Chest. 2017;151(2):245-246. doi:10.1016/j.chest.2016.11.042

The first Global Initiative for Chronic Obstructive Lung Disease (GOLD) report was published in 2001 and has since undergone several updates, with a major revision in 2011 that introduced the ABCD assessment tool to guide initial therapy. This scheme added symptoms (eg, dyspnea) and history of exacerbations to severity measured by using FEV1 to decide on initial therapy; however, many practicing clinicians found it confusing because both spirometry and exacerbation history were considered together. Furthermore, the A-D classification does not seem to perform any better than spirometric grades in predicting serious clinical outcomes such as mortality. The new GOLD 2017 Report has now clarified this situation by separating the spirometric severity from the A-D categories, which are determined according to symptoms and exacerbation history. This change was made because FEV1 measurements have little impact on choice of therapy and are important mainly in initial diagnosis and assessing long-term progression but not for choice of, and response to, therapy.

Chest. 2017;151(2):247-248. doi:10.1016/j.chest.2016.08.1433

Inpatient care for patients with sepsis has placed a substantial and growing burden on health-care systems. Between 1980 and 2000, there was a threefold increase in sepsis incidence. Sepsis is now the most costly hospital condition and the most common diagnosis among patients receiving intensive care. Sepsis also causes significant morbidity and mortality and contributes to one in every two to three hospital deaths. Because of its health-care burden, high mortality, and evidence showing that an early sepsis treatment bundle significantly improves patient outcomes, the Centers for Medicare and Medicaid Services have adopted sepsis care as part of its core inpatient performance measurement program.

Chest. 2017;151(2):249-251. doi:10.1016/j.chest.2016.06.033

Despite advances in asthma initiatives, there continues to be a large population of patients with severe asthma whose condition remains uncontrolled despite the use of inhaled combination corticosteroids and long-acting beta-agonist treatment. For this population, which may include as many as one-third of all patients with asthma, biological therapy is often a treatment consideration in specialist clinics. In contemporary asthma care, and in the scope of this paper, the term “biological agent” indicates the use of a monoclonal antibody. In an attempt to avoid the side effects of oral corticosteroid therapy, specialists often feel obligated to add this therapeutic option. With an anticipated influx of monoclonal antibody therapies soon to come to market, the necessity of appropriately stratifying patients prior to initiating such therapy is of paramount necessity. It is important to recognize that following accepted prescribing criteria does not necessarily equate to anticipated clinical response. Omalizumab provides a prime example in which, based on current prescribing criteria, as many as one-half of the patients who are administered the medication may be poor responders. Postmarket studies of omalizumab suggest that other phenotypic markers such as exhaled fractional nitrous oxide, periostin, and blood eosinophil levels better define predicted response to therapy.

Chest. 2017;151(2):252-254. doi:10.1016/j.chest.2016.08.1453

Management of patients with ground-glass nodules (GGNs) is a common clinical issue. Retrospective surgical series demonstrate that these are primarily lepidic predominant adenocarcinomas, minimally invasive adenocarcinoma, and adenocarcinoma in situ., Although many studies suggest that these cancers have a less aggressive behavior,, we lack good management protocols.

Topics: lung cancer

Editorials: Point and Counterpoint

Chest. 2017;151(2):255-257. doi:10.1016/j.chest.2016.09.041

First let me start by saying that I truly enjoy practicing pulmonary, critical care, and sleep medicine. I entered the field of medicine for all of the same reasons that most other individuals chose the profession: The ability to make a difference in the lives of others, intellectual curiosity, and lifelong learning. I have experienced the practice of medicine in several different clinical settings, including a brief career in academic medicine, 12 years in private practice, and currently as an employed physician.

Topics: lung
Chest. 2017;151(2):257-259. doi:10.1016/j.chest.2016.09.042

Concierge medicine is a form of direct patient contracting in which patients are responsible for payment of an annual fee for enhanced medical services and greater face-to-face physician contact. Direct patient contracting practices have a variety of names: membership medicine, boutique, retainer, direct primary care, and direct subspecialty care. Compounding the nomenclature, significant variability exists in how these practices are structured. Although limited in frequency (grossly estimated to represent 3%-6% of total practices) and geographic distribution, these practices are promoted as innovative alternatives to traditional insurance-based care (Fig 1).,, From the patient’s perspective, the purported advantages include greater physician contact, transparency in costs, and the potential for additional amenities and personalized services. Physicians may find this arrangement advantageous due to the reduced administrative burden, smaller patient panels, consistency in reimbursement, less burnout, and greater work satisfaction. In this Counterpoint editorial, we argue that pulmonary concierge practices require careful consideration and additional unbiased study before their widespread implementation. Despite the obvious benefits, these practices have inherent disadvantages and downstream consequences.

Topics: lung
Chest. 2017;151(2):259-260. doi:10.1016/j.chest.2016.09.043

Although I agree with many of the arguments by Foreman et al on why we should consider limiting the expansion of concierge pulmonary medicine, current and near-future changes in reimbursement and delivery care models will force physicians to make difficult choices on how they practice.

Chest. 2017;151(2):260-261. doi:10.1016/j.chest.2016.09.044

We agree with Dr Freedman’s assessment that disparate pressures have transformed medical practice, in which the notion of a traditional private medical practice is now an antiquated option. The modern paradigm finds that more physicians are employees rather than independent practitioners, administratively managed to achieve financial and other metrics. Loss of control, greater job dissatisfaction, and economic, bureaucratic, and other pressures on practicing physicians have trickled down to influence the career choices of medical students. Medical students consider lifestyle impact, a major criterion, when making ultimate career selections. The motivations that entice physicians to consider practicing concierge medicine have been well articulated in the accompanying Point debate, but the effect on patients and public health is largely unknown and not addressed.

Commentary: Ahead of the Curve

Chest. 2017;151(2):262-277. doi:10.1016/j.chest.2016.10.008

Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age. In particular, acetate, adenosine, alanine, hippurate, succinate, threonine, and trans-aconitate, and pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were all identified as significant in at least two studies. There were also a number of nonreplicated results; however, the literature is not yet sufficiently developed to determine whether these represent spurious findings or reflect the substantial heterogeneity and limited statistical power in the studies and their methods to date. This review highlights the need for additional asthma metabolomic studies to explore these issues, and, further, the need for standardized methods in the way these studies are conducted. We conclude by discussing the potential of translation of these metabolomic findings into clinically useful biomarkers and the crucial role that integrated omics is likely to play in this endeavor.

Original Research: Critical Care Medicine

Chest. 2017;151(2):278-285. doi:10.1016/j.chest.2016.07.010

Background  Reports that septic shock incidence is rising and mortality rates declining may be confounded by improving recognition of sepsis and changing coding practices. We compared trends in septic shock incidence and mortality in academic hospitals using clinical vs claims data.

Methods  We identified all patients with concurrent blood cultures, antibiotics, and vasopressors for ≥ two consecutive days, and all patients with International Classification of Diseases, 9th edition (ICD-9) codes for septic shock, at 27 academic hospitals from 2005 to 2014. We compared annual incidence and mortality trends. We reviewed 967 records from three hospitals to estimate the accuracy of each method.

