple studies of the use of various statins in a variety of centers and disease states have failed to demonstrate harm for statin use in the ICU.2

Chest. 2014;146(6):1436-1437. doi:10.1378/chest.14-2226

We agree that the pleotropic effects of statins provide mechanistic plausibility for treating critically ill patients. However, over the past decades, we have been baited with mechanistically promising antiinflammatory and other treatments, such as anti-tumor necrosis factor therapies, IL-1ra, and drotrecogin α, which have all failed to benefit patients. We are, sadly, left without specific therapies for common critical illnesses, such as sepsis or ARDS. Understandably, we are eager for new therapies.


Chest. 2014;146(6):1438-1443. doi:10.1378/chest.13-2804

If cigarettes were introduced as a new consumer product today, it is unlikely they would receive government regulatory approval. Cigarettes have proven biologic toxicities (carcinogenesis, atherogenesis, teratogenesis) and well-established causal links to human disease. Things were very different in 1913 when the R. J. Reynolds Tobacco Company introduced the first modern cigarette, the iconic Camel. By the early 1950s, definitive scientific reports linked cigarettes and human disease, but it was more than a half century later (2006) that cigarette manufacturers were found guilty by a federal court of deceptive product marketing regarding the health hazards of tobacco use. In the United States, cigarette smoking remains a major but slowly declining problem. But in developing countries, cigarette use is expanding tremendously. In global terms, the epidemic of smoking-caused disease is projected to increase rapidly in coming decades, not decline. Society may have begun to slowly win the smoking battle in the developed world, but we are resoundingly losing the global war on smoking. All is not lost! There is some good news! The 2003 Framework Convention on Tobacco Control, supported strongly by the American College of Chest Physicians, is the first global public health treaty of the new millennium. Many developed societies have begun planning to rid their countries of cigarettes in what is called the Endgame Strategy, and now is the time for the international medical community to help change tobacco policy to a worldwide endgame approach to rid all humanity of smoking-related diseases.

Original Research: Pulmonary Vascular Disease

Chest. 2014;146(6):1444-1451. doi:10.1378/chest.13-2386

BACKGROUND:  D-dimer levels increase with age, and research has suggested that using an age-adjusted D-dimer threshold may improve diagnostic efficiency without compromising safety. The objective of this study was to assess the safety of using an age-adjusted D-dimer threshold in the workup of patients with suspected pulmonary embolism (PE).

METHODS:  We report the outcomes of 923 patients aged > 50 years presenting to our ED with suspected PE, a calculated Revised Geneva Score (RGS), and a D-dimer test. All patients underwent CT pulmonary angiography (CTPA). We compared the false-negative rate for PE of a conventional D-dimer threshold with an age-adjusted D-dimer threshold and report the proportion of patients for whom an age-adjusted D-dimer threshold would obviate the need for CTPA.

RESULTS:  Among 104 patients with a negative conventional D-dimer test result and an RGS ≤ 10, no PE was observed within 90 days (false-negative rate, 0%; 95% CI, 0%-2.8%). Among 273 patients with a negative age-adjusted D-dimer result and an RGS ≤ 10, four PEs were observed within 90 days (false-negative rate, 1.5%; 95% CI, 0.4%-3.7%). We observed an 18.3% (95% CI, 15.9%-21.0%) absolute reduction in the proportion of patients aged > 50 years who would merit CTPA by using an age-adjusted D-dimer threshold compared with a conventional D-dimer threshold.

CONCLUSIONS:  Use of an age-adjusted D-dimer threshold reduces imaging among patients aged > 50 years with an RGS ≤ 10. Although the adoption of an age-adjusted D-dimer threshold is probably safe, the CIs surrounding the additional 1.5% of PEs missed necessitate prospective study before this practice can be adopted into routine clinical care.

Chest. 2014;146(6):1452-1461. doi:10.1378/chest.14-0059

BACKGROUND:  Variation in the use of ICUs for low-risk conditions contributes to health system inefficiency. We sought to examine the relationship between ICU use for patients with pulmonary embolism (PE) and cost, mortality, readmission, and procedure use.

METHODS:  We performed a retrospective cohort study including 61,249 adults with PE discharged from 263 hospitals in three states between 2007 and 2010. We generated hospital-specific ICU admission rate quartiles and used a series of multilevel models to evaluate relationships between admission rates and risk-adjusted in-hospital mortality, readmission, and costs and between ICU admission rates and several critical care procedures.

RESULTS:  Hospital quartiles varied in unadjusted ICU admission rates for PE (range, ≤ 15% to > 31%). Among all patients, there was a small trend toward increased use of arterial catheterization (0.6%-1.1%, P < .01) in hospital quartiles with higher levels of ICU admission. However, use of invasive mechanical ventilation (14.4%-7.9%, P < .01), noninvasive ventilation (6.6%-3.0%, P < .01), central venous catheterization (14.6%-11.3%, P < .02), and thrombolytics (11.0%-4.7%, P < .01) in patients in the ICU declined across hospital quartiles. There was no relationship between ICU admission rate and risk-adjusted hospital mortality, costs, or readmission.

CONCLUSIONS:  Hospitals vary widely in ICU admission rates for acute PE without a detectable impact on mortality, cost, or readmission. Patients admitted to ICUs in higher-using hospitals received many critical care procedures less often, suggesting that these patients may have had weaker indications for ICU admission. Hospitals with greater ICU admission may be appropriate targets for improving efficiency in ICU admissions.

Chest. 2014;146(6):1462-1467. doi:10.1378/chest.13-1008

BACKGROUND:  Several studies have described heart-type fatty acid-binding protein (H-FABP) from early blood samples as a predictor of outcome in acute pulmonary embolism (PE). This systematic review is designed to determine the prognostic value of H-FABP aimed for use in patients with acute PE.

METHODS:  Studies published prior to January 2013 in PubMed, Ovid, and Embase were reviewed, and the relationship between H-FABP and the risk of acute PE-related death or serious complications was evaluated. A summary estimate was calculated using the bivariate random-effects approach, and covariate analysis was used to examine sources of heterogeneity among studies.

RESULTS:  A systematic search revealed six studies containing a total of 618 patients. Elevated H-FABP level was significantly associated with short-term death (within 30 days of embolism) (OR, 40.78; 95% CI, 11.87-140.09) and with complicated clinical events (OR, 32.71; 95% CI, 11.98-89.26). The prevalence of serious complications and death in acute PE was 51% (95% CI, 43%-59%) and 31% (95% CI, 24% -39%), respectively. The combined sensitivity and specificity for the prediction of death and serious complications was 98% and 86%, respectively.

CONCLUSIONS:  H-FABP is associated with an increased risk of mortality or complicated clinical events in patients with acute PE across different studies with a high degree of clinical and methodologic diversity. The result suggests that H-FABP has significant prognostic value for acute PE.

Chest. 2014;146(6):1468-1477. doi:10.1378/chest.14-0235

BACKGROUND:  There is currently little evidence defining the clinical importance of detecting and treating isolated distal DVT (IDDVT). International guidelines vary regarding diagnostic and therapeutic advice. The potential benefits of anticoagulation are unquantified. We sought to evaluate the feasibility of a randomized controlled study within a modern framework and provide a primary outcome point estimate.

