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Current Issue

Editorial

Chest. 2016;150(6):1169-1170. doi:10.1016/j.chest.2016.08.1452

Reporting adverse health experiences resulting from tobacco product use is an important public health initiative. The US Food and Drug Administration (FDA) has a Safety Reporting Portal (SRP) for reporting issues involving tobacco products, in addition to human or animal drug products, foods, and dietary supplements. Although most health-care professionals are familiar with reporting drug-related adverse events, they may be unaware that unexpected health or safety concerns arising from tobacco product use can also be reported. “Tobacco products” means any product made or derived from tobacco and not approved by the FDA for therapeutic use. This includes but is not limited to cigarettes, roll-your-own tobacco, cigars, smokeless tobacco, e-cigarettes, water pipe tobacco, pipe tobacco, and delivery devices and components such as e-cigarette devices and water pipe equipment. Anyone—health-care professionals, researchers, manufacturers, or the public—can submit a report to the SRP.

Chest. 2016;150(6):1171-1173. doi:10.1016/j.chest.2016.06.028

Start with the obvious. Endobronchial ultrasonography (EBUS) has revolutionized the diagnosis and staging of lung cancer and other thoracic pathologic conditions. The literature overflows with support of its benefits, and the paper by Gildea and Nicolacakis in this issue of CHEST alludes to the nearly 1,000 papers published previously. I would go so far as to state that EBUS has had a more profound and practical impact on the care of patients with thoracic cancer and those with benign conditions than all the more recent genetic testing, targeted therapy, high-technology robotics, and other media-worthy treatments of the past 5 years. By properly staging, avoiding unnecessary procedures and risk of complications, directing the patient to the most effective therapy quickly and efficiently, outcomes and quality of life cannot help but be positively impacted.

Chest. 2016;150(6):1174-1176. doi:10.1016/j.chest.2016.09.031

O ye'll tak' the high road, and I'll tak' the low road,And I'll be in Scotland afore ye,Traditional Scottish Song

Chest. 2016;150(6):1177-1178. doi:10.1016/j.chest.2016.07.015

All too often we are reminded that essentially nothing about nontuberculous mycobacterial (NTM) disease is easy or simple, and the role of drug susceptibility/resistance is no exception. Many nontuberculous mycobacteria causing disease display a counterintuitive and frustrating disparity between in vitro drug susceptibility test results and in vivo response to specific antimicrobial agents. This NTM characteristic has been attributed to innate resistance factors that are frequently not reflected in the minimum inhibitory concentration of the antimicrobial agent for the organism., The inducible macrolide resistance (erm) gene in Mycobacterium abscessus subspecies abscessus is one such factor., Innate resistance is also unavoidable.

Chest. 2016;150(6):1179-1180. doi:10.1016/j.chest.2016.10.011

The importance of resuscitation for surviving critical illness and injury has long been recognized and is now a standard and integral part of critical care practice. Our approach to resuscitation has evolved over the past century, encouraged by intense research efforts that have led to clinical trials of alternative resuscitation fluids including hydroxyethyl starch (HES). One of the key understudied aspects of resuscitation is its effect on the duration of illness or injury in relation to the costs of care. It is estimated that each year, 20 to 30 million patients worldwide will receive resuscitation as part of their care. For an integral aspect of commonly delivered care, there is considerable variation in clinical practice regarding the choice of fluid, in part influenced by product availability, local preferences, and costs.

Editorials: Point and Counterpoint

Chest. 2016;150(6):1181-1182. doi:10.1016/j.chest.2016.08.1481

It is logical that an inferior vena cava (IVC) filter can catch clots—like a pasta chef draining noodles through a colander. We have seen them catch these clots, thank goodness. Studies have characterized the comparative clot trapping efficacies of caval filters; however, there are few randomized prospective studies comparing caval filtration with no therapy. Given decades of research, would a patient with DVT and a contraindication to anticoagulation wish to be randomized to the nonfilter group? “Sir, begin your skydive. You may have a parachute in your pack…or a pair of shoes. Pull the ripcord and see.” Therefore, the paucity of controlled trials of filter vs no filter is not surprising. Withholding a relatively benign acute intervention—having a filter placed, is challenging. That said, we readily acknowledge the need to remove filters when this protective value fades. The better question is not, “do filters work?” but rather, “whom do they best help—and for how long?”

Chest. 2016;150(6):1182-1184. doi:10.1016/j.chest.2016.08.1477

Since the Mobin-Uddin umbrella launched in the late 1960s, the implantation of inferior vena cava (IVC) filters has vastly outpaced the quality evidence for their use. In 2012, approximately 250,000 IVC filters were placed in the United States, representing nearly a 1,300-fold increase in 30 years and 25 times the number that were placed in five European countries with comparable total population size.,,,,,, However, despite these staggering volumes, and contrary to expectation, the number of deaths related to venous thromboembolic events (VTEs) in equivalent population sizes were similar in the United States and Europe. We are left asking: what explains the United States’ obsession with IVC filters?

Chest. 2016;150(6):1184-1185. doi:10.1016/j.chest.2016.08.1479

Lessne and Sing raise important considerations regarding the utilization of inferior vena cava (IVC) filters in the United States. A key premise of their argument concerns indications for caval filtration, and they maintain that most filters are currently placed for prophylactic reasons. The references to support this contention are nebulous, and given the huge variability of filter insertion even within similar geographic areas, we doubt that this is known. One of the references cited to support this contention is a review which further cited several studies which also do not prove the contention. In fact, one of the references in this review is from the University of Chicago (one of the author’s institution) in which prophylactic filters comprise < 20% of filters inserted. Incidentally, this same study also reported an 87% retrieval rate showing that with good follow-up, the contention that “optional filters are infrequently removed” is inaccurate. The use of prophylactic filters appears to be decreasing, even in bariatric patients and in trauma centers where prophylactic filter placement is expected to be high., A final complicating factor of this topic is the definition of prophylactic. Does this mean absence of DVT and pulmonary embolism (PE), or DVT but no PE? We favor the former definition, but this is not universal in the published literature.

Chest. 2016;150(6):1185-1186. doi:10.1016/j.chest.2016.08.1482

Our exceptionally worthy opponents justifiably argue that patients with VTE who cannot receive anticoagulation should not be denied a surrogate form of protection with caval filtration. This point is uncontested, and no one advocates for rounding up all inferior vena cava (IVC) filters and tossing them out with the bath water. Unfortunately, this no longer represents the 90% indication, with most filters placed for prophylactic use, where the clinical benefit remains largely unsubstantiated.,

Topics: singing

Commentary

Chest. 2016;150(6):1187-1193. doi:10.1016/j.chest.2016.08.1451

Long-term macrolide therapy offers an evidence-based treatment to reduce frequent exacerbations in stable adult patients with bronchiectasis. There is limited evidence that these agents also attenuate the decline in lung function and improve health-related quality of life. The benefits and risks of long-term macrolide use need to be clearly explored for individual patients. Further work is needed to understand the optimal drug, dose, and regimen, the mechanisms behind these benefits, appropriate patient selection, sustainability of efficacy, potential long-term risk for the lung microbiome; and their use with or without inhaled antibiotic treatment. We reviewed the current evidence on long-term macrolides in adults with bronchiectasis.

Original Research: Sleep Disorders

Chest. 2016;150(6):1194-1201. doi:10.1016/j.chest.2016.04.017

Background  CPAP is the gold standard treatment for OSA and was conceived to be applied through a nasal interface. This study was designed to determine the acute effects of changing the nasal CPAP route to oronasal and oral in upper airway patency during sleep in patients with OSA. We hypothesized that the oronasal route may compromise CPAP’s effectiveness in treating OSA.

