Chest. 2013;143(1):1-4. doi:10.1378/chest.12-2762

As the title implies, the content of this editorial comprises an eclectic collection of newsworthy items. Because scientific misconduct is arguably “the single most potent threat to science’s prestige”1 and because we have come to appreciate that it is often not intuitively obvious to investigators when they perpetrate it,2 we begin our announcements by discussing two types of scientific misconduct that are not generally well recognized. Both are examples of misrepresentation3 of research or the reporting of research, and both involve investigators as well as editors.

Chest. 2013;143(1):4-5. doi:10.1378/chest.12-2520

Consider this scenario. A young patient presents with acute respiratory failure and shock requiring mechanical ventilatory support. She has a nondiagnostic supine chest radiograph and a history of a cardiomyopathy. Physical examination fails to reveal a definite diagnosis. Chest CT scans with contrast, echocardiogram, and lower extremity ultrasound duplex study are ordered. While waiting for these results, the care team starts the patient on heparin, inotropes, and vasopressors and begins antibiotics.

Chest. 2013;143(1):5-7. doi:10.1378/chest.12-1985

An enduring memory for those of us trained during the 1970s in pulmonary and critical care recalls the daily ritual of concluding bedside rounds by walking to radiology, where we suspended our patients’ cut films on a vast wall of view boxes. As our huddle of physicians moved down the illuminated rows, we trainees were mesmerized by the ability of master attending physicians to synthesize the clinical findings we presented with the shadows they saw to create a cohesive diagnosis and plan. The annual CHEST conference was even more memorable. There, a roomful of attending physicians routinely “solved” the most challenging clinical dilemmas we could throw their way as unknowns. We trainees left both dazzled by the clinical pearls we learned, but also committed to honing our own diagnostic skills. Helping patients by solving tough clinical questions in arguably the most diverse and difficult-to-learn specialty in medicine, pulmonary critical care, is not only professionally gratifying but also a lot of fun. As Sherlock Holmes enthused when facing a new mystery, “Come Watson, come!…The game is afoot.”1

Chest. 2013;143(1):7-8. doi:10.1378/chest.12-1751

The systematic review and analysis of critical care telemedicine programs by Kumar et al1 in this issue of CHEST (see page 19) summarizes many of the challenges facing those who seek to learn from a review of a technologic innovation in a complex health-care environment. The most obvious issues relate to total sample size (typically rather small), missing variables (universally an issue), wide variation in costs, and, as a result, questionable conclusions that may be drawn. This is not intended as a criticism of the investigators, but rather recognizes the challenges that faced them.

Chest. 2013;143(1):8-10. doi:10.1378/chest.12-1835

The not common clinical scenario of acute-on-chronic ventilatory failure requiring hospital admission (the so-called “critical care syndrome” of Fletcher et al1) and the frequent occurrence of other life-threatening systemic complications of morbid obesity (recently dubbed the “malignant obesity hypoventilation syndrome” by Marik2) inevitably calls for prompt intervention in the patient with obesity hypoventilation syndrome (OHS). However, OHS is not a monolithic disorder. In a landmark study, Rapoport et al3 observed that some patients with OHS and significant obstructive sleep apnea achieved daytime eucapnia following effective treatment of their sleep-disordered breathing, whereas others remained hypercapnic despite resolution of nocturnal respiratory events. This heterogeneity in the OHS population has subsequently been confirmed by other investigators.4-6 CPAP nonresponders, christened “true Pickwickians” by Rapoport et al,3 tend to be older and exhibit lower (or even normal) apnea-hypopnea indexes (AHIs), more hypoxemia awake and asleep, and greater restrictive ventilatory impairment.6 By definition, this group requires not just a means of sustaining upper airway patency but also ventilatory support during sleep; in some cases, diurnal ventilatory support must also be provided. Moreover, there may be potentially important differences between the two groups in terms of OHS pathogenesis. In CPAP responders, mathematical modeling and empirical observation implicate renal bicarbonate retention due to the repetitive obstructive events as a fundamental mechanism.7-9 Obstructive events that are so frequent and prolonged that interevent ventilation is inadequate to excrete the CO2 load lead to sustained nocturnal hypercapnia.7,8 The ensuing metabolic alkalosis provokes hypoventilatory respiratory compensation for the acid-base disturbance and blunts the ventilatory response to CO2, resulting in daytime hypercapnia.7,8 In contrast, pathogenesis in the “true Pickwickians” may involve the usual suspects implicated in the literature since Bickelmann et al’s10 first description: impaired chest-wall mechanics, respiratory muscle weakness or fatigue, and impaired control of breathing.11 More recently, suspicion has been raised that neurohumoral factors (eg, CNS leptin resistance) may lead to a blunted ventilatory response and diurnal hypercapnia.12

