Current Issue


Chest. 2015;148(4):843-844. doi:10.1378/chest.15-0954

The global prevalence of asthma is estimated to be 300 million and is expected to grow by > 100 million by 2025.1 Patients with severe and difficult-to-treat asthma comprise a small proportion (5%-10%) of all patients with asthma, yet they are responsible for a disproportionate degree of asthma morbidity and costs.2

Topics: asthma
Chest. 2015;148(4):844-846. doi:10.1378/chest.15-0915

The eosinophil has been implicated in airways disease from the mid to late 19th century following the identification of Charcot-Leyden crystals as a consequence of eosinophil products in the sputum of patients with asthma. Advances in sputum induction and processing have enabled the reliable assessment of airway inflammation and demonstrate that although an airway eosinophilia is commonly observed in asthma, it is neither necessary nor sufficient for the development of this disease.1 Interestingly, sputum eosinophilia can be observed in COPD in approximately 10% to 15% of patients.1 Early application of sputum assessment in chronic cough also identified that eosinophilic airway inflammation can be present in the absence of airflow obstruction and airway hyperresponsiveness and that this nonasthmatic eosinophilic bronchitis (NAEB) is a common cause of chronic cough.2

Chest. 2015;148(4):846-848. doi:10.1378/chest.15-0866

In this issue of CHEST (see page 903), Jiang et al1 present a well-done study on the impact of visceral pleural invasion (VPI) in patients with node-negative lung cancer. They conducted a systematic literature review involving > 21,000 patients and demonstrated that VPI reduced overall survival. This was seen for all patients (OR, 0.7; 95% CI, 0.59-0.83; P < .0001), but also within specific size subgroups: 0 to 3 cm (OR, 0.71 [CI, 0.64-0.79]; P < .0001), 3 to 5 cm (OR, 0.69 [CI, 0.56-0.86]; P = .0008), and 5 to 7 cm (OR, 0.7 [CI, 0.54-0.91]; P = .007).1 This meta-analysis provides compelling evidence that VPI is indeed a prognostic factor in patients with lung cancer.

Chest. 2015;148(4):848-851. doi:10.1378/chest.15-1536

Periodic breathing with central sleep apnea (CSA), known as Hunter-Cheyne-Stokes respiration, is among the first recognized sleep-related breathing disorders, described in the early 19th century, and is now recognized to be quite common in patients with chronic heart failure (HF). It remains uncertain whether CSA is simply a marker of underlying cardiac dysfunction or, alternatively, whether CSA exerts a detrimental effect on the failing heart (eg, via hypoxia, arousal, and their associated sympathoexcitation) or if it is a beneficial compensatory mechanism (eg, via increased end-expiratory lung volumes improving oxygenation or via promotion of cardioprotective alkalosis).1 Reports that CSA is associated with increased risk for mortality in patients with HF, along with preliminary findings of improved cardiac function and reduced mortality when CSA was treated with CPAP,2-4 prompted a multicenter randomized controlled trial to investigate the effect of CPAP on transplant-free survival in patients with HF with CSA. This trial was prematurely terminated because of low recruitment, reduced mortality due to secular trends in the medical treatment of HF, and early divergence of the survival curves in favor of the control group (hazard ratio [HR] in first 18 months, 1.5; P = .02).5 Beyond 18 months, survival favored the CPAP arm, but the overall difference between treatment groups was not statistically significant, despite sustained improvement in intermediate measures (left ventricular ejection fraction [LVEF], plasma norepinephrine level, 6-min walk distance).5 The power of this study was limited, CPAP had suboptimal effectiveness in reducing CSA burden, and secondary analysis suggested that survival was improved in those in whom CSA was suppressed,6 leading to the design and initiation of two larger, more adequately powered trials using adaptive servoventilation (ASV), a bilevel positive airway pressure modality that is more effective in reversing CSA in patients with HF.7 These include an ongoing trial enrolling patients with either obstructive or central sleep apnea (Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure [ADVENT-HF])8 and a completed trial enrolling only patients with predominantly CSA (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure [SERVE-HF]),9 with recently publicized results.

Point and Counterpoint

Chest. 2015;148(4):852-854. doi:10.1378/chest.15-1163

A measles outbreak linked to California’s Disneyland has led to > 300 cases in at least seven states, Mexico, and Canada through March 2015. Most cases occurred in people choosing to forego vaccination.1,2 The costs associated with this outbreak exceed those borne by individuals opting out of vaccination: > 10% of the California cases occurred in children too young to be vaccinated, schools and daycares were forced either to close or to enforce policies excluding unvaccinated and vulnerable children for multiple weeks, and health departments spent scores of personnel hours—and hundreds of thousands of dollars from limited budgets—containing the spread of this vaccine-preventable illness.1,2

Chest. 2015;148(4):854-856. doi:10.1378/chest.15-1162

We have no doubt that childhood measles immunization programs aimed at achieving or maintaining herd immunity are justified from both a public health and an ethical perspective. The minor risks that may be associated with the vaccination far outweigh the burden of disease that measles outbreaks produce.1

Chest. 2015;148(4):856-857. doi:10.1378/chest.15-1164

We agree with much of what Drs Schröder-Bäck and Martakis1 argue in their counterpoint editorial. The benefits of vaccination outweigh any individual and societal risks accrued by remaining unvaccinated. Ethical arguments in favor of mandating measles vaccination may outweigh appeals to liberty or individual or parental autonomy. Furthermore, mandates would minimize free-riding and maximize public fairness by appropriately imposing shared burdens across society. Where we largely diverge is how we would balance societal burdens when implementing policy to achieve such goals.

Chest. 2015;148(4):857-858. doi:10.1378/chest.15-1161

We agree with Prof Silverman and Dr Hendrix1 that the risks of measles outbreaks are to be taken very seriously and call for action to raise the immunization rate. We disagree, however, about how to approach this challenge. The question is if measles vaccination should be a mandatory and rigorously enforced requirement for attending school.


Chest. 2015;148(4):859-864. doi:10.1378/chest.15-0358

Atrial fibrillation (AF) that newly occurs during critical illness presents challenges for both short- and long-term management. During critical illness, patients with new-onset AF are clinically evaluated for hemodynamic instability owing to the arrhythmia as well as for potentially reversible arrhythmia triggers. Hemodynamically significant AF that persists during critical illness may be treated with heart rate or rhythm control strategies. Recent evidence suggests that patients in whom AF develops during acute illness (eg, sepsis, postoperatively) have high long-term risks for AF recurrence and for AF-associated complications, such as stroke, heart failure, and death. Therefore, we suggest increased efforts to improve communication of AF events between inpatient and outpatient providers and to reassess patients who had experienced new-onset AF during critical illness after they transition to the post-ICU setting. We describe various strategies for the assessment and long-term management of patients with new-onset AF during critical illness.