Methods  Eighteen patients (mean ± SD age, 44 ± 9 years; BMI, 33.8 ± 4.7 kg/m2; apnea-hypopnea index, 49.0 ± 39.1 events/hour) slept with a customized oronasal mask with nasal and oral sealed compartments connected to a multidirectional valve. Sleep was monitored by using full polysomnography and induced by low doses of midazolam. Nasal CPAP was titrated up to holding pressure. Flow route was acutely changed to the oronasal (n = 18) and oral route (n = 16) during sleep. Retroglossal area was continuously observed by using nasoendoscopy.

Results  Nasal CPAP (14.8 ± 4.1 cm H2O) was able to stabilize breathing in all patients. In contrast, CPAP delivered by the oronasal and oral routes promoted obstructive events in 12 (66.7%) and 14 (87.5%) patients, respectively. Compared with stable breathing during the nasal route, there was a significant and progressive reduction in the distance between the epiglottis and tongue base and the retroglossal area when CPAP was delivered by the oronasal and oral routes.

Conclusions  CPAP delivered through the oronasal route may compromise CPAP’s effectiveness in treating OSA.

Chest. 2016;150(6):1202-1210. doi:10.1016/j.chest.2016.07.012

Background  Based on meta-analyses, the BP-lowering effect of CPAP therapy in patients with OSA is reported to be approximately 2 to 3 mm Hg. This figure is derived from heterogeneous trials, which are often limited by poor CPAP adherence, and thus the treatment effect may possibly be underestimated. We analyzed morning BP data from three randomized controlled CPAP withdrawal trials, which included only patients with optimal CPAP compliance.

Methods  Within the three trials, 149 patients with OSA who were receiving CPAP were randomized to continue therapeutic CPAP (n = 65) or to withdraw CPAP (n = 84) for 2 weeks. Morning BP was measured at home before and after sleep studies in the hospital.

Results  CPAP withdrawal was associated with a return of OSA (apnea-hypopnea index [AHI] at a baseline of 2.8/h and at follow-up of 33.2/h). Office systolic BP (SBP) increased in the CPAP withdrawal group compared with the CPAP continuation group by +5.4 mm Hg (95% CI, 1.8-8.9 mm Hg; P = .003) and in the home SBP group by +9.0 mm Hg (95% CI, 5.7-12.3 mm Hg; P < .001). Office diastolic BP (DBP) increased by +5.0 mm Hg (95% CI, 2.7-7.3 mm Hg; P < .001), and home DBP increased by +7.8 mm Hg (95% CI, 5.6-10.4 mm Hg; P < .001).AHI, baseline home SBP, use of statin drugs, sex, and the number of antihypertensive drugs prescribed were all independently associated with SBP change in multivariate analysis, controlling for age, BMI, smoking status, diabetes, and sleepiness.

Conclusions  CPAP withdrawal results in a clinically relevant increase in BP, which is considerably higher than in conventional CPAP trials; it is also underestimated when office BP is used. Greater OSA severity is associated with a higher BP rise in response to CPAP withdrawal.

Trial Registry  ClinicalTrials.gov; No.: NCT01332175 and NCT01797653) URL: www.clinicaltrials.gov and ISRCTN registry (ISRCTN 93153804) URL: http://www.isrctn.com/.

Original Research: Chest Infections

Chest. 2016;150(6):1211-1221. doi:10.1016/j.chest.2016.05.003

Background  Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease.

Methods  Seventy-one patients received oral macrolides, along with an initial 4-week (n = 28) or 2-week (n = 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24 months (4-week IV group) or for at least 12 months after negative sputum culture conversion (2-week IV group).

Results  Total treatment duration was longer in the 4-week IV group (median, 23.9 months) than in the 2-week IV group (15.2 months; P < .001). The response rates after 12 months of treatment were 89% for symptoms, 79% for CT scanning, and 100% for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100% (P = .057), 91% (P = .177), and 91% (P = .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense.

Conclusions  Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease.

Trial registry  ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.

Chest. 2016;150(6):1222-1232. doi:10.1016/j.chest.2016.06.005

Background  There are few data regarding the impact of nontuberculous mycobacterial lung disease (NTM-LD) on lung function during the clinical course of disease. This study aimed to assess the impact of NTM-LD on lung function decline.

Methods  Treatment outcomes and spirometry data at diagnosis and at least three years later were obtained from 358 patients who were diagnosed with NTM-LD between January 1999 and November 2011 using the prospective NTM registry cohort. For analysis, patients were divided into three groups: those observed without treatment, those who had treatment success, and those in whom treatment failed.

Results  The treatment-failure group (n = 68) had a significantly more rapid decline in FEV1 and FVC compared with the observation (n = 118) and treatment-success (n = 172) groups (–52.2, –30.8, and –28.2 mL/y, respectively; P = .023 for FEV1 decline; –50.4, –28.8, and –26.0 mL/y, respectively; P = .002 for FVC decline). After adjusting for confounding factors, patients with treatment failure had greater FEV1 and FVC declines than did those observed without treatment (adjusted P = .026 for FEV1 decline; adjusted P = .022 for FVC decline) or those treated successfully (adjusted P = .004 for FEV1 decline; adjusted P = .002 for FVC decline). Patients treated successfully had declines in FEV1 and FVC similar to those in the observation group.

Conclusions  The change of lung function was variable over a median 5-year follow-up period. Treatment failure was associated with a substantial decline in lung function in NTM-LD.

Chest. 2016;150(6):1233-1241. doi:10.1016/j.chest.2016.06.004

Background  The use of antipsychotic agents has been associated with increased pneumonia risk, but although people with dementia are particularly susceptible to pneumonia, only one small study has assessed the risk of pneumonia in relation to the use of antipsychotic agents among people with Alzheimer disease (AD).

Methods  We investigated whether the incident use of antipsychotic agents, or specific antipsychotic agents, are related to a higher risk of hospitalization or death due to pneumonia in the Medication and Alzheimer Disease (MEDALZ) cohort. The cohort includes all individuals with AD who received a clinically verified AD diagnosis in Finland in 2005 to 2011 (N = 60,584; incident pneumonia, n = 12,225). A matched comparison cohort without AD (N = 60,584; incident pneumonia, n = 6,195) was used to compare the magnitude of risk. Results were adjusted for a propensity score derived from comorbidities, concomitant medications, and sociodemographic characteristics. Sensitivity analyses with case-crossover design were conducted.

Results  The use of antipsychotic agents was associated with a higher risk of pneumonia (adjusted hazard ratio [HR], 2.01; 95% CI, 1.90-2.13) in the AD cohort and a somewhat higher risk in the non-AD cohort (adjusted HR, 3.43; 95% CI, 2.99-3.93). Similar results were observed with case-crossover analyses (OR, 2.02; 95% CI, 1.75-2.34 in the AD cohort and OR, 2.59; 95% CI, 1.77-3.79 in the non-AD cohort). The three most commonly used antipsychotic agents (quetiapine, risperidone, haloperidol) had similar associations with pneumonia risk.

Conclusions  Regardless of applied study design, treatment duration, or the choice of drug, the use of antipsychotic agents was associated with a higher risk of pneumonia. With observational data, we cannot fully rule out a shared causality between pneumonia and the use of antipsychotic agents, but the risk to benefit balance should be considered when antipsychotic agents are prescribed.

Original Research: Asthma

Chest. 2016;150(6):1242-1250. doi:10.1016/j.chest.2016.09.020

Background  Sleep difficulties are commonly reported by patients with asthma; however, the prevalence of insomnia and its association with disease burden and well-being is unknown. We aimed to determine the prevalence of insomnia, defined as combined sleep-specific complaints with associated daytime symptoms, among a large sample of adults with asthma, and to compare well-being, asthma control, and asthma-related health care utilization in individuals with asthma and insomnia and those without insomnia.

Methods  Baseline data from adults with physician-confirmed asthma enrolled in the Severe Asthma Research Program III was used for analyses (N = 714). Participants completed the Insomnia Severity Index (ISI), Asthma Control Test, Asthma Quality of Life Questionnaire, and Hospital Anxiety and Depression Scale.