METHODS:  In this open-label, external pilot randomized controlled trial, consecutive, symptomatic, ambulatory patients with IDDVT were approached for inclusion. Participants were allocated to receive either therapeutic anticoagulation or conservative management. Patients underwent blinded color-duplex imaging at 7 and 21 days and follow-up at 3 months. Principal feasibility outcomes included recruitment rate and attrition. The principal clinical outcome was a composite including proximal propagation, pulmonary embolism, death attributable to VTE disease, or major bleeding. Analysis was by intention to treat.

RESULTS:  In total, 93 patients with IDDVT were screened, and 70 of those eligible (88.6%) were recruited. All patients but one were followed-up by direct contact after 90 days. Allocation crossover occurred in 15 patients (21.4%). The principal clinical outcome occurred in four of 35 of those conservatively treated (11.4%) and zero of 35 in the anticoagulated group (absolute risk reduction, 11.4%; 95% CI, −1.5 to 26.7, P = .11, number needed to treat of nine). There were no major bleeding episodes.

CONCLUSIONS:  We have established the feasibility of definitive study regarding the value of therapeutic anticoagulation in IDDVT and provide an approximate point estimate for serious complications with a contemporary conservative strategy.

TRIAL REGISTRY:  Current Controlled Trials; No.: ISRCTN75175695; URL: www.controlled-trials.com.

Chest. 2014;146(6):1478-1485. doi:10.1378/chest.14-0809

BACKGROUND:  Cell-free hemoglobin (CFH) is a potent nitric oxide scavenger associated with poor outcomes in several diseases. Pulmonary arterial hypertension (PAH) is characterized by reduced nitric oxide availability. We hypothesized that CFH would be elevated in PAH and would associate with hemodynamics and clinical outcomes.

METHODS:  We measured CFH in 200 consecutively evaluated patients with PAH, 16 unaffected bone morphogenetic receptor protein type 2 (BMPR2) mutation carriers, 19 healthy subjects, and 29 patients with pulmonary venous hypertension (PVH). CFH values were tested for association with hemodynamics, time to hospitalization, and death.

RESULTS:  CFH was elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH (P ≤ .01 all comparisons). There were no differences in CFH across PAH subtypes. CFH modestly correlated with mean pulmonary artery pressure (ρ = 0.16, P = .03) and pulmonary vascular resistance (ρ = 0.21, P = .01) and inversely with cardiac index (ρ = −0.18, P = .02) in patients with PAH. CFH was not associated with hemodynamic response to nitric oxide or death. Patients with the highest CFH levels had increased risk of PAH-related hospitalization when adjusted for age, sex, and PAH cause (hazard ratio, 1.69; 95% CI ,1.08-2.66; P = .02).

CONCLUSIONS:  CFH is elevated in patients with PAH and BMPR2 carriers compared with healthy subjects and patients with PVH. Elevated CFH levels are independently associated with an increased risk of hospitalization. Further study is required to understand the mechanism of CFH elevation and the potential pathologic contribution of CFH in PAH.

Chest. 2014;146(6):1486-1493. doi:10.1378/chest.14-0194

BACKGROUND:  Resting mean pulmonary artery pressure (mPAP) values between 20 and 25 mm Hg are above normal but do not fulfill the criteria for pulmonary hypertension (PH). The clinical relevance of such borderline hemodynamics is a matter of discussion.

METHODS:  We focused on patients who underwent right-sided heart catheterization during rest and exercise for symptoms indicative of PH or due to underlying disease associated with an increased risk for pulmonary arterial hypertension and characterized the patients according to their resting mPAP. Patients with manifest PH (mPAP ≥ 25 mm Hg) were excluded.

RESULTS:  We included 141 patients, 32 of whom presented with borderline hemodynamics (20 < mPAP < 25 mm Hg). Borderline patients were older (65.8 ± 12.5 years vs 57.3 ± 12.5 years, P = .001) and more often had cardiac comorbidities (53% vs 15%, P < .001) or decreased lung function (47% vs 16%, P < .001) as compared with patients with resting mPAP < 21 mm Hg. After correction for age, borderline patients had significantly increased pulmonary vascular resistance (2.7 ± 0.7 Wood units vs 1.8 ± 0.8 Wood units, P < .001) and mPAP/cardiac output (CO) and transpulmonary gradient/CO slopes (both P < .001) as well as lower peak oxygen uptake (16.9 ± 4.6 mL/min/kg vs 20.9 ± 4.7 mL/min/kg, P = .009) and 6-min walk distance (383 ± 120 m vs 448 ± 92 m, P = .001). During follow-up (4.4 ± 1.4 years), the mortality rate of borderline patients vs patients with resting mPAP < 21 mm Hg was 19% vs 4%.

CONCLUSIONS:  In patients undergoing right-sided heart catheterization with exclusion of manifest PH, borderline elevation of pulmonary arterial pressure is associated with cardiac and pulmonary comorbidities, decreased exercise capacity, and a poor prognosis.

Chest. 2014;146(6):1494-1504. doi:10.1378/chest.13-3014

BACKGROUND:  Patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-APAH) experience higher mortality rates than patients with idiopathic disease and those with other connective tissue diseases (CTD-APAH). We sought to identify unique predictors of mortality associated with SSc-APAH in the CTD-APAH population.

METHODS:  The Registry to Evaluate Early and Long-Term PAH Management (REVEAL Registry) is a multicenter, prospective US-based registry of patients with previously and newly diagnosed (enrollment within 90 days of diagnostic right-sided heart catheterization) PAH. Cox regression models evaluated all previously identified candidate predictors of mortality in the overall REVEAL Registry population to identify significant predictors of mortality in the SSc-APAH (n = 500) vs non-SSc-CTD-APAH (n = 304) populations.

RESULTS:  Three-year survival rates in the previously diagnosed and newly diagnosed SSc-APAH group were 61.4% ± 2.7% and 51.2% ± 4.0%, respectively, compared with 80.9% ± 2.7% and 76.4% ± 4.6%, respectively, in the non-SSc-CTD-APAH group (P < .001). In multivariate analyses, men aged > 60 years, systolic BP (SBP) ≤ 110 mm Hg, 6-min walk distance (6MWD) < 165 m, mean right atrial pressure (mRAP) > 20 mm Hg within 1 year, and pulmonary vascular resistance (PVR) > 32 Wood units remained unique predictors of mortality in the SSc-APAH group; 6MWD ≥ 440 m was protective in the non-SSc-CTD-APAH group, but not the SSc-APAH group.

CONCLUSIONS:  Patients with SSc-APAH have higher mortality rates than patients with non-SSc-CTD-APAH. Identifying patients with SSc-APAH who are at a particularly high risk of death, including elderly men and patients with low baseline SBP or 6MWD, or markedly elevated mRAP or PVR, will enable physicians to identify patients who may benefit from closer monitoring and more aggressive treatment.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Original Research: Cardiothoracic Surgery

Chest. 2014;146(6):1505-1512. doi:10.1378/chest.13-3032

BACKGROUND:  Robotic-assisted lobectomy is being offered increasingly to patients. However, little is known about its safety, complication profile, or effectiveness.

