Current Issue


Chest. 2015;147(1):1-3. doi:10.1378/chest.14-2798

It has become our custom to start each New Year by highlighting key accomplishments and topics important to our readers, and heralding innovations and change. Last year we focused on a wide variety of topics from impact factor (IF) to a new visual identity.1

Chest. 2015;147(1):3-5. doi:10.1378/chest.14-1976

COPD is a costly disease. These are words we hear all the time, yet the precise meaning of this phrase is a bit nebulous, and peeking behind the curtain to determine how this is actually measured and evaluated reveals more questions and problems. What are the definitions and approaches to determining these costs?1

  • • Direct medical costs: hospital inpatient payments, physician payments, prescription drugs, medical supplies and devices, nursing home care, and so forth.

  • • Indirect medical costs: premature death, absenteeism, loss of resources, and so forth. There are multiple methods to determining these “costs,” such as the “human capital method” (lost earnings of a patient or caregiver) or the “willingness to pay method” (eg, how much would you be willing to pay to avoid an ED visit?).1

  • • Top-down approach: measures the proportion of a disease related to exposure to the disease or risk factor, and uses aggregated data along with a population-attributable fraction to estimate costs.

  • • Bottom-up approach: estimates costs by calculating the average cost of treatment of the illness and multiplying it by the prevalence of the illness.

  • • Econometric approach: estimates the difference in costs between a cohort of the population with the disease and a cohort of the population without the disease. Regression analysis is used to adjust for polymorbidity.

Chest. 2015;147(1):5-6. doi:10.1378/chest.14-1496

Ventilator-associated pneumonia (VAP) has been a major complication of mechanical ventilation that in years past has led to excess morbidity and mortality and has led to vigorous efforts at prevention. In the past decade, we have seen a dramatic decline in the reported frequency of VAP in the United States, with the advent of the “ventilator bundle” and with a belief that this simple, multimodality intervention could result in “zero VAP,” making pneumonia in patients on mechanical ventilation a potentially nonreimbursable medical error. However, a number of investigators have pointed out that the concept of zero VAP is biologically implausible and is the result of the manipulation of an imperfect clinical definition of pneumonia.1 In an effort to avoid this “gaming” of publicly reported data, the Centers for Disease Control and Prevention and multiple professional organizations have proposed a more “objective” process to monitor, namely that of ventilator-associated events (VAEs), which includes ventilator-associated conditions (VACs), infection-related ventilator-associated complications (IVACs), and VAP.2

Chest. 2015;147(1):7-8. doi:10.1378/chest.14-0874

A syndrome encompasses a number of nosologic entities that do not necessarily share the same cause, pathogenesis, structural abnormalities, and treatment. The identification of a syndrome has different diagnostic and therapeutic implications because it prompts further testing to achieve the diagnosis of a specific disease. For instance, the diagnosis of acute coronary syndrome in a patient presenting with chest pain requires a more-specific diagnosis (ie, acute myocardial infarction) to direct therapy. The discovery of biomarkers has been a key advance to define one of the underlying causative entities (eg, acute myocardial infarction) and, therefore, allows appropriate identification of patients with a specific condition and treatment.

Chest. 2015;147(1):9-10. doi:10.1378/chest.14-1565

A series of epidemiologic studies has shown how atrial fibrillation (AF) is becoming an emerging epidemiologic threat.1 Epidemiologic data have been traditionally derived from populations of North America and Europe and have shown that AF, even in an asymptomatic stage, increases the risk of ischemic stroke, has complex interrelations with heart failure and increased mortality,2 and induces a growing financial burden on health-care systems.3

Point and Counterpoint

Chest. 2015;147(1):11-13. doi:10.1378/chest.14-2233

The mission of the American College of Chest Physicians (now branded as CHEST) is “to champion the prevention, diagnosis, and treatment of chest diseases through education, communication and research.” To achieve this, the Board of Regents outlined five goals in the Strategic Plan for 2013 to 2017, with goal two calling for “a wide array of new relevant and useful guidelines, standards, and complementary programs that continue to guide the profession especially during value based health-care reform.”1 We contend that CHEST evidence-based guidelines (EBGs), long recognized for high quality,2 are global because they focus on topics of global importance, use processes accepted by multinational societies, and include panels of international experts. In addition, support and assistance from CHEST helps countries around the world adapt CHEST EBGs to enhance the ability of local practitioners to implement them.

Chest. 2015;147(1):13-15. doi:10.1378/chest.14-2235

Clinical practice guidelines have proliferated in the last decade, with > 3,700 guidelines reported in the Guidelines International Network database.1 In chest medicine alone, > 150 current guidelines are posted on the websites of official international societies, including the American College of Chest Physicians (now branded as CHEST).2 A central goal in developing guidelines is to provide evidence-based recommendations to optimize care for as many patients as possible. In this context, guidelines should be broadly applicable to impact the care of the most patients possible. Indeed, as stated in CHEST’s Evidence-Based Medicine Overview,3 “our guidelines are used throughout the world” and “have received considerable acclaim and worldwide use.” Also articulating these goals and in keeping with early recommendations,4 the American Thoracic Society Guide to Guidelines for Professional Societies states that guidelines should incorporate “consideration of cost-effectiveness, affordability, and resource implications” and “stakeholder involvement: how to do it right.”5 Key characteristics of an optimal guideline were considered the ability to (1) “globalize the evidence,” (2) “identify ways that help guideline consumers understand and implement guidelines,” (3) “focus on questions that are important to patients and clinicians,” and (4) ensure “adaptation, applicability, and transferability of guidelines.”5

Chest. 2015;147(1):16-17. doi:10.1378/chest.14-2234

Dr Mehta and colleagues1 assert that optimal guidelines have four key characteristics: globalizing evidence; identifying ways to help consumers implement guidelines; focusing on important questions for patients and clinicians; and ensuring adaption, applicability, and transferability of guidelines.2 These are just the first four of 10 “key visions” listed in a 2012 workshop sponsored by the American Thoracic Society/European Respiratory Society that was an effort to standardize COPD evidence-based guidelines (EBGs).2 This represents a derivation of earlier collaborative work by the Institutes of Medicine (IOM) and the Agency for Health Research and Quality (AHRQ), wherein eight “Standards for Developing Trustworthy Guidelines” were developed.3 We stipulate that American College of Chest Physicians (now branded as CHEST) EBGs are developed with close attention to IOM and AHRQ recommendations and reaffirm that CHEST EBGs are global.

Chest. 2015;147(1):17-18. doi:10.1378/chest.14-2236

We appreciate Drs Nathanson and Oulette’s1 response and concur that American College of Chest Physicians (now branded as CHEST) evidence-based guidelines (EBGs) are rigorously prepared and are of high quality. Notwithstanding their considerable value, CHEST EBGs still fail to achieve global coverage. To offer global coverage and relevance, EBGs must satisfy the condition of addressing clinical issues and circumstances of global patient populations (ie, patients throughout the range of socioeconomic circumstances and access to health-care technology and expertise). Our colleagues offer four lines of reasoning to defend their “pro” position; we believe that this rebuttal debunks each.