Results  Of 6.5 million adult hospitalizations, 99,312 (1.5%) were flagged by clinical criteria, 82,350 (1.3%) by ICD-9 codes, and 44,651 (0.7%) by both. Sensitivity for clinical criteria was higher than claims (74.8% vs 48.3%; P < .01), whereas positive predictive value was comparable (83% vs 89%; P = .23). Septic shock incidence, based on clinical criteria, rose from 12.8 to 18.6 cases per 1,000 hospitalizations (average, 4.9% increase/y; 95% CI, 4.0%-5.9%), while mortality declined from 54.9% to 50.7% (average, 0.6% decline/y; 95% CI, 0.4%-0.8%). In contrast, septic shock incidence, based on ICD-9 codes, increased from 6.7 to 19.3 per 1,000 hospitalizations (19.8% increase/y; 95% CI, 16.6%-20.9%), while mortality decreased from 48.3% to 39.3% (1.2% decline/y; 95% CI, 0.9%-1.6%).

Conclusions  A clinical surveillance definition based on concurrent vasopressors, blood cultures, and antibiotics accurately identifies septic shock hospitalizations and suggests that the incidence of patients receiving treatment for septic shock has risen and mortality rates have fallen, but less dramatically than estimated on the basis of ICD-9 codes.

Chest. 2017;151(2):286-297. doi:10.1016/j.chest.2016.11.029

Background  ICU telemedicine improves access to high-quality critical care, has substantial costs, and can change financial outcomes. Detailed information about financial outcomes and their trends over time following ICU telemedicine implementation and after the addition of logistic center function has not been published to our knowledge.

Methods  Primary data were collected for consecutive adult patients of a single academic medical center. We compared clinical and financial outcomes across three groups that differed regarding telemedicine support: a group without ICU telemedicine support (pre-ICU intervention group), a group with ICU telemedicine support (ICU telemedicine group), and an ICU telemedicine group with added logistic center functions and support for quality-care standardization (logistic center group). The primary outcome was annual direct contribution margin defined as aggregated annual case revenue minus annual case direct costs (including operating costs of ICU telemedicine and its related programs). All monetary values were adjusted to 2015 US dollars using Producer Price Index for Health-Care Facilities.

Results  Annual case volume increased from 4,752 (pre-ICU telemedicine) to 5,735 (ICU telemedicine) and 6,581 (logistic center). The annual direct contribution margin improved from $7,921,584 (pre-ICU telemedicine) to $37,668,512 (ICU telemedicine) to $60,586,397 (logistic center) due to increased case volume, higher case revenue relative to direct costs, and shorter length of stay.

Conclusions  The ability of properly modified ICU telemedicine programs to increase case volume and access to high-quality critical care with improved annual direct contribution margins suggests that there is a financial argument to encourage the wider adoption of ICU telemedicine.

Chest. 2017;151(2):298-307. doi:10.1016/j.chest.2016.09.003

Background  The Quality of Dying and Death (QODD) questionnaire is used as a self-reported measure to allow families and clinicians to assess patients’ quality of dying and death. We evaluated end-of-life (EOL) experiences as measured by the QODD completed by families and nurses in the United States and the Netherlands to explore similarities and differences in these experiences and identify opportunities for improving EOL care.

Methods  Questionnaire data were gathered from family members of patients dying in the ICU and nurses caring for these patients. In The Netherlands, data were gathered in three teaching hospitals, and data was gathered from 12 sites participating in a randomized trial in the United States. The QODD consists of 25 items and has been validated in the United States.

Results  Data from 446 patients were analyzed (346 in the United States and 100 in the Netherlands). Dutch patients were older than those in the United States (72 + 10.2 years vs 65 + 16.0 years; P < .0025). The family-assessed overall QODD score was the same in both countries: the Netherlands = median, 9; interquartile range (IQR), 8-10 and the United States = median, 8; IQR, 5-10. US family members rated the quality of two items higher than did the Netherlands families: “time spent with loved ones” and “time spent alone.” Nurse-assessed QODD ratings varied: the single-item QODD summary score was significantly higher in the Netherlands (the Netherlands: median, 9; IQR, 8-10 vs the United States: median, 7; IQR, 5-8; P < .0025), whereas the QODD total score was higher in the United States (the Netherlands: median, 6.9; IQR, 5.5-7.6 vs the United States: median, 7.1; IQR, 5.8-8.4; P = .014), although it did not meet our criteria for statistical significance. Of the 22 nurse-assessed items, 10 were significantly different between the Netherlands and the United States, with eight having higher scores in the United States and 2 having higher scores in the Netherlands.

Conclusions  The QODD was rated similarly by family members in the United States and the Netherlands but varied when assessed by nurses. These differences may be due to organizational or cultural differences between the two countries or to expectations of respondents.

Original Research: Lung Cancer

Chest. 2017;151(2):308-315. doi:10.1016/j.chest.2016.07.007

Background  The long-term outcomes of follow-up care for ground-glass opacity (GGO) lesions need to be clarified.

Methods  Between 2000 and 2005, a total of 226 patients with pure or mixed GGO lesions ≤ 3 cm in size were registered. The CT findings and changes in the findings during the follow-up period and the outcomes of the 226 patients were subsequently reviewed.

Results  Overall, 124 patients underwent resections, 57 did not receive follow-up examinations after 68 months because of stable disease or disease reduction, and 45 are continuing to receive follow-up examinations. Thirty-nine patients exhibited tumor growth during the follow-up period. Among the patients with a ratio of the diameter of consolidation relative to the tumor diameter (CTR) > 0, all cases with tumor growth were identified within 3 years; meanwhile, > 3 years were required to identify tumor growth in 16% of the patients with a CTR of 0. Aggressive cancer occurred in 4% of patients with a CTR of 0 and in 70% of patients with a CTR > 25%. Aggressive cancer was observed in 46% of the patients whose CTR increased during the follow-up period and in 8% of the patients whose tumors increased in size.

Conclusions  A higher CTR and an increase in CTR during follow-up were associated with invasive cancer. A follow-up period of 3 years is considered to be adequate for judging tumor growth in patients with a CTR > 0, whereas a longer follow-up period might be needed for patients with a CTR of 0.

Chest. 2017;151(2):316-328. doi:10.1016/j.chest.2016.09.017

Background  An optimal method of preoperative localization for pulmonary nodules has yet to be established. This systematic review and meta-analysis aimed to compare the success and complication rates associated with three pulmonary nodule localization methods for video-assisted thoracoscopic surgery (VATS): hook-wire localization, microcoil localization, and lipiodol localization.

Methods  We searched the PubMed, MEDLINE, and EMBASE databases for prospective or retrospective English language studies of VATS localization in adult patients. A noncomparative, random effects model–based meta-analysis was performed to obtain pooled success and complication rates for the three localization methods.

