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Current Issue

Editorial

Chest. 2016;150(3):475-477. doi:10.1016/j.chest.2016.03.047
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It was nearly six decades ago when two University of Chicago investigators, Nathaniel Kleitman and Eugene Aserinsky, discovered rapid eye movement (REM) sleep, a stage of sleep that accounts for approximately one-quarter of total sleep time in healthy adults. To date, the preponderance of research on REM sleep has focused on memory, affect, and cognition. In the last few years, however, there has been a growing interest in understanding the consequences of OSA during the two main stages of sleep (REM and non-REM sleep). Although OSA during REM sleep has not been associated with excessive daytime sleepiness or reduced quality of life,, it is important to recognize that there are important autonomic nervous system and cardiorespiratory changes during REM sleep supporting the notion that REM OSA may have worse cardiometabolic consequences than non-REM OSA. From a pathophysiologic point of view, cholinergic-mediated inhibition of the hypoglossal nerve results in the suppression of genioglossus muscle tone and thus substantially increases propensity for upper airway collapse during REM sleep. This scenario in turn can lead to either REM-predominant OSA or simply OSA that becomes more severe during REM sleep. Moreover, REM sleep is associated with greater sympathetic activity, lower vagal tone, and more cardiovascular instability compared with non-REM sleep. REM sleep is also characterized by a reduction in the hypoxic and hypercapnic ventilatory drive. These physiologic phenomena may in part explain why obstructive apneas and hypopneas during REM sleep are longer in duration, associated with significantly greater oxygen desaturation, and lead to greater fluctuations in BP compared with obstructive events in non-REM sleep.,

Chest. 2016;150(3):478-480. doi:10.1016/j.chest.2016.04.001
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Heparin-induced thrombocytopenia (HIT) is an important drug reaction that causes life- and limb-threatening thrombosis. It is considered a “clinical-pathologic” disorder, as the diagnosis is generally made by evaluating various “clinical” criteria (Thrombocytopenia, its Timing of onset, Thrombosis, and absence of oTher explanations, ie, the 4Ts scoring system) and determining whether (“pathologic”) HIT antibodies can be detected in the laboratory. Pathogenic heparin-induced antibodies are of the IgG class and activate platelets via their FcγIIA receptors (platelet IgG receptors), at concentrations of heparin ranging from 0 to 0.5 International Units/mL; characteristically, platelet activation is inhibited at very high heparin concentrations (eg, 100 International Units/mL), as excess heparin disrupts the formation of HIT antigens. HIT antibodies recognize complexes composed of platelet factor 4 (PF4)—a positively charged chemokine found within platelet α-granules—and heparin or certain other polyanions. However, a key problem is that among the many patients who receive heparin and who form anti-PF4/heparin antibodies that are readily detected by enzyme-linked immunosorbent assay (ELISA), only a minority of those antibodies are of the requisite platelet-activating isotype class (IgG), recognize the appropriate antigen site(s), and found in sufficient quantities to trigger platelet activation.

Chest. 2016;150(3):481-482. doi:10.1016/j.chest.2016.05.036
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After decades of failed therapies, mechanistic insights have led to the development of therapies successful in curtailing, but not abrogating, the fibrosis that results in the devastating clinical course of patients with idiopathic pulmonary fibrosis (IPF). Alveolar epithelium undergoing injury from various agents such as inhalation exposures, gastroesophageal reflux, DNA viruses, and mechanisms of oxidative stress can stimulate stress response pathways, mediator release, and apoptosis. This abnormally activated epithelium is thought to promote fibroblast recruitment and activation, which leads to matrix deposition and fibroblast persistence. It follows that there is a growing interest in creating cell-based therapies to help restore a normal wound-healing response.

Chest. 2016;150(3):483-484. doi:10.1016/j.chest.2016.06.010
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Point-of-care critical care ultrasound is finally receiving the attention it deserves. Let's define it just once again so there is no ambiguity to its usefulness for the critically ill. Critical care ultrasound performed at the bedside allows the intensivist to categorize the etiology of all forms of cardiopulmonary failure and/or multiorgan failure, allowing immediate interpretation of the results without the time or clinical dissociation inherent in consultative radiology or echocardiography. This interpretation is then integrated into the clinical picture, along with the history and surface physical examination, and may allow a more complete treatment plan that could reduce the need for ionizing radiation and transport of the patient. CHEST, and all other major international critical care societies, have endorsed critical care ultrasound, and it is hard to find an issue of this Journal without at least 1 article on its usefulness., The utility and ease of point-of-care ultrasound (POCUS) use has spread among other subspecialties, confirmation of which is seen in a recent endorsement of POCUS, including echocardiography, by the president of the American Society for Echocardiography. What a long way we have come. For years, the ultrasound machine, if a critical care unit had one, would sit idle in the corner, hibernating, with its occasional use to guide central line placement or help in distinguishing into which intercostal space the fellow would put the thoracentesis needle. Well, the ultrasound revolution has begun, but like all revolutions, success cannot be based on ideology alone.

Topics: ultrasonography
Chest. 2016;150(3):485-487. doi:10.1016/j.chest.2016.07.009
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The recognition of the association between eosinophils and asthma is not new. Following its discovery by Jones in 1846 and Ehrlich’s identification of its proclivity for aniline dyes to stain its granules, the progress in elucidating the biological characteristics of eosinophils has been described in four phases. The first related to the refinement of staining techniques; the second was the description of the association between eosinophils and allergic diseases, including asthma; the third related to the granular chemical and biological features of eosinophils; and the fourth is the current era of the development of strategies to specifically target the molecular pathways that are involved in the development, maturation, and trafficking of eosinophils.

Topics: asthma , eosinophil

Editorials: Point and Counterpoint

Chest. 2016;150(3):488-490. doi:10.1016/j.chest.2016.06.024
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Guidelines from the National Asthma Education and Prevention Program (2007) recommend managing mild asthma exacerbations with the addition of a short-acting beta agonist to the treatment regimen, and if response is incomplete, adding an oral corticosteroid. Escalating the dose of long-acting controller medication is not recommended as part of management of the acute exacerbation. This approach has several significant problems:

  • Oral corticosteroid medications, although effective, have significant toxicity, even in short bursts.

  • The use of beta agonists relieves asthma symptoms but does not prevent a mild exacerbation from progressing to a severe exacerbation.

  • Nonadherence to the daily use of long-acting controller medication is extremely common.,

Chest. 2016;150(3):490-492. doi:10.1016/j.chest.2016.06.026
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The proposal to treat loss of asthma control with increased inhaled corticosteroids raises a number of issues that need to be examined. First, just what is meant by loss of control? Is this the same as an exacerbation? If not, what’s the difference? For guidance, I looked at a previously published practice parameter. That document summarizes the goal of what they call the yellow zone as “Responding to the symptoms of acute loss of control in the yellow zone with effective interventions can help prevent deterioration to the red zone, necessitating use of systemic corticosteroids and/or urgent medical care.”(p145)

Chest. 2016;150(3):493. doi:10.1016/j.chest.2016.06.027
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Dr Weinberger asks what is loss of control? Are symptoms that need reliever medication a “full blown exacerbation”? Is the “yellow zone” simply a “procrastinator's zone”? Should we just cut to the chase and give oral corticosteroid medication any time a child has symptoms of asthma?