Giants in Chest Medicine

Chest. 2015;147(1):19-20. doi:10.1378/chest.14-1226

The choice to become a physician was clear to young Edward C. Rosenow, III, MD, Master FCCP, as he sought to emulate his father, a prominent and altruistic internist. Dr Rosenow obtained his MD degree from The Ohio State University. He came to Mayo Clinic in 1960 to pursue his residency and has spent nearly 55 years at that hospital. When asked why he decided to spend all his professional life at one institution, he answered very simply, “I was treated like a gentleman, I enjoyed the collegiality, I was surrounded by the best mentors you could imagine, and I appreciated the Mayo culture of caring.” Over the years, he worked his way up the academic ladder to become endowed Professor of Medicine at the Mayo Clinic, the administrative ranks to serve as the chair of the Division of Pulmonary and Critical Care Medicine, and the rank and file of the medical community to become the president of the Mayo medical staff. During his illustrious career, he published > 170 scholarly articles, contributing > 20 book chapters and editing four books. Dr Rosenow, however, focused on four important aspects in his profession:


Chest. 2015;147(1):21-24. doi:10.1378/chest.14-2028

Direct thrombin inhibitor (anti-factor IIa) anticoagulants such as dabigatran and bivalirudin, now established for treatment and prevention of cardiac thromboembolism and VTE, have been repeatedly associated with a significantly increased frequency of thrombosis on abnormal cardiac endothelium when compared head-to-head with indirectly acting therapeutic anticoagulants in studies of sufficient patient number and duration. Although there is uncertainty as to the mechanism, the weight of evidence as a class effect warrants prescribing effective anticoagulants other than direct thrombin inhibitors.

Commentary: Ahead of the Curve

Chest. 2015;147(1):25-30. doi:10.1378/chest.14-1612

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

Original Research: COPD

Chest. 2015;147(1):31-45. doi:10.1378/chest.14-0972

BACKGROUND:  COPD remains a leading cause of morbidity and mortality. The objectives of this study were to estimate (1) national US COPD-attributable annual medical costs by payer (direct) and absenteeism (indirect) in 2010 and projected medical costs through 2020 and (2) state-specific COPD-attributable medical and absenteeism costs in 2010.

METHODS:  We used the 2006-2010 Medical Expenditure Panel Survey, the 2004 National Nursing Home Survey, and 2010 Centers for Medicare and Medicaid Services data to generate cost estimates and 2010 census data to project medical costs through 2020.

RESULTS:  In 2010, total national medical costs attributable to COPD and its sequelae were estimated at $32.1 billion, and total absenteeism costs were $3.9 billion, for a total burden of COPD-attributable costs of $36 billion. An estimated 16.4 million days of work were lost because of COPD. Of the medical costs, 18% was paid for by private insurance, 51% by Medicare, and 25% by Medicaid. National medical costs are projected to increase from $32.1 billion in 2010 to $49.0 billion in 2020. Total state-specific costs in 2010 ranged from $49.1 million in Wyoming to $2.8 billion in California: medical costs ranged from $42.5 million in Alaska to $2.5 billion in Florida and absenteeism costs ranged from $8.4 million in Wyoming to $434.0 million in California.

CONCLUSIONS:  Costs attributable to COPD and its sequelae are substantial and are projected to increase through 2020. Evidence-based interventions that prevent tobacco use and reduce the clinical complications of COPD may result in potential decreased COPD-attributable costs.

Chest. 2015;147(1):46-55. doi:10.1378/chest.14-0764

BACKGROUND:  Relationships between airway inflammation and respiratory potentially pathogenic microorganisms (PPMs) quantified using quantitative polymerase chain reaction (qPCR) in subjects with COPD are unclear. Our aim was to evaluate mediators of airway inflammation and their association with PPMs in subjects with COPD at stable state and during exacerbations.

METHODS:  Sputum from 120 stable subjects with COPD was analyzed for bacteriology (colony-forming units; total 16S; and qPCR targeting Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae), differential cell counts, and inflammatory mediators using the Meso-Scale Discovery Platform. Subjects were classified as colonized if any PPM was identified above the threshold of detection by qPCR. Symptoms were quantified using the visual analog scale.

RESULTS:  At stable state, 60% of subjects were qPCR positive for H influenzae, 48% for M catarrhalis, and 28% for S pneumoniae. Elevated sputum concentrations of IL-1β, IL-10, and tumor necrosis factor (TNF)-α were detected in samples qPCR positive for either H influenzae or M catarrhalis. Bacterial loads of H influenzae positively correlated with IL-1β, IL-8, IL-10, TNF-α, and symptoms; and M catarrhalis correlated with IL-10 and TNF-α. H influenzae qPCR bacterial load was an independent predictor of sputum TNF-α and IL-1β. In 55 subjects with paired exacerbation data, qPCR bacterial load fold change at exacerbation in M catarrhalis but not H influenzae correlated to changes in sputum TNF-α and IL-1β concentrations.

CONCLUSIONS:  At stable state, H influenzae is associated with increased airway inflammation in COPD. The relationship between bacterial load changes of specific pathogens and airway inflammation at exacerbation and recovery warrants further investigation.

Chest. 2015;147(1):56-67. doi:10.1378/chest.13-2482

BACKGROUND:  Elevated urinary albumin-creatinine ratio (UACR) and decreased estimated glomerular filtration rate (eGFR) predict all-cause mortality, but whether these markers of kidney damage and function do so in adults with obstructive lung function (OLF) is unclear. The objective of this study was to examine the associations between UACR and eGFR and all-cause mortality in adults with OLF.

METHODS:  Data of 5,711 US adults aged 40 to 79 years, including 1,390 adults with any OLF who participated in the National Health and Nutrition Examination Survey III (1988-1994), were analyzed. Mortality follow-up was conducted through 2006.

RESULTS:  During the median follow-up of 13.7 years, 650 adults with OLF died. After maximal adjustment, mean levels of UACR were higher in adults with moderate-severe OLF (7.5 mg/g; 95% CI, 6.7-8.5) than in adults with normal pulmonary function (6.2 mg/g; 95% CI, 5.8-6.6) (P = .003) and mild OLF (6.2 mg/g; 95% CI, 5.5-6.9) (P = .014). Adjusted mean levels of eGFR were lower in adults with moderate-severe OLF (87.6 mL/min/1.73 m2; 95% CI, 86.0-89.1) than in adults with normal lung function (89.6 mL/min/1.73 m2; 95% CI, 88.9-90.3) (P = .015). Among adults with OLF, hazard ratios for all-cause mortality increased as levels of UACR, modeled as categorical or continuous variables, increased (maximally adjusted hazard ratio for quintile 5 vs 1: 2.23; 95% CI, 1.56-3.18). eGFR, modeled as a continuous variable but not as quintiles, was significantly associated with mortality.

CONCLUSIONS:  UACR and eGFR, in continuous form, were associated with all-cause mortality among US adults with OLF.

Original Research: Critical Care

Chest. 2015;147(1):68-81. doi:10.1378/chest.14-0544

BACKGROUND:  The Centers for Disease Control and Prevention has shifted policy away from using ventilator-associated pneumonia (VAP) and toward using ventilator-associated conditions (VACs) as a marker of ICU quality. To date, limited prospective data regarding the incidence of VAC among medical and surgical ICU patients, the ability of VAC criteria to capture patients with VAP, and the potential clinical preventability of VACs are available.

