Current Issue


Chest. 2014;146(3):529-530. doi:10.1378/chest.14-0279

Over the past several years, there has been an increasing appreciation of the burden of pulmonary disease caused by nontuberculous mycobacteria (NTM) in both the general population1-3 and in patients receiving immunosuppressive drugs. Soon after the first tumor necrosis factor-α antagonist was introduced into clinical use, the increased risk of mycobacterial infections, TB especially, in patients receiving these agents was recognized.4 Physicians are by now well sensitized to the importance of screening patients with various rheumatic and other systemic inflammatory conditions for TB prior to initiation of treatment with tumor necrosis factor-α blockers. Nearly every practicing pulmonologist by now is aware of the challenges of treating patients with Mycobacterium avium, Mycobacterium xenopi, Mycobacterium abscessus, Mycobacterium kansasii, Mycobacterium fortuitum, and others. It is well appreciated, through both large epidemiologic studies and individual experience, that in economically developed countries that generally have low incidence rates of TB, the burden of NTM infections far outstrips that of TB. Much less well understood, however, are the particular risk factors for developing infections with NTM, the natural history of these infections, and the best approaches to treatment. In this issue of CHEST (see page 563), Brode and colleagues5 make an important contribution to our understanding of the epidemiology of NTM infections and they point the way to important avenues of future research.

Chest. 2014;146(3):532-534. doi:10.1378/chest.14-0636

Approximately 20% of deaths in the United States occur in or shortly after a stay in the ICU, and the proportion of Medicare beneficiaries who spend time in the ICU in the last 30 days of their lives is increasing.1,2 Of the deaths occurring in the ICU, the majority involve decisions to withhold or withdraw life-sustaining treatments. Studies from the past century documented dramatic variability from ICU to ICU in the proportion of deaths preceded by withholding and withdrawing life-sustaining treatments.3 An article by Quill and colleagues4 in this issue of CHEST (see page 573) shows that dramatic variability persists—sixfold—in these decisions from ICU to ICU, even after adjusting for patient and ICU factors.

Second Opinion

Chest. 2014;146(3):535. doi:10.1378/chest.146.3.535

Point and Counterpoint

Chest. 2014;146(3):536-537. doi:10.1378/chest.14-0810

According to the American Thoracic Society/European Respiratory Society document on lung function testing, FEV1 and FVC are the key parameters to assess bronchoreversibility in obstructive lung diseases because spirometry is easy to perform in any setting, repeatable and reproducible, and, thus, suitable to assess either intraday or long-term changes in lung function.1 The acute response to bronchodilators is relatively easy to interpret when changes in FEV1 or FVC exceed the thresholds of their natural intraday variability (ie, 12% of baseline and 200 mL), thus, unequivocally indicating bronchodilation. Although the bronchodilator response does not allow a distinction between bronchial asthma and COPD,2,3 large responses can be taken as strongly suggestive of the former.4 Therefore, we believe that changes in FEV1 or FVC still represent the most suitable first-line method to assess bronchodilator response in clinical practice.

Chest. 2014;146(3):538-541. doi:10.1378/chest.14-0437

We respect the integrity, intelligence, and experience of the experts serving on the American Thoracic Society/European Respiratory Society (ATS/ERS) pulmonary function committees1 and Tan et al2 and the validity of their data. However, we do not agree with some of their statistical analyses and interpretations of bronchodilator responsiveness. Table 9 of the ATS/ERS document states: “An increase in FEV1 and/or FVC ≥ 12% and ≥ 200 mL constitutes a positive bronchodilator response.”1 Relevant portions of this document use the terms “meaningful” and “significant” without using the term “statistically significant” (SS).

Chest. 2014;146(3):541-542. doi:10.1378/chest.14-0811

There are major reasons for testing acute bronchoreversibility in clinical practice. For instance, finding large increments in FEV1 > 400 mL is of great value to confirm the diagnosis of asthma and support therapy. Evaluating whether airflow obstruction is still reversible is also important, even though normal acute responses do not predict effects of chronic treatment and in no case preclude trials with bronchoactive medications. Drs Hansen and Porszasz1 suggest that with respect to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines,2 the perceptive threshold is more suitable for evaluating bronchoreversibility. We will try to convince our readers that exploring lung mechanics with various functional parameters capable of identifying the fundamental and complex changes with bronchodilation is more important than debating the concept of threshold.

Chest. 2014;146(3):542-544. doi:10.1378/chest.14-0618

We welcome the opportunity to respond to Drs Pellegrino and Brusasco.1 We are concerned primarily with their statement that “the acute response to bronchodilators is relatively easy to interpret when changes in FEV1 or FVC exceed the thresholds of their natural intraday variability (ie, 12% of baseline and 200 mL), thus, unequivocally indicating bronchodilation.”1

Giants in Chest Medicine

Chest. 2014;146(3):545-546. doi:10.1378/chest.14-0076

Margaret Turner-Warwick, DBE, DM, PhD, is a very appropriate choice as a Giant in Chest Medicine as she has had a major influence on research and understanding of pulmonary disease over a long period. She was born in London in 1924 and is related to Lord Baden-Powell, the founder of the Boy Scout movement. She studied physiology at Oxford University and qualified in medicine at University College Hospital in London in 1950. During the same year, she married Richard Turner-Warwick, who she met in Oxford and who went on to become a distinguished urologic surgeon. After junior medical posts in London, she decided on a career in respiratory medicine after working at the Brompton Hospital, then as now the major respiratory center in the United Kingdom.

Original Research: Pulmonary Procedures

Chest. 2014;146(3):547-556. doi:10.1378/chest.13-2339

BACKGROUND:  Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is superior to conventional transbronchial needle aspiration (cTBNA) in the staging of lung cancer. However, its efficiency in diagnosis of sarcoidosis when combined with endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) has not been studied. This randomized controlled trial compares diagnostic yield of EBUS-TBNA vs cTBNA in combination with EBB and TBLB.

METHODS:  Patients with clinical diagnosis of sarcoidosis were randomized 1:1 to EBUS-TBNA or cTBNA. All patients underwent TBLB and EBB. The primary outcome was detection of granulomas. The secondary end points were the individual and cumulative yields of various procedures, serious adverse events, and procedure time.