Chest. 2013;143(1):10-12. doi:10.1378/chest.12-1864

In this issue of CHEST (see page 64), Hariri and colleagues1 provide a tantalizing look at a technology that promises to improve biopsy sampling of the lung and to perhaps offer even more to patients with lung diseases. Defining “more” is the essence of the challenge put forth by this illuminating article, which describes the authors’ well-designed correlative evaluation of images acquired by volumetric optical frequency domain imaging (OFDI) and histopathology. Volumetric OFDI is an optical coherence tomography (OCT) imaging technology with rapid acquisition rates that can provide high-resolution images in time frames compatible with clinical usage. OCT, described in 1991 by Huang and colleagues,2 is a noninvasive modality that uses interferometry to produce an image of optical scattering from internal tissue microstructures. This technology can generate two- and three-dimensional images of tissues at resolutions comparable to low-power light microscopy, with tissue penetration depths of several millimeters. Components of the bronchial wall can be resolved, and image representations of architecturally altering processes such as tumors and inflammatory disorders can be generated. Volumetric OFDI can be employed during flexible bronchoscopy or via a needle-based approach.

Second Opinion

Chest. 2013;143(1):13. doi:10.1378/chest.143.1.13


Chest. 2013;143(1):14-18. doi:10.1378/chest.12-1430

Cystic fibrosis (CF) is a life-shortening inherited disease caused by mutations in the CF transmembrane conductance regulator gene (CFTR), which encodes for the CF transmembrane conductance regulator (CFTR) ion channel that regulates chloride and water transport across the surface of epithelial cells. Ivacaftor, a drug recently approved by the US Food and Drug Administration, represents the first mutation-specific therapy for CF. It is a CFTR channel modulator and improves CFTR function in patients with CF who have a G551D mutation. A clinical trial performed to support ivacaftor dose selection demonstrated a dose-response relationship between improvement in FEV1 and decrease in sweat chloride, a measure of CFTR function. Validation of such a relationship between FEV1 and sweat chloride would facilitate development of new drugs that target the defective CFTR. Subsequently, in phase 3 studies, ivacaftor 150 mg bid resulted in significant improvements in FEV1 (10%-12%) and reduction in sweat chloride (approximately 50 mmol/L). However, a decrease in sweat chloride did not correlate with improvement in FEV1, nor did there appear to be a threshold level for change in sweat chloride above which an improvement in FEV1 was apparent. The lack of correlation of sweat chloride with improvement in FEV1 speaks to the multiplicity of factors, physiologic, environmental, and genetic, that likely modulate CF disease severity. Future clinical trials of drugs that are directed to the defective CFTR will need take into account the uncertainty of using even established measurements, such as sweat chloride, as clinical end points.

Original Research: Critical Care

Chest. 2013;143(1):19-29. doi:10.1378/chest.11-3031

Background:  Implementation of telemedicine programs in ICUs (tele-ICUs) may improve patient outcomes, but the costs of these programs are unknown. We performed a systematic literature review to summarize existing data on the costs of tele-ICUs and collected detailed data on the costs of implementing a tele-ICU in a network of Veterans Health Administration (VHA) hospitals.

Methods:  We conducted a systematic review of studies published between January 1, 1990, and July 1, 2011, reporting costs of tele-ICUs. Studies were summarized, and key cost data were abstracted. We then obtained the costs of implementing a tele-ICU in a network of seven VHA hospitals and report these costs in light of the existing literature.