METHODS:  This study was a prospective 12-month cohort study (January 2013 to December 2013).

RESULTS:  We prospectively surveyed 1,209 patients ventilated for ≥ 2 calendar days. Sixty-seven VACs were identified (5.5%), of which 34 (50.7%) were classified as an infection-related VAC (IVAC) with corresponding rates of 7.0 and 3.6 per 1,000 ventilator days, respectively. The mortality rate of patients having a VAC was significantly greater than that of patients without a VAC (65.7% vs 14.4%, P < .001). The most common causes of VACs included IVACs (50.7%), ARDS (16.4%), pulmonary edema (14.9%), and atelectasis (9.0%). Among IVACs, 44.1% were probable VAP and 17.6% were possible VAP. Twenty-five VACs (37.3%) were adjudicated to represent potentially preventable events. Eighty-six episodes of VAP occurred in 84 patients (10.0 of 1,000 ventilator days) during the study period. The sensitivity of the VAC criteria for the detection of VAP was 25.9% (95% CI, 16.7%-34.5%).

CONCLUSIONS:  Although relatively uncommon, VACs are associated with greater mortality and morbidity when they occur. Most VACs represent nonpreventable events, and the VAC criteria capture a minority of VAP episodes.

Chest. 2015;147(1):82-93. doi:10.1378/chest.14-1098

BACKGROUND:  Family satisfaction with end-of-life care in the ICU has not previously been systematically reviewed. Our objective was to perform a review, synthesizing published data identifying factors associated with family satisfaction with end-of-life care in critically ill adult populations.

METHODS:  The following electronic databases were searched: MEDLINE (Medical Literature Analysis and Retrieval System Online), MEDLINE Updated, EMBASE (Excerpta Medical Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycInfo, and PubMed. Two authors reviewed retrieved titles and abstracts. Studies describing nonadult and non-ICU populations or not addressing end-of-life care, family satisfaction, or factors affecting satisfaction were excluded. The remaining articles underwent full review and data extraction by two authors. Quality was assessed using a checklist based on the recommendations of the Consolidated Standards for Reporting Trials group.

RESULTS:  The search yielded 1,072 articles, with 23 articles describing 14 studies meeting inclusion criteria. All studies obtained satisfaction data from family members via surveys and structured interviews. Specific communication strategies increasing satisfaction included: expressions of empathy, nonabandonment, and assurances of comfort and provision of written information. Additionally, support for shared decision-making, family presence at time of death, and specific patient-care measures such as extubation before death were associated with increased satisfaction.

CONCLUSIONS:  Good-quality communication, support for shared decision-making, and specific patient-care measures were associated with increased satisfaction with end-of-life care. Assessing the family’s desire to participate in shared decision-making may also be an important factor. Few interventions increased satisfaction. Future research is needed to further define optimal communication strategies, understand effective integration of palliative care into the ICU, and define significant score changes in survey instruments.

Chest. 2015;147(1):94-101. doi:10.1378/chest.13-3050

BACKGROUND:  Despite its frequency and impact, delirium is poorly recognized in postoperative and critically ill patients. EEG is highly sensitive to delirium but, as currently used, it is not diagnostic. To develop an EEG-based tool for delirium detection with a limited number of electrodes, we determined the optimal electrode derivation and EEG characteristic to discriminate delirium from nondelirium.

METHODS:  Standard EEGs were recorded in 28 patients with delirium and 28 age- and sex-matched patients who had undergone cardiothoracic surgery and were not delirious, as classified by experts using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. The first minute of artifact-free EEG data with eyes closed as well as with eyes open was selected. For each derivation, six EEG parameters were evaluated. Using Mann-Whitney U tests, all combinations of derivations and parameters were compared between patients with delirium and those without. Corresponding P values, corrected for multiple testing, were ranked.

RESULTS:  The largest difference between patients with and without delirium and highest area under the receiver operating curve (0.99; 95% CI, 0.97-1.00) was found during the eyes-closed periods of the EEG, using electrode derivation F8-Pz (frontal-parietal) and relative δ power (median [interquartile range (IQR)] for delirium, 0.59 [IQR, 0.47-0.71] and for nondelirium, 0.20 [IQR, 0.17-0.26]; P = .0000000000018). With a cutoff value of 0.37, it resulted in a sensitivity of 100% (95% CI, 100%-100%) and specificity of 96% (95% CI, 88%-100%).

CONCLUSIONS:  In a homogenous population of nonsedated patients who had undergone cardiothoracic surgery, we observed that relative δ power from an eyes-closed EEG recording with only two electrodes in a frontal-parietal derivation can distinguish among patients who have delirium and those who do not.

Chest. 2015;147(1):102-108. doi:10.1378/chest.14-0564

BACKGROUND:  In a pandemic, needs for ventilators might overwhelm the limited supply. Outcome predictors have been proposed to guide ventilator triage allocation decisions. However, pandemic triage predictors have not been validated. This quantitative simulation study evaluated outcomes resulting from allocation strategies varying in their performance for selecting short-stay survivors as favorable candidates for ventilators.

METHODS:  A quantitative simulation modeled a pandemic surge. Postulated numbers of potential daily admissions presented randomly from a specified population, with a limited number of available ventilators. Patients were triaged to ventilator care vs palliation or turned away to palliation if no ventilator was available. Simulated triage was conducted according to a set of hypothetical triage tools varying in sensitivity and specificity to select favorable ventilator candidates vs first-come, first-served allocation. Death was assumed for palliation. Survival or death was counted for patients who were ventilated according to the specified characteristic of each randomly selected patient.

RESULTS:  Triage predictors with intermediate-quality performance resulted in a median daily mortality of 80%, similar to first-come, first-served allocation. A poor-quality predictor resulted in a worse mortality of 90%. Only a high-quality predictor (sensitivity 90%, specificity 90%) resulted in a substantially lower 60% mortality.

CONCLUSIONS:  Performance of unvalidated pandemic ventilator triage predictors is unknown and possibly inferior to first-come, first-served allocation. Poor performance of unvalidated predictors proposed for triage would represent an inadequate plan for stewarding scarce resources and would deprive some patients of fair access to a ventilator, thus falling short of sound ethical foundations.

Original Research: Cardiovascular Disease

Chest. 2015;147(1):109-119. doi:10.1378/chest.14-0321

BACKGROUND:  Much of the epidemiology of atrial fibrillation (AF) is based on data from Western populations. Despite the huge population of Asia, data on the clinical epidemiology of AF in Asian countries are limited. The current study aimed to investigate the prevalence and incidence of newly diagnosed (ie, incident) AF, as well as lifetime risk, in China and to determine the clinical risk factors contributing to its development.

METHODS:  Using a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in the southwest of China, trends in incident AF were calculated using Kaplan-Meier analysis and Cox regression. The usefulness of the CHADS2 (congestive heart failure, hypertension, age, diabetes, stroke [doubled]) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 [doubled], diabetes, stroke [doubled], vascular disease, age 65-74, and sex category [female]) scores was tested in predicting the occurrence of incident AF.