Results  A total of 46 clinical studies were enrolled, including 30, 9, and 7 studies of hook-wire, microcoil, and lipiodol localization, respectively. The successful targeting rates for hook-wire, microcoil, and lipiodol localization were 0.98 (95% CI, 0.97-0.99), 0.98 (95% CI, 0.96-0.99), and 0.99 (95% CI, 0.98-1.00), respectively, with corresponding successful operative field targeting rates of 0.94 (95% CI, 0.91-0.96), 0.97 (95% CI, 0.95-0.98), and 0.99 (95% CI, 0.98-1.00), respectively. In addition, the successful VATS rates with hook-wire, microcoil, and lipiodol localization were 0.96 (95% CI, 0.94-0.97), 0.97 (95% CI, 0.94-0.99), and 0.99 (95% CI, 0.98-1.00), respectively. Regarding complications, hook-wire, microcoil, and lipiodol localization were associated with pneumothorax rates of 0.35 (95% CI, 0.28-0.43), 0.16 (95% CI, 0.07-0.34), and 0.31 (95% CI, 0.20-0.46), respectively and hemorrhage rates of 0.16 (95% CI, 0.11-0.23), 0.06 (95% CI, 0.03-0.11), and 0.12 (95% CI, 0.05-0.23), respectively.

Conclusions  All three localization methods yielded similarly highly successful targeting rates. However, hook-wire localization had a relatively lower successful operative field targeting rate because of dislodgement or migration. Lipiodol localization had the highest overall success rate, and microcoil localization yielded the lowest complication rates.

Chest. 2017;151(2):329-339. doi:10.1016/j.chest.2016.09.008

Background  The positive impact of hospital operative volume on outcomes following video-assisted thoracoscopic surgery has been established. The goal of this study was to determine whether or not this volume/outcome relationship translates to robot-assisted thoracoscopic surgery (RobATS) lobectomy.

Methods  Patients who underwent RobATS lobectomy were identified between 2008 and 2013 in the Healthcare Cost and Utilization Project National Inpatient Sample database. Hospital volume, as well as demographic, clinical, and health-care system-related factors were selected as potential predictors of outcomes. Outcome variables included length of stay (LOS), inpatient mortality, and complications. Hospitals were designated by quartiles according to annual case volume, with very low-volume defined as the first quartile and high-volume defined as the fourth quartile. Regression analyses were used to identify independent predictors of the outcomes of interest.

Results  A total of 8,253 RobATS lobectomies were identified. Compared with very low-volume centers, patients at high-volume hospitals had a shorter mean LOS (5.8 vs 6.5 days; P = .001) and decreased mortality rate (0.5% vs 1.9%; P < .001) but more complications (28.1% vs 27.6%; P = .025). In multivariable analysis, high hospital volume was prognostic for decreased mortality (OR, 0.134; P< .001) and shorter LOS (0.2 days; SE, 0.05; P<.001). Hospital volume was not prognostic for any complications, including pulmonary, cardiovascular, intraoperative, or infectious complications.

Conclusions  Undergoing lobectomy at high-volume RobATS centers confers favorable mortality and LOS outcomes compared with very low-volume centers. In this relatively early phase of adoption of RobATS, the long-term clinical impact of differences in LOS as well as the lack of clinical impact on the incidence of complications remain to be determined more definitively. However, the beneficial effect of volume on mortality suggests a need for the careful adoption of this promising technology.

Original Research: COPD

Chest. 2017;151(2):340-357. doi:10.1016/j.chest.2016.11.028

Background  Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) combinations are a treatment option for patients with COPD who continue to have symptoms despite treatment with a LAMA or a LABA alone. The Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-1) (NCT01854645) and the Multi-Center Study to Assess the Efficacy and Safety of PT003, PT005, and PT001 in Subjects with Moderate-to-Very Severe COPD (PINNACLE-2) (NCT01854658) trials investigated the efficacy and safety of a novel glycopyrrolate [GP]/formoterol [FF] 18/9.6-μg (GFF) metered dose inhaler (MDI) formulated using the Co-Suspension Delivery Technology in patients with moderate-to-very severe COPD.

Methods  These two phase III trials took place over 24 weeks and were randomized, double blind, and placebo controlled; 2,103 and 1,615 patients (40-80 years of age), respectively, were randomized. Patients received GFF MDI, GP MDI 18 μg, FF MDI 9.6 μg, or placebo MDI (all twice daily), or tiotropium 18 μg dry powder inhaler (once daily in PINNACLE-1 only [open-label active comparator]). Efficacy and safety were assessed.

Results  At week 24, differences in change from baseline in the morning predose trough FEV1 for GFF MDI vs placebo MDI, GP MDI, and FF MDI were 150 mL, 59 mL, and 64 mL in PINNACLE-1 (all P < .0001) and 103 mL, 54 mL, and 56 mL in PINNACLE-2 (all P < .001), respectively. There were no significant safety findings (incidence of adverse events was similar between treatment arms).

Conclusions  We conclude that GFF MDI 18/9.6 μg demonstrated superiority over placebo and monocomponent MDIs and was well tolerated, thus providing an additional treatment option for patients with moderate-to-very severe COPD.

Trial Registry  ClinicalTrials.gov; No.: NCT01854645 and No. NCT01854658; URL: www.clinicaltrials.gov.

Chest. 2017;151(2):358-365. doi:10.1016/j.chest.2016.10.044

Background  The clinical characteristics of patients with emphysema but without airway limitations remain unknown. The goal of this study was to compare the clinical features of current and former smokers without airflow limitation who have radiologic emphysema on chest CT scans vs a control group of current and ex-smokers without emphysema.

Methods  Subjects enrolled had anthropometric characteristics recorded, provided a medical history, and underwent low-dose chest CT scanning. The following parameters were also evaluated: pulmonary function tests including diffusion capacity for carbon monoxide (Dlco), the modified Medical Research Council dyspnea score, COPD assessment test (CAT), and 6-min walk test (6MWT). A comparison was conducted between those with and without CT-confirmed emphysema.

Results  Of the 203 subjects, 154 had emphysema, and 49 did not. Adjusted group comparisons revealed that a higher proportion of patients with emphysema according to low-dose chest CT scanning had an abnormal Dlco value (< 80%) (46% vs 19%; P = .02), a decrease in percentage of oxygen saturation > 4% during the 6MWT (8.5% vs 0; P = .04), and an altered quality of life (CAT score ≥ 10) (32% vs 14%; P = .01). A detailed analysis of the CAT questionnaire items revealed that more patients with emphysema had a score ≥ 1 in the “chest tightness” (P = .05) and “limitation when doing activities at home” (P < .01) items compared with those with no emphysema. They also experienced significantly more exacerbations in the previous year (0.19 vs 0.04; P = .02).

Conclusions  A significant proportion of smokers with emphysema according to low-dose chest CT scanning but without airway limitation had alterations in their quality of life, number of exacerbations, Dlco values, and oxygen saturation during the 6MWT test.