RESULTS:  Of the 130 patients, sarcoidosis was diagnosed in 117 (62 cTBNA, 55 EBUS-TBNA). The two groups were similar at baseline. Granulomas were demonstrated in 104 (53 cTBNA, 51 EBUS-TBNA) patients and were similar in two groups (85.5% vs 92.7%, P = .34). Individually, EBUS-TBNA had the highest yield (41 of 55, 74.5%), which was better than cTBNA (30 of 62, 48.4%, P = .004) or EBB (40 of 111, 36.3%, P < .0001) but not TBLB (78 of 112, 69.6%, P = .54). Adding EBB/TBLB to cTBNA led to an increase in granuloma detection, whereas the addition of TBLB (but not EBB) significantly enhanced the yield of EBUS-TBNA. The procedure time was significantly longer with EBUS-TBNA. No major adverse events occurred.

CONCLUSIONS:  Individually, EBUS-TBNA has the highest diagnostic yield in sarcoidosis, but it should be combined with TBLB for the optimal yield. The diagnostic yield of cTBNA (plus EBB and TBLB) is similar to EBUS-TBNA plus TBLB.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01908868; URL: www.clinicaltrials.gov

Chest. 2014;146(3):557-562. doi:10.1378/chest.13-3057

BACKGROUND:  Indwelling pleural catheters (IPCs) are commonly used to manage malignant effusions. Tumor spread along the catheter tract remains a clinical concern for which limited data exist. We report the largest series of IPC-related catheter tract metastases (CTMs) to date, to our knowledge.

METHODS:  This is a single-center, retrospective review of IPCs inserted over a 44-month period. CTM was defined as a new, solid chest wall lesion over the IPC insertion site and/or the tunneled subcutaneous tract that was clinically compatible with a malignant tract metastasis.

RESULTS:  One hundred ten IPCs were placed in 107 patients (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM often developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases had chest wall pain, and six received palliative radiotherapy to the CTM. Radiotherapy was well tolerated, with no major complications and causing no damage to the catheters. Longer interval after IPC insertion was the sole significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P = .0098) in the multivariate analyses.

CONCLUSIONS:  IPC-related CTM is uncommon but can complicate both mesothelioma and metastatic carcinomas. The duration of interval after IPC insertion is the key risk factor identified for development of CTM. Symptoms are generally mild and respond well to radiotherapy, which can be administered safely without removal of the catheter.

Original Research: Chest Infections

Chest. 2014;146(3):563-572. doi:10.1378/chest.13-2058

OBJECTIVE:  Patients with rheumatoid arthritis (RA) are at increased risk of TB. Little is known about the risk of nontuberculous mycobacteria (NTM) disease in these patients. We sought to ascertain the rate of NTM infection and TB in all residents of Ontario, Canada, with and without RA.

METHODS:  In a cohort study, all Ontarians aged ≥ 15 years in January 2001 were followed until December 2010. Individuals with RA were identified using a validated algorithm to search hospitalization and physician billing claims. We linked Public Health Ontario Laboratory data to identify all cases of laboratory-confirmed TB and NTM disease. Analysis was performed using Cox proportional hazards regression.

RESULTS:  We identified 113,558 Ontarians with RA and 9,760,075 Ontarians without RA. Relative to the non-RA group, adjusted hazard ratios (HRs) and 95% CIs for TB (1.92, [1.50-2.47]) and NTM disease (2.07, [1.84-2.32]) demonstrated increased risks in the RA group. Among those with RA, per 100,000 person-years, NTM disease (HR, 41.6; 95% CI, 37.1-46.5) was more common than TB (HR, 8.5; 95% CI, 6.5-10.8). After full adjustment, people with RA who developed NTM disease were 1.81 times as likely to die than uninfected people with RA.

CONCLUSIONS:  Mycobacterial infections are more common in Ontarians with RA, with NTM disease more likely than TB. NTM disease is associated with an increased risk of death in patients with RA. Given the rising rates of NTM disease worldwide, determining whether this risk is due to the use of immunosuppressive medications vs RA itself is an important objective for future research.

Original Research: Critical Care

Chest. 2014;146(3):573-582. doi:10.1378/chest.13-2529

BACKGROUND:  The magnitude and implication of variation in end-of-life decision-making among ICUs in the United States is unknown.

METHODS:  We reviewed data on decisions to forgo life-sustaining therapy (DFLSTs) in 269,002 patients admitted to 153 ICUs in the United States between 2001 and 2009. We used fixed-effects logistic regression to create a multivariable model for DFLST and then calculated adjusted rates of DFLST for each ICU.

RESULTS:  Patient factors associated with increased odds of DFLST included advanced age, female sex, white race, and poor baseline functional status (all P < .001). However, associations with several of these factors varied among ICUs (eg, black race had an OR for DFLST from 0.18 to 2.55 across ICUs). The ICU staffing model was also found to be associated with DFLST, with an open ICU staffing model associated with an increased odds of a DFLST (OR = 1.19). The predicted probability of DFLST varied approximately sixfold among ICUs after adjustment for the fixed patient and ICU effects and was directly correlated with the standardized mortality ratios of ICUs (r = 0.53, 0.41–0.68).

CONCLUSION:  Although patient factors explain much of the variability in DFLST practices, significant effects of ICU culture and practice influence end-of-life decision-making. The observation that an ICU’s risk-adjusted propensity to withdraw life support is directly associated with its standardized mortality ratio suggests problems with using the latter as a quality measure.

Chest. 2014;146(3):583-589. doi:10.1378/chest.13-2046

BACKGROUND:  ICU-acquired weakness (ICU-AW) has immediate and long-term consequences for critically ill patients. Strategies for the prevention of weakness include modification of known risk factors, such as hyperglycemia and immobility. Intensive insulin therapy (IIT) has been proposed to prevent critical illness polyneuropathy. However, the effect of insulin and early mobilization on clinically apparent weakness is not well known.