RESULTS:  A total of 471,446 individuals (aged ≥ 20 years) were studied, with 1,924,975 person-years of experience. We identified 921 patients with incident AF (62% male; mean age, 62 years). The prevalence of incident AF in subjects aged ≥ 20 years was 0.2 per 100 people, with an incidence of AF of 0.05 per 100 person-years overall. Over an 11-year period, the prevalence of AF increased 20-fold, whereas AF-related stroke increased 13-fold. The lifetime risk of AF was approximately one in five among Chinese adults, and it increased with advancing age. The CHA2DS2-VASc score was superior to the CHADS2 score in predicting the risk of incident AF in our Chinese population (DeLong test, Z = 6.621, P < .001).

CONCLUSIONS:  The AF burden, as well as the risk of AF-related stroke, has increased significantly over the past 11 years in the southwest of China. The public health burden of AF and its complications are greatest in the very elderly, with major implications for health-care systems given the global burden of this common arrhythmia.

Original Research: Sleep Disorders

Chest. 2015;147(1):120-131. doi:10.1378/chest.14-0317

OBJECTIVE:  Nocturnal periodic breathing occurs more frequently in men than in women with various clinical and pathophysiologic conditions. The mechanisms accounting for this sex-related difference are not completely understood. Acetazolamide effectively counteracts nocturnal periodic breathing, but it has been investigated almost exclusively in men. Our aim was to explore possible determinants of nocturnal periodic breathing in a high-altitude setting both in men and in women. We hypothesized that increased hypoxic chemosensitivity in men could be associated with the development of nocturnal periodic breathing at altitude more frequently than in women, and that acetazolamide, by leftward shifting the CO2 ventilatory response, could improve nocturnal periodic breathing at altitude in a sex-independent manner.

METHODS:  Forty-four healthy lowlanders (21 women), randomized to acetazolamide or placebo, underwent cardiorespiratory sleep studies at sea level off treatment and under treatment on the first night after arrival at a 4,559-m altitude. Hypoxic and hypercapnic chemosensitivities were assessed at sea level.

RESULTS:  Men, more frequently than women, exhibited increased hypoxic chemosensitivity and displayed nocturnal periodic breathing at altitude. Acetazolamide leftward shifted the CO2 set point and, at altitude, improved oxygenation and reduced periodic breathing in both sexes, but to a larger extent in men. Hypoxic chemosensitivity directly correlated with the number of apneas/hypopneas at altitude in the placebo group but not in the acetazolamide group.

CONCLUSIONS:  The greater severity of periodic breathing during sleep displayed by men at altitude could be attributed to their increased hypoxic chemosensitivity. Acetazolamide counteracted the occurrence of periodic breathing at altitude in both sexes, modifying the apneic threshold and improving oxygenation.

TRIAL REGISTRY:  EU Clinical Trials Register, EudraCT; No.: 2010-019986-27; URL: https://www.clinicaltrialsregister.eu

Chest. 2015;147(1):132-139. doi:10.1378/chest.14-1307

BACKGROUND:  The association between childhood OSA and endothelial function as measured by flow-mediated dilation (FMD) and its response to OSA treatment are uncertain. The objective of this study was to compare FMD in children with OSA with nonsnoring control subjects and to examine its response to treatment.

METHODS:  Index cases were children aged 6 to 18 years with habitual snoring and polysomnography (PSG)-confirmed OSA (obstructive apnea hypopnea index [OAHI] > 1 events/h). Each case was paired with an age-, sex-, and BMI-matched nonsnoring control subject recruited from our previous community growth survey. All subjects underwent FMD measurement in the morning after overnight PSG. Adenotonsillectomy (AT) was offered to subjects who satisfied predefined AT operation criteria. All cases underwent repeat PSG and FMD assessment 6 months later.

RESULTS:  A total of 63 case-control pairs were recruited. The OSA group had a significantly higher OAHI (median, 5.3 events/h [interquartile range (IQR), 2.6-11.7] vs 0.2 events/h [IQR, 0-0.5], P < .001) and lower FMD (mean ± SD, 7.9% ± 1.3% vs 8.3% ± 0.8%; P = .04) than the control group. Thirty-two case subjects underwent AT. A significant reduction in OAHI was documented in the AT group (−8.8 events/h [IQR, −13.7 to −4.7]; P < .001) accompanied by a significant increase in FMD (+0.6% [IQR, 0.4-1.4]; P < .001), which was not observed in subjects who did not undergo AT.

CONCLUSIONS:  Children with OSA had reduced FMD, which was reversible with treatment.

Original Research: Asthma

Chest. 2015;147(1):140-149. doi:10.1378/chest.14-0843

BACKGROUND:  Acute asthma is a common ED presentation. In a prospective, multicenter cohort study, we determined the frequency and factors associated with asthma relapse following discharge from the ED.

METHODS:  Adults aged 18 to 55 years who were treated for acute asthma and discharged from 20 Canadian EDs underwent a structured ED interview and a follow-up telephone interview 4 weeks later. Standardized antiinflammatory treatment was offered at discharge. Multivariable analyses were performed.

RESULTS:  Of 807 enrolled patients, 58% were women, and the median age was 30 years. Relapse occurred in 144 patients (18%) within 4 weeks of ED discharge. Factors independently associated with relapse occurrence were female sex (women, 22% vs men, 12%; adjusted OR [aOR], 1.9; 95% CI, 1.2-3.0); symptom duration of ≥ 24 h prior to ED visit (long duration, 19% vs short duration, 13%; aOR, 1.7; 95% CI, 1.3-2.3); ever using oral corticosteroids (ever use, 21% vs never use, 12%; aOR, 1.5; 95% CI, 1.1- 2.0); current use of an inhaled corticosteroid ([ICS]/long-acting β-agonist combination product (combination product, 25% vs ICS monotherapy,15%; aOR, 1.9; 95% CI, 1.1-3.2); and owning a spacer device (owning one, 24% vs not owning one, 15%; aOR, 1.6; 95% CI, 1.3-1.9).

CONCLUSIONS:  Despite receiving guideline-concordant antiinflammatory treatments at ED discharge, almost one in five patients relapsed within 4 weeks. Female sex, prolonged symptoms, treatment-related factors, and markers of prior asthma severity were significantly associated with relapse. These results may help physicians target more aggressive interventions for patients at high risk of relapse.

Original Research: Diffuse Lung Disease

Chest. 2015;147(1):150-156. doi:10.1378/chest.14-0041

OBJECTIVE:  People with idiopathic pulmonary fibrosis (IPF) have been shown to be at an increased risk for cardiovascular (CV) disease, but reasons for this are unknown. The aim of this study was to compare the prevalence of common CV risk factors in people with IPF and the general population and establish the incidence of ischemic heart disease (IHD) and stroke after the diagnosis of IPF, controlling for these risk factors.

METHODS:  We used data from a large, UK primary care database to identify incident cases of IPF and matched general-population control subjects. We compared the prevalence of risk factors for CV disease and prescription of CV medications in people with IPF (before diagnosis) with control subjects from the general population and assessed the incidence of IHD and stroke in people with IPF (after diagnosis) compared with control subjects.

RESULTS:  We identified 3,211 cases of IPF and 12,307 control subjects. Patients with IPF were more likely to have a record of hypertension (OR, 1.31; 95% CI, 1.19-1.44), and diabetes (OR, 1.20; 95% CI, 1.07-1.34) compared with control subjects; they were also more likely to have been prescribed several CV drugs. The rate of first-time IHD events was more than twice as high in patients than control subjects (rate ratio, 2.32; 95% CI, 1.85-2.93; P < .001), but the incidence of stroke was only marginally higher (P = .09). Rate ratios for IHD and stroke were not altered substantially after adjusting for CV risk factors.