Chest. 2017;151(2):366-373. doi:10.1016/j.chest.2016.10.003

Background  A subset of patients with COPD demonstrates eosinophilic inflammation either in their sputum or blood. Previous studies regarding the association between increased blood eosinophil levels and poor readmission outcomes are conflicting. The goal of this study was to investigate outcomes following severe COPD exacerbations in patients with higher blood eosinophil levels.

Methods  With an observational study design, data on hospitalizations for severe COPD exacerbation were retrospectively gathered. Patient health data previous to and up to 1 year following the index hospitalization were included. Patients were stratified into the eosinophilic group if the blood eosinophil level on admission was ≥ 200 cells/μL and/or ≥ 2% of the total WBC count. Clinical outcomes were 12-month COPD-related readmission, 12-month all-cause readmission, length of stay, and time to COPD-related readmission. These outcomes were analyzed by using logistic, negative binomial, and Cox regression models.

Results  A total of 167 patients were included; 55 had eosinophilia. Eosinophilia was associated with an increased risk of 12-month COPD-related readmission (OR, 3.59 [95% CI, 1.65-7.82]; P = .0013), an increased risk of 12-month all-cause readmission (2.32 [95% CI, 1.10-4.92]; P = .0277), and a shorter time to first COPD-related readmission (hazard ratio, 2.74 [1.56-4.83]; P = .0005). The length of stay was not statistically different between eosinophilic and noneosinophilic patients. Sensitivity analyses using different eosinophilia definitions revealed a proportional increase in effect size with increasing eosinophil cell count definitions for predicting 12-month readmissions.

Conclusions  Blood eosinophil levels can be used as a biomarker in severe COPD exacerbations for predicting higher readmission rates.

Original Research: Imaging

Chest. 2017;151(2):374-382. doi:10.1016/j.chest.2016.10.039

Background  Some studies suggest that lung ultrasonography could be useful for diagnosing pneumonia; moreover, it has a more favorable safety profile and lower cost than chest radiography and CT. The aim of this study was to assess the accuracy of bedside lung ultrasonography for diagnosing pneumonia in adults through a systematic review and meta-analysis.

Methods  We searched MEDLINE, Scopus, The Cochrane Library, Web of Science, DARE, HTA Database, Google Scholar, LILACS, ClinicalTrials.gov, TESEO, and OpenGrey. In addition, we reviewed the bibliographies of relevant studies. Two researchers independently selected studies that met the inclusion criteria. Quality of the studies was assessed in accordance with the Quality Assessment of Diagnostic Accuracy Studies tool. The summary receiver operating characteristic (SROC) curve and a pooled estimation of the diagnostic odds ratio (DOR) was estimated using a bivariate random-effects analysis. The sources of heterogeneity were explored using predefined subgroup analyses and bivariate meta-regression.

Results  Sixteen studies (2,359 participants) were included. There was significant heterogeneity of both sensitivity and specificity according to the Q test, without clear evidence of threshold effect. The area under the SROC curve was 0.93, with a DOR at the optimal cutpoint of 50 (95% CI, 21-120). A tendency toward a higher area under the SROC curve in high-quality studies was detected; however, these differences were not significant after applying the bivariate meta-regression.

Conclusions  Lung ultrasonography can help accurately diagnose pneumonia, and it may be promising as an adjuvant resource to traditional approaches.

Original Research: Bronchiectasis

Chest. 2017;151(2):383-388. doi:10.1016/j.chest.2016.09.022

Background  Interest in the association of vascular disease with COPD and pneumonia has increased, but there is a lack of research in this area with patients with bronchiectasis.

Methods  A retrospective study of 400 patients attending a specialist bronchiectasis clinic in NHS Lothian (Edinburgh, UK) between May 2013 and September 2014 was conducted. The study assessed the prevalence of vascular disease (ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and atrial fibrillation). Using multivariable models, independent risk factors were identified for vascular disease that developed following the diagnosis of bronchiectasis.

Results  The study included 400 patients. There was preexisting vascular disease (ie, before the diagnosis of bronchiectasis) in 44 patients (11%), and vascular disease occurred after the diagnosis of bronchiectasis after a mean of 9.4 years (95% CI, 6.0-12.8 years) in 45 patients (11%). Independent factors associated with all-cause vascular disease after the diagnosis of bronchiectasis included male sex, hypertension, receiving long-term statin therapy, and having moderate-severity bronchiectasis or worse.

Conclusions  In conclusion, bronchiectasis severity is independently associated with the development of vascular disease after the diagnosis of bronchiectasis. Future studies addressing the impact of primary and secondary prevention are warranted.

Original Research: Diffuse Lung Disease

Chest. 2017;151(2):389-399. doi:10.1016/j.chest.2016.09.028

Background  Surgical lung biopsy (SLB) is invasive and not possible in all patients with undiagnosed interstitial lung disease (ILD). We hypothesized that transbronchial biopsy (TBB) findings combined with clinical and high-resolution CT (HRCT) data leads to a confident diagnosis congruent to SLB and therefore avoids the need for SLB in some patients.

Methods  We evaluated 33 patients being investigated for suspected ILD who underwent HRCT, TBB, and SLB. First, clinicians, radiologists, and a pathologist reviewed the clinical information and HRCT and TBB findings. Clinicians were asked to provide a diagnosis and were also asked if SLB was needed for a more confident diagnosis. Subsequently, the clinical, HRCT, and SLB data were reviewed, and the same participants were asked to provide a final diagnosis. Clinician consensus and overall agreement between TBB- and SLB-based diagnoses were calculated.

Results  Four patients had definite usual interstitial pneumonia (UIP) on HRCT and would not be considered for biopsy using current guidelines. Of the 29 patients without a definitive HRCT diagnosis, the clinicians felt confident of the diagnosis (ie, would not recommend SLB) in six cases. In these cases, there was 100% agreement between TBB and SLB diagnoses. UIP was the most common diagnosis (n = 3) and was associated with an HRCT diagnosis of possible UIP/nonspecific interstitial pneumonia-like. Agreement was poor (33%) between TBB and SLB diagnoses when confidence in the TBB diagnosis was low.

Conclusions  Information from TBB, when combined with clinical and HRCT data, may provide enough information to make a confident and accurate diagnosis in approximately 20% to 30% of patients with ILD.

Chest. 2017;151(2):400-408. doi:10.1016/j.chest.2016.09.002

Background  Diagnostic evaluation of patients with diffuse parenchymal lung disease (DPLD) is best achieved by a multidisciplinary team correlating clinical, radiological, and pathologic features. Surgical lung biopsy remains the gold standard for histopathologic diagnosis of idiopathic interstitial pneumonias. Emerging data suggest an increasing role for transbronchial cryobiopsy (TBC) in DPLD evaluation. We describe our experience with TBC in patients with DPLD.

Methods  We retrospectively reviewed medical records of patients with radiographic features of DPLD who underwent TBC at Mayo Clinic in Rochester, Minnesota from June 2013 to September 2015.