Chest. 2016;150(3):494. doi:10.1016/j.chest.2016.06.025
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Dr Farber acknowledges the efficacy of oral corticosteroids but expresses concern regarding “significant toxicity even in short bursts.” However, examination of children requiring frequent short courses of oral glucocorticoids for acute asthma found no sustained adverse effects. A systematic review did find acute vomiting, transient behavioral changes, and sleep disturbances in 5.4%, 4.7%, and 4.3% of children, respectively, who were given a short course of an oral corticosteroid, predominantly prednisolone. However, vomiting is a formulation issue due to the extremely foul taste of some liquid formulations of prednisolone. Commercial formulations with better taste masking are available; an alternative is a crushed dexamethasone tablet given with sugar or a sweet soft food. The side effects of transient behavioral changes and sleep disturbances are annoying but neither dangerous nor universal. They need to be weighed against the behavioral effects and sleep disturbances associated with loss of asthma control. Moreover, clinical experience has found that those central nervous system effects of prednisolone are less common with methylprednisolone and dexamethasone. Although neither is available in a satisfactory pediatric liquid formulation, they can be given crushed with sweet soft food or sugar. The risk from varicella acquired during a short course of systemic corticosteroids is real and serious but avoidable with routine prior varicella immunization.

Original Research: Sleep Disorders

Chest. 2016;150(3):495-505. doi:10.1016/j.chest.2016.03.010

Background  Evidence linking OSA with hypertension in population studies is conflicting. We examined longitudinal and cross-sectional associations of previously unrecognized OSA, including OSA occurring in rapid eye movement (REM) sleep, with hypertension.

Methods  The Men Androgens Inflammation Lifestyle Environment and Stress (MAILES) study is a longitudinal study of community-dwelling men in Adelaide, South Australia. Biomedical assessments at baseline (2002-2006) and follow-up (2007-2010) identified hypertension (systolic ≥ 140 mm Hg and/or diastolic ≥ 90 mm Hg, or medication) and risk factors. In 2010 to 2011, 837 men without a prior diagnosis of OSA underwent full in-home unattended polysomnography of whom 739 recorded ≥ 30 min of REM sleep. Hypertension at follow-up (concomitant with OSA status) was defined as prevalent hypertension. Recent-onset hypertension was defined as hypertension at biomedical follow-up (56 months mean follow-up [range, 48-74]) in men free of hypertension at baseline.

Results  Severe REM OSA (apnea hypopnea index ≥30/h) showed independent adjusted associations with prevalent (OR, 2.40, 95% CI, 1.42-4.06), and recent-onset hypertension (2.24 [1.04-4.81]). Significant associations with non-REM AHI were not seen. In men with AHI < 10, REM OSA (apnea hypopnea index) ≥ 20/h was significantly associated with prevalent hypertension (2.67 [1.33-5.38]) and the relationship with recent-onset hypertension was positive but not statistically significant (2.32 [0.79-6.84]). Similar results were seen when analyses were confined to men with non-REM AHI < 10.

Conclusions  In men not considered to have OSA (AHI < 10), hypertension was associated with OSA during REM sleep. REM OSA may need consideration as an important clinical entity requiring treatment but further systematic assessment and evidence is needed.

Original Research: Critical Care

Chest. 2016;150(3):506-515. doi:10.1016/j.chest.2016.02.641

Background  Almost without exception, patients with heparin-induced thrombocytopenia/thrombosis (HIT) have antibodies that recognize platelet factor 4 (PF4) in a complex with heparin; however, many heparin-treated patients without HIT are also antibody-positive. A platelet activation test, the serotonin release assay (SRA), is useful for identifying a subset of antibodies that are platelet-activating and most likely to cause HIT. However, this “gold standard” assay for HIT diagnosis is technically demanding and is routinely available only through referral laboratories, limiting its availability for timely diagnosis and management.

Methods  We compared the diagnostic performance of the SRA with that of a technically simple platelet activation assay, the PF4-dependent P-selectin expression assay (PEA), which uses platelets pretreated with PF4 as targets for antibody detection. Archived serum samples from 91 patients for whom clinical information (HIT 4Ts [thrombocytopenia, timing of platelet count fall, thrombosis, and other causes of thrombocytopenia] score) was available were used. Patients with an intermediate 4Ts score and a PF4 ELISA (enzyme-linked immunosorbent assay) optical density ≥ 2.0, or a high 4Ts score and a PF4 ELISA optical density ≥ 1.0, were considered HIT positive; others were designated HIT negative.

Results  The PEA had higher diagnostic accuracy (area under the curve, 0.92 vs 0.82; P = .02) than the SRA, using this definition of HIT. Eleven of 16 serum samples that were PEA positive and SRA negative were HIT positive. Studies done with identical target platelets and serially diluted samples from patients with HIT showed that the PEA is inherently more sensitive than the SRA for the detection of platelet-activating antibodies.

Conclusions  The PEA is technically less demanding than the SRA and may be more accurate for the diagnosis of HIT.

Chest. 2016;150(3):516-523. doi:10.1016/j.chest.2016.04.004

Background  Platelet transfusions are commonly used in critically ill patients, but transfusion thresholds, count increments, and predictors of ineffectual transfusions remain unclear.

Methods  This retrospective study included consecutive adult nononcology patients who received platelet transfusions in ICUs at three Canadian academic hospitals between 2006 and 2015. Data were collected from a validated transfusion database. We determined independent predictors of ineffectual platelet transfusions, defined as transfusions that raised platelet counts by < 5 × 109/L. Reasons for transfusion were adjudicated in a subgroup of patients who underwent transfusion despite normal platelet counts.

Results  We identified 7,320 ICU admissions (n = 7,073 patients) during which 15,879 platelet transfusions were administered. Most admissions (78.7%) were for cardiac surgery. Based on 5,700 analyzable transfusions, the median pretransfusion platelet count was 87 × 109/L (interquartile range [IQR], 57-130). The pretransfusion platelet count was ≥ 50 × 109/L and ≥ 150 × 109/L for 79.6% and 17.8% of transfusions, respectively. Reasons for transfusion despite a normal platelet count were active bleeding or surgery in patients receiving antiplatelet agents or anticoagulants. The median platelet count increment was 23 × 109/L (IQR, 7-44), and 21.8% of transfusions were ineffectual. ABO incompatibility, sepsis, liver disease, and red cell and cryoprecipitate transfusions were associated with a poor platelet count increment.

Conclusions  Platelet transfusions were commonly used in the ICU when platelet counts were ≥ 50 × 109/L. One platelet transfusion increased platelet count by 23 × 109/L. One in five transfusions was ineffectual, and ABO incompatibility was identified as a modifiable risk factor. These data can help direct efforts to reduce platelet overuse and improve transfusion quality.

Chest. 2016;150(3):524-532. doi:10.1016/j.chest.2016.05.034

Background  Quality of care for acute myocardial infarction (AMI) and heart failure (HF) varies across hospitals, but the factors driving variation are incompletely understood. We evaluated the relationship between a hospital’s ICU or coronary care unit (CCU) admission rate and quality of care provided to patients with AMI or HF.