Results  Insomnia (ISI ≥ 10) was identified in 263 participants (37%). Presence of insomnia was associated with higher levels of depression and anxiety symptoms and poorer quality of life. Those with insomnia had a 2.4-fold increased risk for having not well-controlled asthma and a 1.5-fold increased risk for asthma-related health care utilization in the past year compared with those without insomnia.

Conclusions  Insomnia is highly prevalent in asthma and is associated with adverse outcomes. Further studies are needed to gain a better understanding of the interaction between insomnia and asthma control.

Original Research: Critical Care

Chest. 2016;150(6):1251-1259. doi:10.1016/j.chest.2016.08.1460

Background  Although 28% to 49% of severe sepsis hospitalizations have been described as being “culture negative,” there are very limited data on the epidemiology and outcomes of those with culture-negative severe sepsis (CNSS). The objectives of this study were to investigate the proportion and trends of CNSS and its association with mortality.

Methods  Using the Nationwide Inpatient Sample (NIS) database from 2000 to 2010, we identified adults hospitalized with severe sepsis. Those without any specific organism codes were identified as “with CNSS.” We examined the proportion of CNSS hospitalizations and rates of mortality associated with it. We also assessed the independent effect of CNSS on mortality.

Results  Of 6,843,279 admissions of patients with severe sepsis, 3,226,406 (47.1%) had culture-negative results. The age-adjusted proportion of CNSS increased from 33.9% in 2000 to 43.5% in 2010 (P < .001). Those with CNSS had more comorbidities, acute organ dysfunction (respiratory, cardiac, hepatic, and renal dysfunction), and in-hospital mortality (34.6% vs 22.7%; P < .001), although acute kidney injury requiring dialysis was less frequent (5.3% vs 6.1%; P < .001). CNSS was an independent predictor of mortality in those with severe sepsis (OR, 1.75; 95% CI, 1.72-1.77).

Conclusions  CNSS among hospitalized patients is common, and its proportion is on the rise. CNSS is associated with greater acute organ dysfunction and mortality. Having CNSS is an independent predictor of death.

Topics: sepsis, severe , trend
Chest. 2016;150(6):1260-1268. doi:10.1016/j.chest.2016.06.008

Background  Mortality after smoke inhalation–associated acute lung injury (SI-ALI) remains substantial. Age and burn surface area are risk factors of mortality, whereas the impact of patient- and center-level variables and treatments on survival are unknown.

Methods  We performed a retrospective cohort study of burn and non-burn centers at 68 US academic medical centers between 2011 and 2014. Adult inpatients with SI-ALI were identified using an algorithm based on a billing code for respiratory conditions from smoke inhalation who were mechanically ventilated by hospital day 4, with either a length-of-stay ≥ 5 days or death within 4 days of hospitalization. Predictors of in-hospital mortality were identified using logistic regression. The primary outcome was the odds ratio for in-hospital mortality.

Results  A total of 769 patients (52.9 ± 18.1 years) with SI-ALI were analyzed. In-hospital mortality was 26% in the SI-ALI cohort and 50% in patients with ≥ 20% surface burns. In addition to age > 60 years (OR 5.1, 95% CI 2.53-10.26) and ≥ 20% burns (OR 8.7, 95% CI 4.55-16.75), additional risk factors of in-hospital mortality included initial vasopressor use (OR 5.0, 95% CI 3.16-7.91), higher diagnostic-related group–based risk-of-mortality assignment and lower hospital bed capacity (OR 2.3, 95% CI 1.23-4.15). Initial empiric antibiotics (OR 0.93, 95% CI 0.58-1.49) did not impact survival. These new risk factors improved mortality prediction by 9.9% (P < .001).

Conclusions  In addition to older age and major surface burns, mortality in SI-ALI is predicted by initial vasopressor use, higher diagnostic-related group–based risk-of-mortality assignment, and care at centers with < 500 beds, but not by initial antibiotic therapy.

Original Research: COPD

Chest. 2016;150(6):1269-1280. doi:10.1016/j.chest.2016.08.1474

Background  The trends of COPD mortality and prevalence over the past 2 decades across all provinces remain unknown in China. We used data from the Global Burden of Disease Study 2013 (GBD 2013) to estimate the mortality and prevalence of COPD during 1990 to 2013 at a provincial level.

Methods  Following the general analytic strategy used in GBD 2013, we analyzed the age- sex- and province-specific mortality and prevalence of COPD in China. Levels of and trends in COPD mortality and prevalence were assessed for 33 province-level administrative units during 1990 to 2013.

Results  In 2013, there were 910,809 deaths from COPD in China, accounting for 31.1% of the total deaths from COPD in the world. From 1990 to 2013, the age-standardized COPD mortality rate decreased in all provinces, with the highest reduction in Heilongjiang (70.2%) and Jilin (70.0%) and the lowest reduction in Guizhou (26.8%). In 2013, the death rate per 100,000 was highest in Guizhou (196.0) and lowest in Tianjin (34.0) among men and highest in Gansu (141.1) and lowest in Beijing (23.7) among women. The number of COPD cases increased dramatically from 32.4 million in 1990 to 54.8 million in 2013. The age-standardized prevalence rate of COPD remained stable overall and varied little for all provinces.

Conclusions  COPD remains a huge health burden in many western provinces in China. The substantial increase in COPD cases represents an ongoing challenge given the rapidly aging Chinese population. A targeted control and prevention strategy should be developed at a provincial level to reduce the burden caused by COPD.

Chest. 2016;150(6):1281-1290. doi:10.1016/j.chest.2016.07.033

Background  Although FEV1 remains the gold standard for staging COPD, the association between airway remodeling and airflow limitation remains unclear. Endobronchial optical coherence tomography (EB-OCT) was performed to assess the association between disorders of large and medium to small airways and COPD staging. We also evaluated small airway architecture in heavy smokers with normal FEV1 (SNL) and healthy never-smokers.

Methods  We recruited 48 patients with COPD (stage I, n = 14; stage II, n = 15; stage, III-IV, n = 19), 21 SNL, and 17 healthy never-smokers. A smoking history inquiry, as well as spirometry, chest CT, bronchoscopy, and EB-OCT were performed. Mean luminal diameter (Dmean), inner luminal area (Ai), and airway wall area (Aw) of third- to ninth-generation bronchi were measured using EB-OCT.

Results  Patients with more advanced COPD demonstrated greater abnormality of airway architecture in both large and medium to small airways, followed by SNL and never-smokers. Abnormality of airway architecture and EB-OCT parameters in SNL were comparable to those in stage I COPD. FEV1% predicted correlated with Dmean and Ai of seventh- to ninth-generation bronchi in COPD; however, neither Dmean nor Ai of third- to sixth-generation bronchi correlated with FEV1% in stage I and stage II COPD and in SNL.

Conclusions  FEV1-based COPD staging partially correlates with small airway disorders in stage II-IV COPD. Small airway abnormalities detected by EB-OCT correlate with FEV1-based staging in COPD and identify early pathologic changes in healthy heavy smokers.

Original Research: Antithrombotic Therapy

Chest. 2016;150(6):1291-1301. doi:10.1016/j.chest.2016.07.011

Background  OSA is a risk factor for a first episode of pulmonary embolism (PE), although its impact on the risk of thromboembolism recurring is uncertain. Our objective was to explore the prognostic value of OSA after the discontinuation of oral anticoagulation (OAC) in patients with a first episode of PE.

Methods  In 120 consecutive patients who had stopped OAC for a first episode of PE, we performed home respiratory polygraphy and recorded sleep characteristics, classic risk factors for PE, blood pressure measurements, spirometric parameters, physical activity, and levels of D-dimer and prothrombin fragment 1+2 (F1+2). Patients were followed for 5 to 8 years, and the main end point was PE recurrence. Restarting OAC for any thromboembolic event was evaluated as a secondary end point.