Results  Seventy-four patients (33 women [45%]) with a mean age of 63 years (SD, 13.8) were included. The mean maximal diameter of the samples was 9.2 mm (range, 2-20 mm [SD, 3.9]). The median number of samples per procedure was three (range, one to seven). Diagnostic yield was 51% (38 of 74 specimens). The most frequent histopathologic patterns were granulomatous inflammation (12 patients) and organizing pneumonia (OP) (11 patients), resulting in the final diagnoses of hypersensitivity pneumonitis (six patients), cryptogenic OP (six patients), connective tissue disease-associated OP (three patients), drug toxicity (three patients), infection-related OP (two patients), sarcoidosis (two patients), and aspiration (one patient). Other histopathologic patterns included respiratory bronchiolitis (three patients), acute fibrinous and organizing pneumonia (two patients), desquamative interstitial pneumonia (1 patient), diffuse alveolar damage (one patient), pulmonary alveolar proteinosis (one patient), amyloidosis (one patient), eosinophilic pneumonia (one patient), necrotizing vasculitis (one patient), bronchiolitis with food particles (one patient), and malignancy (three patients). Pneumothorax developed in one patient (1.4%), and bleeding occurred in 16 patients (22%).

Conclusions  Our single-center cohort demonstrated a 51% diagnostic yield from TBC; the rates of pneumothorax and bleeding were 1.4% and 22%, respectively. The optimal use of TBC needs to be determined.

Original Research: Pulmonary Vascular Disease

Chest. 2017;151(2):409-416. doi:10.1016/j.chest.2016.09.038

Background  For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity.

Methods  We performed a meta-analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography-detectable RHT for the primary outcome of short-term all-cause mortality and the secondary outcome of short-term PE-related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms “right heart thrombi,” “pulmonary embolism,” and “prognos.*” A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity.

Results  Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography-detectable RHT died (16.7% [95% CI, 13.8-19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0-4.7]). RHT had a significant association with short-term all-cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE-related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0-11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7-13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies.

Conclusions  In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis.

Trial Registry  PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/

Chest. 2017;151(2):417-424. doi:10.1016/j.chest.2016.09.029

Background  Many patients are subjected to the potential risks and morbidity associated with an indwelling inferior vena cava (IVC) filter when standard methods fail to remove the filter. We evaluated the safety and effectiveness of the excimer laser sheath technique for removing embedded IVC filters.

Methods  Over a 5-year period, 251 consecutive patients undergoing laser-assisted filter retrieval were prospectively enrolled. There were 103 men and 148 women (mean, 46 years; range, 15-82 years). Indications for retrieval included symptomatic acute IVC thrombosis, chronic IVC occlusion, and/or pain from filter penetration. Retrieval was also performed to prevent risks from prolonged implantation and potentially to eliminate the need for lifelong anticoagulation. After retrieval failed using three times the standard retrieval force (digitally measured), treatment escalation was attempted using a laser sheath powered by a 308-nm XeCl laser. Success was defined as complete filter detachment and removal from the body. Primary safety outcomes were major procedure-related complications.

Results  Laser-assisted retrieval was successful in 249 of 251 patients (99.2%) (95% CI, 97.2%-99.9%), with a mean implantation of 979 days, range: 37-7,098 days (> 19 years), among retrievable-type filters (n = 211) and permanent-type filters (n = 40). Average force during failed attempts without laser was 6.7 vs 3.8 lbs during laser-assisted retrievals (P < .0001). The major complication rate was 1.6% (95% CI, 0.4%-4.0%), and all were successfully treated. Successful retrieval allowed cessation of anticoagulation in 45 of 46 patients (98%) (95% CI, 88%-99%) and alleviated filter-related morbidity in 55 of 57 patients (96%) (95% CI, 88%-99%).

Conclusions  The excimer laser sheath technique is safe and effective for removing embedded IVC filters refractory to standard retrieval and high force. This technique can be used to alleviate or prevent filter-related morbidity and may allow cessation of filter-related anticoagulation.

Trial Registry  ClinicalTrials.gov; No.: NCT01158482; URL: www.clinicaltrials.gov

Chest. 2017;151(2):425-430. doi:10.1016/j.chest.2016.09.009

Objective  The goal of this study was to investigate the risk of VTE among patients with sarcoidosis.

Methods  A cohort of 345 incident cases of sarcoidosis and 345 sex- and age-matched comparator subjects in Olmsted County, Minnesota, from 1976 to 2013 were identified from the comprehensive medical record linkage system. Medical records were reviewed for DVT and pulmonary embolism (PE). The cumulative incidence was estimated, adjusted for the competing risk of death. Cox proportional hazards models were used to compare the rate of development of these events between patients with sarcoidosis and the nonsarcoidosis comparison cohort.

Results  The prevalence of VTE, DVT, and PE prior to the index date was not significantly different between case and comparator subjects. The risk of incident VTE adjusted for age, sex, and calendar year was significantly higher among patients with sarcoidosis (hazard ratio [HR], 3.04 [95% CI, 1.47-6.29]). Significantly elevated risk was observed in both subtypes of VTE, with an HR of 3.14 (95% CI, 1.32-7.48) for DVT and an HR of 4.29 (95% CI, 1.21-15.23) for PE. A sensitivity analysis including only VTE events that occurred at least 6 months after the index date adjusted for age, sex, and calendar year revealed somewhat lower HRs: VTE, 2.73 (95% CI, 1.30-5.72); DVT, 3.00 (95% CI, 1.25-7.20); and PE, 3.58 (95% CI, 0.98-13.03).

Conclusions  An increased risk of VTE among patients with sarcoidosis was observed in this population-based cohort.

Original Research: Pulmonary Physiology

Chest. 2017;151(2):431-440. doi:10.1016/j.chest.2016.09.027

Background  Discriminating circulatory problems with reduced stroke volume (SV) from deconditioning, in which the muscles cannot consume oxygen normally, by gas exchange parameters is difficult.

Methods  We performed combined stress echocardiography (SE) and cardiopulmonary exercise tests (CPET) in 110 patients (20 with normal effort capacity, 54 with attenuated SV response, and 36 with deconditioning) to evaluate multiple hemodynamic parameters and oxygen content difference (A-o2 Diff) in four predefined activity levels to assess which of the gas measures may help in the discrimination.

Results  Reduced anaerobic threshold (AT), low unchanging peak oxygen pulse, periodic breathing, shallow Δ peak oxygen consumption (o2)/Δwork rate (WR) ratio, and high expired volume per unit time/carbon dioxide production (e/co2) slope were all associated with abnormal SV response (P < .05 for all). The best discriminator was e/co2 slope to o2 ratio (≥ 2.7; area under the curve [AUC], 0.79; P < .0001). The optimal gas exchange model included Δo2/ΔWR < 8.6; e/co2 slope to peak o2 ratio ≥ 2.7, and periodic breathing (AUC of 0.84; P < .0001).

Conclusions  The best single gas exchange parameter to discriminate between circulatory problems and deconditioning is e/co2 slope to peak O2 ratio. Combining it with Δo2/ΔWR and periodic breathing improves the discriminative ability.