Commentary: Ahead of the Curve

Chest. 2015;148(4):865-869. doi:10.1378/chest.14-3172

Mortality caused by acute cardiopulmonary disease is decreasing, and in many countries the population is aging rapidly. Yet, the life-years gained are often spent with multiple chronic and slowly progressive conditions, and this particularly applies to patients with cardiopulmonary disease. Affected individuals often have multiple diagnoses related to the cardiopulmonary-metabolic axis with accelerated aging and gradually progressive failure of organs that provide the body with oxygen and nutrients. This more or less reflects an “engine running out of fuel.” This, for instance, is the case with the concurrent presence of COPD and heart failure in one patient that is often combined with other comorbidities such as atrial fibrillation, renal failure, or diabetes. This asks for a paradigm shift: away from single-disease-oriented patient management and toward patient-tailored multimorbidity medicine. Daily clinical practice is already recognizing this on a daily basis, yet clinical research and guidelines are still lagging behind. Thus, novel research approaches are needed to better guide evidence-based clinical practice. These approaches include the construction of diagnostic models to predict the presence of multiple diseases simultaneously, individual patient data meta-analysis as a method to examine variation in the effects of treatments or diagnostic tests depending on comorbidity, and the construction of therapeutic prediction models that predict the therapeutic effect of drugs based on the presence (or absence) of relevant comorbidity. We argue that multimorbidity should be regarded as a “friend” and not as a “foe” in clinical research addressing the current clinical problems in daily practice.

Original Research: Asthma

Chest. 2015;148(4):870-876. doi:10.1378/chest.14-3056

BACKGROUND:  Systematic assessment of severe asthma can be used to confirm the diagnosis, identify comorbidities, and address adherence to therapy. However, the prospective usefulness of this approach is yet to be established. The objective of this study was to determine whether the systematic assessment of severe asthma is associated with improved quality of life (QoL) and health-care use and, using prospective data collection, to compare relevant outcomes in patients referred with severe asthma to specialist centers across the United Kingdom.

METHODS:  Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics, and health-care use between initial assessment and a median follow-up of 286 days.

RESULTS:  The study population consisted of 346 patients with severe asthma. At follow-up, there were significant reductions in health-care use in terms of primary care or ED visits (66.4% vs 87.8%, P < .0001) and hospital admissions (38% vs 48%, P = .0004). Although no difference was noted in terms of those requiring maintenance oral corticosteroids, there was a reduction in steroid dose (10 mg [8-20 mg] vs 15 mg [10-20 mg], P = .003), and fewer subjects required short-burst steroids (77.4% vs 90.8%, P = .01). Significant improvements were seen in QoL and control using the Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire.

CONCLUSIONS:  To our knowledge, this is the first time that a prospective study has shown that a systematic assessment at a dedicated severe asthma center is associated with improved QoL and asthma control and a reduction in health-care use and oral steroid burden.

Chest. 2015;148(4):877-886. doi:10.1378/chest.14-2413

BACKGROUND:  Consensus on how best to express bronchodilator reversibility (BDR) is lacking. We tested different BDR criteria against the null hypotheses that BDR should show no sex or size bias. To determine the best criterion for defining BDR, we hypothesized that clinically important BDR should be associated with better survival in respiratory patients compared with that of patients without BDR.

METHODS:  We used the first BDR test of 4,231 patients who had known subsequent survival status (50.8% male sex; mean age, 60.9 years; mean survival, 5.2 years [range, 0.1-16.5 years]). BDR for FEV1 was expressed as absolute change, % baseline change, and change as % predicted FEV1.

RESULTS:  Having BDR defined from absolute change was biased toward men (male to female ratio, 2.70) and toward those with larger baseline FEV1. BDR defined by % change from baseline was biased toward those with lower baseline values. BDR defined by % predicted had no sex or size bias. Multivariate Cox regression found those with FEV1 BDR > 8% predicted (33% of the subjects) had an optimal survival advantage (hazard ratio, 0.56; 95% CI, 0.45-0.69) compared with those with FEV1 BDR ≤ 8% predicted. The survival of those with FEV1 BDR > 8% predicted was not significantly different from that of those with FEV1 BDR > 14% predicted but was significantly better than that of those with FEV1 BDR < 0.

CONCLUSIONS:  We have shown that expressing FEV1 BDR as % predicted avoids sex and size bias. FEV1 BDR > 8% predicted showed optimal survival advantage and may be the most appropriate criterion to define clinically important reversibility.

Original Research: Signs and Symptoms of Chest Disease

Chest. 2015;148(4):887-894. doi:10.1378/chest.14-2351

OBJECTIVE:  The long-term prognosis of nonasthmatic eosinophilic bronchitis (NAEB) is still unclear. The aim of this study was to observe the frequency of relapse among patients with NAEB and the likelihood of NAEB developing into chronic airflow obstruction over time.

METHODS:  Patients with NAEB were followed for at least 1 year between 2003 and 2013. During this period, we evaluated clinical symptoms, sputum eosinophil count, spirometry, and bronchial hyperresponsiveness. A linear mixed model was adopted to determine the relationship between time and lung function.

RESULTS:  A total of 234 patients with NAEB were identified, of whom 141 were followed for > 1 year (median, 4.1 years). Up to 59.6% of patients had a relapse after treatment. Both allergic rhinitis (OR, 4.37; 95% CI, 1.049-18.203; P = .043) and sputum eosinophilia after 4 weeks of treatment with inhaled corticosteroids (OR, 9.493; 95% CI, 2.381-37.850; P = .001) were risk factors for relapse. Among the 141 patients, mild asthma developed in eight (5.7%). During the follow-up period, no progressive decline in FVC, FEV1, and FEV1/FVC were observed (P > .05). Although the proportion of small airway dysfunction (maximum midexpiratory flow [MMEF] < 65%) significantly increased at the last visit in all groups (all P < .05), only the relapse group showed an MMEF decline at the end of follow-up (P < .05) in the linear mixed model.

CONCLUSIONS:  More than 50% of patients with NAEB have repeated episodes associated with persistent sputum eosinophilia after treatment and allergic rhinitis. In the current cohort, chronic airway obstruction does not develop despite small airway dysfunction increases over time.

Chest. 2015;148(4):895-902. doi:10.1378/chest.15-0308

BACKGROUND:  Although patients may find it difficult to describe their breathing discomfort, most are able to select statements among a list to describe their experience. The primary objective of this study was to examine sensitivity and specificity of descriptors of breathing discomfort prospectively in patients with common respiratory conditions as well as those patients who had refractory dyspnea.

METHODS:  Outpatients answered “Yes” or “No” for each of 15 statements describing breathing discomfort, next selected the best three that most closely applied, and then completed the Hospital Anxiety Depression Scale-Anxiety subscale. Sensitivity, specificity, and predictive values were calculated for the descriptors by diagnosis.