Results  During the follow-up period, 19 patients had a PE recurrence, and 16 of them had an apnea-hypopnea index (AHI) ≥ 10 h–1. In a multivariate Cox regression model, an AHI ≥ 10 h–1 (hazard ratio [HR], 20.73; 95% CI, 1.71-251.28), mean nocturnal oxygen saturation (nSao2) (HR, 0.39; 95% CI, 0.20-0.78), time with Sao2 < 90% (CT90%) (HR, 0.90; 95% CI, 0.82-0.98), and D-dimer level (HR, 1.001; 95% CI, 1.00-1.002) were identified as independent risk factors for recurrent PE. Twenty-four patients resumed OAC, and AHI ≥ 10 h–1 (HR, 20.66; 95% CI, 2.27-188.35), mean nSao2 (HR, 0.54; 95% CI, 0.32-0.94), and Epworth Sleepiness Scale (ESS) (HR, 0.73; 95% CI, 0.56-0.97) were retained as independent risk factors for the resumption of OAC.

Conclusions  After a first episode of PE, OSA is an independent risk factor for PE recurrence or restarting OAC for a new thromboembolic event.

Chest. 2016;150(6):1302-1312. doi:10.1016/j.chest.2016.07.013

Background  The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) has been a major advance for stroke prevention in atrial fibrillation (AF). Patients and clinicians now have a choice between different NOACs, but there is no direct comparative effectiveness evidence to guide decision-making. We aimed to compare the effectiveness and safety of dabigatran, rivaroxaban, and apixaban in clinical practice.

Methods  Using a large US administrative claims database, we created three one-to-one propensity-score-matched cohorts of patients with nonvalvular AF who were users of dabigatran, rivaroxaban, or apixaban between October 1, 2010 and February 28, 2015 (rivaroxaban vs dabigatran, n = 31,574; apixaban vs dabigatran, n = 13,084; and apixaban vs rivaroxaban, n = 13,130). The primary outcomes were stroke and systemic embolism (effectiveness) and major bleeding (safety) that occurred during treatment. Cox proportional hazards models were used to compare outcomes in propensity-score-matched cohorts.

Results  We found no differences between the three NOACs in the risk of stroke or systemic embolism (hazard ratio [HR], 1.00; 95% CI, 0.75-1.32 for rivaroxaban vs dabigatran; HR, 0.82; 95% CI, 0.51-1.31 for apixaban vs dabigatran; and HR, 1.05; 95% CI, 0.64-1.72 for apixaban vs rivaroxaban). Apixaban was associated with a lower risk of major bleeding (HR, 0.50; 95% CI, 0.36-0.70; P < .001 vs dabigatran and HR, 0.39; 95% CI, 0.28-0.54; P < .001 vs rivaroxaban). Rivaroxaban was associated with an increased risk of major bleeding (HR, 1.30; 95% CI, 1.10-1.53; P < .01) and intracranial bleeding (HR, 1.79; 95% CI, 1.12-2.86; P < .05) compared with dabigatran.

Conclusions  Dabigatran, rivaroxaban, and apixaban appear to have similar effectiveness, although apixaban may be associated with a lower bleeding risk and rivaroxaban may be associated with an elevated bleeding risk.

Original Research: Pulmonary Vascular Disease

Chest. 2016;150(6):1313-1322. doi:10.1016/j.chest.2016.07.036

Background  Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension. The aim of the study was to evaluate the incremental prognostic value of echocardiography of the right ventricle and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients.

Methods  One hundred and thirty treatment-naïve patients with idiopathic pulmonary arterial hypertension were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-min walk distance plus an increase in functional class, or nonelective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic, and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done.

Results  During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical, and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (model 1). With addition of echocardiographic and CPET variables (model 2), peak O2 pulse (peak o2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (area under the curve, 0.81 vs 0.66, respectively; P = .005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC + low O2 pulse showed a 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk, 41.1 and 25.3, respectively), compared with high RVFAC + high O2 pulse (P = .0001).

Conclusions  Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration.

Original Research: Genetic and Developmental Disorders

Chest. 2016;150(6):1323-1332. doi:10.1016/j.chest.2016.06.029

Background  Lung clearance index (LCI) has good clinimetric properties and an acceptable feasibility profile as a surrogate end point in cystic fibrosis (CF). Although most studies to date have been in children, increasing numbers of adults with CF also have normal spirometric findings. Further study of LCI as an end point in adults with CF is required. Therefore, the purpose of this study was to determine the clinimetric properties of LCI across the age range of people with CF.

Methods  Clinically stable adults and children with CF and age-matched healthy control subjects were recruited.

Results  LCI and spirometry data for 110 subjects with CF and 61 control subjects were collected at a stable visit. The CF Questionnaire-Revised (CFQ-R) was completed by 80 of 110 subjects with CF. Fifty-six subjects with CF completed a second stable visit. The LCI coefficient of variation percent was 4.1% in adults and 6.3% in children with CF. The coefficient of repeatability of LCI was 1.2 in adults and 1.3 in children. In both adults and children, LCI (area under the receiving operator characteristic curve [AUCROC] = 0.93 and 0.84, respectively) had greater combined sensitivity and specificity to discriminate between people with CF and control subjects when compared with FEV1 (AUCROC = 0.88 and 0.60, respectively) and forced expiratory flow at 25% to 75% of the curve (AUCROC = 0.87 and 0.68, respectively). LCI correlated significantly with the CFQ-R treatment burden in adults (r = –0.37; P < .01) and children (r = –0.50; P < .01). Washout tests were successful in 90% of subjects with CF and were perceived as comfortable and easy to perform in both adults and children.

Conclusions  These data support the use of LCI as a surrogate outcome measure in CF clinical trials in adults as well as in children.

Original Research: Disaster Medicine

Chest. 2016;150(6):1333-1340. doi:10.1016/j.chest.2016.07.005

Background  World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, whereas persistence of BHR has not been investigated.

Methods  A total of 173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after September 11, 2001 (9/11) (baseline methacholine challenge test), were reevaluated in 2013 and 2014 (follow-up methacholine challenge test). FEV1 measurements were obtained from the late pre-9/11, early post-9/11, and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded.

Results  Bronchial reactivity remained stable (within 1 doubling dilution) for most (n = 101, 58%). Sixteen of 28 (57%) with BHR (provocative concentration of methacholine producing a 20% decline in FEV1 <8 mg/mL) at baseline had BHR at follow-up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR, 6.46) and that BHR at follow-up was associated with an estimated 15.4 mL/y greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use.

Conclusions  Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.

Evidence-Based Medicine

Chest. 2016;150(6):1341-1360. doi:10.1016/j.chest.2016.08.1458
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Background  We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome.

Methods  Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux?

Results  We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely.

Conclusions  The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Translating Basic Research Into Clinical Practice

Chest. 2016;150(6):1361-1370. doi:10.1016/j.chest.2016.07.030

The incidence of pleural infection has been rising in recent years. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) has significantly reduced the need for surgery, and its impact on clinical care is rising worldwide. Efforts are underway to optimize the delivery regimen and establish the short and longer term effects of this therapy. The complex interactions of bacterial infection within the pleura with inflammatory responses and clinical interventions (antibiotics and tPA/DNase or other fibrinolysins) require further studies to improve future treatment options. Intrapleural instillation of tPA potently induces pleural fluid formation, principally via a monocyte chemotactic protein (MCP)-1 dependent mechanism. Activation of transcriptional programs in pleural resident cells and infiltrating cells during pleural infection and malignancy results in the local secretion of a cocktail of proinflammatory signaling molecules (including MCP-1) within the pleural confines that contributes to effusion formation. Understanding the biology of these molecules and their interaction may provide novel targets for pleural fluid control.