Methods  A retrospective cohort study of Medicare beneficiaries hospitalized in 2010 with AMI or HF was performed. Hospitals were grouped into quintiles according to their risk- and reliability-adjusted ICU admission rates for AMI or HF. We examined the rates that hospitals failed to deliver standard AMI or HF processes of care (process measure failure rates), 30-day mortality, 30-day readmissions, and Medicare spending after adjusting for patient and hospital characteristics.

Results  Hospitals in the lowest quintile had ICU admission rates < 29% for AMI or < 8% for HF. Hospitals in the top quintile had rates > 61% for AMI or > 24% for HF. Hospitals in the highest quintile had higher process measure failure rates for some but not all process measures. Hospitals in the top quintile had greater 30-day mortality (14.8% vs 14.0% [P = .002] for AMI; 11.4% vs 10.6% [P < .001] for HF), but no differences in 30-day readmissions or Medicare spending were seen compared with hospitals in the lowest quintile.

Conclusions  Hospitals with the highest rates of ICU admission for patients with AMI or HF delivered lower quality of care and had higher 30-day mortality for these conditions. Hospitals with high ICU use may be targets to improve care delivery.

Original Research: Transplantation

Chest. 2016;150(3):533-543. doi:10.1016/j.chest.2016.03.021

Background  Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF.

Methods  We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated.

Results  No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent.

Conclusions  Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Original Research: COPD

Chest. 2016;150(3):544-553. doi:10.1016/j.chest.2016.05.014
OPEN ACCESS

Background  Geographic clusters in prevalence and hospitalizations for COPD have been identified at national, state, and county levels. The study objective is to identify county-level geographic accessibility to pulmonologists for adults with COPD.

Methods  Service locations of 12,392 practicing pulmonologists and 248,160 primary care physicians were identified from the 2013 National Provider Identifier Registry and weighted by census block-level populations within a series of circular distance buffer zones. Model-based county-level population counts of US adults ≥ 18 years of age with COPD were estimated from the 2013 Behavioral Risk Factor Surveillance System. The percentages of all estimated adults with potential access to at least one provider type and the county-level ratio of adults with COPD per pulmonologist were estimated for selected distances.

Results  Most US adults (100% in urbanized areas, 99.5% in urban clusters, and 91.7% in rural areas) had geographic access to a primary care physician within a 10-mile buffer distance; almost all (≥ 99.9%) had access to a primary care physician within 50 miles. At least one pulmonologist within 10 miles was available for 97.5% of US adults living in urbanized areas, but only for 38.3% in urban clusters and 34.5% in rural areas. When distance increased to 50 miles, at least one pulmonologist was available for 100% in urbanized areas, 93.2% in urban clusters, and 95.2% in rural areas. County-level ratios of adults with COPD per pulmonologist varied greatly across the United States, with residents in many counties in the Midwest having no pulmonologist within 50 miles.

Conclusions  County-level geographic variations in pulmonologist access for adults with COPD suggest that those adults with limited access will have to depend on care from primary care physicians.

Chest. 2016;150(3):554-562. doi:10.1016/j.chest.2016.05.020

Background  The beneficial effects of smoking cessation on the progression of COPD are well established. Nevertheless, many patients with COPD continue to smoke.

Methods  In this nationwide hospital-based prospective follow-up study, we examined rates of smoking cessation and clinical and sociodemographic determinants of smoking cessation in 3,233 patients with COPD who smoked on outpatient contact during 2008 to 2012. Using multivariate Cox regression, we calculated hazard ratios (HRs) of quitting.

Results  Within 1 and 5 years from first outpatient contact, the probability of quitting was 19% and 45%, respectively. In adjusted analyses, patients were less likely to quit if they were younger, with an HR of 0.84 (95% CI, 0.71-0.99) for patients aged 50 to 69 years and 0.53 (95% CI, 0.37-0.76) for patients aged 30 to 49, compared with those aged 70 years or older, who had lower income (HR, 0.79; 95% CI, 0.67-0.94), lived alone (HR, 0.75; 95% CI, 0.64-0.88), were unemployed (HR, 0.70; 95% CI, 0.54-0.90), had milder COPD with an HR of 0.67 (95% CI, 0.53-0.84) for Global Initiative for Chronic Obstructive Lung Disease (GOLD) A and 0.61 (95% CI, 0.47-0.80) for GOLD B compared with GOLD D, had Medical Research Council (MRC) dyspnea scale score < 4 (HR 0.80, 95% CI 0.68-0.95), or no history of exacerbations treated on an outpatient basis. (HR, 0.80; 95% CI, 0.68-0.93).

Conclusions  These findings reinforce that young and socioeconomically disadvantaged patients have more difficulties achieving timely smoking cessation. A novel finding is that patients with milder COPD are less likely to quit. The findings suggest a need for interventional studies focusing on these subgroups to ensure abstinence to halt disease progression.

Original Research: Pulmonary Vascular Disease

Chest. 2016;150(3):563-571. doi:10.1016/j.chest.2016.05.007

Background  Testosterone replacement therapy (TRT) prescriptions have increased several-fold in the last decade. There have been concerns regarding a possible increased incidence of DVT and pulmonary embolism (PE) with TRT. Few data support the association between TRT and DVT/PE. We evaluated the incidence of DVT and PE in men who were prescribed TRT for low serum total testosterone (sTT) levels.

Methods  This is a retrospective cohort study, conducted using data obtained from the Veterans Affairs Informatics and Computing Infrastructure. We compared the incidence of DVT/PE between those who received TRT and subsequently had normal on-treatment sTT levels (Gp1), those who received TRT but continued to have low on-treatment sTT (Gp2), and those who did not receive TRT (Gp3). Those with prior history of DVT/PE, cancer, hypercoagulable state, and chronic anticoagulation were excluded.

Results  The final cohort consisted of 71,407 subjects with low baseline sTT. Of these, 10,854 did not receive TRT (Gp3) and 60,553 received TRT. Of those who received TRT, 38,362 achieved normal sTT (Gp1) while 22,191 continued to have low sTT (Gp2). The incidence of DVT/PE was 0.5%, 0.4%, and 0.4% in Gp1, Gp2, and Gp3, respectively. Univariate, multivariate, and stabilized inverse probability of treatment weights analyses showed no statistically significant difference in DVT/PE-free survival between the various groups.

Conclusions  This study did not detect a significant association between testosterone replacement therapy and risk of DVT/PE in adult men with low sTT who were at low to moderate baseline risk of DVT/PE.

Chest. 2016;150(3):572-596. doi:10.1016/j.chest.2016.05.021

Background  Cesarean sections (CS) are believed to be associated with greater risks of postpartum VTE. Our objective was to systematically review the evidence on this association and on the absolute risk of VTE following CS.

Methods  We searched PubMed, Embase, and conference proceedings from 1980 to November 2015 for reports on the associations of delivery methods with postpartum VTE and on the incidence of VTE following CS. Studies on thrombophilia or recurrent VTE were excluded, and the search was restricted to prospective studies when assessing the incidence of VTE. Pooled relative and absolute risks were estimated with random effects models.

Results  The search retrieved 28 mostly retrospective observational studies comparing risks of VTE following CS and following vaginal deliveries (VD) (> 53,000 VTE events) and 32 prospective studies reporting risks of VTE following CS (218 VTE events). Compared with VD, the relative risk of VTE following CS ranged from 1 to 22, with a meta-analytic OR of 3.7 (95% CI, 3.0-4.6). Adjustment for age and BMI had a marginal influence on the estimated pooled OR. Associations were observed for both elective and emergency CS, with stronger estimates of associations for emergency CS. The pooled incidence was 2.6 VTE per 1,000 CS (95% CI, 1.7-3.5) and was greater in studies with a longer and better follow-up in the postpartum period (4.3 per 1,000 CS).