RESULTS:  “Work/effort” descriptors were selected as the best three by patients with COPD (n = 68), respiratory muscle weakness (n = 11), and refractory dyspnea (n = 17). Along with “work/effort” descriptors, “My chest feels tight” was among the best three in asthma (n = 22), with 38% sensitivity and 88% specificity. Along with “work/effort” descriptors, “My breathing is shallow” was among the best three in interstitial lung disease (n = 8), with 33% sensitivity and 84% specificity. Affective descriptors “frightening” (61% vs 31%, P = .002) and “awful” (66% vs 37%, P = .004) were reported more frequently in those with high anxiety scores compared with low anxiety scores.

CONCLUSIONS:  Although no descriptor achieved satisfactory sensitivity and specificity for identifying a particular condition, chest “tightness” was unique for asthma, whereas “shallow breathing” was unique for interstitial lung disease. Affective descriptors were associated with high anxiety scores.

Original Research: Lung Cancer

Chest. 2015;148(4):903-911. doi:10.1378/chest.14-2765

BACKGROUND:  Visceral pleural invasion (VPI) is considered an aggressive and invasive factor in non-small cell lung cancer (NSCLC). Recent studies found that depending on tumor size, VPI influences T stage, but there is no consensus on whether VPI is important in node-negative NSCLC. In addition, its role in stage IB NSCLC is still uncertain. In this meta-analysis, we assessed the role of VPI in node-negative NSCLC according to various tumor sizes and especially in stage IB disease.

METHODS:  A systematic literature search of four databases (EBSCO, PubMed, Ovid, and Springer) was performed to find relevant articles. The primary end point was 5-year overall survival. Pooled ORs were calculated using control as a reference group, and significance was determined by the Z-test.

RESULTS:  Thirteen relevant studies in 27,171 patients were included in this study. The number of patients with VPI was 5,821 (21%). VPI was a significant adverse prognostic factor in patients with tumor size ≤ 3 cm (OR, 0.71; 95% CI, 0.64-0.79; P < .001), > 3 but ≤ 5 cm (OR, 0.69; 95% CI, 0.56-0.86; P < .001), and > 5 but ≤ 7 cm (OR, 0.70; 95% CI, 0.54-0.91; P = .007). A further comparison was made with stage IB NSCLC. Tumor size ≤ 3 cm with VPI was associated with a better survival than tumor size > 3 but ≤ 5 cm regardless of VPI (OR, 1.31; 95% CI, 1.19-1.45; P < .001). Exploratory analysis found no survival benefit between tumor size ≤ 3 cm with VPI and tumor size > 3 but ≤ 5 cm without VPI (OR, 1.16; 95% CI, 0.95-1.43; P = .15); however, the prognosis for tumor size > 3 but ≤ 5 cm with VPI was not as good as that for tumor size ≤ 3 cm with VPI.

CONCLUSIONS:  VPI together with tumor size has a synergistic effect on survival in node-negative NSCLC. Patients with stage IB NSCLC and larger tumor size with VPI might be considered for adjuvant chemotherapy after surgical resection and need careful preoperative evaluation and postoperative follow-up. Further randomized clinical trials to determine the impact of adjuvant chemotherapy in patients with stage IB NSCLC with VPI are warranted.

Original Research: Critical Care

Chest. 2015;148(4):912-918. doi:10.1378/chest.15-0341

BACKGROUND:  Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS).

METHODS:  Adult patients in the ICU were prospectively enrolled from January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous causes after reviewing the hospitalization course in electronic medical records.

RESULTS:  One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio, 191; interquartile range, 122-253). Fifty-nine patients (44%) received a diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines relative to all zones examined) was predictive of miscellaneous cause vs CPE or ARDS (receiver operating characteristic area under the curve [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left-sided pleural effusion (> 20 mm), moderately or severely decreased left ventricular function, and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87).

CONCLUSIONS:  Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

Chest. 2015;148(4):919-926. doi:10.1378/chest.15-0445

BACKGROUND:  Recent emphasis has been placed on methods to predict fluid responsiveness, but the usefulness of using fluid boluses to increase cardiac index in critically ill patients with ineffective circulation or oliguria remains unclear.

METHODS:  This retrospective analysis investigated hemodynamic responses of critically ill patients in the ARDS Network Fluid and Catheter Treatment Trial (FACTT) who were given protocol-based fluid boluses. Fluid responsiveness was defined as ≥ 15% increase in cardiac index after a 15 mL/kg fluid bolus.

RESULTS:  A convenience sample of 127 critically ill patients enrolled in FACTT was analyzed for physiologic responses to 569 protocolized crystalloid or albumin boluses given for shock, low urine output (UOP), or low pulmonary artery occlusion pressure (PAOP). There were significant increases in mean central venous pressure (9.9 ± 4.5 to 11.1 ± 4.8 mm Hg, P < .0001) and mean PAOP (11.6 ± 3.6 to 13.3 ± 4.3 mm Hg, P < .0001) following fluid boluses. However, there were no significant changes in UOP, and there were clinically small changes in heart rate, mean arterial pressure, and cardiac index. Only 23% of fluid boluses led to a ≥ 15% change in cardiac index. There was no significant difference in the frequency of fluid responsiveness between boluses given for shock or oliguria vs boluses given only for low PAOP (24.0% vs 21.8%, P = .59). There were no significant differences in 90-day survival, need for hemodialysis, or return to unassisted breathing between patients defined as fluid responders and fluid nonresponders.

CONCLUSIONS:  In this cohort of critically ill patients with ARDS who were previously resuscitated, the rate of fluid responsiveness was low, and fluid boluses only led to small hemodynamic changes.

Chest. 2015;148(4):927-935. doi:10.1378/chest.14-3098

BACKGROUND:  Patients with systemic rheumatic diseases (SRDs) may require ICU management for SRD exacerbation or treatment-related infections or toxicities.

METHODS:  This was an observational study at 10 university-affiliated ICUs in France. Consecutive patients with SRDs were included. Determinants of ICU mortality were identified through multivariable logistic analysis.

RESULTS:  Three hundred sixty-three patients (65.3% women; median age, 59 years [interquartile range, 42-70 years]) accounted for 381 admissions. Connective tissue disease (primarily systemic lupus erythematosus) accounted for 66.1% of SRDs and systemic vasculitides for 26.2% (chiefly antineutrophil cytoplasm antibodies-associated vasculitides). SRDs were newly diagnosed in 43 cases (11.3%). Direct admission to the ICU occurred in 143 cases (37.9%). Reasons for ICU admissions were infection (39.9%), SRD exacerbation (34.4%), toxicity (5.8%), or miscellaneous (19.9%). Respiratory involvement was the leading cause of admission (56.8%), followed by shock (41.5%) and acute kidney injury (42.2%). Median Sequential Organ Failure Assessment (SOFA) score on day 1 was 5 (3-8). Mechanical ventilation was required in 57% of cases, vasopressors in 33.9%, and renal replacement therapy in 28.1%. ICU mortality rate was 21.0% (80 deaths). Factors associated with ICU mortality were shock (OR, 3.77; 95% CI, 1.93-7.36), SOFA score at day 1 (OR, 1.19; 95% CI, 1.10-1.30), and direct admission (OR, 0.52; 95% CI, 0.28-0.97). Neither comorbidities nor SRD characteristics were associated with survival.