Results:  Our systematic review identified eight studies reporting tele-ICU costs. These studies suggested combined implementation and first year of operation costs for a tele-ICU of $50,000 to $100,000 per monitored ICU-bed. Changes in patient care costs after tele-ICU implementation ranged from a $3,000 reduction to a $5,600 increase in hospital cost per patient. VHA data suggested a cost for implementation and first year of operation of $70,000 to $87,000 per ICU-bed, depending on the depreciation methods applied.

Conclusions:  The cost of tele-ICU implementation is substantial, and the impact of these programs on hospital costs or profits is unclear. Until additional data become available, clinicians and administrators should carefully weigh the clinical and economic aspects of tele-ICUs when considering investing in this technology.

Chest. 2013;143(1):30-36. doi:10.1378/chest.12-0424

Background:  Patient-ventilator asynchrony is common during noninvasive ventilation (NIV) with pressure support ventilation (PSV). We examined the effect of neurally adjusted ventilatory assist (NAVA) delivered through a facemask on synchronization in patients with acute respiratory failure (ARF).

Methods:  This was a prospective, physiologic, crossover study of 13 patients with ARF (median PaO2/FIO2, 196 [interquartile range (IQR), 142-225]) given two 30-min trials of NIV with PSV and NAVA in random order. Diaphragm electrical activity (EAdi), neural inspiratory time (TIn), trigger delay (Td), asynchrony index (AI), arterial blood gas levels, and patient discomfort were recorded.

Results:  There were significantly fewer asynchrony events during NAVA than during PSV (10 [IQR, 5-14] events vs 17 [IQR, 8-24] events, P = .017), and the occurrence of severe asynchrony (AI > 10%) was also less under NAVA (P = .027). Ineffective efforts and delayed cycling were significantly less with NAVA (P < .05 for both). NAVA was also associated with reduced Td (0 [IQR, 0-30] milliseconds vs 90 [IQR, 30-130] milliseconds, P < .001) and inspiratory time in excess (10 [IQR, 0-28] milliseconds vs 125 [IQR, 20-312] milliseconds, P < .001), but TIn was similar under PSV and NAVA. The EAdi signal to its maximal value was higher during NAVA than during PSV (P = .017). There were no significant differences in arterial blood gases or patient discomfort under PSV and NAVA.

Conclusion:  In view of specific experimental conditions, our comparison of PSV and NAVA indicated that NAVA significantly reduced severe patient-ventilator asynchrony and resulted in similar improvements in gas exchange during NIV for ARF.

Trial registry:  ClinicalTrials.gov; No.: NCT01426178; URL: www.clinicaltrials.gov.

Original Research: Sleep Disorders

Chest. 2013;143(1):37-46. doi:10.1378/chest.11-2848

Background:  Unintentional leaks, patient-ventilatory asynchrony, and obstructive or central events (either residual or induced by noninvasive positive pressure ventilation [NPPV]) occur in patients treated with NPPV, but the impact of ventilator settings on these disturbances has been little explored. The objective of this study was to investigate the impact of backup respiratory rate (BURR) settings on the efficacy of ventilation, sleep structure, subjective sleep quality, and respiratory events in a group of patients with obesity hypoventilation syndrome (OHS).

Methods:  Ten stable patients with OHS treated with long-term nocturnal NPPV underwent polysomnographic recordings and transcutaneous capnography on 3 consecutive nights with three different settings for BURR in random order: spontaneous (S) mode, low BURR, and high BURR. No other ventilator parameter was modified.

Results:  The S mode was associated with the occurrence of a highly significant increase in respiratory events, mainly of central and mixed origin, when compared with both spontaneous/timed (S/T) modes. Accordingly, the oxygen desaturation index was significantly higher in the S mode than in either of the S/T modes. The results of nocturnal transcutaneous Pco2 (Ptcco2) (mean value and time spent with Ptcco2 > 50 mm Hg) were similar over the three consecutive nocturnal recordings. The quality of sleep was perceived as slightly better, and the number of perceived arousals as lower with the low- vs high-BURR (S/T) mode.

Conclusions:  In a homogenous group of patients treated with long-term NPPV for obesity-hypoventilation, changing BURR from an S/T mode with a high or low BURR to an S mode was associated with the occurrence of a highly significant increase in respiratory events, of mainly central and mixed origin.