METHODS:  Patients undergoing lobectomy in in the United States from 2008 to 2011 were identified in the Nationwide Inpatient Sample. In-hospital mortality, complications, length of stay, and cost for patients undergoing robotic-assisted lobectomy were compared with those for patients undergoing thoracoscopic lobectomy.

RESULTS:  We identified 2,498 robotic-assisted and 37,595 thoracoscopic lobectomies performed from 2008 to 2011. The unadjusted rate for any complication was higher for those undergoing robotic-assisted lobectomy than for those undergoing thoracoscopic lobectomy (50.1% vs 45.2%, P < .05). Specific complications that were higher included cardiovascular complications (23.3% vs 20.0%, P < .05) and iatrogenic bleeding complications (5.0% vs 2.0%, P < .05). The higher risk of iatrogenic bleeding complications persisted in multivariable analyses (adjusted OR, 2.64; 95% CI, 1.58-4.43). Robotic-assisted lobectomy costs significantly more than thoracoscopic lobectomy ($22,582 vs $17,874, P < .05).

CONCLUSIONS:  In this early experience with robotic surgery, robotic-assisted lobectomy was associated with a higher rate of intraoperative injury and bleeding than was thoracoscopic lobectomy, at a significantly higher cost.

Original Research: COPD

Chest. 2014;146(6):1513-1520. doi:10.1378/chest.13-2759

BACKGROUND:  Most patients with a clinical diagnosis of COPD have not had spirometry to confirm airflow obstruction (AFO). Overweight and obese patients report more dyspnea than normal weight patients, which may be falsely attributed to AFO. We sought to determine whether overweight and obese patients who received a clinical diagnosis of COPD were more likely to receive a misdiagnosis (ie, lack of AFO on spirometry) and be subsequently treated with inhaled medications.

METHODS:  The cohort comprised US veterans with COPD (International Classification of Diseases, 9th Revision, code; inhaled medication use; or both) and spirometry measurements from one of three Pacific Northwest Veterans Administration Medical Centers. The measured exposures were overweight and obesity (defined by BMI categories). Outcomes were (1) AFO on spirometry and (2) escalation or deescalation of inhaled therapies from 3 months before spirometry to 9 to 12 months after spirometry. We used multivariable logistic regression with calculation of adjusted proportions for all analyses.

RESULTS:  Fifty-two percent of 5,493 veterans who had received a clinical diagnosis of COPD had AFO. The adjusted proportion of patients with AFO decreased as BMI increased (P < .01 for trend). Among patients without AFO, those who were overweight and obese were less likely to remain off medications or to have therapy deescalated (adjusted proportions: normal weight, 0.69 [95% CI, 0.64-0.73]; overweight, 0.62 [95% CI, 0.58-0.65; P = .014]; obese, 0.60 [95% CI, 0.57-0.63; P = .001]).

CONCLUSIONS:  Overweight and obese patients are more likely to be given a misdiagnosis of COPD and not have their inhaled medications deescalated after spirometry demonstrated no AFO. Providers may be missing potential opportunities to recognize and treat other causes of dyspnea in these patients.

Chest. 2014;146(6):1521-1530. doi:10.1378/chest.13-2859

BACKGROUND:  Increased arterial stiffness as measured by aortic pulse wave velocity (aPWV) predicts cardiovascular events and mortality and is elevated in patients with COPD. Prior investigation suggests that a long-acting β-agonist (LABA)/inhaled corticosteroid (ICS) lowers aPWV in patients with baseline aPWV ≥ 11 m/s. This study compared the effect of the ICS/LABA fluticasone furoate/vilanterol (FF/VI), 100/25 μg, delivered via the ELLIPTA dry powder inhaler, with tiotropium bromide (TIO), 18 μg, on aPWV.

METHODS:  This multicenter, randomized, blinded, double-dummy, parallel-group, 12-week study compared FF/VI and TIO, both administered once daily. The primary end point was aPWV change from baseline at 12 weeks. Safety end points included adverse events (AEs), vital signs, and clinical laboratory tests.

RESULTS:  Two hundred fifty-seven patients with COPD and aPWV ≥ 11 m/s were randomized; 87% had prior cardiovascular events and/or risk. The mean difference in aPWV between FF/VI and TIO at week 12 was not significant (P = .484). Because the study did not contain a placebo arm, a post hoc analysis was performed to show that both treatments lowered aPWV by an approximate difference of 1 m/s compared with baseline. The proportion of patients reporting AEs was similar with FF/VI (24%) and TIO (18%). There were no changes in clinical concern for vital signs or clinical laboratory tests.

CONCLUSIONS:  No differences on aPWV were observed between FF/VI and TIO. However, further studies with a placebo arm are required to establish definitively whether long-acting bronchodilators lower aPWV. Both treatments demonstrated an acceptable tolerability profile.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01395888; URL: www.clinicaltrials.gov.

Chest. 2014;146(6):1531-1542. doi:10.1378/chest.14-0117

BACKGROUND:  Arformoterol tartrate (arformoterol, 15 μg bid) is a nebulized long-acting β2-agonist approved for maintenance treatment of COPD.

METHODS:  This was a multicenter, double-blind, randomized, placebo-controlled study. Patients (aged ≥ 40 years with baseline FEV1 ≤ 65% predicted, FEV1 > 0.50 L, FEV1/FVC ≤ 70%, and ≥ 15 pack-year smoking history) received arformoterol (n = 420) or placebo (n = 421) for 1 year. The primary assessment was time from randomization to respiratory death or first COPD exacerbation-related hospitalization.

RESULTS:  Among 841 patients randomized, 103 had ≥ 1 primary event (9.5% vs 15.0%, for arformoterol vs placebo, respectively). Patients who discontinued treatment for any reason (39.3% vs 49.9%, for arformoterol vs placebo, respectively) were followed for up to 1 year postrandomization to assess for primary events. Fewer patients receiving arformoterol than placebo experienced COPD exacerbation-related hospitalizations (9.0% vs 14.3%, respectively). Twelve patients (2.9%) receiving arformoterol and 10 patients (2.4%) receiving placebo died during the study. Risk for first respiratory serious adverse event was 50% lower with arformoterol than placebo (P = .003). Numerically more patients on arformoterol (13; 3.1%) than placebo (10; 2.4%) experienced cardiac serious adverse events; however, time-to-first cardiac serious adverse event was not significantly different. Improvements in trough FEV1 and FVC were greater with arformoterol (least-squares mean change from baseline vs placebo: 0.051 L, P = .030 and 0.075 L, P = .018, respectively). Significant improvements in quality of life (overall St. George’s Hospital Respiratory Questionnaire and Clinical COPD Questionnaire) were observed with arformoterol vs placebo (P < .05).

CONCLUSIONS:  Arformoterol demonstrated an approximately 40% lower risk of respiratory death or COPD exacerbation-related hospitalization over 1 year vs placebo. Arformoterol was well-tolerated and improved lung function vs placebo.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00909779; URL: www.clinicaltrials.gov

Chest. 2014;146(6):1543-1553. doi:10.1378/chest.14-0543

BACKGROUND:  The association between HIV and emphysema remains incompletely understood. We sought to determine whether HIV is an independent risk factor for emphysema severity and whether markers of HIV severity and systemic biomarkers of inflammation (IL-6), altered coagulation (D-dimer), and immune activation (soluble CD14) are associated with emphysema.