CONCLUSIONS:  In patients with SRDs, critical care management is mostly needed only in patients with a previously known SRD; however, diagnosis can be made in the ICU for 12% of patients. Infection and SRD exacerbation account for more than two-thirds of these situations, both targeting chiefly the lungs. Direct admission to the ICU may improve outcomes.

Original Research: Sleep Disorders

Chest. 2015;148(4):936-944. doi:10.1378/chest.14-2973

BACKGROUND:  During pregnancy, upper airway resistance is increased, predisposing vulnerable women to pregnancy-related OSA. Elevation of the upper body increases upper airway cross-sectional area (CSA) and improves severity of OSA in a subgroup of nonpregnant patients (positional-dependent sleep apnea). We tested the hypothesis that elevated position of the upper body improves OSA early after delivery.

METHODS:  Following institutional review board approval, we conducted a randomized, crossover study on two postpartum units of Massachusetts General Hospital. Women during the first 48 h after delivery were included. Polysomnography was performed in nonelevated and 45° elevated upper body position. Upper airway CSA was measured by acoustic pharyngometry in nonelevated, 45° elevated, and sitting body position.

RESULTS:  Fifty-five patients were enrolled, and measurements of airway CSA obtained. Thirty patients completed polysomnography in both body positions. Elevation of the upper body significantly reduced apnea-hypopnea index (AHI) from 7.7 ± 2.2/h in nonelevated to 4.5 ± 1.4/h in 45° elevated upper body position (P = .031) during sleep. Moderate to severe OSA (AHI > 15/h) was diagnosed in 20% of postpartum patients and successfully treated by elevated body position in one-half of them. Total sleep time and sleep architecture were not affected by upper body elevation. Change from nonelevated to sitting position increased inspiratory upper airway CSA from 1.35 ± 0.1 cm2 to 1.54 ± 0.1 cm2 during wakefulness. Position-dependent increase in CSA and decrease in AHI were correlated (r = 0.42, P = .022).

CONCLUSIONS:  Among early postpartum women, 45° upper body elevation increased upper airway CSA and mitigated sleep apnea. Elevated body position might improve respiratory safety in women early after delivery.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01719224; URL: www.clinicaltrials.gov

Chest. 2015;148(4):945-952. doi:10.1378/chest.15-0229

BACKGROUND:  OSA is a common condition that has been associated with atrial fibrillation (AF), but there is a paucity of data from large longitudinal cohorts to establish whether OSA is a risk factor for AF independent of obesity and other established risk factors.

METHODS:  We studied patients attending a sleep clinic referred for in-laboratory polysomnography for possible OSA between 1989 and 2001. Whole-population hospital data in Western Australia for 1970 to 2009 were linked to sleep study cases to determine incident AF hospitalization to 2009. Cox regression analyses were used to assess the independent association of OSA with incident AF.

RESULTS:  Study case subjects (6,841) were predominantly middle aged (48.3 ± 12.5 years old) and men (77%), and 455 developed AF during a median 11.9 years of follow-up. Univariate predictors of AF included age, BMI, hypertension, diabetes, valvular heart disease, coronary or peripheral artery disease, heart failure, and COPD (all P < .001). After multivariable adjustment, independent predictors of incident AF were an apnea/hypopnea index (AHI) > 5/h (hazard ratio [HR], 1.55; 95% CI, 1.21-2.00), log (AHI + 1) (HR, 1.15; 95% CI, 1.06-1.26), and log (time with oxygen saturation < 90% + 1) (HR, 1.12; 95% CI, 1.06-1.19). There were no interactions between age, sex, or BMI and AHI for AF development.

CONCLUSIONS:  OSA diagnosis and severity are independently associated with incident AF. Clinical trials are required to determine if treatment of OSA will reduce the burden of AF.

Original Research: COPD

Chest. 2015;148(4):953-961. doi:10.1378/chest.15-0416

BACKGROUND:  Dyspnea is the major source of disability in COPD. In COPD, environmental cues (eg, the prospect of having to climb stairs) become associated with dyspnea and may trigger dyspnea even before physical activity commences. We hypothesized that brain activation relating to such cues would be different between patients with COPD and healthy control subjects, reflecting greater engagement of emotional mechanisms in patients.

METHODS:  Using functional MRI (FMRI), we investigated brain responses to dyspnea-related word cues in 41 patients with COPD and 40 healthy age-matched control subjects. We combined these findings with scores on self-report questionnaires, thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enabled identification of brain networks responsible for pain processing despite absence of a physical challenge.

RESULTS:  Patients with COPD demonstrated activation in the medial prefrontal cortex and anterior cingulate cortex, which correlated with the visual analog scale (VAS) response to word cues. This activity independently correlated with patient responses on questionnaires of depression, fatigue, and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex, and precuneus correlated with the VAS dyspnea scale but not with the questionnaires.

CONCLUSIONS:  The findings suggest that engagement of the emotional circuitry of the brain is important for interpretation of dyspnea-related cues in COPD and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and the findings suggest that such mechanisms may be relevant in COPD.

Chest. 2015;148(4):962-970. doi:10.1378/chest.14-2311

BACKGROUND:  COPD imposes a large public health burden internationally and in the United States. The objective of this study was to examine trends in mortality from COPD among US adults from 1968 to 2011.

METHODS:  Data from the National Vital Statistics System from 1968 to 2011 for adults aged ≥ 25 years were accessed, and trends in mortality rates were examined with Joinpoint analysis.

RESULTS:  Among all adults, age-adjusted mortality rate rose from 29.4 per 100,000 population in 1968 to 67.0 per 100,000 population in 1999 and then declined to 63.7 per 100,000 population in 2011 (annual percentage change [APC] 2000-2011, −0.2%; 95% CI, −0.6 to 0.2). The age-adjusted mortality rate among men peaked in 1999 and then declined (APC 1999-2011, −1.1%; 95% CI, −1.4 to −0.7), whereas the age-adjusted mortality rate among women increased from 2000 to 2011, peaking in 2008 (APC 2000-2011, 0.4%; 95% CI, 0.0-0.9). Despite a narrowing of the sex gap, mortality rates in men continued to exceed those in women. Evidence of a decline in the APC was noted for black men (1999-2011, −1.5%; 95% CI, −2.1 to −1.0) and white men (1999-2011, −0.9%; 95% CI, −1.3 to −0.6), adults aged 55 to 64 years (1989-2011, −1.0%; 95% CI, −1.2 to −0.8), and adults aged 65 to 74 years (1999-2011, −1.2%; 95% CI, −1.6 to −0.9).