Recent Advances in Chest Medicine

Chest. 2016;150(6):1371-1386. doi:10.1016/j.chest.2016.07.027
OPEN ACCESS

Among the interstitial lung diseases (ILDs), idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis, and fibrotic connective tissue disease-related ILD are associated with a worse prognosis, with death occurring as a result of both respiratory failure and serious associated comorbidities. The recent development and approval of the antifibrotic agents nintedanib and pirfenidone, both of which reduced the rate of decline in lung function in patients with IPF in clinical trials, offer hope that it may be possible to alter the increased mortality associated with IPF. Although chronic hypersensitivity pneumonitis and connective tissue disease related-ILD may be associated with an inflammatory component, the evidence for the use of immunosuppressive agents in their treatment is largely limited to retrospective studies. The lack of benefit of immunosuppressive therapy in advanced fibrosis argues for rigorous clinical trials using antifibrotic therapies in these types of ILD as well. Patients with fibrotic ILD may benefit from identification and management of associated comorbid conditions such as pulmonary hypertension, gastroesophageal reflux, and OSA, which may improve the quality of life and, in some cases, survival in affected individuals. Because early assessment may optimize posttransplantation outcomes, lung transplant evaluation should occur early in patients with IPF and those with other forms of fibrotic ILD.

Topics in Practice Management

Chest. 2016;150(6):1387-1393. doi:10.1016/j.chest.2016.05.009

Endobronchial ultrasonography (EBUS) has become an invaluable tool in the diagnosis of patients with a variety of thoracic abnormalities. The majority of EBUS procedures are used to diagnose and stage mediastinal and hilar abnormalities, as well as peripheral pulmonary targets, with a probe-based technology. Nearly 1,000 articles have been written about its use and utility. New Current Procedural Terminology (CPT) codes have been introduced in 2016 to better capture the work and clinical use associated with the various types of EBUS procedures. The existing 31620 code has been deleted and replaced by three new codes: 31652, 31653, and 31654. These new codes have been through the valuation process, and the new rule for reimbursement has been active since January 1, 2016 with National Correct Coding Initiative correction as of April 1, 2016. The impact of these new codes will result in a net reduction in professional and technical reimbursement. This article describes the current use of EBUS and explains the current codes and professional reimbursement.

Contemporary Reviews in Critical Care Medicine

Chest. 2016;150(6):1394-1402. doi:10.1016/j.chest.2016.03.044

The critically ill, asplenic patient presents a variety of management challenges. Historically, the focus of the care of the asplenic population has been the prevention and management of infection, including the often-fatal overwhelming postsplenectomy infection with encapsulated organisms such as Streptococcus pneumoniae. Recently, however, there has been increasing recognition of the spleen’s function in areas outside of immunity because the asplenic state has been identified as a risk factor for such vascular complications as thrombosis and pulmonary hypertension resulting from dysregulated inflammation and coagulation. Because of the relatively small size of this population and the relative infrequency with which critical illness occurs in it, there are few controlled trials that can serve as a basis for therapeutic maneuvers; thus, optimal management requires an astute clinician with an understanding of the pathogenetic mechanisms underlying the reported consequences of splenectomy. The purpose of this review is to explore the pathophysiology of the asplenic state—impairment in adaptive immunity, loss of blood filtration, endothelial dysfunction, and dysregulated coagulation—and how it leads to infection, thrombosis, and pulmonary hypertension as well as to discuss the implications of these conditions on the management of the critically ill, splenectomized patient.

Pectoriloquy

Chest. 2016;150(6):1403. doi:10.1016/j.chest.2016.07.020
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    Agreement to participate,
    Blueprint of the investigation,
    Details the why and how of the treatment,
    One’s expected experiences as volunteer,
    Sets forth criteria for participation.

    Answers the question, Why me?
    Describes the extent of the screening,
    Explains the nature of randomization,
    Differences in arms of the study,
    Disclaimers address benefits to participating.

    Does not shy away from truth,
    Impact of experimental drug enumerated,
    Quality of life becomes matter of judgment,
    Seminal questions for volunteer: Will it aid me?
    Willingness to trust the investigator exhibited.

    No answers to some questions available,
    Stats from other trials at best indicators,
    Need to seek advice from family and friends,
    Digging deep to find in heart and mind courage,
    To assume mantle of strength near heroic.

Chest. 2016;150(6):1404. doi:10.1016/j.chest.2016.07.024
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    The lights are flashing
    but it isn't Christmas
    …and bells, bells & horns
    & peculiarly seductive sirens,
    a moving Renaissance band
    playing those crazy
    Medieval instruments:
    Sacbut, Bladder Pipe, Serpent…
    I hear your steady drum beat,
    a tympanic Pavane,
    lub-dub, lub-dub,
    traveling
    through serpent's pipes.
    My a capella Madrigal:
    Take a deep breath, another,
    then a murmuration of Starlings,
    caged.
    We both breathe the same Ayre
    as the band marches on.

Chest. 2016;150(6):1405. doi:10.1016/j.chest.2016.07.045
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    I spent a lot of time last week
    parsing definitions & making
    choices. By putting my initials
    here, instead of there, I instruct
    the future to do this or that to me
    when I can’t speak for myself.

    The document must be signed,
    witnessed, notarized, which
    takes some doing when you are
    not well. So I arranged a meeting
    with the Cancer Center’s notary
    & brought my document. We sat

    in a corner of the lobby, going
    over the initialings & affixing
    signatures. For witnesses, we
    asked random workers from
    Admitting. We laughed & joked,
    strangers going through this

    necessary ritual. They are used
    to it, of course, but I suspect
    a light touch of unease passed
    through them. We all knew why
    I was signing this right now.
    (I was the one in the wheelchair.)

    They had been picked out
    by chance that day to be confronted
    with this reminder, a dark wing
    passing through the sunlight,
    trailing a faint shadow. That’s
    why we joked so much, no doubt.

Chest. 2016;150(6):1405. doi:10.1016/j.chest.2016.07.046
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    They wheel you through
    an S-shaped labyrinth
    with photographs of flowers
    so close-up you can see
    individual grains of pollen.

    The technicians ask you
    what kind of music you like
    & find a Sirius channel
    to play through the
    big speakers in the ceiling.

    They help you up
    onto the long glass table
    mounted beneath what can
    only be described as a ray-gun.
    It’s going to shoot x-rays

    through your hip & spine.
    That’s where the malady
    has emerged to hurt you.
    They’re going to hit it with
    a million volts for five days

    running. They paste on little
    targets & they line you up.
    Some noise, the music swells,
    a whine. That’s all there is
    to it. The cells of hope divide

    & multiply. They wheel you
    Same
    time tomorrow
    wafts scents of flowers to you.
    You don’t know what to think.

Correspondence

Chest. 2016;150(6):1406. doi:10.1016/j.chest.2016.08.1480
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I have read with the greatest interest the article by Masa et al published in CHEST (July 2016) who demonstrated that severe oxygen desaturation was associated with reduced cardiovascular morbidity in patients with obesity hypoventilation syndrome (OHS). The authors discussed a putative role of ischemia preconditioning (IP) potentially contributing to the beneficial effects observed in these patients. In my opinion, this point should be addressed in greater detail.

Chest. 2016;150(6):1406-1407. doi:10.1016/j.chest.2016.09.036
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We are grateful to Dr Burtscher for his interest in our article “Protective Cardiovascular Effect of Sleep Apnea Severity in Obesity Hypoventilation Syndrome” published in CHEST (July 2016). Dr Burtscher poses two main questions: (1) Is the term ischemia preconditioning used appropriately in our study or rather should we be referring to hypoxic preconditioning? and (2) does hypoxemia and hypercapnia during wakefulness in obesity hypoventilation syndrome (OHS) evoke a protective cardiovascular effect in contrast to patients with severe OSA who experience hypoxemia only during sleep?