METHODS:  We performed a cross-sectional analysis of 114 participants with HIV infection and 89 participants without HIV infection in the Examinations of HIV-Associated Lung Emphysema (EXHALE) study. Participants underwent chest CT imaging with blinded semiquantitative interpretation of emphysema severity, distribution, and type. We generated multivariable logistic regression models to determine the risk of HIV for radiographic emphysema, defined as > 10% lung involvement. Similar analyses examined associations of plasma biomarkers, HIV RNA, and recent and nadir CD4 cell counts with emphysema among participants with HIV infection.

RESULTS:  Participants with HIV infection had greater radiographic emphysema severity with increased lower lung zone and diffuse involvement. HIV was associated with significantly increased risk for > 10% emphysema in analyses adjusted for cigarette smoking pack-years (OR, 2.24; 95% CI, 1.12-4.48). In multivariable analyses restricted to participants with HIV infection, nadir CD4 < 200 cells/μL (OR, 2.98; 95% CI, 1.14-7.81), and high soluble CD14 level (upper 25th percentile) (OR, 2.55; 95% CI, 1.04-6.22) were associated with increased risk of > 10% emphysema. IL-6 and D-dimer were not associated with emphysema in HIV.

CONCLUSIONS:  HIV is an independent risk factor for radiographic emphysema. Emphysema severity was significantly greater among participants with HIV infection. Among those with HIV, nadir CD4 < 200 cells/μL and elevated soluble CD14 level were associated with emphysema, highlighting potential mechanisms linking HIV with emphysema.

Chest. 2014;146(6):1554-1565. doi:10.1378/chest.13-2855

OBJECTIVE:  The aim of this work was to investigate if regional differences of specific gas volume (SVg) in the different regions (lobes and bronchopulmonary segments) in healthy volunteers and patients with severe emphysema can be used as a tool for planning lung volume reduction (LVR) in emphysema.

METHODS:  CT scans of 10 healthy subjects and 10 subjects with severe COPD were obtained at end-inspiration (total lung capacity [TLC]) and end-expiration (residual volume [RV]). For each subject, ΔSVg (ΔSVg = SVg,TLC − SVg,RV, where SVg,TLC and SVg,RV are specific gas volume at TLC and RV, respectively) vs ΔV (ΔV = V,TLC−V,RV, where V,TLC and V,RV are lung volume at TLC and RV, respectively) was plotted for the entire lung, each lobe, and all bronchopulmonary segments. For each subject, a heterogeneity index (HI) was defined to quantify the range of variability of ΔSVg/ΔV in all bronchopulmonary regions.

RESULTS:  In patients with COPD, SVg,TLC and SVg,RV were significantly higher and ΔSVg variations lower than in healthy subjects (P < .001). In COPD, ΔSVg/ΔV slopes were lower in upper lobes than in lower lobes. In healthy subjects, the entire lung, lobes, and bronchopulmonary segments all showed similar ΔSVg/ΔV slopes, whereas in COPD a high variance was found. As a consequence, HI was significantly higher in subjects with COPD than in healthy subjects (0.80 ± 0.34 vs 0.15 ± 0.10, respectively; P < .001).

CONCLUSIONS:  SVg variations within the lung are highly homogeneous in healthy subjects. Regions with low ΔSVg/ΔV (ie, more pronounced gas trapping) should be considered as target areas for LVR. Regions with negative values of ΔSVg/ΔV identify where collateral ventilation is present. HI is helpful to assess the patient in the different stages of disease and the effect of different LVR treatments.

Original Research: Critical Care

Chest. 2014;146(6):1566-1573. doi:10.1378/chest.14-0566

BACKGROUND:  ICUs are increasingly staffed with nurse practitioners/physician assistants (NPs/PAs), but it is unclear how NPs/PAs influence quality of care. We examined the association between NP/PA staffing and in-hospital mortality for patients in the ICU.

METHODS:  We used retrospective cohort data from the 2009 to 2010 APACHE (Acute Physiology and Chronic Health Evaluation) clinical information system and an ICU-level survey. We included patients aged ≥ 17 years admitted to one of 29 adult medical and mixed medical/surgical ICUs in 22 US hospitals. Because this survey could not assign NPs/PAs to individual patients, the primary exposure was admission to an ICU where NPs/PAs participated in patient care. The primary outcome was patient-level in-hospital mortality. We used multivariable relative risk regression to examine the effect of NPs/PAs on in-hospital mortality, accounting for differences in case mix, ICU characteristics, and clustering of patients within ICUs. We also examined this relationship in the following subgroups: patients on mechanical ventilation, patients with the highest quartile of Acute Physiology Score (> 55), and ICUs with low-intensity physician staffing and with physician trainees.

RESULTS:  Twenty-one ICUs (72.4%) reported NP/PA participation in direct patient care. Patients in ICUs with NPs/PAs had lower mean Acute Physiology Scores (42.4 vs 46.7, P < .001) and mechanical ventilation rates (38.8% vs 44.2%, P < .001) than ICUs without NPs/PAs. Unadjusted and risk-adjusted mortality was similar between groups (adjusted relative risk, 1.10; 95% CI, 0.92-1.31). This result was consistent in all examined subgroups.

CONCLUSIONS:  NPs/PAs appear to be a safe adjunct to the ICU team. The findings support NP/PA management of critically ill patients.

Chest. 2014;146(6):1574-1577. doi:10.1378/chest.14-0728

BACKGROUND:  Point-of-care ultrasonography performed by frontline intensivists offers the possibility of reducing the use of traditional imaging in the medical ICU (MICU). We compared the use of traditional radiographic studies between two MICUs: one where point-of-care ultrasonography is used as a primary imaging modality, the other where it is used only for procedure guidance.

METHODS:  This study was a retrospective 3-month chart review comparing the use of chest radiographs, CT scans (chest and abdomen/pelvis), transthoracic echocardiography performed by the cardiology service, and DVT ultrasonography studies performed by the radiology service between two MICUs of similar size and acuity and staffing levels.

RESULTS:  Total number of admissions, patient demographics, and disease acuity were similar between MICUs. Comparing the non-point-of-care ultrasonography MICU with the point-of-care ultrasonography MICU, there were 3.75 ± 4.6 vs 0.82 ± 1.85 (P < .0001) chest radiographs per patient, 0.10 ± 0.31 vs 0.04 ± 0.20 (P = .0007) chest CT scans per patient, 0.17 ± 0.44 vs 0.05 ± 0.24 (P < .0001) abdomen/pelvis CT scans per patient, 0.20 ± 0.47 vs 0.02 ± 0.14 (P < .0001) radiology service-performed DVT studies per patient, and 0.18 ± 0.40 vs 0.07 ± 0.26 (P < .0001) cardiology service-performed transthoracic echocardiography studies per patient, respectively.

CONCLUSIONS:  The use of point-of-care ultrasonography in an MICU is associated with a significant reduction in the number of imaging studies performed by the radiology and cardiology services.