CONCLUSIONS:  In the United States, the mortality rate from COPD has declined since 1999 in men and some age groups but appears to be still rising in women, albeit at a reduced pace.

Chest. 2015;148(4):971-985. doi:10.1378/chest.14-2535

BACKGROUND:  COPD ranks within the top three causes of mortality in the global burden of disease, yet it remains largely underdiagnosed. We assessed the underdiagnosis of COPD and its determinants in national and international surveys of general populations.

METHODS:  We analyzed representative samples of adults aged ≥ 40 years randomly selected from well-defined administrative areas worldwide (44 sites from 27 countries). Postbronchodilator FEV1/FVC < lower limit of normal (LLN) was used to define chronic airflow limitation consistent with COPD. Undiagnosed COPD was considered when participants had postbronchodilator FEV1/FVC < LLN but were not given a diagnosis of COPD.

RESULTS:  Among 30,874 participants with a mean age of 56 years, 55.8% were women, and 22.9% were current smokers. Population prevalence of (spirometrically defined) COPD ranged from 3.6% in Barranquilla, Colombia, to 19.0% in Cape Town, South Africa. Only 26.4% reported a previous lung function test, and only 5.0% reported a previous diagnosis of COPD, whereas 9.7% had a postbronchodilator FEV1/FVC < LLN. Overall, 81.4% of (spirometrically defined) COPD cases were undiagnosed, with the highest rate in Ile-Ife, Nigeria (98.3%) and the lowest rate in Lexington, Kentucky (50.0%). In multivariate analysis, a greater probability of underdiagnosis of COPD was associated with male sex, younger age, never and current smoking, lower education, no previous spirometry, and less severe airflow limitation.

CONCLUSIONS:  Even with substantial heterogeneity in COPD prevalence, COPD underdiagnosis is universally high. Because effective management strategies are available for COPD, spirometry can help in the diagnosis of COPD at a stage when treatment will lead to better outcomes and improved quality of life.

Chest. 2015;148(4):986-994. doi:10.1378/chest.14-2878

BACKGROUND:  In COPD, a decreased inspiratory capacity to total lung capacity ratio (IC/TLC) is associated with dynamic hyperinflation and poor exercise capacity. The association with upper-extremity force measured by handgrip strength (HGS) and 6-min walk distance (6MWD) has not been previously described. We hypothesized that IC/TLC affects muscle strength in the upper and lower extremities, affecting HGS and 6MWD.

METHODS:  We prospectively measured lung function, HGS, and 6MWD in 27 patients with COPD and 12 healthy nonsmokers twice, 1 year apart. The patients were classified according to level of hyperinflation: IC/TLC > 25% or IC/TLC ≤ 25%.

RESULTS:  Patients with COPD had reduced lung function, static hyperinflation, and reduced HGS and 6MWD compared with the control subjects on both evaluations (P < .01). There was a statistically significant deterioration in HGS, IC/TLC, and 6MWD after 1-year follow-up in the COPD compared with the control group (P < .001). More hyperinflation (IC/TLC < 0.25) was associated with lower HGS and 6MWD (P < .001). Changes in IC/TLC correlated with changes in HGS (r = 0.429, P < .05). Multivariate analysis determined that IC/TLC is an independent factor associated with HSG and 6MWD.

CONCLUSIONS:  HGS and 6MWD are reduced in patients with COPD, particularly in those with hyperinflation and evidence of longitudinal deterioration not seen in control subjects. This finding suggests that resting hyperinflation may exert a detrimental effect on cardiac function and plays a role in reduced exercise performance in patients with COPD.

Chest. 2015;148(4):995-1002. doi:10.1378/chest.15-0264

BACKGROUND:  With body growth from childhood, the lungs can enlarge by either increasing the volume of air in the periphery (as would occur with inspiration) or by increasing the number of peripheral acinar units. In the former case, the lung tissue density would decrease with inflation, whereas in the latter case, the lung density would be relatively constant as the lung grows. To address this fundamental structural issue, we measured the CT scan density in human subjects of widely varying size at two different lung volumes.

METHODS:  Five hundred one subjects were enrolled in the study. They underwent a chest CT scan at full inspiration and another scan at end expiration. Spirometry, body plethysmography, and diffusing capacity of the lung for carbon monoxide were also measured.

RESULTS:  There was a strong correlation between the size of the lungs measured at full inspiration on CT scan and the mean lung density (r = −0.72, P = .001). People with larger lungs had significantly lower mean lung density. These density changes among different subjects overlapped the density changes within subjects at different lung volumes.

CONCLUSIONS:  Lung structure in subjects with larger lungs is different from that in subjects with smaller lungs. Tissue volume does not increase in proportion to lung size, as would be required if larger lungs just had more alveoli. These observations suggest that the growth of the lung into adulthood is not accompanied by new alveoli, but rather by enlargement of existing structures. The presence of greater air spaces in larger lungs could impact the occurrence and pathogenesis of spontaneous pneumothorax or COPD.

Original Research: Respiratory Care

Chest. 2015;148(4):1003-1010. doi:10.1378/chest.14-2696

OBJECTIVE:  Lung expansion techniques (LETs) are widely used to prevent postoperative pulmonary complications (PPCs). However, the effects of each of these techniques on thoracoabdominal mechanics and PPC incidence after abdominal surgery remain unclear. The objective of this study was to compare the effects of LET on pulmonary volumes, respiratory muscle activation, and PPC incidence after major, elective upper abdominal surgery.

METHODS:  This randomized controlled trial enrolled 137 patients who were randomly assigned into four groups: control (n = 35), flow incentive spirometry (n = 33), deep breathing (n = 35), and volume incentive spirometry (n = 34). Each intervention was performed tid during 5 consecutive days. Subsequently, PPCs (pneumonia, atelectasis, or severe hypoxemia) were analyzed by a blinded assessor until hospital discharge. Lung volumes (optoelectronic plethysmography) and inspiratory muscular activation (surface electromyography) were assessed before and 3 days after surgery. Intention-to-treat analysis was performed.

RESULTS:  Before surgery, all groups were homogenous for age, sex, BMI, lung function, and thoracoabdominal mechanics. After surgery, no difference was observed in the lung volumes and inspiratory muscular activation during the lung expansion technique (P > .05). The PPC incidence was higher in the deep breathing group (P < .05). Higher American Society of Anesthesiologists scores and surgery duration were the only predictors of PPC (n = 14, 11.2%).