Trial registry:  ClinicalTrials.gov; No.: NCT01130090; URL: www.clinicaltrials.gov

Chest. 2013;143(1):47-55. doi:10.1378/chest.11-3124

Background:  The occurrence and mechanisms of nocturnal hypoxemia in precapillary pulmonary hypertension (PH) are not clearly defined.

Methods:  In an observational, prospective, and transversal design, we studied 46 clinically stable patients with PH and a BMI < 35 kg/m2, an FEV1 > 60% predicted, and idiopathic pulmonary arterial hypertension (n = 29) or chronic thromboembolic pulmonary hypertension (n = 17). They underwent nocturnal polysomnography with transcutaneous capnography.

Results:  Most patients (69.6%) had New York Heart Association functional class II disease. Mean pulmonary artery pressure was 44 ± 13 mm Hg, and the cardiac index was 3.2 ± 0.6 L/min/m2. Duration of sleep time spent with oxygen saturation as measured by pulse oximetry < 90% was 48.9% ± 35.9%, and 38 of 46 patients (82.6%) had nocturnal hypoxemia. Mean apnea-hypopnea index was 24.9 ± 22.1/h, and 41 patients (89%) had sleep apnea. The major mechanism of nocturnal hypoxemia was a ventilation/perfusion mismatch alone or associated with obstructive apneic events. Multivariate logistic regression identified both FEV25%-75% (OR, 0.9519; 95% CI, 0.9089-0.9968; P = .036) and mean pulmonary artery pressure (OR, 1.1068; 95% CI, 1.0062-1.2175; P = .037) as significant predictors of nocturnal hypoxemia. Clinical symptoms were not predictive of nocturnal hypoxemia.

Conclusions:  The occurrence of nocturnal hypoxemia is high in PH and should be screened for systematically. Further studies are needed to determine the impact of nocturnal hypoxemia on the outcome of patients with PH.

Trial registry:  ClinicalTrials.gov; No.: NCT01371669; URL: www.clinicaltrials.gov

Chest. 2013;143(1):56-63. doi:10.1378/chest.12-0334

Background:  Patent foramen ovale (PFO) may contribute to nocturnal desaturation in patients with obstructive sleep apnea (OSA), and the effect of PFO closure in OSA is unknown. Our study tested the hypotheses that: (1) patients with severe OSA have a higher prevalence of PFO compared with healthy control subjects, (2) patients with severe OSA with clinically significant PFO experience more nocturnal desaturation than those without, and (3) PFO closure reduces nocturnal desaturation.

Methods:  Patients with severe OSA and healthy control subjects underwent contrast transthoracic echocardiography and transcranial Doppler to detect PFO and determine shunt size. A subgroup of patients with OSA with large shunts underwent percutaneous PFO closure. Polysomnography was performed at baseline and 1, 6, and 12 months postclosure.

Results:  One hundred patients with OSA (mean [SD] age, 52 [10] years; apnea-hypopnea index [AHI], 54 [18] events/h) and 50 control subjects (age, 52 [11] years; AHI, 2 [2] events/h) were studied. PFO prevalence was 43% in patients with OSA and 30% in control subjects (P = .16). Large shunts were detected in 18% of patients with OSA and 6% of control subjects (P = .049). Patients with OSA with clinically significant shunts had higher oxygen-desaturation index (ODI)/AHI ratios than patients without (ratio, 1.05 [0.27] vs 0.86 [0.26], P = .004). Six patients with OSA underwent PFO closure, which was not associated with a reduction in ODI (baseline, 48 [18]; 12 months, 51 [19] events/h; P = .92) or percentage of the night with arterial oxygen saturation < 90% (baseline, 23% [16%]; 12 months, 20% [22%]; P = .35).

Conclusions:  Patients with severe OSA have a higher prevalence of PFO with large shunts compared with control subjects. The ODI/AHI ratio is increased in patients with OSA with clinically significant shunts. PFO closure does not reduce nocturnal desaturation.