METHODS:  This is a secondary analysis of all patients with mechanical ventilation (N = 104) previously enrolled in a randomized controlled trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of functional independence. Every patient had IIT and blinded muscle strength testing on hospital discharge to determine the incidence of clinically apparent weakness. The effects of insulin dose and early mobilization on the incidence of ICU-AW were assessed.

RESULTS:  On logistic regression analyses, early mobilization and increasing insulin dose prevented the incidence of ICU-AW (OR, 0.18, P = .001; OR, 0.001, P = .011; respectively) independent of known risk factors for weakness. Early mobilization also significantly reduced insulin requirements to achieve similar glycemic goals as compared with control patients (0.07 units/kg/d vs 0.2 units/kg/d, P < .001).

CONCLUSIONS:  The duel effect of early mobilization in reducing clinically relevant ICU-AW and promoting euglycemia suggests its potential usefulness as an alternative to IIT.

Chest. 2014;146(3):590-599. doi:10.1378/chest.14-0191

BACKGROUND:  There are few data on characteristics and outcomes among patients with lung transplantation (LT) requiring admission to the medical ICU (MICU) beyond the perioperative period.

METHODS:  We interrogated the registry database of all admissions to the MICU at Cleveland Clinic (a 53-bed closed unit) to identify patients with history of LT done > 30 days ago (n = 101; mean age, 55.4 ± 12.6 years; 53 men, 48 women). We collected data regarding demographics, history of bronchiolitis obliterans syndrome, preadmission FEV1, clinical and laboratory variables at admission, MICU course, length of stay, hospital survival, and 6-month survival.

RESULTS:  The most common indication for MICU admission was acute respiratory failure (n = 51, 50.5%). Infections were most frequently responsible for respiratory failure, whereas acute rejection (cellular or humoral) was less likely (16%). Nearly one-fourth of the patients required hemodialysis (24.1%), and more than one-half required invasive mechanical ventilation (53.5%). Despite excellent hospital survival (88 of 101), 6-month survival was modest (56.4%). APACHE (Acute Physiology and Chronic Health Evaluation) III score at admission and single LT were independent predictors of hospital survival but did not predict outcome at 6 months. Functional status at discharge was the only independent predictor of 6-month survival (adjusted OR, 5.1; 95% CI, 1.1-22.7; P = .035).

CONCLUSIONS:  Acute rejection is an infrequent cause of decompensation among patients with LT requiring MICU admission. For patients admitted to the MICU, 6-month survival is modest. Functional status at the time of discharge is an independent predictor of survival at 6 months.

Original Research: Sleep Disorders

Chest. 2014;146(3):600-610. doi:10.1378/chest.13-2228

BACKGROUND:  Poor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA.

METHODS:  Subjects with newly diagnosed OSA were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. The intervention group received usual care plus a brief motivational enhancement education program directed at enhancing the subjects’ knowledge, motivation, and self-efficacy to use CPAP through the use of a 25-min video, a 20-min patient-centered interview, and a 10-min telephone follow-up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data were downloaded at the completion of this 3-month study.

RESULTS:  One hundred subjects with OSA (mean ± SD, age 52 ± 10 years; Epworth Sleepiness Scales [ESS], 9 ± 5; median [interquartile range] apnea-hypopnea index, 29 [20, 53] events/h) prescribed CPAP treatment were recruited. The intervention group had better CPAP use (higher daily CPAP usage by 2 h/d [Cohen d = 1.33, P < .001], a fourfold increase in the number using CPAP for ≥ 70% of days with ≥ 4 h/d [P < .001]), and greater improvements in daytime sleepiness (ESS) by 2.2 units (P = .001) and treatment self-efficacy by 0.2 units (P = .012) compared with the control group.

CONCLUSIONS:  Subjects with OSA who received motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01173406; URL: www.clinicaltrials.gov

Original Research: COPD

Chest. 2014;146(3):611-623. doi:10.1378/chest.13-2784

BACKGROUND:  Although high-dose N-acetylcysteine (NAC) has been suggested to reduce COPD exacerbations, it is unclear which category of patients with COPD would benefit most from NAC treatment. The objective of this study was to compare the effect of high-dose NAC (600 mg bid) between high-risk and low-risk Chinese patients with COPD.

METHODS:  Patients with spirometry-confirmed stable COPD were randomized to treatment with either NAC 600 mg bid or placebo in addition to their usual treatments. Patients were followed up every 16 weeks for a total of 1 year. Further analysis was performed according to each patient’s exacerbation risk at baseline as defined by the current GOLD (Global Initiative for Chronic Obstructive Lung Disease) strategy to analyze the effect of high-dose NAC in high-risk and low-risk patients.

RESULTS:  Of the 120 patients with COPD randomized (men, 93.2%; mean age, 70.8 ± 0.74 years; prebronchodilator FEV1, 53.9 ± 2.0%; baseline characteristics comparable between treatment groups), 108 (NAC, 52; placebo, 56) completed the 1-year study. For high-risk patients (n = 89), high-dose NAC compared with placebo significantly reduced exacerbation frequency (0.85 vs 1.59 [P = .019] and 1.08 vs 2.22 [P = .04] at 8 and 12 months, respectively), prolonged time to first exacerbation (P = .02), and increased the probability of being exacerbation free at 1 year (51.3% vs 24.4%, P = .013). This beneficial effect of high-dose NAC vs placebo was not significant in low-risk patients.

CONCLUSIONS:  High-dose NAC (600 mg bid) for 1 year reduces exacerbations and prolongs time to first exacerbation in high-risk but not in low-risk Chinese patients with COPD.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01136239; URL: www.clinicaltrials.gov

Original Research: Asthma

Chest. 2014;146(3):624-632. doi:10.1378/chest.14-0183

BACKGROUND:  Asthma, a common chronic disease among adults and children in the United States, results in nearly one-half million hospitalizations annually. There has been no evaluation of asthma hospitalizations for American Indian and Alaska Native (AI/AN) people since a previous study using data for 1988-2002. In this study, we describe the epidemiology and trends for asthma hospitalizations among AI/AN people and the general US population for 2003-2011.

METHODS:  Hospital discharge records with a first-listed diagnosis of asthma for 2003-2011 were examined for AI/AN people, using Indian Health Service (IHS) data, and for the general US population, using the Nationwide Inpatient Sample. Average annual crude and age-adjusted hospitalization rates were calculated.