CONCLUSIONS:  Several CV risk factors were more prevalent in people with IPF; however, this did not account for the increased rate of IHD in this group of patients.

Chest. 2015;147(1):157-164. doi:10.1378/chest.14-0359

BACKGROUND:  Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of this study was to evaluate the impact of LC on survival of patients with associated IPF.

METHODS:  A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared.

RESULTS:  Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%.

CONCLUSIONS:  In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.

Chest. 2015;147(1):165-172. doi:10.1378/chest.14-0272

BACKGROUND:  Undifferentiated connective tissue disease (UCTD) involves conditions characterized by both having symptoms of connective tissue disease (CTD) and autoantibodies but not fulfilling the criteria of a specific CTD. The frequency or prognosis of the usual interstitial pneumonia (UIP) pattern in UCTD is unknown, which may be confused with idiopathic pulmonary fibrosis (IPF). This study aimed to investigate the frequency of the UIP pattern in interstitial pneumonia related to UCTD and compare its prognosis with that of IPF and UCTD-nonspecific interstitial pneumonia (UCTD-NSIP).

METHODS:  The medical records of 788 patients presumptively diagnosed with idiopathic interstitial pneumonia at Asan Medical Center from January 2005 to December 2012 were retrospectively reviewed. UCTD was diagnosed according to the criteria by Corte and colleagues, and the prognoses were compared between UCTD-UIP and UCTD-NSIP and between UCTD-UIP and IPF.

RESULTS:  Among 105 patients with UCTD (13.3% of total subjects), 44 had a UIP pattern (by surgical lung biopsy: 24; by high-resolution CT scan: 20), 29 had a nonspecific interstitial pneumonia pattern (by surgical lung biopsy), and nine had an organizing pneumonia pattern (by biopsy). The overall survival of the UCTD-UIP group was shorter than that of the UCTD-NSIP group (P = .021) but significantly better than that of the IPF group (P = .042).

CONCLUSIONS:  A UIP pattern, which seems to be frequent in UCTD, showed a poorer prognosis than that of UCTD-NSIP. However, the prognosis of UCTD-UIP was significantly better than that of IPF, highlighting the importance of searching for underlying UCTD in suspected IPF cases.

Chest. 2015;147(1):173-179. doi:10.1378/chest.13-2424

OBJECTIVE:  The outcomes of patients with idiopathic pulmonary fibrosis (IPF) who undergo hospitalization have not been well characterized. We sought to determine the frequency of all-cause and respiratory-related hospitalizations and to evaluate their impact on the subsequent course and survival of patients with IPF.

METHODS:  The records of patients with IPF evaluated at a tertiary center were examined for the cause and duration of hospitalization. Data on subsequent patient outcomes were collated.

RESULTS:  The IPF cohort consisted of 592 patients, 25.3% of whom were hospitalized subsequent to their IPF diagnosis. A respiratory-related cause accounted for 77.3% of these hospitalizations. The median transplant-free survival for all patients was 23.3 months (interquartile range [IQR], 7.6-63.6 months) from the time of consultation. Transplant-free survival after hospital admission was much lower for patients with a respiratory hospitalization compared with those with a nonrespiratory hospitalization (median survival, 2.8 months [IQR, 0.63-16.2 months] vs 27.7 months [IQR, 7.4-59.6 months]; P = .0004). Multivariate analyses demonstrated that both all-cause and respiratory-related hospitalizations were strongly associated with mortality after adjusting for baseline demographics. Among patients with a respiratory hospitalization, 22.4% died while in the hospital, whereas 16.4% eventually went on to lung transplantation.

CONCLUSIONS:  Hospitalizations are common events in patients with IPF. Most hospitalizations are respiratory-related and are associated with high in-hospital mortality and limited survival beyond discharge. Both all-cause and respiratory hospitalizations are associated with mortality, and therefore, either could be used as an end point in IPF clinical trials.

Chest. 2015;147(1):180-187. doi:10.1378/chest.14-0758

BACKGROUND:  Combined simvastatin and sirolimus therapy reduces tuberous sclerosis complex 2-null lesions and alveolar destruction in a mouse model of lymphangioleiomyomatosis (LAM), suggesting that therapy with both drugs may benefit patients with LAM.

METHODS:  To determine whether simvastatin changed the prevalence of adverse events or altered the therapeutic effects of sirolimus, we recorded adverse events and changes in lung function in patients with LAM treated with simvastatin plus sirolimus (n = 14), sirolimus alone (n = 44), or simvastatin alone (n = 20).

RESULTS:  Sirolimus-related adverse events in the simvastatin plus sirolimus and sirolimus-only groups were 64% and 66% for stomatitis, 50% and 52% for diarrhea, 50% and 45% for peripheral edema, 36% and 61% for acne, 36% and 30% for hypertension, 29% and 27% for proteinuria, 29% and 27% for leukopenia, and 21% and 27% for hypercholesterolemia. The frequency of simvastatin-related adverse events in the simvastatin-only and simvastatin plus sirolimus groups were 60% and 50% for arthralgias and 35% and 36% for myopathy. Before simvastatin plus sirolimus therapy, FEV1 and diffusing capacity of the lung for carbon monoxide (Dlco) yearly rates of change were, respectively, −1.4 ± 0.2 and −1.8 ± 0.2% predicted. After simvastatin plus sirolimus therapy, these rates changed to +1.2 ± 0.5 (P = .635) and +0.3 ± 0.4% predicted (P = .412), respectively. In 44 patients treated with sirolimus alone, FEV1 and Dlco rates of change were −1.7 ± 0.1 and −2.2 ± 0.1% predicted before treatment and +1.7 ± 0.3 and +0.7 ± 0.3% predicted after treatment (P < .001).

CONCLUSIONS:  Therapy with sirolimus and simvastatin does not increase the prevalence of drug adverse events or alter the therapeutic effects of sirolimus.

Original Research: Pulmonary Vascular Disease

Chest. 2015;147(1):188-197. doi:10.1378/chest.14-0263

BACKGROUND:  Pulmonary arterial hypertension (PAH) is a progressive disease with high rates of morbidity and mortality. Current therapies improve symptoms, functional capacity, and, in select cases, survival. Little is known about patient factors that may predict the likelihood of patient-important, clinically relevant responses to therapy such as the 6-min walk distance (6MWD) and health-related quality of life (HRQoL).

METHODS:  Data from the randomized clinical trial of tadalafil in PAH were used. Adjusted logistic regression models were created to examine the relationship between baseline characteristics and odds of achieving the minimal important difference (MID) in three parameters, defined as either a > 33-m increase in 6MWD, a > 5-unit increase in physical component summary score of the Medical Outcomes Study Short Form-36 (SF-36), or a > 5-unit increase in mental component summary score of the SF-36.

RESULTS:  The study included 405 subjects. Younger age, male sex, lower baseline 6MWD, and disease etiology were associated with greater odds of achieving the MID for the 6-min walk test. Active treatment, younger age, and male sex were associated with greater odds of achieving the MID for the physical component summary score. Male sex was associated with greater odds of achieving the MID for the mental component summary score.