Original Research: Interventional Pulmonology

Chest. 2013;143(1):64-74. doi:10.1378/chest.11-2797

Background:  Lung cancer is the leading cause of cancer-related mortality. Radiology and bronchoscopy techniques do not have the necessary resolution to evaluate lung lesions on the microscopic scale, which is critical for diagnosis. Bronchial biopsy specimens can be limited by sampling error and small size. Optical frequency domain imaging (OFDI) provides volumetric views of tissue microstructure at near-histologic resolution and may be useful for evaluating pulmonary lesions to increase diagnostic accuracy. Bronchoscopic OFDI has been evaluated in vivo, but a lack of correlated histopathology has limited the ability to develop accurate image interpretation criteria.

Methods:  We performed OFDI through two approaches (airway-centered and parenchymal imaging) in 22 ex vivo lung specimens, using tissue dye to precisely correlate imaging and histology.

Results:  OFDI of normal airway allowed visualization of epithelium, lamina propria, cartilage, and alveolar attachments. Carcinomas exhibited architectural disarray, loss of normal airway and alveolar structure, and rapid light attenuation. Squamous cell carcinomas showed nested architecture. Atypical glandular formation was appreciated in adenocarcinomas, and uniform trabecular gland formation was seen in salivary gland carcinomas. Mucinous adenocarcinomas showed alveolar wall thickening with intraalveolar mucin. Interstitial fibrosis was visualized as signal-dense tissue, with an interstitial distribution in mild interstitial fibrotic disease and a diffuse subpleural pattern with cystic space formation in usual interstitial pneumonitis.

Conclusions:  To our knowledge, this study is the first demonstration of volumetric OFDI with precise correlation to histopathology in lung pathology. We anticipate that OFDI may play a role in assessing airway and parenchymal pathology, providing fresh insights into the volumetric features of pulmonary disease.

Chest. 2013;143(1):75-81. doi:10.1378/chest.12-0689

Background:  Electromagnetic Navigation Bronchoscopy (ENB) (InReach iLogic system; superDimension Inc) is a relatively new discipline, with promising diagnostic and therapeutic applications in patients with lung lesions. Navigation is performed in a magnetic field and, therefore, has been considered relatively contraindicated in patients with pacemakers and automated implantable cardioverter-defibrillators (AICDs). Potential risks include altering the function and shutting off the device, device damage, lead displacement, and potential overheating. Over the past decade, there has been extensive literature about the safety of pacemakers in either the 1.5-T or 3-T magnetic fields used in current MRI scanners. Although the magnetic field used in ENB is significantly weaker, 0.0001 T or approximately equal to the earth’s gravity, its safety in patients with pacemakers is yet to be elucidated. We present our initial experience with ENB in patients with cardiac implanted electrical devices.

Methods:  Twenty-four procedures in 24 patients with lung lesions and permanent pacemakers were performed. A cardiac electrophysiologist and programmer were present during the procedure. At baseline, the pacers were interrogated, and ECG was recorded. Continuous cardiac monitoring was performed during the procedure, and at the end, the pacer settings and function were reinterrogated to check for any changes.

Results:  The procedures were all successfully concluded. None of the patients suffered any arrhythmias or disruption to their pacemakers’ function.

Conclusion:  ENB appears to be safe when performed in patients with pacemakers and AICDs. Larger multicenter studies are needed to prove the final safety in this patient population.

Original Research: COPD

Chest. 2013;143(1):82-90. doi:10.1378/chest.12-0649

Background:  Antibiotics are widely used in acute exacerbations of COPD (AE-COPD), but their additional benefit to a therapeutic regimen that already includes steroids is uncertain. We evaluated the association between antibiotic therapy and outcomes among a large cohort of patients treated with steroids who were hospitalized with AE-COPD and compared the effectiveness of three commonly used antibiotic regimens.

Methods:  We conducted a retrospective cohort study of patients aged ≥ 40 years hospitalized for AE-COPD from January 1, 2006, through December 1, 2007, at 410 acute care hospitals throughout the United States.