RESULTS:  The average annual asthma hospitalization rates for AI/AN people and the general US population decreased from 2003-2005 to 2009-2011 (32% and 11% [SE, 3%], respectively). The average annual age-adjusted rate for 2009-2011 was lower for AI/AN people (7.6 per 10,000 population) compared with the general US population (13.2 per 10,000; 95% CI, 12.8-13.6). Age-specific AI/AN rates were highest among infants and children 1 to 4 years of age. IHS regional rates declined in all regions except Alaska.

CONCLUSIONS:  Asthma hospitalization rates are decreasing for AI/AN people and the general US population despite increasing prevalence rates. AI/AN people experienced a substantially lower age-adjusted asthma hospitalization rate compared with the general US population. Although the rates for AI/AN infants and children 1 to 4 years of age have declined substantially, they remain higher compared with other age groups. Improved disease management and awareness should help to further decrease asthma hospitalizations, particularly among young children.

Original Research: Lung Cancer

Chest. 2014;146(3):633-643. doi:10.1378/chest.13-2499

BACKGROUND:  Histologic classification of lung adenocarcinoma subtype has a prognostic value in most studies. However, lung adenocarcinoma characteristics differ across countries. Here, we aimed at validating the prognostic value of this classification in a large French series of lung adenocarcinoma.

METHODS:  We reviewed 407 consecutive lung adenocarcinomas operated on between 2001 and 2005 and reclassified them according to the International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification and subsequently graded them into low, intermediate, and high grade. We analyzed the relevance of this classification according to clinical, pathologic, and molecular analysis.

RESULTS:  Patients (median age, 61 years; 288 men) underwent lobectomy (n = 378) or pneumonectomy (n = 29). Patients’ overall survival at 5 and 10 years was 53.2% and 32.6%, respectively. Union for International Cancer Control stage distribution was 189 stage I, 104 stage II, 107 stage III, and seven stage IV. Low-grade tumor was found in one patient, intermediate grade in 275 patients, and high grade in 131 patients. KRAS and EGFR mutations were detected in 34% and 9.6%, respectively. Histologic grade was significantly correlated with extent of resection (P = .01), thyroid transcriptional factor-1 expression (P = .00000001), vascular emboli (P = .03), and EGFR mutations (P = .01). Mucinous adenocarcinomas were associated with KRAS mutations (P = .003). At univariate analysis, age, extent of resection, histologic grade, pleural invasion, vascular emboli, pathologic T and N, and stage were predictive of survival. At multivariate analysis, age (P = .0001), histologic grade (P = .03), and stage (P = .000003) were independent prognostic factors.

CONCLUSIONS:  IASLC/ATS/ERS classification of lung adenocarcinomas predicts survival in French population. Histologic grade correlates with clinical, pathologic and molecular parameters suggesting different oncogenic pathways.

Chest. 2014;146(3):644-649. doi:10.1378/chest.14-0159

BACKGROUND:  The prognosis of N2 non-small cell lung cancer (NSCLC) has been reported to be heterogeneous. The recently revised Japanese nodal classification subcategorizes N2 disease according to the tumor-bearing lobe. We evaluated the prognostic impact of the Japanese nodal classification and its ability to define favorable N2 disease in resected NSCLC.

METHODS:  A total of 496 patients with NSCLC who underwent lobectomy with systematic lymph node dissection between 1998 and 2009 were analyzed retrospectively. N2 status was subdivided into N2a-1 and N2a-2, according to the Japanese nodal classification. Overall survival (OS), disease-free survival (DFS), and clinicopathologic features were compared between the two groups.

RESULTS:  There were 67 cases with N2 disease. The outcome of resected N2a-2 NSCLC was far poorer than that of the N2a-1 group (5-year OS, 28% vs 62%, P < .001; 5-year DFS, 5% vs 35%, P < .001). Multivariate analysis revealed that pathologic N2a-2 was an independent prognostic factor (hazard ratio, 2.86; P < .05). Patients in the N2a-2 group showed more involved nodes and stations, less skip metastasis, and more locoregional recurrence than did patients in the N2a-1 group. The outcome of the N2a-1 group was satisfactory, and there was no significant difference in OS and DFS between N1 and N2a-1.

CONCLUSIONS:  The Japanese nodal classification is able to identify a favorable N2 subgroup in resected NSCLC. Nodal staging by the Japanese system should be considered when a clinical trial of N2 disease is designed.

Chest. 2014;146(3):650-658. doi:10.1378/chest.13-2379

BACKGROUND:  The risk of VTE before anticancer therapy in patients with lung cancer is not well defined.

METHODS:  A total of 673 hospitalized patients with newly diagnosed lung cancer were examined for VTE within 1 week after admission at five hospitals between January 2009 and January 2011. Additionally, VTE diagnoses within the last 3 months were reviewed. All VTE events were confirmed with imaging studies. Blood cell count and serum carcinoembryonic antigen (CEA) levels were measured before initial treatment.

RESULTS:  VTE events occurred in 89 of the 673 patients (13.2%) enrolled in this study. Forty-two patients (6.2%) developed lower extremity DVT alone, 33 patients (4.9%) developed pulmonary embolism (PE) alone, and 14 patients (2.1%) developed both DVT and PE. By multivariate logistic regression analysis, distant metastasis (OR, 2.2; 95% CI, 1.2-3.9) and leukocytosis (OR, 2.8; 95% CI, 1.5-5.4) were significantly associated with DVT, adenocarcinoma (OR, 2.1; 95% CI, 1.1-4.4) and anemia (OR, 4.6; 95% CI, 1.4-14.5) were significantly associated with PE, and an elevated CEA level in tertiles was linearly associated with PE (P for trend = .06). The area under the receiver operating characteristic curve for the prognostic or diagnostic CEA values was 0.68 (95% CI, 0.59-0.76; P < .001).

CONCLUSIONS:  The prevalence of VTE was high in patients with newly diagnosed lung cancer. In patients with lung cancer, the factors associated with DVT might be different from those associated with PE. An elevated CEA level might facilitate the identification of patients at a higher risk of developing PE.