Evidence-Based Medicine

Chest. 2017;151(2):441-454. doi:10.1016/j.chest.2016.10.054

Background  Cough is a common symptom experienced by athletes, particularly after exercise. We performed a systematic review to assess the following in this population: (1) the main causes of acute and recurrent cough, either exercise-induced or not, (2) how cough is assessed, and (3) how cough is treated in this population. From the systematic review, suggestions for management were developed.

Methods  This review was performed according to the CHEST methodological guidelines and Grading of Recommendations Assessment, Development and Evaluation framework until April 2015. To be included, studies had to meet the following criteria: participants had to be athletes and adults and adolescents aged ≥ 12 years and had to complain of cough, regardless of its duration or relationship to exercise. The Expert Cough Panel based their suggestions on the data extracted from the review and final grading by consensus according to a Delphi process.

Results  Only 60 reports fulfilled the inclusion criteria, and the results of our analysis revealed only low-quality evidence on the causes of cough and how to assess and treat cough specifically in athletes. Although there was no formal evaluation of causes of cough in the athletic population, the most common causes reported were asthma, exercise-induced bronchoconstriction, respiratory tract infection (RTI), upper airway cough syndrome (UACS) (mostly from rhinitis), and environmental exposures. Cough was also reported to be related to exercise-induced vocal cord dysfunction among a variety of less common causes. Although gastroesophageal reflux disease (GERD) is frequent in athletes, we found no publication on cough and GERD in this population. Assessment of the causes of cough was performed mainly with bronchoprovocation tests and suspected disease-specific investigations. The evidence to guide treatment of cough in the athlete was weak or nonexistent, depending on the cause. As data on cough in athletes were hidden in a set of other data (respiratory symptoms), evidence tables were difficult to produce and were done only for cough treatment in athletes.

Conclusions  The causes of cough in the athlete appear to differ slightly from those in the general population. It is often associated with environmental exposures related to the sport training environment and occurs predominantly following intense exercise. Clinical history and specific investigations should allow identification of the cause of cough as well as targeting of the treatment. Until management studies have been performed in the athlete, current guidelines that exist for the general population should be applied for the evaluation and treatment of cough in the athlete, taking into account specific training context and anti-doping regulations.

Topics: cough , athlete

Translating Basic Research Into Clinical Practice

Chest. 2017;151(2):455-467. doi:10.1016/j.chest.2016.09.012

There is a great interest in developing biomarkers to enable precision medicine and improve health outcomes of patients with COPD. However, biomarker development is extremely challenging and expensive, and translation of research endeavors to date has been largely unsuccessful. In most cases, biomarkers fail because of poor replication of initial promising results in independent cohorts and/or inability to transfer the biomarker from a discovery platform to a clinical assay. Ultimately, new biomarker assays must address 5 questions for optimal clinical translation. They include the following: is the biomarker likely to be (1) superior (will the test outperform current standards?); (2) actionable (will the test change patient management?); (3) valuable (will the test improve patient outcomes?); (4) economical (will the implementation of the biomarker in the target population be cost-saving or cost-effective?); and (5) clinically deployable (is there a pathway for the biomarker and analytical technology to be implemented in a clinical laboratory?)? In this article we review some of the major barriers to biomarker development in COPD and provide possible solutions to overcome these limitations, enabling translation of promising biomarkers from discovery experiments to clinical implementation.

Recent Advances in Chest Medicine

Chest. 2017;151(2):468-480. doi:10.1016/j.chest.2016.05.024

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are progressive and debilitating diseases characterized by gradual obstruction of the pulmonary vasculature, leading to elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). If untreated, they can result in death due to right-sided heart failure. Riociguat is a novel soluble guanylate cyclase (sGC) stimulator that is approved for the treatment of PAH and CTEPH. We describe in detail the role of the nitric oxide-sGC-cyclic guanosine monophosphate (cGMP) signaling pathway in the pathogenesis of PAH and CTEPH and the mode of action of riociguat. We also review the preclinical data associated with the development of riociguat, along with the efficacy and safety data of riociguat from initial clinical trials and pivotal phase III randomized clinical trials in PAH and CTEPH.

Special Features

Chest. 2017;151(2):481-491. doi:10.1016/j.chest.2016.10.041

Aspiration of a foreign body into the lower airways is a common occurrence and can cause significant morbidity and mortality in humans. Most foreign bodies of the tracheobronchial tree are inanimate. However, the medical literature includes reports of live foreign bodies in the airways. Fish, leeches, and roundworms are the most common live foreign bodies of the lower airways. Fishermen are more prone to experience a live fish aspiration, whereas substandard conditions may expose individuals to leech and roundworm infestations. The dangers of and the approaches to the management of these foreign bodies differ from those associated with aspirated inanimate objects. The focus of this review of the medical literature was on live foreign body aspiration and its management.

Contemporary Reviews in Critical Care Medicine

Chest. 2017;151(2):492-499. doi:10.1016/j.chest.2016.10.006

Clinicians have traditionally dichotomized bacteria as friendly commensals or harmful pathogens. However, the line separating the two has become blurred with the recognition that the intestinal microbiome is a complex entity in which species can shift sides—from friend to foe and back again—based on crucial factors in their local environment. Significant disruptions in the homeostasis of the microbiome, a phenomenon called dysbiosis, is increasingly associated with a host of untoward effects. Patients in the ICU are at high risk for dysbiosis given the high rate of antibiotic use, acute changes in diet, and the stress of critical illness. Probiotics are living microbes of human origin that when ingested in sufficient quantities, can colonize sites such as the oropharynx and GI tract and provide benefits to the host. In recent years, we have increasingly explored the utility of using probiotics to reverse the intestinal dysbiosis associated with critical illness, thereby reducing select ICU complications associated with increased morbidity and mortality. Although these preliminary efforts have demonstrated varying degrees of success, our present studies suffer from a host of limitations that hinder the strength of their conclusions and the generalizability of their results. Probiotic investigations have been further hobbled by current regulatory requirements, which were designed to serve as the framework for pharmaceutical research. Although such measures are intended to ensure patient safety, they inadvertently impose barriers that stifle innovation regarding nutraceuticals. This review strives to summarize the current evidence regarding the efficacy and safety of probiotics in the ICU as well as to provide an overview of the obstacles probiotic researchers face going forward.

Contemporary Reviews in Sleep Medicine

Chest. 2017;151(2):500-506. doi:10.1016/j.chest.2016.09.026

Since initial reports 40 years ago on pediatric OSA syndrome (OSAS) as a distinct and prevalent clinical entity, substantial advances have occurred in the delineation of diagnostic and treatment approaches. However, despite emerging and compelling evidence that OSAS increases the risk for cognitive, cardiovascular, and metabolic end-organ morbidities, routine assessment of such morbidities is seldom conducted in clinical practice. One of the major reasons for such discrepancies resides in the relatively labor-intensive and onerous steps that would be required to detect the presence of any of such morbidities, further adding to the already elevated cost of diagnosing the disorder. To circumvent these obstacles, the search for biomarker signatures of pediatric OSA and its cognitive and cardiometabolic consequences was launched, and considerable progress has occurred since then. Here, we review the current evidence for the presence of morbidity-related biomarkers among children with OSAS, and explore future opportunities in this promising arena.