Chest. 2016;150(6):1407-1408. doi:10.1016/j.chest.2016.08.1469
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We recently read with great interest the article by Masa et al, published in CHEST (July 2016), in which the authors examined the association between OSA severity and cardiovascular morbidity in patients with obesity hypoventilation syndrome (OHS). Surprisingly, their results showed an inverse relationship between cardiovascular morbidity and severity of OSA, except for ischemic heart disease. As hypothesized by Lavie and Lavie, the cycles of apneic/hypopneic events in OSA that resemble cycles of ischemia/reperfusion could exert a protective effect from more severe ischemic and cardiovascular events, similar to ischemic preconditioning. There is the possibility that these factors may be a particular characteristic of OHS. Moreover, Cadby et al reported an independent association between the presence and severity of OSA and incident atrial fibrillation in a large clinic-based cohort group over a median 12-year follow-up period. What is the role of nocturnal hypoventilation and of tonic desaturation in the etiopathogenesis of cardiologic comorbidity?

Chest. 2016;150(6):1408. doi:10.1016/j.chest.2016.08.1470
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We are grateful to Dr Castellana and colleagues for their interest in our article recently published in CHEST. In their letter, they question the role of nocturnal hypoventilation and of tonic oxygen desaturation in the pathogenesis of cardiovascular comorbidity.

Chest. 2016;150(6):1408-1409. doi:10.1016/j.chest.2016.08.1467
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We read with interest the recent article published by Masa et al in CHEST (July 2016) reporting that the prevalence of cardiovascular morbidity (CVM) in obesity hypoventilation syndrome (OHS) was lower in patients with the highest OSA severity. The authors suggested ischemic preconditioning as a potential protective mechanism explaining this unexpected inverse relationship between OSA severity and CVM. Through a logistic regression, they compared CVM between three oxygen desaturation index-based tertiles, but one could be surprised by the phenotypic contrast of the severest oxygen desaturation index subgroup. Indeed, these patients were younger (‒7 to ‒8 years) and more active physically (+12%-+14%, 6-meter walking distance), included fewer hypertensive (‒9% to ‒14%) and diabetic patients (‒10%), and were predominantly men (+19%-+25%) and more obese (BMI, +8%-+10%). Considering these phenotypic differences, the conclusions should be interpreted with caution and need to be further confirmed. With this perspective, a biomarker approach would be helpful for evaluating the cardiovascular risk. Among potential candidates, circulating high-sensitivity cardiac troponin T (hs-cTnT) would be of great interest, since it has been shown to be detectable with increased concentrations in more than 70% of patients with severe OSA and has proved to be an independent factor associating OSA severity and risk of heart failure. Accordingly, an increased level of hs-cTnI, the “rival” biomarker, has also been found to be independently associated with OSA severity. The initial studies did not find any relationship between circulating troponin concentrations and OSA severity because they used first-generation troponin assays, which were not sufficiently sensitive. Since that time, the “high-sensitivity” generations have appeared and are characterized by an optimal analytical precision, that is, a coefficient of variation ≤ 10% at the 99th percentile of troponin concentrations in a normal reference population, defined as 14 ng/L for hs-cTnT. Interestingly, the higher median hs-cTnT concentration was previously found to be 6 ng/L (interquartile range, 4-10) in patients with severe OSA, which is a level similar to that associated with incident coronary heart disease (hazard ratio [HR], about 1.3), mortality (HR, about 1.5), and hospitalization for heart failure (HR, about 2.2) in the general population (hs-cTnT: range, 6- 8 ng/L). Since it has never been evaluated in OHS but is related to OSA severity and is predictive of CVM, hs-cTnT concentrations could be relevantly assayed in the present study if a plasma/serum bank is available or should at least be introduced in further studies aiming at verifying these controversial results.

Chest. 2016;150(6):1409-1410. doi:10.1016/j.chest.2016.08.1468
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We agree with Dr Monneret and colleagues that our findings of a cardioprotective effect of OSA severity (as measured by the oxygen desaturation index) in patients with OHS should be considered preliminary in nature and taken as hypothesis generating. It is important to note that our analytic approach using multivariate regression modeling cannot adjust for all possible confounders. As such, using a biomarker such as high-sensitivity troponin would be of significant value to provide further insights into whether OSA severity is associated with a lower rate of cardiovascular morbidity in patients with OHS. Ultimately, if this association is confirmed in future studies, there is a great interest to understand the molecular mechanisms resulting in cardiovascular protection and whether it has clinical implications.

Chest. 2016;150(6):1410-1411. doi:10.1016/j.chest.2016.08.1475
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We would like to congratulate Masa and colleagues (July 2016) for elaborating on a novel concept that highlights the data and potential mechanisms of cardiovascular protection in patients with severe OSA and obesity hypoventilation syndrome. Of interest, the authors found that patients with severe OSA (in the third tertile) had the lowest prevalence of cardiovascular morbidity. However, the ischemic preconditioning hypothesis, as a plausible mechanism, may not be generalizable for all conditions included in their definition of cardiovascular morbidity.

Chest. 2016;150(6):1411. doi:10.1016/j.chest.2016.09.019
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We are grateful to Dr Chugh and colleagues for their interest in our article.

Chest. 2016;150(6):1411-1412. doi:10.1016/j.chest.2016.08.1472
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I have read with great interest and pleasure the excellent review by Martínez-García et al entitled “Cancer and OSA: Current Evidence from Human Studies” published in CHEST (August 2016). The authors shed light on this important and aporetical topic.

Chest. 2016;150(6):1412. doi:10.1016/j.chest.2016.08.1471
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At the outset, we wish to thank Dr Marvisi for his interest in our article. As the authors of the letter have stated, in the past few years some outstanding research groups have described other pathophysiological pathways linking OSA with cancer, some orchestrated by hypoxia,,, and some by sleep fragmentation.,,,, Some of these pathways are related to alterations to the immune system in macrophages/monocytes, natural killer cells, lymphocytes, and other immune cells.,,,,, Interesting studies and reviews of the role of microvesicles/exosomes and the impact on the sympathetic/catecholaminergic system and other pathophysiological pathways have recently been published.,,, For this reason, we decided to focus our review on clinical studies in humans that deal with the relationship between OSA and cancer incidence and mortality. In fact, we only outlined some basic ideas about pathophysiology in the introductory paragraph of the review, and the last paragraph was dedicated to the limitations of the clinical studies. We encourage the authors to read the excellent revisions made by Gozal et al,, for further information, one of which was recently published in CHEST.

Chest. 2016;150(6):1412-1413. doi:10.1016/j.chest.2016.08.1478
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In this issue of CHEST (December 2016), O’Neill et al presented data on the clinimetric properties of the lung clearance index (LCI) in children and adults with cystic fibrosis (CF). It was encouraging to see that the variability and intra-test repeatability of the LCI are comparable in adults and children with CF. The intra-visit and inter-visit repeatability findings provide insight into the normal variability of the LCI in health and disease and are necessary to establish thresholds for meaningful changes for interventional studies and to identify disease progression. Although O’Neill et al present valuable results, we believe that they have missed an opportunity to fully explore the clinimetric properties of the LCI.

Chest. 2016;150(6):1413-1414. doi:10.1016/j.chest.2016.09.037
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We thank Dr Oude Engberink and colleagues for their helpful and insightful commentary regarding our article recently published in CHEST on aspects of intra-visit and inter-visit repeatability of the lung clearance index (LCI) in health and in cystic fibrosis (CF) disease. The primary aim of our study was to compare adults and children with CF, and thus this area was the focus of our report. However, we agree that further analysis and comparison of healthy control (HC) and disease data can add to existing findings and further inform thresholds for clinically meaningful changes.