Conclusions  The risk of VTE was fourfold greater following CS than following VD; seemed independent of other VTE risk factors; and was greater following emergency CS than following elective CS. On average, three in 1,000 women will develop a VTE following CS.

Original Research: Antithrombotic Therapy

Chest. 2016;150(3):597-605. doi:10.1016/j.chest.2016.04.015

Background  Anticoagulation with warfarin following bioprosthetic mitral valve replacement (BMVR) is recommended by multiple practice guidelines. We assessed practice variability and patient characteristics associated with warfarin prescription following BMVR.

Methods  We analyzed 7,637 patients in the Society of Thoracic Surgeons Database (January 1, 2008 to June 30, 2011) who were discharged following isolated primary nonemergent BMVR. Patients requiring preoperative warfarin, those with preoperative atrial fibrillation, or those with a contraindication to warfarin were excluded. The association between patient, hospital, and surgeon characteristics and warfarin prescription were evaluated.

Results  Fifty-eight percent of this cohort (median age, 66 years; female sex, 58.7%) was prescribed warfarin. Patients receiving warfarin were older (67 vs 65 years; P < .0001), were less likely to have had preoperative stroke (9.3% vs 12.1%; P < .001), CHF (51.4% vs 54.1%; P < .02), or dialysis (4.9% vs 9.0%; P < 0.001), and had a longer postoperative length of stay (8.0 vs 7.0 days; P < 0.01). Warfarin was prescribed less often for patients with postoperative GI events (44.4% vs 55.6%; P < .001) but more often for patients with postoperative myocardial infarction (75.8% vs 24.2%; P < .001) or new atrial fibrillation (68% vs 32%; P < .001) and those requiring blood transfusions intraoperatively (55.7% vs 44.3%; P < .001) or postoperatively (57% vs 43%; P < .03). Similar rates of warfarin prescription were observed in patients requiring reoperation for bleeding (54.9% vs 45.1%; P = .20) and those with postoperative stroke (53.6 % vs 46.4 %; P = .30). After adjusting for patient characteristics, significant surgeon and hospital variation in warfarin prescription at hospitals was observed.

Conclusions  Although patient characteristics and postoperative events may be associated with the prescription of warfarin following BMVR, substantial surgeon and hospital variability remains. This variability largely ignores the established practice guidelines and warrants further study to define the optimal anticoagulation strategy in patients undergoing BMVR.

Original Research: Tobacco Cessation and Prevention

Chest. 2016;150(3):606-612. doi:10.1016/j.chest.2016.04.012

Background  The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and endothelial function in healthy smokers and nonsmoker adults.

Methods  A crossover, single-blind study was performed in 40 healthy subjects (20 smokers and 20 nonsmokers, matched for age and sex). First, all subjects smoked traditional tobacco cigarettes. One week later, the same subjects smoked an e-Cigarette with the same nominal nicotine content. Blood samples were drawn just before and after smoking, and markers of oxidative stress, nitric oxide bioavailability, and vitamin E levels were measured. Flow-mediated dilation (FMD) was also measured.

Results  Smoking both e-Cigarettes and traditional cigarettes led to a significant increase in the levels of soluble NOX2-derived peptide and 8-iso-prostaglandin F2α and a significant decrease in nitric oxide bioavailability, vitamin E levels, and FMD. Generalized estimating equation analysis confirmed that all markers of oxidative stress and FMD were significantly affected by smoking and showed that the biologic effects of e-Cigarettes vstraditional cigarettes on vitamin E levels (P = .413) and FMD (P = .311) were not statistically different. However, e-Cigarettes seemed to have a lesser impact than traditional cigarettes on levels of soluble NOX2-derived peptide (P = .001), 8-iso-prostaglandin F2α (P = .046), and nitric oxide bioavailability (P = .001).

Conclusions  Our study showed that both cigarettes have unfavorable effects on markers of oxidative stress and FMD after single use, although e-Cigarettes seemed to have a lesser impact. Future studies are warranted to clarify the chronic vascular effects of e-Cigarette smoking.

Original Research: Lung Cancer

Chest. 2016;150(3):613-620. doi:10.1016/j.chest.2016.05.001
OPEN ACCESS

Background  A “trigger” algorithm was used to identify delays in follow-up of abnormal chest imaging results in a large national clinical data warehouse of electronic health record (EHR) data.

Methods  We applied a trigger in a repository hosting EHR data from all Department of Veterans Affairs health-care facilities and analyzed data from seven facilities. Using literature reviews and expert input, we refined previously developed trigger criteria designed to identify patients potentially experiencing delays in diagnostic evaluation of chest imaging flagged as “suspicious for malignancy.” The trigger then excluded patients in whom further evaluation was unnecessary (eg, those with terminal illnesses or with already completed biopsies). The criteria were programmed into a computerized algorithm. Reviewers examined a random sample of trigger-positive (ie, patients with trigger-identified delay) and trigger-negative (ie, patients with an abnormal imaging result but no delay) records and confirmed the presence or absence of delay or need for additional tracking (eg, repeat imaging in 6 months). Analysis included calculating the trigger’s diagnostic performance (ie, positive predictive value, negative predictive value, sensitivity, specificity).

Results  On application to 208,633 patients seen between January 1, 2012, and December 31, 2012, a total of 40,218 chest imaging tests were performed; 1,847 of the results were suspicious for malignancy, and 655 (35%) were trigger-positive. Review of 400 randomly selected trigger-positive patients found 158 (40%) with confirmed delays and 84 (21%) requiring additional tracking (positive predictive value, 61% [95% CI, 55.5-65.3]). Review of 100 trigger-negative patients identified 97 without delay (negative predictive value, 97%; [95% CI, 90.8-99.2]). Sensitivity and specificity were 99% (95% CI, 96.2-99.7) and 38% (95% CI, 32.1-44.3), respectively.

Conclusions  Application of triggers on “big” EHR data may aid in identifying patients experiencing delays in diagnostic evaluation of chest imaging results suspicious for malignancy.

Chest. 2016;150(3):621-630. doi:10.1016/j.chest.2016.05.006

Background  Positron emission tomography (PET) is a diagnostic tool for lung cancer evaluation. No studies have ascertained practice patterns and determined the appropriateness of PET imaging in a large group of US patients with screen-detected lung nodules.

Methods  We analyzed participants in the National Lung Screening Trial (NLST) with positive screening test results and identified individuals with a PET scan performed prior to lung cancer diagnosis (diagnostic PET). Appropriate scan was defined as one performed in a patient with a nodule ≥ 0.8 cm. Logistic regression was used to assess factors associated with diagnostic PET scan use and appropriateness of PET scan use.

Results  Diagnostic PET imaging was performed in 1,556 of 14,195 patients (11%) with positive screen results; 331 of these (21%) were inappropriate. PET scan use by endemic fungal disease area was comparable although patients from the Northeast/Southeast were twice as likely as the West to have a diagnostic PET. Trial arm, older age, sex, nodule size ≥ 0.8 cm, upper lobe location, and spiculated margin were variables positively associated with use. Trial arm, older age, and spiculated margin were positively associated with appropriate use. Only 561 diagnostic PETs (36%) were recommended by a radiologist and 284 PETs performed for nodules < 0.8 cm (86%) were ordered despite no recommendation from a radiologist.