Chest. 2014;146(3):659-669. doi:10.1378/chest.13-2900

BACKGROUND:  Ideally, quality indicators are developed with the input of professional groups involved in the care of patients. This project, led by the Thoracic Oncology Network and Quality Improvement Committee of the American College of Chest Physicians (CHEST), had the goal of developing quality indicators related to the evaluation and staging of patients with lung cancer.

METHODS:  Evidence-based guidelines were used to generate a list of process-of-care quality indicators, and project members revised the content and wording of this list. A survey of the Steering Committee of the Thoracic Oncology Network was performed to rate the validity, feasibility, and relevance of the indicators. Predefined thresholds were used to select indicators from the list. This process was repeated for the selected indicators through a survey available to all members of the Thoracic Oncology Network. Three academic medical centers determined if the surviving indicators were feasible and relevant within their practices.

RESULTS:  Eighteen quality indicators were drafted. Eleven survived the first round of voting, and seven survived the second round of voting. One was related to tissue acquisition for molecular testing, four were related to staging and stage documentation, one was related to smoking cessation counseling, and one was related to documentation of a performance status measure. The indicators were feasible and relevant within the practices assessed.

CONCLUSIONS:  We have defined seven process-of-care quality indicators related to the evaluation and staging of patients with lung cancer, which are felt to be valid, feasible, and relevant by lung cancer specialists.

Chest. 2014;146(3):670-679. doi:10.1378/chest.13-2568

BACKGROUND:  Lung cancer is the leading cause of cancer-related mortality. Surgical removal of the tumor at an early stage can be curative. However, lung cancer diagnosis at an early stage remains challenging. There is evidence that free fatty acids play a role in cancer development.

METHODS:  Serum samples from 55 patients with lung cancer were propensity matched with samples from 165 similar pulmonary patients without known cancer. Patients were propensity matched on age, sex, smoking history, family history of lung cancer, and chronic diseases that might affect free fatty acid levels.

RESULTS:  Free fatty acids arachidonic acid (AA) and linoleic acid (LA) and their metabolites hydroxyeicosatetraenoic acids (HETEs)(5-HETE, 11-HETE, 12-HETE, and 15-HETE) were an estimated 1.8- to 3.3-fold greater in 37 patients with adenocarcinoma vs 111 patients without cancer (all P < .001). Areas under the receiver operating characteristic curve were significantly > 0.50, discriminating patients with lung cancer and control subjects for six of eight biomarkers and two of seven phospholipids tested, and ranged between 0.69 and 0.82 (all P < .001) for patients with lung cancer vs control subjects. AA, LA, and 15-HETE had observed sensitivity and specificity > 0.70 at the best cutpoint. Concentrations of free fatty acids and their metabolites were similar in 18 patients with squamous cell carcinoma and 54 control subjects without cancer.

CONCLUSIONS:  Serum fatty acids and their metabolites demonstrate good sensitivity and specificity for the identification of adenocarcinoma of the lung.

Original Research: Imaging

Chest. 2014;146(3):680-685. doi:10.1378/chest.13-2306

BACKGROUND:  Electromyographic evaluation of diaphragmatic neuromuscular disease in patients with COPD is technically difficult and potentially high risk. Defining standard values for diaphragm thickness and thickening ratio using B-mode ultrasound may provide a simpler, safer means of evaluating these patients.

METHODS:  Fifty patients with a diagnosis of COPD and FEV1 < 70% underwent B-mode ultrasound. Three images were captured both at end expiration (Tmin) and at maximal inspiration (Tmax). The thickening ratio was calculated as (Tmax/Tmin), and each set of values was averaged. Findings were compared with a database of 150 healthy control subjects.

RESULTS:  There was no significant difference in diaphragm thickness or thickening ratio between sides within groups (control subjects or patients with COPD) or between groups, with the exception of the subgroup with severe air trapping (residual volume > 200%), in which the only difference was that the thickening ratio was higher on the left (P = .0045).

CONCLUSIONS:  In patients with COPD presenting for evaluation of coexisting neuromuscular respiratory weakness, the same values established for healthy control subjects serve as the baseline for comparison. This knowledge expands the role of ultrasound in evaluating neuromuscular disease in patients with COPD.

Original Research: Pulmonary Vascular Disease

Chest. 2014;146(3):686-708. doi:10.1378/chest.13-2634

BACKGROUND:  Health-related quality of life (HRQoL) is severely impaired in pulmonary arterial hypertension (PAH). We aimed to assess the effect of PAH-specific therapies on HRQoL.

METHODS:  A literature search was performed in MEDLINE and Embase databases (January 1990 to September 2013) to retrieve prospective placebo-controlled randomized trials of at least 6 weeks duration reporting the effect of PAH-specific therapies on HRQoL in adult patients with PAH. The articles were independently reviewed, and the validity of the trials was assessed using the Cochrane’s Risk of Bias Tool.

RESULTS:  The literature search identified 1,172 titles. Seventeen articles reporting on 14 trials were retrieved, all of which were associated with a low risk of bias. The median study duration of the different trials was 12 weeks. Most patients had idiopathic PAH or PAH associated with connective tissue disease. A variety of HRQoL questionnaires were used in these trials, and most were generic. HRQoL results were most commonly minimally detailed, and some pivotal trials did not even assess HRQoL. Nevertheless, these trials consistently demonstrated statistically significant improvements in HRQoL with PAH-specific therapies, especially for the physical domains. In most cases, however, these improvements were smaller than the minimal important difference in HRQoL previously reported in PAH.

CONCLUSION:  This review shows that PAH-specific therapies improve HRQoL in PAH. However, it remains difficult to draw any firm conclusion about the clinical significance of these improvements. Further work is mandatory to validate PAH-specific questionnaires that are responsive to clinical changes as well as to establish their interpretability.

Chest. 2014;146(3):709-718. doi:10.1378/chest.13-2988

BACKGROUND:  Patients with pulmonary arteriovenous malformations (PAVMs) are unusual because hypoxemia results from right-to-left shunting and not airway or alveolar disease. Their surprisingly well-preserved exercise capacity is not generally appreciated.