CONCLUSIONS:  Age, sex, baseline functional capacity, and disease etiology are variably associated with the likelihood of achieving clinically relevant responses in patient-important outcomes to PAH-specific therapy such as 6MWD and HRQoL. The increased likelihood of response in men compared with women is a novel finding and may reflect pathophysiologic differences between sexes.

Chest. 2015;147(1):198-208. doi:10.1378/chest.13-3035

BACKGROUND:  Elevated mean right atrial pressure (RAP) measured by cardiac catheterization is an independent risk factor for mortality. Prior studies have demonstrated a modest correlation with invasive and noninvasive echocardiographic RAP, but the prognostic impact of estimated right atrial pressure (eRAP) has not been previously evaluated in patients with pulmonary arterial hypertension (PAH).

METHODS:  A retrospective analysis of 121 consecutive patients with PAH based on right-sided heart catheterization and echocardiography was performed. The eRAP was calculated by inferior vena cava diameter and collapse using 2005 and 2010 American Society of Echocardiography (ASE) definitions. Accuracy and correlation of eRAP to RAP was assessed. Kaplan-Meier survival analysis by eRAP, right atrial area, and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) risk criteria as well as univariate and multivariate analysis of echocardiographic findings was performed.

RESULTS:  Elevation of eRAP was associated with decreased survival time compared with lower eRAP (P < .001, relative risk = 7.94 for eRAP > 15 mm Hg vs eRAP ≤ 5 mm Hg). Univariate analysis of echocardiographic parameters including eRAP > 15 mm Hg, right atrial area > 18 cm2, presence of pericardial effusion, right ventricular fractional area change < 35%, and at least moderate tricuspid regurgitation was predictive of poor survival. However, multivariate analysis revealed that eRAP > 15 mm Hg was the only echocardiographic risk factor that was predictive of mortality (hazard ratio = 2.28, P = .037).

CONCLUSIONS:  Elevation of eRAP by echocardiography at baseline assessment was strongly associated with increased risk of death or transplant in patients with PAH. This measurement may represent an important prognostic component in the comprehensive echocardiographic evaluation of PAH.

Original Research: Lung Cancer

Chest. 2015;147(1):209-215. doi:10.1378/chest.14-0534

BACKGROUND:  Patients with clinical N1 (cN1) lung cancer based on imaging are at risk for malignant mediastinal nodal involvement (N2 disease). Endosonography with a needle technique is suggested over surgical staging as a best first test for preoperative invasive mediastinal staging. The addition of a confirmatory mediastinoscopy seems questionable in patients with a normal mediastinum on imaging. This prospective multicenter trial investigated the sensitivity of preoperative linear endosonography and mediastinoscopy for mediastinal nodal staging of cN1 lung cancer.

METHODS:  Consecutive patients with operable and resectable cN1 non-small cell lung cancer underwent a lobe-specific mediastinal nodal staging by endosonography. The primary study outcome was sensitivity to detect N2 disease. The secondary end points were the prevalence of N2 disease, the negative predictive value (NPV) of both endosonography and endosonography with confirmatory mediastinoscopy, and the number of patients needed to detect one additional N2 disease with mediastinoscopy.

RESULTS:  Of the 100 patients with cN1 on imaging, 24 patients were diagnosed with N2 disease. Invasive mediastinal nodal staging with endosonography alone has a sensitivity of 38%, which can be increased to 73% by adding a mediastinoscopy. NPV was 81% and 91%, respectively. Ten mediastinoscopies are needed to detect one additional N2 disease missed by endosonography.

CONCLUSIONS:  Endosonography alone has an unsatisfactory sensitivity to detect mediastinal nodal metastasis in cN1 lung cancer, and the addition of a confirmatory mediastinoscopy is of added value.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01456429; URL: www.clinicaltrials.gov

Chest. 2015;147(1):216-223. doi:10.1378/chest.14-1180

BACKGROUND:  Solitary fibrous tumors of the pleura (SFTPs) are infrequent neoplasms with no standardized criteria to predict risk of recurrence after curative surgery. The aim of the present study is to validate a recently proposed recurrence score in a large European cohort of patients with SFTP.

METHODS:  Validation of a previously published scoring system was assessed in a population of 113 patients who underwent complete resection of SFTPs. Patients were scored according to the pleural origin, morphology, size, hypercellularity, presence of necrosis or hemorrhage, and number of mitoses in their SFTPs. Receiver operating characteristic curves were plotted for the score. Time to recurrence analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.

RESULTS:  After a mean follow-up of 13.2 ± 7.3 years, there were nine recurrences (8.0%). Score performance to predict recurrence was as follows: sensitivity = 78%, specificity = 74%, positive likelihood ratio = 3.0, and negative likelihood ratio = 0.3. A cutoff of 3 points was used to classify 79 patients (69.9%) at low risk and 34 patients (30.1%) at high risk for recurrence. A high-risk classification was significantly associated with more recurrences during follow-up (P = .004), worse overall survival (P = .0008), more extensive lung resections (P = .001), and the use of adjuvant therapies (P = .009). The present score outperformed England’s criteria (P = .049) and de Perrot classification (P < .001) when predicting SFTP recurrence.

CONCLUSIONS:  The proposed scoring system, which combines common clinical and histologic features of resected SFTPs, remains predictive of recurrence in a separate patient population. The simple score may guide the postoperative surveillance of this uncommon tumor.

Translating Basic Research Into Clinical Practice

Chest. 2015;147(1):224-231. doi:10.1378/chest.14-0781

Volatile organic compounds (VOCs) are produced by virtually all metabolic processes of the body. As such, they have potential to serve as noninvasive metabolic biomarkers. Since exhaled VOCs are either derived from the respiratory tract itself or have passed the lungs from the circulation, they are candidate biomarkers in the diagnosis and monitoring of pulmonary diseases in particular. Good examples of the possibilities of exhaled volatiles in pulmonary medicine are provided by the potential use of VOCs to discriminate between patients with lung cancer and healthy control subjects and to noninvasively diagnose infectious diseases and the association between VOCs and markers of disease activity that has been established in obstructive lung diseases. Several steps are, however, required prior to implementation of breath-based diagnostics in daily clinical practice. First, VOCs should be studied in the intention-to-diagnose population, because biomarkers are likely to be affected by multiple (comorbid) conditions. Second, breath collection and analysis procedures need to be standardized to allow pooling of data. Finally, apart from probabilistic analysis for diagnostic purposes, detailed examination of the nature of volatile biomarkers not only will improve our understanding of the pathophysiologic origins of these markers and the nature of potential confounders but also can enable the development of sensors that exhibit maximum sensitivity and specificity toward specific applications. By adhering to such an approach, exhaled biomarkers can be validated in the diagnosis, monitoring, and treatment of patients in pulmonary medicine and contribute to the development of personalized medicine.