Conclusions  PET imaging was differentially used in the NLST and inappropriately used in many cases against radiologist recommendations. These data suggest PET imaging may be overused in the lung cancer screening population and may contribute to excess health-care costs.

Original Research: Diffuse Lung Disease

Chest. 2016;150(3):631-639. doi:10.1016/j.chest.2016.05.015

Background  Cystic lung disease (CLD) in Sjögren syndrome (SS) is a condition with unclear prognostic implications. Our objectives in this study are to determine its frequency, progression over time, and associated risk factors and complications.

Methods  Eighty-four patients with primary or secondary SS and chest imaging, chest radiograph, or CT scan were retrospectively evaluated for CLD. Thirteen patients with cysts were found. Baseline characteristics of all patients were collected. A multivariate logistic regression model was used to look for predictors of CLD in patients with CT scan. Additional imaging, SS activity, and complications from CLD and SS were collected for the patients with cysts.

Results  CLD had a frequency of 15.4% for all patients with chest imaging. Not all cysts were evident on radiography, and CLD frequency was 30.9% for the patients with chest CT scan. Six patients had cysts without other radiographic findings. CLD was associated with older age (OR, 1.1; 95% CI, 1.0-1.16), a diagnosis of secondary SS (OR, 12.1; 95% CI, 1.12-130.4), and seropositivity for anti-SS-related antigen A/Ro autoantibodies (OR, 26.9; 95% CI, 1.44-93.61). There was no radiologic progression of CLD for 12 patients after a 4-year median follow-up. Lung function did not exhibit temporal worsening. CLD did not correlate with a specific pattern in pulmonary function testing. Two patients had secondary infectious complications of the cysts.

Conclusions  CLD is a relatively common condition in SS that does not progress on serial radiologic and lung function follow-up. CLD, without other radiographic findings, may represent a direct manifestation of SS.

Original Research: Pulmonary Procedures

Chest. 2016;150(3):640-651. doi:10.1016/j.chest.2016.04.013

Background  Lung ultrasonography (LUS) has been used for noninvasive detection of pulmonary edema. Semiquantitative LUS visual scores (visual LUS [V-LUS]) based on B lines are moderately correlated with pulmonary capillary wedge pressure (PCWP) and extravascular lung water (EVLW). A new computer-aided quantitative LUS (Q-LUS) analysis has been recently proposed. This study investigated whether Q-LUS better correlates with PCWP and EVLW than V-LUS and to what extent positive end-expiratory pressure (PEEP) affects the assessment of pulmonary edema by Q-LUS or V-LUS.

Methods  Forty-eight mechanically ventilated patients with PEEP of 5 or 10 cm H2O and monitored by PCWP (n = 28) or EVLW (n = 20) were studied.

Results  PCWP was significantly and strongly correlated with Q-LUS gray (Gy) unit value (r2 = 0.70) but weakly correlated with V-LUS B-line score (r2 = 0.20). EVLW was significantly and more strongly correlated with Q-LUS Gy unit mean value (r2 = 0.68) than with V-LUS B-line score (r2 = 0.34). Q-LUS showed a better diagnostic accuracy than V-LUS for the detection of PCWP >18 mm Hg or EVLW ≥ 10 mL/kg. With 5-cm H2O PEEP, the correlations with PCWP or EVLW were stronger for Q-LUS than V-LUS. With 10-cm H2O PEEP, the correlations with PCWP or EVLW were still significant for Q-LUS but insignificant for V-LUS. Interobserver reproducibility was better for Q-LUS than V-LUS.

Conclusions  Both V-LUS and Q-LUS are acceptable indicators of pulmonary edema in mechanically ventilated patients. However, at high PEEP only Q-LUS provides data that are significantly correlated with PCWP and EVLW. Computer-aided Q-LUS has the advantages of being not only independent of operator perception but also of PEEP.

Original Research: Chest Infections

Chest. 2016;150(3):652-660. doi:10.1016/j.chest.2016.04.020

Background  Previous studies suggest that smoking is independently associated with decreased mortality in patients with pneumonia. We hypothesized that this is a result of acquiring differential pneumococcal serotypes (ie, smokers with pneumococcal pneumonia are more likely to experience bacteremia, with low case fatality rate (CFR) serotypes). We tested this hypothesis in a population-based cohort of patients with bacteremic pneumococcal pneumonia (BPP).

Methods  Our prospective population-based clinical registry included 1,636 adults (≥ 18 years) with BPP who were hospitalized between 2000 and 2010 in northern Alberta, Canada. Using multivariable logistic regression, we determined the adjusted risk of all-cause in-hospital mortality according to smoking status (current vs not current) and conducted stratified analyses by serotypes (low CFR vs all other CFRs) according to smoking status.

Results  The average patient age was 54 years, 57% were men, 49% were current smokers, and 41% had low-CFR serotypes. Overall, 62 of 809 current smokers died in the hospital vs 164 of 827 nonsmokers (8% vs 20%; adjusted OR, 0.52; 95% CI, 0.36-0.77; P = .001). Current smokers were more likely to have low-CFR-serotype isolates than were nonsmokers (53% vs 29%; adjusted OR, 1.67; 95% CI, 1.31-2.12; P < .001) and in models adjusted for low-CFR serotype, smoking remained independently associated with reduced mortality (P = .001).

Conclusions  Compared with nonsmokers, current smokers with BPP had a decreased risk of in-hospital mortality and were more likely to experience bacteremia with low CFR serotypes. These findings, at least in part, may explain why previous studies showed that smoking was associated with lower mortality in patients with pneumonia.

Original Research: Genetic and Developmental Disorders

Chest. 2016;150(3):661-672. doi:10.1016/j.chest.2016.04.006

Background  Increased expression of the human epididymis protein 4 (HE4) was previously described in lung biopsy samples from patients with cystic fibrosis (CF). It remains unknown, however, whether serum HE4 concentrations are elevated in CF.

Methods  Seventy-seven children with CF from six Hungarian CF centers and 57 adult patients with CF from a Czech center were enrolled. In addition, 94 individuals with non-CF lung diseases and 117 normal control subjects with no pulmonary disorders were analyzed. Serum HE4 levels were measured by using an immunoassay, and their expression was further investigated via the quantification of HE4 messenger RNA by using quantitative reverse transcription polymerase chain reaction in CF vs non-CF respiratory epithelium biopsy specimens. The expression of the potential regulator miR-140-5p was analyzed by using an UPL-based quantitative reverse transcription polymerase chain reaction assay. HE4 was measured in the supernatants from unpolarized and polarized cystic fibrosis bronchial epithelial cells expressing wild-type or F508del-CFTR.