Results:  Of the 53,900 patients who met the inclusion criteria, 85% were treated with antibiotics in the first 2 hospital days; 50% were treated with a quinolone, 22% with macrolides plus cephalosporin, and 9% with macrolide monotherapy. Compared with patients not treated with antibiotics, those who received antibiotics had lower mortality (1% vs 1.8%, P < .0001). In multivariable analysis, receipt of antibiotics was associated with a 40% reduction in the risk of in-hospital mortality (RR, 0.60; 95% CI, 0.50-0.73) and a 13% reduction in the risk of 30-day readmission for COPD (RR, 0.87; 95% CI, 0.79-0.96). The risk of late ventilation and readmission for Clostridium difficile colitis was not significantly different between the two groups. We found little difference in the outcomes associated with three common antibiotic treatment choices.

Conclusions:  Our results suggest that the addition of antibiotics to a regimen that includes steroids may have a beneficial effect on short-term outcomes for patients hospitalized with AE-COPD.

Chest. 2013;143(1):91-97. doi:10.1378/chest.12-0775

Background:  COPD is associated with significant cardiovascular mortality. Left ventricular hypertrophy (LVH) is a pivotal cardiovascular risk factor. The prevalence of LVH in COPD is currently unknown.

Methods:  We performed a pilot study of 93 normoxemic patients with COPD and 34 control subjects. Patients underwent echocardiography to measure left ventricular (LV) dimensions, ECG, measurement of serum B-type natriuretic peptide (BNP) levels, and 24-h BP recording. Spirometry and oxygen saturations were also recorded.

Results:  The oxygen saturations of patients with COPD were normal, at 96.5% (95% CI, 96.1%-97.0%), with a mean FEV1 of 70.0% predicted (95% CI, 65.2%-74.8%). A total of 30.1% of patients with COPD met the echocardiographic criteria for LVH based on LV mass index, with more LVH in female patients than in male patients (43.2% vs 21.4%, P = .02). The LV mass index in patients with COPD was 96.2 g/m2 (95% CI, 90.1-102.7 g/m2) vs 82.9 g/m2 (95% CI, 75.8-90.6 g/m2) in control subjects (P = .017). The LV mass index remained high in patients with COPD in the absence of a hypertension history (94.5 g/m2 vs 79.9 g/m2, P = .015) and with 24-h systolic BP < 135 mm Hg (96.7 g/m2 vs 82.5 g/m2, P = .024). The LV ejection fraction (mean = 63.4%) and BNP (mean = 28.7 pg/mL) were normal in patients with COPD. The mean 24-h BP was normal in patients with COPD, at 125/72 mm Hg. ECG was less sensitive for detecting LVH than was echocardiography.

Conclusion:  LVH with normal LV ejection fraction and BNP levels was present in a significant proportion of normotensive, normoxemic patients with COPD, especially female patients. Clinical trials are, therefore, indicated to evaluate treatments to regress LVH in patients with COPD.

Chest. 2013;143(1):98-106. doi:10.1378/chest.11-3220

Background:  D6 is an atypical chemokine receptor involved in chemokine degradation and resolution of acute inflammatory responses in mice. Emerging evidence suggests that D6 might behave differently in human chronic inflammatory conditions. We, therefore, investigated the involvement of D6 in the immune responses in COPD, a chronic inflammatory condition of the lung.

Methods:  D6 expression was quantified by immunohistochemistry in surgical resected lung specimens from 16 patients with COPD (FEV1, 57% ± 6% predicted) and 18 control subjects with normal lung function (nine smokers and nine nonsmokers). BAL was also obtained and analyzed by flow cytometry, immunofluorescence, and molecular analysis for further assessment of D6 involvement.

Results:  D6 expression in the lung was mainly detected in alveolar macrophages (AMs). The percentage of D6+ AMs was markedly increased in patients with COPD as compared with both smoker and nonsmoker control subjects (P < .0005 for both). D6 expression was detected at both transcript and protein level in AMs but not in monocyte-derived macrophages. Finally, D6 expression was positively correlated with markers of immune activation (CD8+ T lymphocytes, IL-32, tumor necrosis factor-α, B-cell activating factor of the tumor necrosis factor family, phospho-p38 mitogen-activated protein kinase) and negatively with lung function (FEV1, FEV1/FVC).