Recent Advances in Chest Medicine

Chest. 2015;147(1):232-241. doi:10.1378/chest.14-0800

Dyspnea is the most prevalent symptom among patients with cardiac and respiratory diseases. It is an independent predictor of mortality in patients with heart disease, COPD, and the elderly. Studies using naloxone to block opioid-receptor signaling demonstrate that endogenous opioids modulate dyspnea in patients with COPD. Neuroimaging studies support a cortical-limbic network for dyspnea perception. A 2012 American Thoracic Society statement recommended that dyspnea be considered across three different constructs: sensory (intensity), affective (distress), and impact on daily activities. The 2013 GOLD (Global Initiative for Chronic Obstructive Lung Disease) executive summary recommended a treatment paradigm for patients with COPD based on the modified Medical Research Council dyspnea score. The intensity and quality of dyspnea during exercise in patients with COPD is influenced by the time to onset of critical mechanical volume constraints that are ultimately dictated by the magnitude of resting inspiratory capacity. Long-acting bronchodilators, either singly or in combination, provide sustained bronchodilation and lung deflation that contribute to relief of dyspnea in those with COPD. Opioid medications reduce breathing discomfort by decreasing respiratory drive (and associated corollary discharge), altering central perception, and/or decreasing anxiety. For individuals suffering from refractory dyspnea, a low dose of an opioid is recommended initially, and then titrated to achieve the lowest effective dose based on patient ratings. Acupuncture, bronchoscopic volume reduction, and noninvasive open ventilation are experimental approaches shown to ameliorate dyspnea in patients with COPD, but require confirmatory evidence before clinical use.

Topics: dyspnea

Special Features

Chest. 2015;147(1):242-250. doi:10.1378/chest.14-0531

Recently, we reported a number of key, common medications that affect the air passages in a variety of fashions. The purpose of this article is to provide a comprehensive review of the literature on the subject, including supportive articles published in languages other than English. The presented information was gathered by a review of the English literature, by cross referencing, and by communication with other interventional pulmonologists. We identified several additional medications causing either direct or systemic effects on the air passages. In this review, we update the clinical presentation, mechanism of injury, diagnosis, and management of the airway complications related to these medications.

Topics in Practice Management

Chest. 2015;147(1):251-258. doi:10.1378/chest.12-0072

Asthma is a chronic inflammatory disease that affects an estimated 25 million people in the United States. In 70% to 90% of cases, asthma is associated with IgE-mediated mechanisms, which have proved central to allergen-induced inflammation in preclinical and clinical models. The importance of IgE levels in patients with moderate to severe asthma has been confirmed in randomized controlled studies with a targeted IgE blocker. Advances in laboratory methods to detect and quantify allergen-specific IgE antibodies have allowed for a quick-and-easy diagnosis of allergic IgE-mediated sensitivities in the office. Pulmonologists tend to order in vitro tests to measure allergen-specific IgE rather than to perform allergen skin testing, which is seen as the purview of allergists. This article reviews the importance of allergen testing in patients with asthma—whether by skin testing or by in vitro methods—and highlights the advantages, limitations, and interpretation of results derived from each method. Additionally, this article includes suggested documentation and administrative details for physician reporting in the office setting.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;147(1):259-265. doi:10.1378/chest.14-0877

The ventilatory strategy for ARDS has been regularly amended over the last 40 years as knowledge of the pathophysiology of ARDS has increased. Initially focused mainly on the lung with the objectives of “opening the lung” and optimizing arterial oxygen saturation, this strategy now also takes into account pulmonary vascular injury and its effects on the right ventricle and on hemodynamics. Hemodynamic devices now available at the bedside, such as echocardiography, allow intensivists to evaluate respiratory settings according to right ventricular tolerance. Here, we review the pathophysiology of pulmonary vascular dysfunction in ARDS, consider the beneficial and deleterious effects of mechanical ventilation, describe the incidence and meaning of acute cor pulmonale based on recent studies in large series of patients, and propose a new, although not strictly validated, approach based on the protection of both the lung and right ventricle. One of our conclusions is that evaluating the right ventricle may help intensivists to assess the balance between recruitment and overdistension induced by the ventilatory strategy. Prone positioning with its beneficial effects on the lung and also on hemodynamics (the right ventricle) is a good illustration of this. Readers should be aware that most of the information given in this article reflects the point of view of the authors. Although based on clinical observations, clinical studies, and well-known pathophysiology, there is no evidence-based medicine to support this clinical commentary. Other approaches may be favored, in which case our article should be read as another attempt to help intensivists to improve management of ARDS.

Contemporary Reviews in Sleep Medicine

Chest. 2015;147(1):266-274. doi:10.1378/chest.14-0500

OSA is a common chronic disorder that is associated with significant morbidity and mortality including cardiovascular, metabolic, and neurocognitive disease and increased cancer-related deaths. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia (IH) is now being recognized as a potential major factor contributing to the pathogenesis of OSA-related comorbidities. OSA-related high-frequency IH is characterized by cycles of hypoxemia with reoxygenation that is distinctly different than sustained low-frequency hypoxia and contributes to ischemia-reperfusion injury. Data from both animal and human studies support mechanistic links between IH and its adverse impact at the tissue level. IH promotes oxidative stress by increased production of reactive oxygen species and angiogenesis, increased sympathetic activation with BP elevation, and systemic and vascular inflammation with endothelial dysfunction that contributes to diverse multiorgan chronic morbidity and mortality affecting cardiovascular disease, metabolic dysfunction, cognitive decline, and progression of cancer. Data from observational studies in large population groups also support the role for hypoxia in the pathogenesis of OSA comorbidity. Treatment with CPAP to reverse OSA-related symptoms and comorbidities has been shown to provide variable benefit in some but not all patient groups. Early treatment with CPAP makes intuitive sense to promote maximal functional recovery and minimize residual injury. More studies are needed to determine the interacting effects of IH and obesity, differential effects of both short-term and long-term hypoxemia, and the effect of CPAP treatment.


Chest. 2015;147(1):275. doi:10.1378/chest.14-1527

After chemo, my mother smokes out on the screened porch.
I choose a knife, peel back the skins of four pounds of red onions,
release their sting. The knife is not sharp enough but I am good
at chopping. Know how to hold the ovals down on the board,
line them up and slice them into thin rounds that fall away
from their centers into a tangled heap until my eyes weep
of their own accord. My mother comes into the kitchen
and I wipe my eyes, say, The onions are strong.
At home, I would use olive oil. Here, I use butter.
Stand over the pot rearranging the onions with a spoon.
My mother empties her ashtray.
Come sit on the porch, she says.
I shake my head, tell her, I have to cook the onions slow,
a long time.
My mother’s hair has not grown back yet.
She weighs barely one hundred pounds.
I hear her lighter ignite out on the porch.
The onions soften. You are not supposed
to let them brown. I add black pepper
for her blood, beef broth for her bones,
white wine for her spirit, three tablespoons of cognac
for the nights she stayed up telling her secrets.
Love is always tainted. I add salt.