Results  Median serum HE4 levels were significantly elevated in children with CF (99.5 [73.1-128.9] pmol/L) compared with control subjects (36.3 [31.1-43.4] pmol/L; P < .0001). This observation was replicated in adults with CF (115.7 [77.8-148.7] pmol/L; P < .0001). In contrast, abnormal but lower HE4 concentrations were found in cases of severe bronchitis, asthma, pneumonia, and bronchiectasis. In patients with CF, the concentrations of HE4 were positively correlated with overall disease severity and C-reactive protein concentrations, whereas a significant inverse relationship was found between HE4 and the spirometric FEV1 value. Relative HE4 mRNA levels were significantly upregulated (P = .011) with a decreased miR-140-5p expression (P = .020) in the CF vs non-CF airway biopsy specimens. Twofold higher HE4 concentrations were recorded in the supernatant of polarized F508del-CF transmembrane conductance regulator/bronchial epithelial cells compared with wild-type cells.

Conclusions  HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease.

Original Research: Disorders of the Pleura

Chest. 2016;150(3):673-679. doi:10.1016/j.chest.2016.05.008

Background  Pleurodesis performed either by pleurectomy or pleural abrasion is recommended in the approach to primary spontaneous pneumothorax to avoid recurrence. However, the efficacy of parietal pleural abrasion in producing pleurodesis is questioned. This study aims to determine the efficacy of apical abrasion alone, abrasion plus fibrin sealant application, and pleurectomy in producing pleurodesis in rabbits.

Methods  Rabbits were subjected to video-assisted thoracic surgery alone (control) or to video-assisted thoracic surgery with apical gauze abrasion, abrasion plus fibrin sealant instillation, or apical pleurectomy. Blood samples were collected preoperatively and 48 h and 28 days postoperatively to measure total leukocytes (white blood cell count), neutrophil counts, and serum interleukin (IL)-8 levels. After 28 days the animals were sacrificed for macroscopic evaluation of the degree of apical pleurodesis and microscopic evaluation of local pleural fibrosis and collagen deposition.

Results  White blood cell and neutrophil counts were similar in all groups, whereas the serum IL-8 level peaked at 48 h in all groups and decreased after 28 days, except in the pleurectomy group. After 28 days the abrasion plus fibrin sealant and pleurectomy groups had significantly more pleural adhesions, pleural fibrosis, and collagen deposition than the abrasion alone group, mainly due to thick mature fibers.

Conclusions  Abrasion with local fibrin sealant instillation is as effective as pleurectomy in producing pleurodesis in rabbits. Apical pleurectomy elicits a more persistent elevation of serum IL-8 levels than apical abrasion alone or abrasion plus fibrin adhesive instillation.

Translating Basic Research into Clinical Practice

Chest. 2016;150(3):680-693. doi:10.1016/j.chest.2016.06.009

Mast cells (MCs) are present in connective tissue and at mucosal surfaces in all classes of vertebrates. In health, they contribute to tissue homeostasis, host defense, and tissue repair via multiple receptors regulating the release of a vast stockpile of proinflammatory mediators, proteases, and cytokines. However, these potentially protective cells are a double-edged sword. When there is a repeated or long-term stimulus, MC activation leads to tissue damage and dysfunction. Accordingly, MCs are implicated in the pathophysiologic aspects of numerous diseases covering all organs. Understanding the biology of MCs, their heterogeneity, mechanisms of activation, and signaling cascades may lead to the development of novel therapies for many diseases for which current treatments are lacking or are of poor efficacy. This review will focus on updates and developments in MC biology and their clinical implications, with a particular focus on their role in respiratory diseases.

Recent Advances in Chest Medicine

Chest. 2016;150(3):694-704. doi:10.1016/j.chest.2016.03.012

Bronchial thermoplasty (BT) is a therapeutic intervention that delivers targeted thermal energy to the airway walls with the goal of ablating the smooth muscle in patients with severe persistent asthma. Since the publication of the original preclinical studies, three large randomized clinical trials evaluating its impact on asthma control have been performed. These trials have shown improvements in asthma-related quality of life and a reduction in asthma exacerbations following treatment with BT. However, there remains significant controversy regarding the true efficacy of BT and the interpretation of these studies, particularly the Asthma Intervention Research 2 trial. In this article, we will discuss these controversies and present the latest evidence on the use of BT in asthma, specifically the 5-year longitudinal evaluation of patients. In addition, we will discuss new insights into the histopathologic changes that occur in the airways following BT, as well as the feasibility of performing the procedure in patients with very severe asthma. We also will discuss the ongoing translational and clinical investigations regarding the underlying mechanism of action and methods to improve patient selection for this procedure.

Topics in Practice Management

Chest. 2016;150(3):705-713. doi:10.1016/j.chest.2016.05.010

Pulmonary hypertension (PH) is an increasingly recognized cause of morbidity and mortality, and in the past 20 years, there has been a rapid expansion in research and available therapies. Although it is defined quite simply as a mean pulmonary arterial pressure of ≥ 25 mm Hg, PH encompasses a heterogeneous group of disease processes. In the past, PH was classified as primary or secondary, but as understanding of the various contributing diseases has increased, classification systems have attempted to group these diseases by clinical features and disease mechanism. The evaluation of patients with suspected PH can be cumbersome, and a careful and methodical approach is needed to ensure timely and accurate diagnosis, correct physiological classification, and appropriate treatment. In this review, we discuss the classification and diagnostic evaluation of PH in adults as well as some of the billing and coding considerations involved in this evaluation.

Medical Ethics

Chest. 2016;150(3):714-721. doi:10.1016/j.chest.2016.05.026

Disputes regarding life-prolonging treatments are stressful for all parties involved. These disagreements are appropriately almost always resolved with intensive communication and negotiation. Those rare cases that are not require a resolution process that ensures fairness and due process. We describe three recent cases from different countries (the United States, United Kingdom, and Ontario, Canada) to qualitatively contrast the legal responses to intractable, policy-level disputes regarding end-of-life care in each of these countries. In so doing, we define the continuum of clinical and social utility among different types of dispute resolution processes and emphasize the importance of public reason-giving in the societal discussion regarding policy-level solutions to end-of-life treatment disputes. We argue that precedential, publicly available, written rulings for these decisions most effectively help to move the social debate forward in a way that is beneficial to clinicians, patients, and citizens. This analysis highlights the lack of such rulings within the United States.

Contemporary Reviews in Critical Care Medicine

Chest. 2016;150(3):722-731. doi:10.1016/j.chest.2016.03.003

Neuromuscular disorders are increasingly recognized as a cause of both short- and long-term physical morbidity in survivors of critical illness. This recognition has given rise to research aimed at better understanding the risk factors and mechanisms associated with neuromuscular dysfunction and physical impairment associated with critical illness, as well as possible interventions to prevent or treat these issues. Among potential risk factors, bed rest is an important modifiable risk factor. Early mobilization and rehabilitation of patients who are critically ill may help prevent or mitigate the sequelae of bed rest and improve patient outcomes. Research studies and quality improvement projects have demonstrated that early mobilization and rehabilitation are safe and feasible in patients who are critically ill, with potential benefits including improved physical functioning and decreased duration of mechanical ventilation, intensive care, and hospital stay. Despite these findings, early mobilization and rehabilitation are still uncommon in routine clinical practice, with many perceived barriers. This review summarizes potential risk factors for neuromuscular dysfunction and physical impairment associated with critical illness, highlights the potential role of early mobilization and rehabilitation in improving patient outcomes, and discusses some of the commonly perceived barriers to early mobilization and strategies for overcoming them.