Chest. 2017;151(2):507. doi:10.1016/j.chest.2016.09.047

    Thick black horses stand,
        waiting to draw.

    We have been here all along, but never before.
    You there in your private office and me here in my public hall,
        in the same room, thinking the same with different thoughts
        searching the lies of truth

    We imagine now what we imagined before,
        but in shadows cast into light made from shadows
        we cannot imagine.

    The big black horses snort heavy gray clouds of used wet air.
    They stamp their hooves, cracking the ice.

    Shoot the damned horses.

Chest. 2017;151(2):508. doi:10.1016/j.chest.2016.07.037

    How much we take for granted,
    I reflect,
    remembering a long hike with my husband
    when I could focus on
    the valley unfurling beneath us, each step
    as easy as breathing,
    and how turning off the light each night
    meant sleep, then
    greeting the day as if it were an endless expanse.
    Now each day is a negotiation
    and the hours are few, but I have learned that
    few can be many.
    I have discovered a world that flees
    grief and illness,
    but that with friends and my loved one
    few can be many.
    I have discovered how to reach out
    to those we ignore,
    the depth of compassion, the hidden cost
    of a new kind of learning,
    and that despite the static of endless nights,
    unpredictable days,
    these prisons are not within myself.

Chest. 2017;151(2):509. doi:10.1016/j.chest.2016.07.031

    Judas uterus imploded spawning fake babies and a terrible sea of red. The healers
    poked and prodded archaic wands, thick and thin, to diagnose my affliction. The cure—
    suspend my lady parts in mid-air to sever the troublesome masses while I lie in a sleep induced by the anesthetic sister of tequila margarita.

    When the projected two hours doubled, Mama demanded and received an explanation:
    my womb hosted more guests than had RSVP’D. After six hours, I awoke hoarse with a
    stapled belly and catheter in tow. Three days in, art mirrored life as I beheld a glossy photo of fifteen lumps of flesh posed left to right in descending order on a steel table.
    Home I went with an image to archive apart from snapshots of travel and girlhood.

    The painkillers worked; however, they summoned dreams of black folk who dwelled
    above an ocean of oil and traveled by chutes and ladders. Prostrate rest was the antidote
    for a little while. Then gradually, I sat upright which led to virtual shopping. Though stooped and slowly, I walked as needed. Inevitably, came the urge to paint my face.

    Recuperation granted time to get my house in order. Sporting hideous gold fabric, the Victorian chaise was project prime. To a warehouse, off I went sifting and searching through aisles of brocades and burlaps. True I stayed: velvet again, crimson of course. By the time the upholsterers returned the relic, I was standing upright and able to recline gracefully.

    At last, an open window framed a lovely sun drenched day in March. Trees, lush and green, danced in the cool breeze and their leaves lullabied my prognosis: I would be fine, and death knew I was decorating.

Chest. 2017;151(2):510. doi:10.1016/j.chest.2016.07.032

    There are memories that linger in the air, that remain like dirt under a fingernail.


Chest. 2017;151(2):511-512. doi:10.1016/j.chest.2016.11.002

Pleural disease is a common health problem and is estimated to affect > 3,000 people per million population. Pleural effusion is the most common condition in this group, and in approximately 75% of cases, the clinical history, physical examination, radiographic techniques, and pleural fluid analysis will identify a cause for the pleural effusion, with the remaining 25% requiring further invasive diagnostic procedures.

Chest. 2017;151(2):512-513. doi:10.1016/j.chest.2016.10.060

There has been increasing interest in transbronchial cryobiopsy for diagnosis in interstitial lung disease. As we highlighted in our systematic review and cost analysis, this has the potential to be cost saving in the setting of a payment by results system. Recently, it has been demonstrated in a porcine model that a new sheath cryoprobe gives equivalent biopsy quality without the need for en bloc bronchoscope removal or an endotracheal tube. This has the potential to shorten procedure times by 34.8% and reduce bleeding by 81.8% and the incidence of pneumothorax by 66.7%.

Chest. 2017;151(2):513-514. doi:10.1016/j.chest.2016.11.018

We thank Dr Sharp et al for their comments. Mounting evidence suggests that transbronchial cryobiopsy (TBC) could represent a paradigm shift in our management of patients with lung disease, promising a high diagnostic yield with a safety profile similar to that of conventional bronchoscopic forceps biopsy. This evidence, however, remains limited overall, and, practically, techniques for TBC seem to vary considerably across centers, as illustrated by the broad range of diagnostic yields and procedural complications.

Chest. 2017;151(2):514. doi:10.1016/j.chest.2016.11.051

We wholeheartedly agree with Sharp and colleagues that cost saving is another potential benefit to transbronchial cryobiopsies in addition to safety and effectiveness. Well-designed and conducted, randomized controlled studies are needed to better define the position of transbronchial cryobiopsies in the diagnostic algorithm of interstitial and other lung diseases. There is also heterogeneity in the way the procedure is performed, so we also advocate for an evidence-based guideline to provide best practice recommendations for this procedure.

Chest. 2017;151(2):514-515. doi:10.1016/j.chest.2016.10.063

We have read with great interest the article written by Alonso-Fernández et al published in CHEST (December 2016). However, there are some key aspects to take into account for proper practical implications.

Chest. 2017;151(2):515-516. doi:10.1016/j.chest.2016.11.031

We appreciate the interest in our article about the role of OSA as a risk factor for recurrent pulmonary embolism (PE) as well as the comments related to its interpretation and clinical implications.

Chest. 2017;151(2):516-517. doi:10.1016/j.chest.2016.10.064

The recent review by Fuehner et al in an issue of CHEST (August 2016) regarding perioperative care in lung transplantation has highlighted the need for further research into the unique challenges for this special cohort. Although current guidelines on ventilation strategies for newly transplanted lungs have been extrapolated from studies in patients with ARDS and the general ICU population, these studies have specifically excluded lung transplant recipients from their analyses. Because it is difficult to define the optimal ventilation strategy for lung transplant recipients when limited data are available on their perioperative care, we share the authors’ view that large prospective studies into this field are needed.

Chest. 2017;151(2):517-518. doi:10.1016/j.chest.2016.11.048

We thank Thakuria and colleagues for their interest in our article recently published in CHEST and their comments. Although limited data are available, lung-protective ventilation strategies are gaining increased awareness in the early postoperative period following lung transplantation. Most of the recommendations have been extrapolated from literature recommendations for ARDS. Verbeek and Myles concluded that a combination of low tidal volume (< 6 mL/kg), moderate positive end-expiratory pressure (PEEP), and inspiratory pressure < 20 cm H2O above PEEP would be beneficial in lung transplantation ventilation.