Chest. 2015;147(1):276-277. doi:10.1378/chest.14-1669

  In the days after white earbuds left
  fashion I was put in a bit of a bind:
  How best to communicate to the public that I do not
  want to talk when I am on the elevator?
  With the largesse of the new noisecancelers
  I can keep the switch lit while the battery on my phone dies
  and in this position you mock-harrumph while I hiss-air-boom.
  Kidding: you are not paying attention at all.
  Except when we’re running.
  When are we not, after all?
  After work, you ask after my Bose, how they are canceling.
  We are on a run, and it has been weeks,
  in that it has been, like, three and a half weeks,
  since I last ran into you.
  You were, you texted through my phone,
  just so busy reading about how busy you are all the time.
And this run we go on
to have the luxury to have the sincere pleasure
to warm again to one another
via a stadium go-around)
is a curt jog cum sprint along the I don’t know.
I forget what that body of water is called.
  The first ten would be warm were it
  not for my exercise-induced asthma
  so I claim, for time, a snort through my lying turbinates
  knock-knock albuterol and samidzat pseudoephedrine
  coughing up guaifenesin with whatever scrape-able noxious something
  clear as tin (allergies!) and voice plaqued
  I am unable to contain my contempt without the use of a spacer.
  Slight little thing!
  You, who call yourself chub,
  I can’t believe you can even talk while you’re working out.
  At times it seems you live to offend,
  dicking around with your metrics.
  To stick a Bovie on me
  is to do your 20 curls, 10 mountain-climbers, 800-meter run
  except that times we can scale.
  And I know our friend on our same app
  she is keeping a running feed.
  And patch or no patch
  it takes a thrum in the blood to remain at 115.
  Who can replace my bronchioles’ cytokine grab-ass?
  It is just me joining the half-an-hour earlier group.

Chest. 2015;147(1):278. doi:10.1378/chest.14-1811

I read Real Simple, a flappy shield to screen
sick sea of peering eyes. I follow round
cracked cobblestones that curve and wend by pond,
through a tendriled trellis arching over a bench
past dangling yellow roses where I spy
the lady of the garden squatting down
in grubby jeans and clogs with floppy hat,
no job to do but taming wilding weeds.
No people take her clothes and make her lie,
no x-ray beams undress her through a gown.
In open air she smiles. I turn the page
and see her friends, they come one day to help
but this is not a party, it is clear.
They come so she can show them how to pull
the choking weeds for she must leave to fight
a different growth, the one that lies within.
I slap the pages shut and sling it down.
I close my eyes, then open them to see
a painting on the wall, a bobbing boat,
pink shimmer on the water sparking waves,
tinged mauves and golds on clouds, a softened spray
like blossoms in a garden by Monet.
So here’s my chance, it’s all I need to do,
to mount the boat, unfurl the sails, untie
the rope that tethers sailboat to the dock,
push off, slip round the bend and out to sea.

Chest. 2015;147(1):279. doi:10.1378/chest.14-1802

The doctor enters me
part by part
into her laptop
as if to crack
the code of who I am.
–Minus one appendix,
that vestigial structure
a mystery
–Plus four scars.
I earned them
–Minus fifty skipped
heart beats an hour.
Who would miss them
–Plus one frozen
Who uses it
–Minus one thyroid.
It had cancer
–Plus a page
of aches and pains.
I’m used to them
–Minus sundry lumps
and bumps.
They were good
for nothing
I think we have it all,
she says. Would you
like a printout?

Ultrasound Corner

Chest. 2015;147(1):e1-e4. doi:10.1378/chest.14-1161

A 75-year-old woman presented to the ED complaining of dyspnea, fever, and a productive cough for 1 week. A recent diagnosis was made of a poorly differentiated squamous cell lung cancer of the right upper lobe with a large endotracheal lesion. On physical examination in the ED, her vital signs were as follows: BP, 112/72 mm Hg; heart rate, 78 beats/min; temperature, 39.1°C; and oxygen saturation, 94% on room air. She appeared cachectic, with good dentition, and in mild respiratory distress. Auscultation revealed coarse rhonchi on the right anterior and posterior upper chest. Initial laboratory results were only significant for leukocytosis (15,400 cells/μL), with 93% of neutrophils; her basic metabolic and liver function panels were unremarkable. The initial chest radiograph was read as “unchanged right upper lung mass.”

Selected Reports

Chest. 2015;147(1):e5-e7. doi:10.1378/chest.14-0814

Thoracentesis is considered a relatively safe and well-established procedure commonly done at the bedside with minimal risk of complication. Thoracentesis-related hemothorax is uncommon; however, it may be life-threatening. We describe a case of a 19-year-old woman with persistent fever and pleural effusion, in which thoracentesis resulted in tension hemothorax due to intercostal artery laceration. It is important for proceduralists to understand not only the tortuosity of the intercostal artery covering 25% to 50% of the intercostal space, but also the presence of traversing collateral arteries. Herein, we discuss the potential benefit of vascular ultrasonography with color Doppler during thoracentesis, with the goal of avoiding vessel injury and hemorrhage.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;147(1):e8-e12. doi:10.1378/chest.14-0615

A 47-year-old man with no significant past medical history, originally from Indonesia, was brought to the ED of an urban US medical center after being found collapsed on the sidewalk in respiratory distress and with an altered sensorium. Upon arrival to the ED, he was tachypneic, with increased work of breathing and an oxygen saturation of 88% on 100% nonrebreather mask, so he was immediately intubated. Following intubation, he became profoundly hypotensive, requiring aggressive crystalloid resuscitation and vasopressor support. Broad-spectrum antimicrobials were administered, including ceftriaxone, vancomycin, levofloxacin, and oseltamivir. Further history elicited subsequently from family members revealed that the patient had returned from a 2-week vacation in Indonesia 6 days prior to presentation. According to relatives, he appeared to be in his usual state of health upon his return and was not seen by anyone thereafter, but in the interim he reportedly had an episode of epistaxis, and text messages received from him became progressively more bizarre.

Topics: shock , traveler
Chest. 2015;147(1):e13-e17. doi:10.1378/chest.14-1172

A 65-year-old Asian man with a history of chronic hepatitis B infection presented to our pulmonary clinic for second opinion of his chronic, persistent, nonproductive cough. He was evaluated 10 months earlier with chest CT scan, which revealed a large lingular nodular opacity that was diagnosed as nodular cryptogenic organizing pneumonia by CT scan-guided percutaneous lung biopsy. Systemic corticosteroids were initiated and continued over the next 10 months. The dry cough persisted, and he developed intermittent left-sided pleuritic chest pain. He denied fevers, night sweats, hemoptysis, weight loss, or dyspnea. He was a lifelong nonsmoker and moved to the United States from China during childhood.

Chest. 2015;147(1):e18-e21. doi:10.1378/chest.14-0935

A 44-year-old woman was brought to the ED from John F. Kennedy International Airport. The patient was returning with her son from a 3-month visit to Bangladesh. Her journey started with a 4-h flight from Dhaka, Bangladesh to Dubai, United Arab Emirates. She consumed 240 mL of whiskey during the flight. This was followed by a 14-h flight from Dubai to New York. According to the patient’s son, she did not consume any alcohol during the second flight. The patient was in her usual state of health with normal mentation throughout her journey. Upon landing, she started complaining of shortness of breath. After disembarking, she was witnessed to have seizure-like activity with involuntary passage of urine, following which she collapsed. The patient was intubated by emergency medical services in the field.


Chest. 2015;147(1):e22. doi:10.1378/chest.14-2064
Chest. 2015;147(1):e23. doi:10.1378/chest.14-2087
Chest. 2015;147(1):e23-e24. doi:10.1378/chest.14-2300
Chest. 2015;147(1):e25-e26. doi:10.1378/chest.14-2315

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