METHODS:  To examine why exercise tolerance is preserved, cardiopulmonary exercise tests were performed while breathing room air in 21 patients with radiologically proven PAVMs, including five restudied 3 to 12 months after embolization when their PAVMs had regressed. Where physiologic matching was demonstrable, comparisons were made with 12 healthy control subjects.

RESULTS:  The majority of patients achieved their predicted work rate despite a resting arterial oxygen saturation (Sao2) of 80% to 96%. Peak work rate and oxygen consumption (V. o2) were no lower in patients with more hypoxemia. Despite higher Sao2 following embolization (median, 96% and 90%; P = .009), patients achieved similar work rates and similar peak V. o2. Strikingly, treated patients reset to virtually identical peak oxygen pulses (ie, V. o2 per heart beat) and in many cases to the same point on the peak oxygen pulse/work rate plot. The 21 patients had increased minute ventilation (V. e) for given increases in CO2 production (V. e/V. co2 slope), but perceived dyspnea was no greater than in the 12 control subjects or in the same patients before compared to after embolization comparison. Overall, work rate and peak V. o2 were associated not with oxygenation parameters but with V. e/V. co2 slope, BMI, and anaerobic threshold.

CONCLUSIONS:  Patients with hypoxemia and PAVMs can maintain normal oxygen delivery/V. o2 during peak exercise. Following improvement of Sao2 by embolization, patients appeared to reset compensatory mechanisms and, as a result, achieved similar peak V. o2 per heart beat and peak work rates.

Original Research: Antithrombotic Therapy

Chest. 2014;146(3):719-726. doi:10.1378/chest.13-2976

BACKGROUND:  The efficacy and safety of anticoagulation with use of vitamin K antagonists (VKAs) is highly dependent on the quality of anticoagulation control as reflected by the average time in a therapeutic range of 2.0 to 3.0. A clinical dilemma is trying to predict which anticoagulation-naive patients with atrial fibrillation (AF) would do well on a VKA (with a time in therapeutic range > 70%) and which are less likely to do well on a VKA but could be managed with novel oral anticoagulants.

METHODS:  The cohort comprised 8,120 patients, among whom 4,637 patients were receiving VKA. We investigated whether the SAMe-TT2R2 (sex female, age < 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control], tobacco use [doubled], race [doubled]) score could discriminate among patients with AF who were likely to have a labile international normalized ratio (INR) during follow-up as well as stroke/thromboembolism (TE), clinically relevant bleeding (defined as severe bleeding and as Bleeding Academic Research Consortium [BARC]-defined major bleeding), and death while being treated with a VKA.

RESULTS:  During a mean follow-up of 1,016 ± 1,108 days, there was a significant increase in risk of severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P = .002) and a significant increase in risk of major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44; P = .0005) in patients with AF with a high SAMe-TT2R2 score (> 2). Increasing SAMe-TT2R2 score was associated with an increasing risk of labile INR (P = .004), stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P < .0001), and death (P = .002) at follow-up. Among the patients taking VKAs, the SAMe-TT2R2 score was predictive of labile INR (C statistic approximately 0.58) as well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C statistic, 0.54-0.57 for events), reflecting the suboptimal time in therapeutic range in such patients. This was not the case for patients who were not taking VKAs.

CONCLUSIONS:  We demonstrate that the SAMe-TT2R2 score was predictive for an increasing risk of stroke/TE, severe bleeding, major BARC bleeding, and death, reflecting poor anticoagulation control (and labile INRs) among patients with AF given VKAs.

Original Research: Education, Research, And Quality Improvement

Chest. 2014;146(3):727-734. doi:10.1378/chest.13-2828

BACKGROUND:  Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting.

METHODS:  Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process.

RESULTS:  We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future.

CONCLUSIONS:  This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

Chest. 2014;146(3):735-761. doi:10.1378/chest.13-2993

BACKGROUND:  The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. We describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination.

METHODS:  A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updated the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using the web-based Making GRADE the Irresistible Choice Guideline Authoring and Publication Platform.

RESULTS:  We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9 and condensed and restructured them into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best-practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates, and reevaluation of the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013.

CONCLUSIONS:  New strategies for adapting, updating, and disseminating trustworthy guidelines proved feasible and will provide Norwegian health-care professionals and patients with up-to-date guidance tailored to national circumstances.

Original Research: Bronchiectasis

Chest. 2014;146(3):762-774. doi:10.1378/chest.14-0126

BACKGROUND:  Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis.

METHODS:  Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter.

RESULTS:  Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators.

CONCLUSIONS:  AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

Original Research: Diffuse Lung Disease

Chest. 2014;146(3):775-785. doi:10.1378/chest.13-2388

BACKGROUND:  The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF.

METHODS:  We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups.

RESULTS:  There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses.

CONCLUSIONS:  Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF.

Original Research: Pulmonary Physiology

Chest. 2014;146(3):786-794. doi:10.1378/chest.14-0043

BACKGROUND:  Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners.

METHODS:  The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure.

RESULTS:  Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function.

CONCLUSIONS:  Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

Chest. 2014;146(3):795-803. doi:10.1378/chest.14-0166

BACKGROUND:  Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA.

METHODS:  Children with SMA aged < 10 years were recruited. FOT was performed every 3 months for 12 months (five visits). Spirometry and assisted and unassisted peak cough flow (PCF) were performed where possible. Polysomnography was performed on children with type 2 SMA. Clinical information included SMA type, chest infections, Cobb angle, medications, and mobility. Regression analysis assessed relationships between FOT and FVC, PCF, and apnea/hypopnea index (AHI). Analysis of variance sought relationships to clinical characteristics.

RESULTS:  Twelve children (seven male) were recruited; mean age was 6.26 (± 2.59) years. Respiratory reactance at 8 Hz (Xrs8) (mean z score, +1.41; SD, 1.90; P < .03) and respiratory resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P < .001) and Rrs8z score worsened (rate of change +0.51, P < .001). No relationship (P > .05) was found between clinical characteristics and FOT values.