CONCLUSIONS:  LETs do not modify the changes on thoracoabdominal mechanics or prevent PPCs after abdominal surgery. The indiscriminate use of LETs should not be routinely prescribed to prevent PPCs; however, more studies are required to confirm our results and to change the standard practice.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT01993602; URL: www.clinicaltrials.gov

Original Research: Diffuse Lung Disease

Chest. 2015;148(4):1011-1018. doi:10.1378/chest.14-3078

BACKGROUND:  Interstitial lung disease (ILD) is a heterogeneous group of rare diseases that primarily affect the pulmonary interstitium. Studies have implicated a role for telomere length (TL) maintenance in ILD, particularly in idiopathic interstitial pneumonia (IIP). Here, we measure TL in a wide spectrum of sporadic and familial cohorts of ILD and compare TL between patient cohorts and control subjects.

METHODS:  A multiplex quantitative polymerase chain reaction method was used to measure TL in 173 healthy subjects and 359 patients with various ILDs, including familial interstitial pneumonia (FIP). The FIP cohort was divided into patients carrying TERT mutations, patients carrying SFTPA2 or SFTPC mutations, and patients without a proven mutation (FIP-no mutation).

RESULTS:  TL in all cases of ILD was significantly shorter compared with those of control subjects (P range: .038 to < .0001). Furthermore, TL in patients with idiopathic pulmonary fibrosis (IPF) was significantly shorter than in patients with other IIPs (P = .002) and in patients with sarcoidosis (P < .0001). Within the FIP cohort, patients in the FIP-telomerase reverse transcriptase (TERT) group had the shortest telomeres (P < .0001), and those in the FIP-no mutation group had TL comparable to that of patients with IPF (P = .049). Remarkably, TL of patients with FIP-surfactant protein (SFTP) was significantly longer than in patients with IPF, but similar to that observed in patients with other sporadic IIPs.

CONCLUSIONS:  The results show telomere shortening across all ILD diagnoses. The difference in TL between the FIP-TERT and FIP-SFTP groups indicates the distinction between acquired and innate telomere shortening. Short TL in the IPF and FIP-no mutation groups is indicative of an innate telomere-biology defect, while a stress-induced, acquired telomere shortening might be the underlying process for the other ILD diagnoses.

Chest. 2015;148(4):1019-1026. doi:10.1378/chest.15-0825

BACKGROUND:  Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease.

METHODS:  Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita.

RESULTS:  Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed.

CONCLUSIONS:  This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

Chest. 2015;148(4):1027-1033. doi:10.1378/chest.15-0456

BACKGROUND:  Lymphangioleiomyomas occur in 38% of patients with sporadic lymphangioleiomyomatosis (LAM) and may cause pain and increased abdominal girth, mimicking the presence of a malignancy. Lymphatic involvement in LAM is closely associated with elevated serum levels of vascular endothelium growth factor-D (VEGF-D). Because lymphangioleiomyomas undergo diurnal variation in volume, we hypothesized that daytime ingestion of food, by increasing chyle formation and lymphatic flow, is the cause of an increase in lymphangioleiomyoma volume.

METHODS:  Subjects had abdominopelvic sonograms and blood drawn for measurement of serum VEGF-D levels under nonfasting (day 1) and fasting (day 2) conditions. The size of the lymphangioleiomyomas was determined by a radiologist who was blinded to the subjects’ status. The Wilcoxon signed rank test was used to determine whether the nonfasting tumor size was different from the fasting tumor size.

RESULTS:  Thirty-five women were studied (aged 45.2 ± 8.5 years; FEV1, 82% ± 25%; diffusing capacity of the lung for carbon monoxide, 64% ± 25% predicted). Images suitable for volume measurements were obtained in 30 subjects. Fasting decreased the tumor size by 20.7 ± 39.3 cm3 (24% ± 40%, P < .001). Fasting VEGF-D levels (10,650 ± 900 pg/mL) were not significantly different from nonfasting values (12,100 ± 800 pg/mL, P = .56).

CONCLUSIONS:  Lymphangioleiomyoma volume decreased during the fasting state. Conversely, a combination of food intake and decreased chyle flow through lymphatics partially obstructed by LAM cells may account for increases in lymphangioleiomyoma size. Imaging studies performed under fasting conditions may help in determining whether an abdominal tumor is a result of LAM or malignancy.

Chest. 2015;148(4):1034-1042. doi:10.1378/chest.14-2889

BACKGROUND:  The National Heart, Lung, and Blood Institute-sponsored IPF Clinical Research Network (IPFnet) studies enrolled subjects with idiopathic pulmonary fibrosis (IPF) to evaluate drug therapies in treatment trials. An adjudication committee (AC) provided a structured review of cases in which there was uncertainty or disagreement regarding diagnosis or clinical event classification. This article describes the diagnosis and adjudication processes.

METHODS:  The diagnostic process was based on review of clinical data and high-resolution CT scans with central review of lung biopsies when available. The AC worked closely with the data coordinating center to obtain clinical, radiologic, and histologic data and to communicate with the clinical centers. The AC used a multidisciplinary discussion model with four clinicians, one radiologist, and one pathologist to adjudicate diagnosis and outcome measures.

RESULTS:  The IPFnet trials screened 1,015 subjects; of these, 23 cases required review by the AC to establish eligibility. The most common diagnosis for exclusion was suspected chronic hypersensitivity pneumonitis. The AC reviewed 88 suspected acute exacerbations (AExs), 93 nonelective hospitalizations, and 16 cases of bleeding. Determination of AEx presented practical challenges to adjudicators, as necessary clinical data were often not collected, particularly when subjects were evaluated outside of the primary study site.

CONCLUSIONS:  The IPFnet diagnostic process was generally efficient, but a multidisciplinary adjudication committee was critical to assure correct phenotype for study enrollment. The AC was key in adjudicating all adverse outcomes in two IPFnet studies terminated early because of safety issues. Future clinical trials in IPF should consider logistical and cost issues as they incorporate AExs and hospitalizations as outcome measures.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00517933, NCT00650091, NCT00957242; URL: www.clinicaltrials.gov

Original Research: Pulmonary Vascular Disease

Chest. 2015;148(4):1043-1054. doi:10.1378/chest.15-0300

BACKGROUND:  Pulmonary arterial hypertension (PAH) is a rare, severe disease characterized by worsening right-sided heart failure, decreasing functional status, and poor survival. The present study characterizes the 5-year survival in the United States of a new and previous diagnosis of PAH in patients stratified by baseline functional class (FC). The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) is a 55-center observational US registry of the demographics, disease course, and management of patients with World Health Organization (WHO) group 1 PAH.

METHODS:  The REVEAL Registry enrolled newly and previously diagnosed patients aged ≥ 3 months with WHO group 1 PAH consecutively from March 2006 to December 2009. Demographics, disease characteristics, and hemodynamic data were collected at enrollment. Survival analysis was conducted by FC and other subgroups in patients aged ≥ 18 years.

RESULTS:  Survival differences between previously diagnosed and newly diagnosed patients at 1 year (90.4% vs 86.3%) were maintained to 5 years; 5-year survival for previously diagnosed patients was 65.4% compared with 61.2% for newly diagnosed patients. Previously diagnosed patients in FC I, II, III, and IV had an estimated 5-year survival rate of 88.0%, 75.6%, 57.0%, and 27.2%, respectively, compared with 72.2%, 71.7%, 60.0%, and 43.8% for newly diagnosed patients in FC I, II, III, and IV, respectively.