Chest. 2014;146(6):1578-1585. doi:10.1378/chest.13-2922

BACKGROUND:  To facilitate the clinical diagnosis of ventilator-associated pneumonia (VAP) in the ICU, the Clinical Pulmonary Infection Score (CPIS) has been proposed but has shown a low diagnostic performance in subsequent studies. We propose a new score based on procalcitonin level and chest echography with the aim of improving VAP diagnosis: the Chest Echography and Procalcitonin Pulmonary Infection Score (CEPPIS).

METHODS:  This retrospective pilot study recruited patients admitted to the Intensive Care Unit of the Emergency Department, Careggi University Hospital (Florence, Italy), from January 2009 to December 2011. Patients were retrospectively divided into a microbiologically confirmed VAP group or a control group based on diagnosis of VAP and positive tracheal aspirate culture.

RESULTS:  A total of 221 patients were included, with 113 in the microbiologically confirmed VAP group and 108 in the control group. A CEPPIS > 5 retrospectively fixed was significantly better in predicting VAP (OR, 23.78; sensitivity, 80.5%; specificity, 85.2%) than a CPIS > 6 (OR, 3.309; sensitivity, 39.8%; specificity, 83.3%). The receiver operating characteristic area under the curve analysis also showed a significantly higher diagnostic value for CEPPIS > 5 than CPIS > 6 (0.829 vs 0.616, respectively; P < .0001).

CONCLUSIONS:  In this pilot, exploratory analysis, CEPPIS is effective in predicting VAP. Prospective validation is needed to confirm the potential value of this score to facilitate VAP diagnosis.

Chest. 2014;146(6):1586-1593. doi:10.1378/chest.14-0681

BACKGROUND:  It has been suggested that the complementary use of echocardiography could improve the diagnostic accuracy of lung ultrasonography (LUS) in patients with acute respiratory failure (ARF). Nevertheless, the additional diagnostic value of echocardiographic data when coupled with LUS is still debated in this setting. The aim of the current study was to compare the diagnostic accuracy of LUS and an integrative cardiopulmonary ultrasound approach (thoracic ultrasonography [TUS]) in patients with ARF.

METHODS:  We prospectively recruited patients consecutively admitted for ARF to the ICU of a university teaching hospital over a 12-month period. Inclusion criteria were age ≥ 18 years and the presence of criteria for severe ARF justifying ICU admission. We compared both LUS and TUS approaches and the final diagnosis determined by a panel of experts using machine learning methods to improve the accuracy of the final diagnostic classifiers.

RESULTS:  One hundred thirty-six patients were included (age, 68 ± 15 years; sex ratio, 1). A three-dimensional partial least squares and multinomial logistic regression model was developed and subsequently tested in an independent sample of patients. Overall, the diagnostic accuracy of TUS was significantly greater than LUS (P < .05, learning and test sample). Comparisons between receiver operating characteristic curves showed that TUS significantly improves the diagnosis of cardiogenic edema (P < .001, learning and test samples), pneumonia (P < .001, learning and test samples), and pulmonary embolism (P < .001, learning sample).

CONCLUSIONS:  This study demonstrated for the first time to our knowledge a significantly better performance of TUS than LUS in the diagnosis of ARF. The value of the TUS approach was particularly important to disambiguate cases of hemodynamic pulmonary edema and pneumonia. We suggest that the bedside use of artificial intelligence methods in this setting could pave the way for the development of new clinically relevant integrative diagnostic models.

Chest. 2014;146(6):1594-1603. doi:10.1378/chest.14-0182

OBJECTIVE:  Although end-of-life care in the ICU accounts for a large proportion of health-care costs, few studies have examined the association between costs and satisfaction with care. The objective of this study was to investigate the association of ICU costs with family- and nurse-assessed quality of dying and family satisfaction.

METHODS:  This was an observational study surveying families and nurses for patients who died in the ICU or within 30 h of transfer from the ICU. A total of 607 patients from two Seattle hospitals were included in the study. Survey data were linked with administrative records to obtain ICU and hospital costs. Regression analyses assessed the association between costs and outcomes assessing satisfaction with care: nurse- and family-assessed Quality of Death and Dying (QODD-1) and Family Satisfaction in the ICU (FS-ICU).

RESULTS:  For family-reported outcomes, patient insurance status was an important modifier of results. For underinsured patients, higher daily ICU costs were significantly associated with higher FS-ICU and QODD-1 (P < .01 and P = .01, respectively); this association was absent for privately insured or Medicare patients (P = .50 and P = .85, QODD-1 and FS-ICU, respectively). However, higher nurse-assessed QODD-1 was significantly associated with lower average daily ICU cost and total hospital cost (P < .01 and P = .05, respectively).

CONCLUSIONS:  Family-rated satisfaction with care and quality of dying varied depending on insurance status, with underinsured families rating satisfaction with care and quality of dying higher when average daily ICU costs were higher. However, patients with higher costs were assessed by nurses as having a poorer quality of dying. These findings highlight important differences between family and clinician perspectives and the important role of insurance status.

Original Research: Chest Infections

Chest. 2014;146(6):1604-1611. doi:10.1378/chest.14-0196

BACKGROUND:  The objective of this study was to evaluate pulmonary abnormalities of pleural TB by CT scanning and to determine CT scan findings for the development of the paradoxical response (PR).

METHODS:  CT scans were performed for 349 patients with pleural TB (between 2008 and 2013). We excluded 34 patients with coexisting pulmonary disease (n = 13) or a totally collapsed lung (n = 21). We analyzed CT scans focusing on pulmonary abnormalities such as the presence of consolidation, cavitation, interlobular septal thickening, and micronodules and their distribution. In addition, we recorded the development of PR during follow-up and statistically analyzed differences in clinical and CT scan findings between patients with and without PR.

RESULTS:  A total of 270 of 315 patients (86%) had pulmonary abnormalities. Common CT scan findings were micronodules (n = 209 [77%]), interlobular septal thickening (n = 202 [75%]), and consolidation (n = 120 [44%]). Cavitation was seen in 49 patients (18%). Among 209 with micronodules, the nodules were in the subpleural region (n = 146 [70%]), peribronchovascular interstitium (n = 113 [54%]), and centrilobular region (n = 64 [31%]). PR occurred in 81 patients (26%), and patients with PR tended to be young, male, and without underlying disease (P < .05 by t test, Pearson χ2 test). Subpleural micronodules were more common in patients with PR than in those without PR (Pearson χ2, P = .025).

CONCLUSIONS:  Pulmonary abnormalities are very common in pleural TB. The most common CT scan findings were micronodules in the subpleural and peribronchovascular interstitium and interlobular septal thickening, suggesting the lymphatic spread of TB. In addition, PR is not rare in patients with pleural TB, especially in young, previously healthy, male patients who show subpleural nodules on initial CT scans.

Chest. 2014;146(6):1612-1618. doi:10.1378/chest.13-2255

BACKGROUND:  The US Centers for Disease Control and Prevention has implemented a new, multitiered definition for ventilator-associated events (VAEs) to replace their former definition of ventilator-associated pneumonia (VAP). We hypothesized that the new definition could be implemented in an automated, efficient, and reliable manner using the electronic health record and that the new definition would identify different patients than those identified under the previous definition.