Contemporary Reviews in Sleep Medicine

Chest. 2016;150(3):732-743. doi:10.1016/j.chest.2016.04.016

Consumer-driven sleep-tracking technologies are becoming increasingly popular with patients with sleep disorders and the general population. As the list of sleep-tracking technologies continues to grow, clinicians and researchers are faced with new challenges and opportunities to incorporate these technologies into current practice. We review diagnostic tools used in sleep medicine clinical practice, discuss categories of consumer sleep-tracking technologies currently available, and explore the advantages and disadvantages of each. Potential uses of consumer sleep-tracking technologies to enhance sleep medicine patient care and research are also discussed.

Pectoriloquy

Chest. 2016;150(3):744. doi:10.1016/j.chest.2016.03.038
FREE TO VIEW

    Your fingers stained with blood
    claw into parchment of skin.
    Bits of apple-turkey sausage cook

    in four circles of a Swiss Plett Pan.
    The chef breaks eggs onto
    sausage, we wait for them to gel.

    Four cousins wait for your liver
    to fail even more, to swell
    beyond deluge. The chef slides

    egg-sausage onto toasted English
    muffins, drips guacamole
    & mild mango salsa on top. How

    could your fade out be better,
    this closure of three-quarters
    of a century with a Plett Pan brunch?

    Forgive us, we forgot the pancake
    mix, but never the smoked
    salmon that you say in your still deep

    baritone is the best you've ever tasted.
    God knows, we've all eaten
    our share when we called it lox, when

    our parents were in the line of fire.
    I say it's like latte to grandma's
    children's coffee that she boiled

    in a white enamel pan in her brownstone
    in Baltimore. Our mothers:
    four siblings—two cancers, one dementia

    one old age—all four exiting in their
    nineties. We wait for hospice,
    for the dew of morphine. For the cancer

    to break open its shackles, to let you go
    tango closer to the moon,
    the quarter-moons of your cuticles

    obscured by blood & salsa as you raise
    egg-sausage to fragility. Your
    laugh raucous as ever. You retell

    the time your mother soaked her pedal
    pushers, socks & shoes with urine
    on a visit to a Turkish toilet in Paris—

    your mother too old to crouch. Your
    father, dumbstruck, as she resumed
    her quiche, though last time you said

    it was something else. Your eyes blue
    sateen while you make us listen
    to Mostel's “If I Were a Rich Man”

    on your iPhone. We wait for you,
    the second in our generation.
    I wipe mango blood off your fingers,

    kiss each one of them, linger, as in a sort
    of ritual adieu, a bonding around
    a campfire. We wait for the ultimate

    fragment to burn. Oh brunch of blood,
    oh Swiss pancake pan. Oh dear
    cousin who will dare to exit the circle.

Chest. 2016;150(3):745. doi:10.1016/j.chest.2016.03.036
FREE TO VIEW

    We ate Shrimp Diablo cut loose
    with margaritas colossal
    sal
    startled one doctor said
    maybe a rib re-broke rib re-broke
    pain grew and meds then
    dolor
    another doctor said stage 4
    we wished he had said stage door
    pain gasped pressed
    staggered screamed we searched
    for error solution illusion
    breath breath breathe in you
    damp worn-out corrupted lung
    exhale nightmare inhale lavender
    breathe out terror inhale
    rose dew mellifluous disguise
    wear a boutonnière of gardenia
    search for a white tux in your lobe-
    closet bow tie cummerbund
    slick your cilia perfume your pleurae
    stroke yourself with relish
    of wish you are swimming in the deep
    end the deepest end lung
    hold on to your breath breath breath
    choke the cells may they
    evaporate like steam a well
    a spring a smoke ring.

Correspondence

Chest. 2016;150(3):746. doi:10.1016/j.chest.2016.05.037
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We read with great interest “Outcomes of Nurse Practitioner-Delivered Critical Care: A Prospective Cohort Study” recently published in CHEST (May 2016).

Chest. 2016;150(3):746-747. doi:10.1016/j.chest.2016.06.015
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We appreciate the interest demonstrated by Drs Alrajab and Abubaker in our study of critically ill adults cared for by acute care nurse practitioners (ACNPs). Among almost 10,000 patients admitted to a tertiary medical ICU over 3 years, we observed no difference in outcomes between patients cared for by ACNPs vs resident physicians. Drs Alrajab and Abudbaker express concerns over the ability of ACNPs to handle complex patients and the generalizability of ACNP-delivered critical care to community ICUs.

Chest. 2016;150(3):747-748. doi:10.1016/j.chest.2016.05.029
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Quantification of subjective morbidity is essential in research and clinical management of patients with respiratory disease. The St. George’s Respiratory Questionnaire (SGRQ) was designed to measure health status impairment in airways disease. It has been used extensively since its original publication and has been evaluated in various respiratory diseases, including COPD. A PubMed and Scopus database search for SGRQ in the title, abstract, or keywords revealed more than 1,000 papers. The original version has been in existence for more than 2 decades, and has been translated into more than 70 different languages with appropriate linguistic and cultural validation.

Chest. 2016;150(3):748-749. doi:10.1016/j.chest.2016.06.021
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We read the article by Desmarais and Elliott, published in a recent issue of CHEST (April 2016), with great interest. In their report, the authors describe a familial chronic thromboembolic pulmonary hypertension (CTEPH) pair consisting of a 54-year-old woman and her maternal aunt, which represents the first description of familial CTEPH. Herein, we describe another familial CTEPH pair consisting of two Japanese brothers who are 2 years apart in age.

Chest. 2016;150(3):750. doi:10.1016/j.chest.2016.05.039
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We have read with great interest the paper by Franchini et al published in CHEST (August 2016), which reported on a randomized clinical trial comparing the effects of dry nasal low-flow oxygen (NLFO) and cold bubble humidified NLFO on nasal mucociliary clearance (MCC), mucus properties, inflammation, and symptoms in subjects with chronic hypoxemia requiring long-term domiciliary oxygen therapy. A few issues come to mind.

Chest. 2016;150(3):750-751. doi:10.1016/j.chest.2016.06.040
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We thank Drs Vargas and Esquinas for their interest in our manuscript. We fully agree that a third study arm including heated humidification would have provided a worthy comparison. Indeed, we have previously published that in infants receiving chronic oxygen therapy, heated humidification reduced the work of breathing and improved clinical outcomes when compared with a heat and moisture exchanger. Minimal adequate air humidification during invasive mechanical ventilation is reported to be 30 mg H2O/L. This is 50% greater humidity than that provided by the cold bubble humidifier in our study. However, the 2015 British Thoracic Society guidelines still state that humidification is unnecessary for patients receiving nasal low-flow oxygen therapy. The additional cost of a heated humidifier during nasal low-flow oxygen therapy is not covered by Brazilian Government Health Insurance, making our results most representative of the British Thoracic Society guidelines and of actual practice here. We were, therefore, also unable to obtain heated humidifiers for this study.

Chest. 2016;150(3):751-753. doi:10.1016/j.chest.2016.06.041
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In the February 2016 issue of CHEST, Buu and colleagues importantly shed light on outcomes disparities for Hispanic patients with cystic fibrosis (CF) in California over a 20-year span. This vulnerable, yet increasingly growing population, now represents 8.2% of patients with CF in the United States. Authors found Hispanic patients with CF had a 2.81 times higher rate of death compared with non-Hispanics yet similar lung function declines (FEV1), even when adjusting for important variables including insurance status, neighborhood median household income, bacterial infection, and CFTR genotype.