CONCLUSIONS:  FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

Translating Basic Research Into Clinical Practice

Chest. 2014;146(3):804-812. doi:10.1378/chest.14-0439

Pulmonary TB remains a leading global health issue, but the current Bacille Calmette-Guérin (BCG) vaccine fails to control it effectively. Much effort has gone into developing safe and effective boost vaccine candidates for use after the BCG prime vaccination. To date, almost all the lead candidates are being evaluated clinically via a parenteral route. Abundant experimental evidence suggests that parenteral boosting with a virus-based vaccine is much less effective than respiratory mucosal boosting, because the former fails to activate a type of T cell capable of rapidly transmigrating into the airway luminal space in the early phase of the Mycobacterium tuberculosis infection. The next few years will determine whether parenteral boosting with some of the lead vaccine candidates, particularly the protein-based vaccines, improves protection in humans over that by BCG. Much effort is needed to develop respiratory mucosal boost vaccines and to identify the reliable immune protective correlates in humans.

Special Features

Chest. 2014;146(3):813-834. doi:10.1378/chest.14-0710

This article describes the curricular milestones and entrustable professional activities for trainees in pulmonary, critical care, or combined fellowship programs. Under the Next Accreditation System of the Accreditation Council for Graduate Medical Education (ACGME), curricular milestones compose the curriculum or learning objectives for training in these fields. Entrustable professional activities represent the outcomes of training, the activities that society and professional peers can expect fellowship graduates to be able to perform unsupervised. These curricular milestones and entrustable professional activities are the products of a consensus process from a multidisciplinary committee of medical educators representing the American College of Chest Physicians (CHEST), the American Thoracic Society, the Society of Critical Care Medicine, and the Association of Pulmonary and Critical Care Medicine Program Directors. After consensus was achieved using the Delphi process, the document was revised with input from the sponsoring societies and program directors. The resulting lists can serve as a roadmap and destination for trainees, program directors, and educators. Together with the reporting milestones, they will help mark trainees’ progress in the mastery of the six ACGME core competencies of graduate medical education.

Medical Ethics

Chest. 2014;146(3):835-840. doi:10.1378/chest.13-2909

  In the 13 years since their promulgation, the Health Insurance Portability and Accountability Act (HIPAA) rules and their enforcement have shown considerable evolution, as has the context within which they operate. Increasingly, it is the health information circulating outside the HIPAA-protected zone that is concerning: big data based on HIPAA data that have been acquired by public health agencies and then sold; medically inflected data collected from transactions or social media interactions; and the health data curated by patients, such as personal health records or data stored on smartphones. HIPAA does little here, suggesting that the future of health privacy may well be at the state level unless technology or federal legislation can catch up with state-of-the-art privacy regimes, such as the latest proposals from the European Commission.

Topics in Practice Management

Chest. 2014;146(3):841-847. doi:10.1378/chest.13-1875

Simple spirometry and body plethysmography have been routinely used in children aged > 5 years. New techniques based on physiologic concepts that were first described almost 50 years ago are emerging in research and in clinical practice for measuring pulmonary function in children. These techniques have led to an increased understanding of the pediatric lung and respiratory mechanics. Impulse oscillometry (IOS), a simple, noninvasive method using the forced oscillation technique, requires minimal patient cooperation and is suitable for use in both children and adults. This method can be used to assess obstruction in the large and small peripheral airways and has been used to measure bronchodilator response and bronchoprovocation testing. New data suggest that IOS may be useful in predicting loss of asthma control in the pediatric population. This article reviews the clinical applications of IOS, with an emphasis on the pediatric setting, and discusses appropriate coding practices for the clinician.

Contemporary Reviews in Critical Care Medicine

Chest. 2014;146(3):848-857. doi:10.1378/chest.13-2645

The medical community has used implantable mechanical circulatory support devices at increasing rates for patients dying from heart failure and cardiogenic shock. Newer-generation devices offer a more durable and compact option when compared with bulky early-generation devices. This article is a succinct introduction and overview of the hemodynamic principles and complications after device implantation for ICU clinicians. We review the concepts of device physiology, clinical pearls for perioperative management, and common medical complications after device implantation.

Contemporary Reviews in Sleep Medicine

Chest. 2014;146(3):858-868. doi:10.1378/chest.13-1778

Adaptive servoventilation (ASV) is an automated treatment modality used to treat many types of sleep-disordered breathing. Although default settings are available, clinician-specified settings determined in the sleep laboratory are preferred. Depending on the device, setting choices may include a fixed expiratory positive airway pressure (EPAP) level or a range for autotitrating EPAP; minimum and maximum inspiratory positive airway pressure or pressure support values; and type of backup rate algorithm or a selectable fixed backup rate. ASV was initially proposed for treatment of central sleep apnea and Hunter-Cheyne-Stokes breathing associated with congestive heart failure (CHF), and numerous observational studies have demonstrated value in this setting. Other studies have reported varying efficacy in patients with complex sleep apnea syndromes, including those with mixtures of obstructive and central sleep-disordered breathing associated with CHF, renal failure, or OSA with central apneas developing on conventional positive airway pressure therapy. Patients with opioid-induced sleep apnea, both obstructive and central, may also respond to ASV. The variability in response to ASV in a given patient along with the myriad choices of specific models and settings demand a high degree of expertise from the clinician. Finally, randomized controlled studies are needed to determine long-term clinical efficacy of these devices.