METHODS:  We conducted a retrospective cohort analysis using an automated algorithm to analyze all patients admitted to the ICU at a single urban, tertiary-care hospital from 2008 to 2013.

RESULTS:  We identified 26,466 consecutive admissions to the ICU, 10,998 (42%) of whom were mechanically ventilated and 675 (3%) of whom were identified as having any VAE. Any VAE was associated with an adjusted increased risk of death (OR, 1.91; 95% CI, 1.53-2.37; P < .0001). The automated algorithm was reliable (sensitivity of 93.5%, 95% CI, 77.2%-98.8%; specificity of 100%, 95% CI, 98.8%-100% vs a human abstractor). Comparison of patients with a VAE and with the former VAP definition yielded little agreement (κ = 0.06).

CONCLUSIONS:  A fully automated method of identifying VAEs is efficient and reliable within a single institution. Although VAEs are strongly associated with worse patient outcomes, additional research is required to evaluate whether and which interventions can successfully prevent VAEs.

Original Research: Lung Cancer

Chest. 2014;146(6):1619-1626. doi:10.1378/chest.14-0204

BACKGROUND:  Visceral pleural invasion (VPI) may impact non-small cell lung cancer (NSCLC) survival. However, previous studies are mixed as to whether VPI is an independent prognostic factor in early-stage cancers and whether its effect is size dependent. In the current American Joint Committee on Cancer (AJCC) staging system, VPI leads to upstaging of cancers < 3 cm but not of those 3 to 7 cm in size.

METHODS:  Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 16,315 patients with stage I-II NSCLC treated with lobectomy. We used the Kaplan-Meier method and Cox regression to assess the association of VPI with lung cancer-specific (primary outcome) and overall survival. Based on these results, we created a revised VPI staging classification.

RESULTS:  Overall, 3,389 patients (21%) had VPI. Kaplan-Meier analysis stratified by tumor size showed worse cancer-specific survival in patients with VPI (P < .0001). VPI was independently associated with decreased lung cancer-specific survival (hazard ratio, 1.38; 95% CI, 1.29-1.47) after controlling for tumor size and other confounders; this effect was not size dependent. In our revised classification, tumors < 7 cm with VPI were upstaged to the next T category.

CONCLUSIONS:  VPI is a prevalent finding associated with worse prognosis in early-stage lung cancer, even among patients with tumors > 3 cm, a factor not captured in the current staging system. Patients with VPI may be considered candidates for more aggressive treatment.

Original Research: Tobacco Cessation and Prevention

Chest. 2014;146(6):1627-1632. doi:10.1378/chest.14-0459

BACKGROUND:  Programs aimed at increasing physical activity in daily life (PADL) have generated growing interest to prevent the deleterious effects of physical inactivity. Recent literature has shown that a short-term protocol using pedometers increased PADL in smokers with normal lung function. However, the long-term effects of such a protocol were not yet studied. The objective of this study was to evaluate the results of 1-year follow-up after a program aimed at increasing PADL in smokers with normal lung function.

METHODS:  Twenty-four smokers were followed (15 men; mean [interquartile range (IQR)], 51 [41-57] years of age; BMI, 26 [22-29] kg/m2; 20 [20-30] cigarettes/d). Subjects were assessed at baseline, immediately after completion of the program, and 1 year later for PADL, lung function, 6-min walking distance (6MWD), smoking habits, quality of life, anxiety, and depression. The 5-month program used pedometers and informative booklets as interventions.

RESULTS:  The gains achieved after the program were maintained in the long term: steps/d (postprogram vs 1-year follow-up, mean [IQR]: 10,572 [9,804-12,237] vs 10,438 [9,151-12,862]); 6MWD (625 [530-694] m, 88 [81-97] % predicted vs 609 [539-694] m, 89 [81-96] % predicted), anxiety (34 [26-41] points vs 35 [36-47] points) and depression (6 [2-9] points vs 5 [2-11] points) (P > .05 for all). One year after the program, 20% of the subjects had quit smoking.

CONCLUSIONS:  In smokers with normal lung function, improvements in daily physical activity, exercise capacity, anxiety, and depression obtained through a 5-month program aimed at increasing physical activity are sustained 1 year after completion of the program. Furthermore, such a program can contribute to smoking cessation in this population.

Evidence-Based Medicine

Chest. 2014;146(6):1633-1648. doi:10.1378/chest.14-1481

Bronchopulmonary C-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. These vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. Other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. The responsiveness and morphology of the airway vagal sensory nerve subtypes and the extrapulmonary sensory nerves that regulate coughing are described. The brainstem and higher brain control systems that process this sensory information are complex, but our current understanding of them is considerable and increasing. The relevance of these neural systems to clinical phenomena, such as urge to cough and psychologic methods for treatment of dystussia, is high, and modern imaging methods have revealed potential neural substrates for some features of cough in the human.

Translating Basic Research Into Clinical Practice

Chest. 2014;146(6):1649-1657. doi:10.1378/chest.14-0713

The past decade has seen an enormous advancement in the therapy for lung cancer, predominantly seen in adenocarcinoma, ranging from the introduction of histology-based drugs to the discovery of targetable mutations. These events have led to a personalized therapeutic approach with the delivery of drugs that target specific oncogenic pathways active in a given tumor with the intent of acquiring the best response rate. The discovery of sensitizing mutation in the epidermal growth factor receptor gene as the basis for clinical response to tyrosine kinase inhibitors led to a systematic search for other molecular targets in lung cancer. Currently, there are several molecular alterations that can be targeted by experimental drugs. These new discoveries would not be possible without a parallel technological evolution in diagnostic molecular pathology. Next-generation sequencing (NGS) is a technology that allows for the evaluation of multiple molecular alterations in the same sample using a small amount of tissue. Selective evaluation of targeted cancer genes, instead of whole-genome evaluation, is the approach that is best suited to enter clinical practice. This technology allows for the detection of most molecular alteration with a single test, thus saving tissue for future discoveries. The use of NGS is expected to increase and gain importance in clinical and experimental approaches, since it can be used as a diagnostic tool as well as for new discoveries. The technique may also help us elucidate the interplay of several genes and their alteration in the mechanism of drug response and resistance.

Recent Advances in Chest Medicine

Chest. 2014;146(6):1658-1666. doi:10.1378/chest.14-0305

Fungal lung infections are widely encountered and present both diagnostic and therapeutic challenges. The increasing prevalence of fungal infections is correlated with increasing numbers of immunocompromised patients, enhanced awareness of these infections, and improved methodologies for diagnosis. Fortunately, additional antifungal agents are available to combat these important infections. This review covers the clinical approach to fungal lung infections encountered in pulmonary and critical care practice.