Chest. 2017;151(2):518-519. doi:10.1016/j.chest.2016.11.047

We read with interest Dr Simpson’s editorial entitled “New Sepsis Criteria: A Change We Should Not Make” in a recent issue of CHEST (May 2016). The author argues against clinical implementation of the SEPSIS-3 guidelines for defining sepsis. SEPSIS-3 has solved a major problem of SEPSIS-2, which required the presence of systemic inflammatory response syndrome (SIRS) + suspected infection to define sepsis. For most physicians, the term “sepsis” is usually reserved for patients with a severe infection deserving critical care. Using the SEPSIS-2 criteria would “overestimate” the number of cases of this disease by considering uncomplicated infection as sepsis. Conversely, the SEPSIS-2 definition excludes a number of patients with potentially deleterious infection because SIRS is absent in one of eight patients with infection and organ dysfunction. We agree with Dr Simpson that the lethality of sepsis demands a screening mechanism exhibiting high sensitivity, but in our opinion, specificity does not have to be sacrificed. It is clear that the SEPSIS-2 and SEPSIS-3 definitions leave in “no men’s land” those patients with an infection and a potential complicated outcome neither fulfilling the criteria of SIRS nor showing signs of organ failure at clinical presentation.

Chest. 2017;151(2):519-520. doi:10.1016/j.chest.2016.11.050

Bermejo-Martin and colleagues make a point about my recent editorial in CHEST with which I wholeheartedly agree: that we must ultimately move from diagnosing sepsis by using syndrome to diagnosing sepsis by using pathophysiology. Much as acute coronary syndrome is confirmed to be acute myocardial infarction by an increased level of circulating troponin I or by localized ST-segment elevation, we need confirmatory studies that are indicative of infection-induced organ dysfunction or severe sepsis. The authors propose several candidate immunologic studies that could ultimately be used to define sepsis. I agree with them that large-scale prospective testing and defining are necessary before any of these candidates can be accepted individually or collectively as the diagnostic features of severe sepsis.

Chest. 2017;151(2):520-521. doi:10.1016/j.chest.2016.11.046

We read with great interest the recent article in CHEST (September 2016) entitled “Hypertension Is Associated With Undiagnosed OSA During Rapid Eye Movement Sleep.” In their article, Appleton et al demonstrated that an apnea-hypopnea index during rapid eye movement sleep (REM AHI) > 30 events/h is independently related to the presence of hypertension (HTN). Interestingly, they also confirmed the relationship between REM OSA and HTN among patients without OSA (due to an AHI < 10 events/h). The authors remarked that the role of OSA in the development of HTN is due to its impact on endothelial damage. On the other hand, it is well known that HTN also is responsible for vascular dysfunction. In this regard, we would like to highlight the important impact of the simultaneous presence of OSA and HTN on the risk of atherosclerosis. Pathophysiologically, it is widely accepted that the role of both conditions in the development of endothelial damage is mediated by inflammation., Indeed, in patients with HTN, increased blood pressure stimulates inflammatory mechanisms, in which the vasoactive peptides angiotensin II and endothelin-1 have a key role. On the other hand, in patients with OSA, the hypoxia-reoxygenation cycle and sleep fragmentation trigger the generation of reactive oxygen species, and inflammation. Therefore, in patients with OSA and HTN, there is the possibility that all the aforesaid mechanisms operate simultaneously and/or synergistically. In this regard, Drager et al demonstrated additive effects of OSA and HTN on carotid intima-media thickness, diameter, and distensibility. Moreover, our group has recently evaluated the consequences of the coexistence of OSA and HTN on intima-media thickness, and on inflammatory markers of atherosclerosis (such as interleukin-6 and pentraxin-3). These early markers of atherosclerosis were significantly increased in hypertensive patients with OSA compared with normotensive patients with OSA, hypertensive patients without OSA, or control subjects.

Ultrasound Corner

Chest. 2017;151(2):e21-e24. doi:10.1016/j.chest.2016.05.043
Chest. 2017;151(2):e25-e27. doi:10.1016/j.chest.2016.05.042

A 70-year-old man presented to the hospital after an ankle fracture sustained 3 weeks prior. He started having shortness of breath 3 days prior to admission along with intermittent dizziness. He did not have any significant past medical history. He denied chest pain, loss of consciousness, or any constitutional symptoms.

Chest Imaging and Pathology for Clinicians

Chest. 2017;151(2):e29-e34. doi:10.1016/j.chest.2016.11.022

A man in his 20s with a history of classical Hodgkin’s lymphoma was admitted with fever. His original lymphoma diagnosis was made 3 years prior, when he had presented with lymphadenopathy and a mediastinal mass. He had relapsed disease despite chemotherapy and radiation. As a result, he underwent autologous peripheral blood stem cell transplant (SCT) 6 months prior to current presentation and subsequently allogeneic SCT 2 months prior for added graft vs tumor effect.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2017;151(2):e35-e39. doi:10.1016/j.chest.2016.08.1459

A 27-year-old man with OSA, posttraumatic stress disorder, and chronic mechanical back pain presented with a 3-day history of acute atraumatic worsening of his low back pain as well as right groin numbness that was exacerbated by walking. He also complained of bilateral leg “heaviness,” pain, and swelling, all becoming so severe that he rented a wheelchair for mobility.

Chest. 2017;151(2):e41-e44. doi:10.1016/j.chest.2016.08.1441

A 66-year-old woman presented to an urgent care clinic for 2 to 3 weeks of general malaise, nausea/vomiting, night sweats, and dyspnea. On examination, she was tachycardic, and her laboratory evaluation was normal except for a lactate level of 4.4 mmol/L and platelet count of 118 × 109/L. CT imaging was performed. Two days later in the follow-up clinic, the patient’s international normalized ratio (INR) was elevated, and she was hospitalized with initial findings of disseminated intravascular coagulation (DIC) (ie, INR > 10, platelets 97 × 109/L, fibrinogen < 60 mg/dL, positive D-dimer result). Bone marrow aspirate and peripheral blood smears were unrevealing. On day 4 of her hospitalization, the patient developed severe lactic acidosis (24 mmol/L) and hypoglycemia (11 mg/dL), and she was transferred to our institution. The patient had a history of a benign ovarian tumor, was a nonsmoker, did not drink alcohol, and was not taking any medications prior to admission. No ingestions or environmental exposures were noted.

Chest. 2017;151(2):e45-e48. doi:10.1016/j.chest.2016.08.1463

A 6-month-old infant with a past medical history of hypoxic ischemic encephalopathy was referred for evaluation of snoring. She was born at 41 weeks’ gestational age to a 25-year-old gravida 1, para 1 mother via vacuum-assisted delivery due to cardiac decelerations. The infant’s Apgar scores were 1, 4, and 6 with nuchal cord and meconium at delivery. She was started on positive-pressure ventilation but eventually required intubation at approximately 40 minutes of life. Brain MRI showed abnormal areas of restricted diffusion, involving the corpus callosum, bilateral posterior limb of the internal capsules, and possible scattered areas of frontal and occipital lobe cortices.

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