Chest. 2014;146(3):869-870. doi:10.1378/chest.14-0031

—Hi, it’s Dr. R…How can I help you?
My cough came back.
—Do you want that same medicine?
Yup. Can you refill it?
—Yes, Same drug?
—4 times a day?
—Take as needed only.
—One refill?
—Did it work last time?
Yup, but the cough came back.
—So you want to refill it?
—Same as before?
—Anything else?
Nope, just that medicine.
—Picking it up today?
Today is fine.
—I’ll write for 4 ounces.
Good; same as before?
—Same as before.
Feel better.
—Hi, it’s Dr. R…How can I help you?
My cough came back.
—OK what’s it like?
Well I don’t want to exaggerate;
it is certainly not like what Keats had in Rome,
treated as he was with a diet of anchovy and a piece of daily bread.
Hemorrhaging blood, they even bled him on top of that.
All he wanted was some opium,
not really to end his cough, which after all was
tuberculous, but really to kill himself.
No, my cough is more irritative, reflexive to humors coming in,
like the cough of Dylan Thomas,
which was of course worsened by New York smog and irish whisky,
his ACTH injections and the morphine
—I see. It sounds to me more like a hybrid of Kafka’s laryngeal cough
and Rousseau’s prolific catarrh.
Yes, exactly.
—OK, I’ll call in a prescription.
Feel better.
—Hi, it’s Dr R…How can I help you?
Doctor, thank God you called.
I have the most ungodly cough again.
God knows I prayed and prayed it would
never come back like, you know,
Rita’s did. It wakes up the angels at night. It blasts
trumpets to the heavens. So now
I pray to God I won’t get pneumonia
like my brother-in-law had.
I’ve tried everything. Oh my God,
nothing’s worked, I coughed all
during the service this morning,
had to leave early, in front of my
so religious sister-in-law…
I was wicked embarrassed, God forgive me.
—I see.
By God do you mean the detached transcendent demiurge of
Aristotle or the pantheism of Spinoza?
I mean the ontological spiritualism
of Aquinas and Augustine, yet also nurtured
by Islamic neoplatonism.
—I understand, that’s helpful.
I’ll call in a prescription.
Feel better.

Chest. 2014;146(3):871. doi:10.1378/chest.13-3009

After the code,
a perfusing rhythm
back and a new
chest tube to suction,
my chief offered
some feedback on
my central line:
the needle was
in the wrong place,
just like me.

Chest. 2014;146(3):871. doi:10.1378/chest.14-0205

North for my tenth summer.
Auntie positions my brush: Look
with the eye, sketch what you see.
You’re too thin, she fusses and fries
Moon Over Miami, its ochre yolks ascendant
in a sky of red bologna & seared toast.
My chewed nails, she overlooks,
my calluses that cushion my pen when I write,
my teeth marks on fingers sucked for comfort.
Clouds on my nail beds? She tallies:
You have seven secret loves!
Like her sables, her fingertips splay,
and flirt as they plait braids,
and flit between canvas and stove.
In a cabana at the lake, I spy her surgical scar.
I long to soothe its jagged threads. Decades later,
she’ll die alone, B-movie on TV, last cigarette
smoldered to ash in her fingers, her fridge nearly bare:
one egg, a slice of bread, a dried salami curl.
Everywhere paintings. Her last work: shirt soaked red
as if scalpel sliced from breastbone to scapula
to expose rosebuds, tightly furled.

Chest. 2014;146(3):872. doi:10.1378/chest.14-0228

In the doctor’s shining enamel castle
the physician’s assistant taps your vein,
pushes your heart, listening deeply to the fog
flowing in & out of the darkened harbor
of your chest. She dresses you down
for an EKG, sensing your pale, naked fear.
She attaches you to an asthma tube
yet after all this, there’s still no answer.
It’s midday now after months of illness
and the tight net of winter has lifted its grip
yet still there creeps the familiar guilt:
the halting thought that you’ve abandoned
the grand duties of work for another fruitless trip.
On the long drive home, the busy policeman of your life
watches the faces of crossing guards
searching for signs of judgment.
Instead, you discover a carnival: the Haitian lady
in speckled eyeshadow twirls a long feather boa.
A Navy veteran shepherds lost children
through the sea of traffic. Pass by now, he says.
   Pass on by, little ones.
The oceans part, you breathe and contort,
tossing up curses at the cloud of unknowing
and the brutal thump-thump of the man upstairs,
until at last, in spite of yourself, you arrive home safely
and at the end of it all, you find words of comfort
traveling down the telephone line:
An old Quaker friend – her voice clear as light–
offers what truth this day demands:
  To find the reason for your illness,
  go deeper, she says, go down to the root.

Ultrasound Corner

Chest. 2014;146(3):e78-e80. doi:10.1378/chest.13-2977

A woman in her 80s with hypertension and dyslipidemia was seen in the ED complaining of progressive dyspnea for 3 days. She was found to be tachypneic and hypoxemic and was admitted to the internal medicine service with a provisional diagnosis of heart failure. A thoracic CT scan revealed small bilateral pleural effusions, a small pericardial effusion, and no evidence of pulmonary embolism (PE). She was treated with diuretics and afterload reduction.

Selected Reports

Chest. 2014;146(3):e81-e83. doi:10.1378/chest.13-2795

Pulmonary hypertension (PH) is a known complication of Gaucher disease (GD) and splenectomy. Although it resembles World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH), PH due to GD or splenectomy is part of WHO group 5. There are no clinical trials testing therapies in PH due to GD or splenectomy. Several reports suggest that PAH-specific therapies are beneficial in patients with PH due to GD, although data are insufficient to formulate a treatment algorithm for these patients. The tyrosine kinase inhibitor imatinib has been investigated in the treatment of severe PAH, but not in PH WHO group 5. We report a patient with GD and splenectomy who developed PH that progressed while on conventional PAH-specific therapy and improved once imatinib was added to her treatment regimen. This is the first report, to our knowledge, describing significant subjective and objective improvements in response to imatinib in a patient with WHO group 5 PH.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2014;146(3):e84-e87. doi:10.1378/chest.14-0251
Chest. 2014;146(3):e88-e91. doi:10.1378/chest.14-0283

A 56-year-old man presented to the ED of an outside hospital with 2 days of bleeding gums and easy bruising. He denied episodes of melena, hematemesis, or hematuria and had no epistaxis. Routine blood work showed pancytopenia and evidence of diffuse intravascular coagulation. A bone marrow biopsy confirmed the diagnosis of acute promyelocytic leukemia. He was transferred to our hospital for treatment.

Chest Imaging and Pathology for Clinicians

Chest. 2014;146(3):e92-e96. doi:10.1378/chest.13-2790

A 54-year-old man was referred with nonresolving pneumonia. He had been treated for community-acquired pneumonia 6 weeks earlier. He reported grade 2 dyspnea, malaise, and a nonproductive cough. He had also experienced three episodes of minimal hemoptysis but denied weight loss, fever, or any other constitutional symptoms. He was a nonsmoker and was being treated for dyslipidemia.


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