Medical Ethics

Chest. 2014;146(6):1667-1672. doi:10.1378/chest.14-0513

Efforts to answer the question of whether or when physicians may unilaterally refuse to provide treatments they deem medically futile, but that are nonetheless demanded by patients or their surrogates, have been characterized as intractable failures. We propose a new look at this old problem and suggest reframing the debate in terms of the implicit social contract, in healthy democracies, between the medical profession and the society it serves. This ever-evolving contract is predicated upon providing patients with beneficial and desired medical care within the constraints of scarce resources and the characteristics of our health-care system. The contract ranges over a continuum of decisions, from those that do not need an explicit negotiated agreement with the patient or surrogate, to those that do. Between these two poles lies a contentious gray area, where the rights and obligations of patients and physicians are being shaped continuously by the many forces that are at play in a democratic society, including professional guidelines, social advocacy, legislation, and litigation. We provide examples of how this gray area has been and is negotiated around rights to refuse and demand a variety of life-sustaining treatments, and anticipate conflicts likely to arise in the future. Reframing the futility debate in this way reveals that the issue is not a story of intractable failure, but rather, a successful narrative about how democracies balance the legitimate perspectives of patients and physicians against a backdrop of societal constraints and values.

Contemporary Reviews in Sleep Medicine

Chest. 2014;146(6):1673-1680. doi:10.1378/chest.14-0772

Smoking and OSA are widely prevalent and are associated with significant morbidity and mortality. It has been hypothesized that each of these conditions adversely affects the other, leading to increased comorbidity while altering the efficacy of existing therapies. However, while the association between smoking and OSA is plausible, the evidence is less than conclusive. Cigarette smoking may increase the severity of OSA through alterations in sleep architecture, upper airway neuromuscular function, arousal mechanisms, and upper airway inflammation. Conversely, some evidence links untreated OSA with smoking addiction. Smoking cessation should improve OSA, but the evidence to support this is also limited. This article reviews the current evidence linking both conditions and the efficacy of various treatments. Limitations of the current evidence and areas in need of future investigation are also addressed.

Contemporary Reviews in Critical Care Medicine

Chest. 2014;146(6):1681-1689. doi:10.1378/chest.14-1133

Critical care practitioners must frequently make decisions about their patients’ ability to swallow food, liquids, and pills. These decisions can be particularly difficult given the incompletely defined epidemiology, diagnostic criteria, and prognostic features of swallowing disorders in critically ill patients. Furthermore, the consequences of improper decisions—namely, aspiration, malnutrition, hunger, and thirst—can be devastating to patients and their families. This review outlines the problem of swallowing dysfunction in critically ill patients and then addresses the most clinically relevant questions that critical care practitioners face today. First, we review the epidemiology of swallowing dysfunction in critically ill patients. Next, we describe the different diagnostic tests for swallowing dysfunction and describe a general approach to the initial assessment for swallowing disorders. Finally, we explore the existing treatments for swallowing dysfunction. Given the burden of swallowing dysfunction in patients recovering from critical illness, enabling critical care practitioners to manage these disorders, while stimulating new investigation into their pathophysiology, diagnosis, and management, will enhance our care of critically ill patients.


Chest. 2014;146(6):1690. doi:10.1378/chest.14-1389

Even the dying wince, their stench
makes you gag –you can't ask
must rely on their skin
and its yellowing glaze
with just enough sunlight left
for directions back
–they languish at night
looking for what must be
those tiny rocks mourners leave
as if the dead could still
find refuge in a few simple words
placed near –the dying need this doubt
to go further, not sure why
their eyes once had such power
and now can't open to demand
where to make a boundary line
that's safe once inside
with all those stars, far off
not yet arrived
as still warm dirt and mornings.

Chest. 2014;146(6):1691. doi:10.1378/chest.14-1490

Lo! Pangs return without warning to catch the prey unprepared.
As the sly serpent uncoils, slithering skirmishes precede the war.
From whence it hails, a wicked world of mucosal morass.
Who is accountable for summoning the latent beast?
Does entombed pathogen elicit futile efforts at extirpation?
Or is innate self-loathing manifest as immune civil war?
Only sibilant borborygmi augur the impending fury; No herald trumpets here.
Ironic self-extispicy.
With nociceptors ablaze, the day is greeted de rigueur.
Only a temper shortened, or humor less effusive, belie the raging conflict within.
The armory holds arrows bent and archaic rapiers dulled by time.
Warriors so woefully equipped do not beard the beast this day.
With no option for retreat, compromise and concession rule.
Meals less succulent and agendas abridged are offered in peace.
Less pain accepted as reconciliation to draw an armistice nigh.
The yardstick shortened.
Suddenly, without warning, the wicked writhing abates.
Whether from pharmacopeia or desperate incantation, the dragon grows weary.
Passion ebbing, claws retract, and under peristaltic cover it retreats.
A colicky yawn the only clue of where it waits in interictal torpor.
Cautious probing draws no response. A hesitant normalcy eases into place.
Recurrent taunts of a peace indefinite weigh heavily.
A familiar path pocked by previous false promissory truces.
Sardonic optimism.

Chest. 2014;146(6):1692. doi:10.1378/chest.14-1493

I was one of them, too,
mutant Drosophila,
wings poised like shields,
cinnabar eyes dotted
with thin bristles like a forest
of evenly-spaced pines.
Green fluorescent protein construct
tucked away gingerly.
Translucent, quiet, clean.
Waiting for the next generation.
I drop secret eggs. My progeny
crawl through the gene pool.
In another dream, I was
once again a fruit fly,
a grain of rice feeling
my way around the bell
of a raspberry, my skin
in perfect tension.
I became the fruit’s tongue,
my body striking the sides
as I tried to find an opening,
an exit. I circled around
and around the bell,
this ringing instrument,
until I stopped and hung
perpendicular to the ground,
as if resting. How do you
interpret motionlessness?
The body catches on fine hairs
as if catching on fire.
My grandfather, who survived
floods, hurricanes, famine,
a war, didn’t talk much.
When he died, we burned
him to his bones,
skin, hair, cancer
A privacy in this
sudden fluorescence,
as if the body,
letting go of one secret,
can finally keep the others.

Chest. 2014;146(6):1693. doi:10.1378/chest.14-1494

Mid-July, 1970—
you ran away with him to D.C.
Even then, the rebellions were starting.
This time, it was your body,
lighting itself on fire
little by little, one bursa each month,
tearing down its own house.
Pain built an altar in your living room.
Your neck teething.
The bones in your hands picked apart
by the rat beaks of seagulls.
You’ve learned to dress your story
for various occasions.
You exaggerate and dilute with such ease.
Mostly, you dress it down,
the stiff clinic rooms, the acrid bathroom bleach
washing out. Anger drying
like a basket of damp shirts.
In this persistent snow, I think the attenuation
of a marriage.
Tonight, my neck is knotted
into a child’s fist
refusing to uncurl.
This is what little I know of pain:
it consumes,
it consumes.
Even now, when you’ve lived through
the burning, the worst of it,
you don’t drop crumbs for the way back.
You will not indulge the wild animals.
You have stepped into a different city.


Chest. 2014;146(6):1694. doi:10.1378/chest.14-2560

An error occurred in the remarks for recommendation 2.11 in the “Antithrombotic Therapy in Neonates and Children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines” (Chest 2012;141(2)(Suppl):e737S-e801S). It can be found on pages e739S and e763S.

Chest. 2014;146(6):1694. doi:10.1378/chest.14-2902

An error occurred in the remarks for “Antithrombotic Therapy in Neonates and Children” recommendation 2.11 on page 42S of “Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines” (Chest. 2012;141(2)(Suppl):7S-47S).