Chest. 2016;150(3):753. doi:10.1016/j.chest.2016.07.008
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We thank Rho et al for sharing the data for Hispanic patients with cystic fibrosis (CF) at their center at the University of Texas Southwestern Medical Center in response to our report of mortality rates for Hispanic patients with CF in California. Their data continue to highlight the importance of the growing number of Hispanic patients with CF. We support the authors’ call for a comprehensive analysis of health outcome for Hispanic patients with CF using national data.

Chest. 2016;150(3):753-755. doi:10.1016/j.chest.2016.06.036
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We read with interest the article by Hu and colleagues in a recent issue of CHEST (January 2016). However, we noted several key omissions, which are subsequently discussed.

Chest. 2016;150(3):755. doi:10.1016/j.chest.2016.06.037
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We appreciate the reader’s interest in our study and have prepared the following response to the reader’s questions.

Chest. 2016;150(3):755-756. doi:10.1016/j.chest.2016.06.044
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We would like to congratulate Thadani et al for their recent report in CHEST (May 2016) that attempted to expand on an unstudied cause and effect model for the occurrence of atrial fibrillation (AF) in men undergoing bisphosphonate therapy. This subanalysis found that bisphosphonate use in elderly men was associated with a greater OR of prevalent nocturnal AF when examined by using a multivariable adjusted model but not clinically relevant incident AF. However, there are a few concerning methodologic deficiencies that may have misguided the conclusion.

Chest. 2016;150(3):756-757. doi:10.1016/j.chest.2016.06.038
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We read with great interest the recent article published by Cillóniz et al in CHEST (August 2016), a descriptive and exploratory study about community-acquired pneumonia (CAP) due to Pseudomonas aeruginosa. The authors reported that 64% of cases of P aeruginosa CAP received inappropriate empirical therapy. Moreover, P aeruginosa and inappropriate empirical treatment are independent risk factors associated with mortality in CAP. However, we would like to raise two points of concern.

Chest. 2016;150(3):757. doi:10.1016/j.chest.2016.06.039
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We appreciate the correspondence of Dr Kashiura et al regarding our recent publication on Community-Acquired Pneumonia due to Multidrug and non-Multidrug Resistant Pseudomonas aeruginosa published in CHEST (August 2016). Kashiura et al raise concerns that for P aeruginosa infection, initial appropriate empirical treatment requires two antibiotics. In response to their comments, our definition was based on the recommendations of the 2007 American Thoracic Society/Infectious Diseases Society of America community-acquired pneumonia (CAP) guidelines and on our previous study. Regarding to the debate surrounding whether to use combination therapy or monotherapy for P aeruginosa CAP, the reason for recommending combination therapy is the possibility of multidrug-resistant (MDR) P aeruginosa infection. We would simply like to point out that our study population included immunocompetent patients with CAP, unlike the studies mentioned, by Dr Kashiura et al, which had a heterogeneous population, including immunosuppressed patients. We believe that future research may identify which specific population may benefit from combination therapy.

Selected Reports

Chest. 2016;150(3):e65-e71. doi:10.1016/j.chest.2016.02.682

We report three cases of pulmonary disease suggesting fibrosis in two familial and one sporadic case. Pulmonary symptoms were associated with various clinical features of systemic inflammation and vasculitis involving the skin, and appeared at different ages. A strong interferon signature was found in all three cases. Disease was not responsive to corticosteroids, and lung transplantation was considered for all three subjects at an early age. One of them underwent double-lung transplantation, but she immediately experienced a primary graft dysfunction and died soon after. Recognized causes of familial interstitial lung disease were all excluded. All three subjects had a mutation in the previously described autoinflammatory disease called SAVI (stimulator of interferon genes [STING]-associated vasculopathy with onset in infancy). These cases emphasize the need to consider this possibility in children and young adults with lung fibrosis after common causes have been ruled out.

Ultrasound Corner

Chest. 2016;150(3):e73-e76. doi:10.1016/j.chest.2015.12.045
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A 50-year-old woman with a history of hypertension and tobacco use was brought in by ambulance after sudden loss of consciousness with persistent coma. She was intubated in the field for airway protection and was profoundly hypertensive on presentation to the emergency department. On arrival, she underwent CT imaging of the brain, which revealed a Hunt and Hess grade 5, Fisher grade 3 subarachnoid hemorrhage (SAH) (Fig 1), with a 5-mm anterior communicating artery aneurysm (Fig 2).

Chest. 2016;150(3):e77-e79. doi:10.1016/j.chest.2016.03.065
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A 24-year-old woman was evaluated in our ED for 2 weeks’ duration of subjective fevers, chills, and generalized fatigue. Her history is significant for intravenous (IV) drug abuse. Review of systems did not reveal any other symptoms such as chest pain, shortness of breath, or headaches. On presentation, she had blood pressure of 124/62, heart rate of 97 beats/min, respiratory rate of 18 breaths/min, and oral temperature of 100.2°F. Pulse oximetry was 97% on room air. Physical examination was unremarkable. Electrocardiogram was normal. Chest radiography showed normal cardiac silhouette with normal lung fields. Laboratory workup showed an erythrocyte sedimentation rate of 38 mm/h, a C-reactive protein of 105 mg/L, and total leukocytic count of 14,000/mm3. Blood culture was drawn, and broad-spectrum antibiotics were administered. Given her history of IV drug abuse, we proceeded to a two-dimensional transthoracic echocardiogram (TTE) to rule out infective endocarditis.

Topics: fever , disasters , abscess

Chest Imaging and Pathology for Clinicians

Chest. 2016;150(3):e81-e85. doi:10.1016/j.chest.2016.03.040
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A 64-year-old male former smoker with a history of prostate cancer presented to our pulmonary clinic, complaining of nonproductive cough for 10 years. Prior evaluation included treatment for upper airway cough syndrome and gastroesophageal reflux, stopping angiotensin-converting enzyme inhibitor, and initiation of inhaled β-agonists. Esophageal pH monitoring indicated silent reflux, and proton pump inhibitor therapy was started. He continued to cough and complain of dyspnea. Physical examination produced unremarkable results, with no evidence of lymphadenopathy. Pulmonary function tests showed a pseudo-restrictive pattern with air trapping, hyperreactivity, and incomplete bronchodilator responsiveness: FEV1, 2.48 L (69% of predicted); FVC, 3.57 L (75% of predicted); FEV1/FVC, 92%; total lung capacity, 7.00 L (100% of predicted); and residual volume, 3.05 L (136% of predicted). Laboratory studies, including a complete metabolic panel, prostate-specific antigen test, and complete blood count, yielded normal results.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;150(3):e87-e91. doi:10.1016/j.chest.2016.03.008
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A 34-year-old white woman who was 30 weeks’ pregnant initially presented to her primary care physician with a cough for which she was given antibiotics, but she had persistent symptoms. These were followed by chest pain, as a result of which she was referred to our department. She had a past medical history of hypertension, and currently was in her sixth pregnancy, with no reported complications in the previous pregnancies. Review of systems was otherwise negative. She had a three-pack-year smoking history, but denied smoking during her current pregnancy.

Topics: pregnancy , chest pain , cough

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