Chest. 2016;150(6):1414-1417. doi:10.1016/j.chest.2016.09.034
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Pulmonary embolism response teams (PERTs) have been rapidly developing in the United States to bring multidisciplinary care to patients with acute pulmonary embolism.,,, However, the diversity of PERT program structure and their association with hospital characteristics have not yet been described.

Chest. 2016;150(6):1417-1419. doi:10.1016/j.chest.2016.09.033
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Lung ultrasonography (LUS) is a concept introduced recently to confirm problems associated with the lungs and the pleura. Since many international authors and organizations recommend LUS examination in clinical settings, there is a necessity to train clinicians in the identification of normal and pathologic findings associated with LUS. The purpose of this study was to create a low-cost ultrasonographic phantom to simulate normal and pathologic ultrasonographic findings of LUS. All aspects of this project were approved by the Institutional Review Board at the Dongguk University Ilsan Hospital (No. 2015-89).

Chest. 2016;150(6):1419-1420. doi:10.1016/j.chest.2016.09.032
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Few studies of pleural infection in ICUs exist, yet they suggest variable etiology and substantial associated mortality.,,,, None of these studies have examined long-term outcomes, and most were published more than a decade ago. The current incidence, microbiology, and long-term outcomes for these patients remain unclear, hindering treatment advances.

Chest. 2016;150(6):1421. doi:10.1016/j.chest.2016.10.033
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Drs Wolfe and Kress coauthored a terrifically clinically useful and scholarly assemblage of common ICU and related procedures and their hemorrhagic risks, as well as thoughtful approaches to reducing risk in a recent issue of CHEST (July 2016). However, I think their analysis regarding, and view that, preprocedural blood product or other infusions to reduce bleeding risks are often wrong, is wrong itself. Here’s why:

  • 1.

    They cite (their reference 56) the sole prospective controlled study of preprocedure transfusion as showing “no difference in bleeding complications in those who underwent transfusion prophylactically and those who did not.” Here’s what the article’s authors concluded instead: “Due to limited inclusion, noninferiority of omitting FFP transfusion could not be demonstrated.” There was only one major bleed among the 81 patients enrolled. The study was stopped early due to poor accrual. Patients were excluded from that study if they’d received warfarin, which is often exactly the type of patient ICU physicians want to treat with a hemostasis-improving infusion before a procedure.

  • 2.

    Drs Wolfe and Kress note that after infusions of fresh frozen plasma, for example, blood tests like the prothrombin time often fail to improve significantly. But the point is not to fix the blood test, it is to reduce patient risk. Replenishing depleted factors temporarily can reduce bleeding risk and improve the safety margin. As Dr Baron explained in a recent thoughtful and well-documented Point/Counterpoint article in CHEST that focused on coagulopathy and central venous line insertion, “Why take chances?”

  • 3.

    Volume overload (particularly in anuric patients) and further lung injury from fresh frozen plasma infusion is certainly a concern. But lack of proof of benefit, based on meta-analyses of case series, is not. Ascertainment of bleeding in these series is not assiduous, and as a leading pulmonary physician pointed out decades ago, “Absence of evidence is not evidence of absence.”

Chest. 2016;150(6):1421-1422. doi:10.1016/j.chest.2016.10.034
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We thank Dr Davidson for his interest and thoughtful comments regarding our review. In response to his first comment, we agree that there are important limitations to the study by Müller et al. Its small size and limited patient population diminishes its generalizability, but this does not mean that its findings should be disregarded. The fact that only one in 81 patients enrolled had a major bleeding complication echoes the low incidence of major bleeding complications found in other studies, which is an important point to consider when weighing the risks and benefits of the routine use of preprocedural blood transfusions. We also agree with the second point that if a transfusion is to be given, it should not be done to fix a laboratory test result but should be carried out with the intention of reducing patient risk. We cannot, however, dismiss the fact that blood tests, specifically prothrombin time or international normalized ratio, are often the trigger used by physicians to give transfusions prior to an invasive procedure. Therefore, we believe it is important to be aware of the limitations in “fixing” laboratory-based coagulopathy with fresh frozen plasma transfusions. Even more important, though, is awareness of the potential harm associated with transfusion of blood products. The potential complications— including risk of infection, volume overload, lung injury, and increased mortality in some cases—are well documented. Given the relative paucity of evidence supporting the routine use of transfusions to decrease bleeding risk, we maintain that the overt risk of harm from transfusion should bring into question the utility of this practice. We welcome and encourage further research on this topic to help guide clinical decision-making.

Chest. 2016;150(6):1422-1423. doi:10.1016/j.chest.2016.09.039
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Liu et al, authors of an article in a recent issue of CHEST (August 2016), used an innovative design and sophisticated statistical analysis to systematically identify occupational sarcoidosis associations with the intent of inferring causation. However, the Bradford Hill criteria (biological plausibility, association strength, consistency, temporality, and dose response) are unsatisfied due to design limitations and observations.

Chest. 2016;150(6):1423-1424. doi:10.1016/j.chest.2016.10.004
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We appreciate Dr Reich’s careful review and positive and carefully thought-out comments about our study, its design, and analysis recently published in CHEST (August 2016). The study we undertook used a novel dataset to determine an association between sarcoidosis and more severe forms of sarcoidosis (death) and occupation; the intent of our study was never to propose a causal relationship because this conclusion is not possible with a case-control study like ours. However, we did confirm a number of prior associations noted between occupation and sarcoidosis (eg, such as some of those found in the National Institutes of Health’s A Case Control Etiologic Study of Sarcoidosis [ACCESS] study). We did find some differences from prior studies and acknowledged that these findings could be due to some of the limitations in using this dataset. These limitations include the fact that not all occupations were known, that other confounders may have existed (eg, exposures outside of work or in the workplace), and the fact that we did not have information on the temporality of exposures and disease onset, to name a few. Finally, it was our hope to help support and provide potential hypothesis-generating data that could build on our findings to evaluate exposures and antigens that may be triggers for sarcoidosis in future studies, beyond the scope of our dataset.

Chest. 2016;150(6):1424. doi:10.1016/j.chest.2016.09.046
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In the interesting article in a recent issue of CHEST (September 2016), Marchi and colleagues find that abrasion with local fibrin sealant instillation is as effective as pleurectomy in producing pleurodesis in rabbits.

Chest. 2016;150(6):1424-1425. doi:10.1016/j.chest.2016.10.012
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We thank Dr Acton for his comments regarding our paper in CHEST (September 2016). The author questioned us about finding that there was no pleurodesis but concluding that abrasion with fibrin sealant was as effective as pleurectomy in producing pleurodesis in rabbits. We believe that the confusion arises from the definition of pleurodesis. Pleurodesis is defined as “fusion of the visceral and parietal pleura to prevent collapse of the lung with pneumothorax or accumulation of pleural fluid with pleural effusions.” As stated in our paper, only in animal models it is possible to document the quality and extent of macroscopic pleural adhesions, microscopic pleural inflammation, and collagen deposition after the various forms of pleural interventions used to induce pleurodesis. We would agree that our rabbits did not have complete obliteration of the pleural space after the interventions were performed in a 3-cm area of the apex of the right pleural cavity, mimicking the apical pleurectomy or pleurodesis by abrasion commonly used in clinical practice to control recurrent pneumothorax. However, the rabbits did have significant local adhesions, microscopic pleural thickening, and collagen deposition when abrasion plus sealant application or pleurectomy was performed. We consider this partial pleurodesis and believe that the local adhesions and the collagen deposition make recurrence of the pneumothorax less likely. We will therefore stand by our conclusions.