CONCLUSIONS:  Patient survival of advanced PAH remains poor at 5 years despite treatment advances. New York Heart Association FC remains one of the most important predictors of future survival. These observations reinforce the importance of continuous monitoring of FC in patients with PAH.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Chest. 2015;148(4):1055-1062. doi:10.1378/chest.14-2546

BACKGROUND:  It is unclear whether recent advances in pulmonary arterial hypertension therapy can be safely applied to sarcoidosis-associated pulmonary hypertension (SAPH). Evidence for prostacyclin (PG) therapy in SAPH is limited.

METHODS:  We conducted a single-center, retrospective review of 46 patients with sarcoidosis, 26 of whom had SAPH. Thirteen received PG as monotherapy or in combination with oral vasodilators.

RESULTS:  Follow-up right-sided heart catheterization at a mean of 12.7 months revealed improved cardiac output, cardiac index, and pulmonary vascular resistance. Functional class and N-terminal pro-brain natriuretic peptide levels also improved in patients treated with PG. No significant change in oxygen requirement was seen with vasodilator therapy initiation. At 2 years, 15 patients with SAPH survived, including eight on PG, and at 5 years, seven survived, including five on PG. Survival was significantly reduced in patients with SAPH compared with patients who had sarcoidosis without pulmonary hypertension. Multivariate analysis demonstrated that the use of PG therapy in SAPH is not associated with increased mortality.

CONCLUSIONS:  Many patients with severe SAPH showed significant hemodynamic and clinical improvement on long-term IV or subcutaneous PG therapy and had survival outcomes similar to patients with moderate SAPH on oral vasodilator therapy.

Translating Basic Research Into Clinical Practice

Chest. 2015;148(4):1063-1072. doi:10.1378/chest.14-2663

Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as “oncogene addiction.” On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

Recent Advances in Chest Medicine

Chest. 2015;148(4):1073-1082. doi:10.1378/chest.15-0076

A central tenet of caring for patients with ARDS is to treat the underlying cause, be it sepsis, pneumonia, or removal of an offending toxin. Identifying the risk factor for ARDS has even been proposed as essential to diagnosing ARDS. Not infrequently, however, the precipitant for acute hypoxemic respiratory failure is unclear, and this raises the question of whether a histologic lung diagnosis would benefit the patient. In this review, we consider the historic role of pathology in establishing a diagnosis of ARDS and the published experience of surgical and transbronchial lung biopsy in patients with ARDS. We reflect on which pathologic diagnoses influence treatment and suggest a patient-centric approach to weigh the risks and benefits of a lung biopsy for critically ill patients who may have ARDS.

Special Features

Chest. 2015;148(4):1083-1092. doi:10.1378/chest.14-3218

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease. Until recently, the standard therapy for this disease has been essentially supportive, with the exception of a minority of patients who were eligible for lung transplantation. The development pathway for novel medications for IPF has been complicated. There have been several challenges, including an incomplete understanding of the pathogenesis, unpredictable clinical course, lack of validated biomarkers, the low clinical predictive value of animal models of lung injury, and the need to commit to large clinical trials of long duration to obtain initial evidence of clinical efficacy. Despite these challenges, the combination of recent advances in translational medicine and the unprecedented increase in clinical data accumulated from recent large clinical trials has stimulated an increase in the number of clinical development programs for IPF. Clinical programs are increasingly characterized by rational target selection, preclinical optimization of therapeutic molecules, and an emphasis on efficient clinical trial design. A lower rate of functional decline in patients treated with pirfenidone and nintedanib was demonstrated in large clinical trials. In October 2014, these two drugs became the first agents to be approved by the US Food and Drug Administration for the treatment of IPF. (Pirfenidone had already been approved in several countries outside the United States.) In November 2014, the European Medicines Agency approved the use of nintedanib for IPF. The landscape for management of IPF has markedly changed with the advent of approved therapeutic options for IPF. In this article, we review the strategies that are being used to increase the likelihood of success in clinical development programs of novel disease-modifying agents in IPF.

Contemporary Reviews in Critical Care Medicine

Chest. 2015;148(4):1093-1104. doi:10.1378/chest.14-1998

Managing critically ill obstetric patients in the ICU is a challenge because of their altered physiology, different normal ranges for laboratory and clinical parameters in pregnancy, and potentially harmful effects of drugs and interventions on the fetus. About 200 to 700 women per 100,000 deliveries require ICU admission. A systematic five-step approach is recommended to enhance maternal and fetal outcomes: (1) differentiate between medical and obstetric disorders with similar manifestations, (2) identify and treat organ dysfunction, (3) assess maternal and fetal risk from continuing pregnancy and decide if delivery/termination of pregnancy will improve outcome, (4) choose an appropriate mode of delivery if necessary, and (5) optimize organ functions for safe delivery. A multidisciplinary team including the intensivist, obstetrician, maternal-fetal medicine specialist, anesthesiologist, neonatologist, nursing specialist, and transfusion medicine expert is key to optimize outcomes. Severe preeclampsia and its complications, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and amniotic fluid embolism, which cause significant organ failure, are reviewed. Obstetric conditions that were not so common in the past are increasingly seen in the ICU. Thrombotic thrombocytopenic purpura of pregnancy is being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing because of the large number of pregnant women with scars from previous cesarean section. With more complex fetal surgical interventions being performed for congenital disorders, maternal complications are increasing. Ovarian hyperstimulation syndrome is also becoming common because of treatment of infertility with assisted reproduction techniques. Part II will deal with common medical disorders and their management in critically ill pregnant women.

Contemporary Reviews in Sleep Medicine

Chest. 2015;148(4):1105-1114. doi:10.1378/chest.15-0584

Sleep-disordered breathing (SDB) has a high prevalence in sarcoidosis. This high prevalence may be the result of increased upper airways resistance from sarcoidosis of the upper respiratory tract, corticosteroid-induced obesity, or parenchymal lung involvement from sarcoidosis. OSA is a form of SDB that is particularly common in patients with sarcoidosis. Sarcoidosis and SDB share many similar symptoms and clinical findings, including fatigue, gas exchange abnormalities, and pulmonary hypertension (PH). Sarcoidosis-associated fatigue is a common entity for which stimulants may be beneficial. Sarcoidosis-associated fatigue is a diagnosis of exclusion that requires an evaluation for the possibility of OSA. Hypercapnia is unusual in a patient with sarcoidosis without severe pulmonary dysfunction and, in this situation, should prompt evaluation for alternative causes of hypercapnia, such as SDB. PH is usually mild when associated with OSA, whereas the severity of sarcoidosis-associated PH is related to the severity of sarcoidosis. PH caused by OSA usually responds to CPAP, whereas sarcoidosis-associated PH commonly requires the use of vasodilators. Management of OSA in sarcoidosis is problematic because corticosteroid treatment of sarcoidosis may worsen OSA. Aggressive efforts should be made to place the patient on the lowest effective dose of corticosteroids, which involves early consideration of corticosteroid-sparing agents. Because of the significant morbidity associated with SDB, early recognition and treatment of SDB in patients with sarcoidosis may improve their overall quality of life.