CHEST Reviewers

Chest. 2014;146(6):1695-1701. doi:10.1378/chest.14-6643

CHEST would like to thank the individuals listed below who served as reviewers in 2014. Without their generous assistance, the Journal would not be able to function. The expert evaluation of manuscripts by these people is a primary reason that CHEST is one of the most respected journals in its field. We extend our appreciation. Because of production restraints, we have only listed those who completed reviews by mid-October 2014. Those who completed reviews after then will be listed next year.

Selected Reports

Chest. 2014;146(6):e186-e189. doi:10.1378/chest.14-0350

Hypersensitivity pneumonitis (HP) is a diffuse granulomatous lung disease resulting from inhalation of an antigen to which an individual has been previously sensitized. Hot tub lung is an increasingly common form of HP associated with inhalation of water aerosols containing Mycobacterium avium complex organisms that contaminate hot tub water. Granulomatous lung disorders, most classically sarcoidosis, have been associated with unregulated 1-α-hydroxylase expression by macrophages present in the granulomas, causing conversion of 25-OH-vitamin D to the active form of vitamin D, 1,25(OH)2 vitamin D, and, thus, hypercalcemia. To our knowledge, this is the first confirmed case of hypercalcemia secondary to elevated 1,25(OH)2 vitamin D levels associated with HP.

Chest. 2014;146(6):e190-e194. doi:10.1378/chest.14-0394

Malignant pleural effusions cause significant morbidity, but there is no gold standard minimally invasive treatment. A new therapeutic approach combines talc pleurodesis and indwelling pleural catheters (IPCs) to enable outpatient management. This case series summarizes the safety and efficacy data of all patients (24) with a symptomatic malignant pleural effusion who underwent talc pleurodeses via IPCs between December 2010 and July 2013. Successful pleurodesis was achieved in 22 procedures (92%). There was one empyema, one hydropneumothorax, one recurrent effusion, and two minor complications: one drain site wound infection and one complaint of chest pain. Twenty-two procedures (92%) were performed in the outpatient setting. This report confirms the safety and efficacy of administering talc slurry through IPCs in an outpatient setting. Studies in a larger cohort are necessary to define the role of this novel approach in the treatment algorithm of patients with this condition.

Ultrasound Corner

Chest. 2014;146(6):e195-e197. doi:10.1378/chest.14-0265

Chest Imaging and Pathology for Clinicians

Chest. 2014;146(6):e198-e203. doi:10.1378/chest.14-0796

A 40-year-old woman (a nonsmoker) with history of idiopathic thrombocytopenic purpura and a platelet count > 90,000 cells/μL without specific medication was referred to pulmonary clinic for evaluation of multiple pulmonary nodules. The patient presented to an outside hospital with fatigue, lack of energy, and dyspnea on exertion for 2 years. She denied fever, cough, chest pain, or weight loss. An initial chest radiograph showed bilateral multiple pulmonary nodules. A chest CT scan revealed multiple nodular lesions, varying in size, in all lobes of both lungs. There was no mediastinal lymphadenopathy or pleural effusion. There was no significant hypermetabolic activity on a subsequent fluorodeoxyglucose PET scan/CT scan, and there had been no significant change. She underwent CT scan-guided percutaneous transthoracic biopsy and bronchoscopy with transbronchial biopsies, all of which were inconclusive. An open lung biopsy was considered.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2014;146(6):e204-e207. doi:10.1378/chest.14-0221

A 44-year-old woman was referred by her primary care physician for a polysomnogram for further workup of excessive daytime sleepiness. She reported a 6-month history of uncontrollably falling asleep. She frequently dozed off while watching television, sitting inactive in public places, and talking to people. She had dozed off while driving, but had not had any driving accidents. Her Epworth Sleepiness Scale score was 21 of 24. She admitted to snoring, but no apneas were witnessed by her bed partner. She denied symptoms of morning headaches, gasping for air, leg jerking during sleep, cataplexy, sleep paralysis, hypnagogic hallucinations, gastroesophageal reflux during sleep, or insomnia. She usually went to bed at 10:00 pm and woke up at 9:00 am. She reported three to four nocturnal awakenings per night. She denied taking naps. Medical history included chronic pain from cervical spinal stenosis, hypothyroidism, hyperlipidemia, depression, restless legs, migraines, and gastroesophageal reflux disease. She had no known cardiac illnesses. Medications included levothyroxine, 50 μg daily; duloxetine, 60 mg daily; cyclobenzaprine, 10 mg tid; omeprazole, 20 mg daily; trazodone, 50 mg daily; gabapentin, 600 mg daily; tolterodine, 2 mg bid; cetirizine, 10 mg daily; extended-release oral morphine sulfate, 15 mg bid; and immediate-release oral morphine sulfate, 15 mg qid as needed for pain.

Chest. 2014;146(6):e208-e211. doi:10.1378/chest.14-0761

A 71-year-old woman, nonsmoker, with a history of metastatic breast cancer was referred for evaluation of worsening pulmonary infiltrates. She described slowly increasing exertional dyspnea and cough in the preceding 3 months. Twenty-two years before, she had been diagnosed with invasive ductal carcinoma of the left breast, for which she underwent a left modified radical mastectomy and prophylactic right simple mastectomy and bilateral breast reconstruction using silicone implants. She subsequently underwent combination chemotherapy. She did well during the following 7 years until an enlarging liver lesion was noted that proved to be metastatic breast cancer, for which she underwent a right hepatectomy. Five years later, she developed intrathoracic and supraclavicular lymphadenopathy, a left pleural effusion, and cervical spine lesions. A biopsy specimen from a supraclavicular lymph node showed metastatic breast cancer, for which she started letrozole therapy with resolution of intrathoracic findings. Twelve months before presentation she underwent bilateral capsulectomy with silicone implant exchange because of pain from implant contracture. Her medications included letrozole, 2.5 mg once a day, and vitamin and Chinese herbal supplements. Her family history was positive for breast cancer in her maternal grandmother.


Chest. 2014;146(6):e212. doi:10.1378/chest.14-1651
Chest. 2014;146(6):e212-e213. doi:10.1378/chest.14-1837
Chest. 2014;146(6):e214-e215. doi:10.1378/chest.14-1873
Chest. 2014;146(6):e216-e220. doi:10.1378/chest.14-1827
Chest. 2014;146(6):e221. doi:10.1378/chest.14-0786
Chest. 2014;146(6):e222-e225. doi:10.1378/chest.14-2055
Chest. 2014;146(6):e226. doi:10.1378/chest.14-1988
Chest. 2014;146(6):e226-e227. doi:10.1378/chest.14-2043
Chest. 2014;146(6):e228-e229. doi:10.1378/chest.14-1941
Chest. 2014;146(6):e230. doi:10.1378/chest.14-2098
Chest. 2014;146(6):e230-e231. doi:10.1378/chest.14-2158
Chest. 2014;146(6):e232-e233. doi:10.1378/chest.14-1002
Chest. 2014;146(6):e234-e235. doi:10.1378/chest.14-1189
Chest. 2014;146(6):e236-e237. doi:10.1378/chest.14-1835
Chest. 2014;146(6):e238. doi:10.1378/chest.14-2211

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543