Chest. 2016;150(6):1425-1426. doi:10.1016/j.chest.2016.09.040
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In the article by Bosslet et al published in CHEST (September 2016), the authors contrasted processes for extramural resolution of intractable conflicts about medical futility or inappropriate treatment at the end of life in the United States, Canada, and the United Kingdom. They concluded that there is insufficient public reason-giving regarding conflicts about end-of-life care in the United States. The authors, however, focused on US reason-giving that is supportive of forgoing life-sustaining treatment (eg, in re Quinlan). The US Supreme Court’s landmark decisions in Vacco v Quill and Washington v Glucksberg were not mentioned. These cases provide informative reason-giving for American society and the medical profession regarding why medically terminating a human life is not a constitutional right. We comment on an emerging trend in medical ethics and practice that can be inferred from Bosslet et al’s analysis.

Chest. 2016;150(6):1426. doi:10.1016/j.chest.2016.09.045
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We appreciate the comments by Rady et al regarding our analysis of the importance of legal reason-giving in the social discourse surrounding disputes regarding discontinuation of life-prolonging treatments. We make three points in response. First, they point out that considerable and informative reason-giving was provided by Vacco v Quill and Washington v Glucksberg. This is true, and these cases have cast a considerable judicial shadow over the debate regarding medical aid in dying. However, these cases are outside the scope of our analysis, which focused on nonconsensual recommendations to forego further life-prolonging treatments.

Reviewer Acknowledgment

Chest. 2016;150(6):1427-1431. doi:10.1016/j.chest.2016.10.013

CHEST would like to thank the individuals listed below who served as reviewers in 2016. Without their generous assistance, the Journal would not be able to function. The expert evaluation of manuscripts by these people is a primary reason that CHEST is one of the most respected journals in its field. We extend our appreciation. Because of production restraints, we have only listed those who completed reviews by mid-October 2016. Those who completed reviews after then will be listed next year.

Selected Reports

Chest. 2016;150(6):e143-e145. doi:10.1016/j.chest.2016.03.026

Although endobronchial coils for the treatment of severe emphysema are associated with an acceptable safety profile, adverse events such as pneumothorax and thoracic pain may occur. The coils are indicated as a permanent implant and are deemed very difficult to remove. We describe the first successful removal of two coils 10 months after placement in a patient who experienced persistent thoracic pain. This case report highlights that very distal (subpleural) coil placement may induce pneumothorax and subsequent thoracic pain and that nonsurgical removal of coils up to 10 months after implantation is feasible.

Chest. 2016;150(6):e147-e150. doi:10.1016/j.chest.2016.03.027

Hyperbaric oxygen therapy, the administration of 100% oxygen at pressures > 1 atm, is believed to promote wound healing by increasing angiogenesis and collagen synthesis. To our knowledge, this treatment modality has never been described in patients with tracheal radionecrosis. Here, we report the case of a 55-year-old man diagnosed with stage IIIB lung adenocarcinoma who was treated with chemotherapy and concomitant external intensity-modulated radiotherapy involving the left lung and mediastinum. Nine months later, he presented with neck pain, cough with mucopurulent sputum, and fever. A PET-CT scan revealed a fissure in the posterior wall of the left upper trachea. Flexible bronchoscopy showed a tracheal ulceration with a small left posterior wall fissure that extended into the mediastinum. To our knowledge, this is the first report in the literature that suggests that treatment with hyperbaric oxygen therapy, local debridement, and antibiotics is a feasible and successful management option for patients with complicated tracheal radionecrosis.

Ultrasound Corner

Chest. 2016;150(6):e151-e153. doi:10.1016/j.chest.2016.04.041

A 78-year-old man with a medical history of COPD, prostate cancer status post radiation and hormonal therapy, coronary artery disease, sick sinus syndrome status post pacemaker, and paroxysmal atrial fibrillation on anticoagulation was admitted to the medical service for a new dry cough, weakness, dyspnea, and a 20-pound unintentional weight loss. The physical examination was notable for cervical and inguinal lymphadenopathy. His chest radiograph was significant for a left pleural effusion. He underwent a cervical lymph node core biopsy that was positive for diffuse large B-cell lymphoma (DLBCL). During his hospital stay, the patient continued to have worsening shortness of a breath. A repeat chest radiograph was concerning for increasing pleural effusion. The pulmonary service was consulted for consideration of thoracentesis. The patient was afebrile, his heart rate was 99 beats/min, blood pressure 138/89 mm Hg, and oxygen saturation on a 2-L nasal cannula was 92%. The lung examination revealed decreased breath sounds over the left lower lung field. The pulmonary consult team performed a goal-directed ultrasonography examination (Video 1).

Chest. 2016;150(6):e155-e157. doi:10.1016/j.chest.2016.04.040

A 67-year-old man is discharged from a peripheral hospital after a short stay in orthopedics for mild thoracic trauma. He is readmitted to the ED 2 hours later for severe dyspnea. His medical history includes acute myocardial ischemia and paroxysmal atrial fibrillation.

Chest Imaging and Pathology for Clinicians

Chest. 2016;150(6):e159-e165. doi:10.1016/j.chest.2016.08.1449

A 40-year-old woman consulted our ED for a 7-month history of left dorsal back pain and dyspnea. The pain was initially dull and mechanical. Her general practitioner started nonsteroidal antiinflammatory drugs and physiotherapy, which provided partial relief. One week before consulting, the intensity of the pain increased, and she started to feel shortness of breath when performing her daily activities. She had lost 5 kg during the previous month. The patient was a healthy woman who lived in an urban area of Barcelona, Spain. She did not smoke or take drugs of abuse, and she worked as a butcher. During the initial evaluation, her blood pressure was 131/76 mm Hg, heart rate was 120 beats/min, temperature was 36.2°C, and ambient air pulse oximetry was 98%.

Topics: back pain

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2016;150(6):e167-e170. doi:10.1016/j.chest.2016.05.017

A 48-year-old African-American male subject presented with progressive fatigue, jaundice, and new-onset leukopenia 12 weeks after undergoing bilateral lung transplantation for advanced pulmonary sarcoidosis. His transplant surgery and immediate posttransplantation course were uneventful. Induction immunosuppression included methylprednisolone 500 mg intraoperatively and basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation. His maintenance immunosuppression posttransplantation was prednisone 20 mg daily, tacrolimus with target tacrolimus levels 10 to 15 ng/mL, and mycophenolate mofetil 750 mg twice daily. Both the donor and recipient were seropositive for cytomegalovirus and Epstein-Barr virus. Infectious disease prophylaxis consisted of valganciclovir, trimethoprim/sulfamethoxazole, and voriconazole. Results of the surveillance bronchoscopy conducted after the lung transplant were negative for acute cellular rejection or infection at 4 and 12 weeks’ posttransplantation. Findings on spirometry had continuously improved since transplantation.

Chest. 2016;150(6):e171-e174. doi:10.1016/j.chest.2016.06.022

A woman in her 60s with a history of hepatitis C with cirrhosis and major depressive disorder with psychotic features was admitted to the inpatient psychiatric unit for suicidal ideation. She was initially treated with a combination of sertraline and paliperidone. The paliperidone was subsequently changed to risperidone and ultimately to olanzapine. She developed worsening mental status and was then treated for catatonia with benzodiazepines. Over 2 days, her mental status continued to worsen and she developed fever and tachycardia. She was transferred to the ICU and endotracheally intubated for inability to protect her airway. She was started on lactulose via orogastric tube but showed no improvement in her mental status after 2 days despite having two or three bowel movements per day.

Chest. 2016;150(6):e175-e178. doi:10.1016/j.chest.2016.10.009

A man in his 20s with no medical history presented with 2 days of progressively worsening shortness of breath accompanied by subjective fevers, chills, body aches, decreased appetite, night sweats, and cough producing nonbloody sputum. He denied childhood lung diseases, allergies, or a family history of lung disease. He did not smoke cigarettes but had smoked hookah in Saudi Arabia before moving to the United States 1 month before presentation and had restarted 2 days before the start of symptoms. He denied travel outside of the northeastern United States. He did not take medications, use illicit drugs, or engage in high-risk behavior.

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