Topics in Practice Management

Chest. 2015;148(4):1115-1119. doi:10.1378/chest.15-0704

Chronic care management describes the services provided to patients with two or more chronic conditions that pose risks of exacerbation, clinical deterioration, or death. These services extend beyond the typical face-to-face office visit and require coordination and oversight by a physician or other qualified health-care professional to maintain and modify as necessary a comprehensive and multidisciplinary plan of care. New codes for 2015 describe chronic care management services per calendar month. While the new services acknowledge the role and importance of coordination by primary care providers, they are also appropriate for specialists who oversee the management of all of the chronic conditions of a patient and provide access, education, care coordination, communication, and health information exchange with other providers.


Chest. 2015;148(4):1120. doi:10.1378/chest.15-0845

There aren’t many liver conversations at dinner parties.
People don’t hug their livers the way they put a hand to their hearts.
They don’t cradle their infants thinking Oh your lovely oversized liver.
Rolling together in bed they don’t say Hmmm, let me spoon your liver.
The hard working liver doesn’t get the credit like T-cells do.
It’s not visible like spilled blood or common like skin,
exotic like spleen or mentioned like the stomach.
Most people don’t even know what the liver does.
When they stamp their foot in anger they don’t think
there goes my liver again. They don’t connect the liverish feel of it.
Lying under the umbrella of the diaphragm,
massaged by breath and supported by a tube of intestine,
weighty brown and green lobules drape across the middle of the body.
I growl with the strength of my liver
and silently detoxify, metabolize, synthesize, and store
support for every function I’ve ever been to.

Chest. 2015;148(4):1121. doi:10.1378/chest.15-0989

Adapted from “Funeral Blues” by W. H. Auden
(As popularized by the Movie: Four Weddings and a Funeral)
Stop all the clocks, reverse the DNR,
Prevent the patient dying, keep them as they are,
Silence no alarms, set the code to blue,
Put away the coffin, transfer to ICU.
Let the doctors circle, shouting orders ‘round the bed,
Scribble on their charts the message He is Not Dead.
Put tubes straight through the white neck of the one they love,
Let everyone who touches wear a latex glove.
He is not dead, and yet his eyes are not alive,
He breathes, he feeds, he bleeds, but can no longer thrive.
At noon, at midnight, no change, no fight;
I thought that he could last forever: I am right.
CPR’s not wanted now: agreed by everyone,
Pack up the ventilator, for its work is done.
Pour out platitudes: “we did all we could”
For nothing now can ever come to any good.
(With respect to our patients, colleagues, and W. H. Auden)

Selected Reports

Chest. 2015;148(4):e106-e108. doi:10.1378/chest.15-0240

A 68-year-old man with recurrent medullary thyroid cancer underwent cervical tracheal resection and reconstruction. His course was complicated by tracheal anastomotic dehiscence, right carotid blowout, and ultimately cervical tracheoplasty with AlloDerm. Given the complex vascular interventions and upper-airway anatomy, a custom-designed Montgomery T-tube was designed for him. Three-dimensional digital reconstruction of his upper airways was obtained from a CT scan. The T-tube was designed and fabricated based on the digital trachea model and was subsequently placed successfully. Follow-up CT scan and bronchoscopy confirmed placement and revealed no granulation tissue at 4 weeks. The patient was discharged to home with the ability to phonate. To our knowledge, this is the first demonstration of three-dimensional modeling of an upper-airway defect with subsequent T-tube design using engineering software. The success of this case demonstrates a possible avenue for personalized airway prosthesis design and manufacturing in the future.

Topics: dehiscence , trachea , t-tube

Ultrasound Corner

Chest. 2015;148(4):e109-e111. doi:10.1378/chest.14-2884

A previously healthy man in his 50s presented to an ED complaining of a 1-week history of generalized malaise, weakness, subjective fevers, chills, decreased appetite, and nonbloody diarrhea. He was given a diagnosis of a viral illness and discharged with acetaminophen and ibuprofen. His symptoms continued, and follow-up with his primary physician revealed an elevated serum creatinine level (5.84 mg/dL) from a previously normal baseline. He was referred to the ED.

Topics: septic shock

Chest Imaging and Pathology for Clinicians

Chest. 2015;148(4):e112-e117. doi:10.1378/chest.15-0624

A 33-year-old man, never smoker, presented with acute-onset dyspnea secondary to bilateral pulmonary emboli. Echocardiography at the time revealed a right atrial myxoma, for which he underwent resection, followed by anticipated lifelong therapeutic anticoagulation therapy.

Pulmonary, Critical Care, and Sleep Pearls

Chest. 2015;148(4):e118-e121. doi:10.1378/chest.15-0281

A 44-year-old man presented with a 3-day history of persistent upper-back pain, chest discomfort, and dyspnea. He denied any precipitating events such as trauma or vigorous activity before the presentation of symptoms. His exercise capacity had been excellent. He is a lifetime nonsmoker and never had significant lung problems apart from intermittent asthma for which he had several ED visits in the past. Chest CT scan performed during an asthma exacerbation 2 years earlier demonstrated two left-side lung blebs. He had no prior surgical procedures.

Topics: pneumothorax , pleura
Chest. 2015;148(4):e122-e125. doi:10.1378/chest.15-0388

A 60-year-old black woman presented with nonproductive cough of 1-month duration. She had also experienced rapidly progressive dyspnea for 1 week and one bout of vomiting a day before presentation. Her symptoms had failed to improve with a course of amoxicillin-clavulanate. Her medical history was significant for diabetes mellitus and liver transplant 19 years earlier for hepatitis C cirrhosis, for which she was receiving tacrolimus and mycophenolate. She was a current smoker with 40 pack-years of smoking history.


Chest. 2015;148(4):e126. doi:10.1378/chest.15-1215
Chest. 2015;148(4):e127. doi:10.1378/chest.15-1212
Chest. 2015;148(4):e127-e128. doi:10.1378/chest.15-1463
Chest. 2015;148(4):e129. doi:10.1378/chest.15-1262
Chest. 2015;148(4):e130. doi:10.1378/chest.15-1457
Chest. 2015;148(4):e131-e132. doi:10.1378/chest.15-0963
Chest. 2015;148(4):e132-e133. doi:10.1378/chest.15-1573
Chest. 2015;148(4):e134. doi:10.1378/chest.15-1327
Chest. 2015;148(4):e134-e135. doi:10.1378/chest.15-1440

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