Conclusions:  D6 is expressed in AMs from patients with COPD, and its expression correlates with the degree of functional impairment and markers of immune activation. Upregulation of D6 in AMs could indicate that, besides its known scavenger activity in acute inflammation, D6 may have additional roles in chronic inflammatory conditions possibly promoting immune activation.

Original Research: ASTHMA

Chest. 2013;143(1):107-116. doi:10.1378/chest.12-0416

Background:  Elevated fractional excretion of exhaled nitric oxide (FENO) reflects airway inflammation, but few studies have established its normal values. This study aims to establish the normal values and thresholds for the clinical interpretation of FENO in the US general population.

Methods:  Thirteen thousand two hundred seventy-five subjects aged 6 to 80 years sampled for the National Health and Nutrition Examination Survey (NHANES) 2007-2010 underwent interviews, physical examination, and FENO analysis at 50 mL/s using an online chemiluminescence device according to American Thoracic Society/European Respiratory Society guidelines. After excluding subjects with self-reported asthma and subjects with wheeze in the prior 12 months, prediction equations for the natural logarithm (ln) of FENO were constructed using age, sex, ethnicity, height, BMI, active/passive smoke exposure, and hay fever episodes as covariates.

Results:  The fifth to 95th percentile values of FENO were 3.5 to 36.5 parts per billion (ppb) for children < 12 years of age and 3.5 to 39 ppb for subjects 12 to 80 years of age. Using multiple linear regression, prediction equations explained only 10.3% to 15.7% of the variation in the general population. In the general population, 39% to 45% had ln(FENO) levels > 2 SD of the predicted means. When applied to the general population inclusive of subjects who reported asthma but who did not have attacks within the past year, nearly identical results were obtained.

Conclusions:  Assuming 95% of the healthy US general population had no clinically significant airway inflammation as assessed by FENO, values exceeding the 95th percentiles indicated abnormality and a high risk of airway inflammation. A large variation of normal FENO values existed in the general population, which was poorly predicted by multiple linear regression models.

Chest. 2013;143(1):117-122. doi:10.1378/chest.12-1070

Background:  Asthma is a worldwide problem. It cannot be prevented or cured, but it is possible, at least in principle, to control asthma with modern management. Control usually is assessed by history of symptoms, physical examination, and measurement of lung function. A practical problem is that these measures of control may not be in agreement. The aim of this study was to describe agreement among different measures of asthma control in children.

Methods:  A prospective sequential sample of children aged 4 to 11 years with atopic asthma attending a routine follow-up evaluation were studied. Patients were assessed with the following four steps: (1) fraction of exhaled nitric oxide (FENO), (2) spirometry, (3) Childhood Asthma Control Test (cACT), and (4) conventional clinical assessment by a pediatrician. The outcome for each test was coded as controlled or uncontrolled asthma. Agreement among measures was examined by cross-tabulation and κ statistics.

Results:  Eighty children were enrolled, and nine were excluded. Mean FENO in pediatrician-judged uncontrolled asthma was double that of controlled asthma (37 parts per billion vs 15 parts per billion, P < .005). There was disagreement among measures of control. Spirometric indices revealed some correlation, but of the unrelated comparisons, those that agreed with each other most often (69%) were clinical assessment by the pediatrician and the cACT. Worst agreement was noted for FENO and cACT (49.3%).

Conclusion:  Overall, different measures to assess control of asthma showed a lack of agreement for all comparisons in this study.

Original Research: Lung Cancer

Chest. 2013;143(1):123-129. doi:10.1378/chest.12-1068

Background:  Studies have shown that for the same quantity of cigarettes smoked, women are more likely to develop heart disease than men, but studies in lung cancer have produced conflicting results. We studied the association between smoking quantity and lung cancer in men and women.

Methods:  Using data from The Health Improvement Network (a UK medical research database), we generated a data set comprising 12,121 incident cases of lung cancer and 48,216 age-, sex-, and general practice-matched control subjects. We used conditional logistic regression to calculate ORs for lung cancer according to highest-ever-quantity smoked in men and women separately.

Results:  The odds of lung cancer in women who had ever smoked heavily compared with those who had never smoked were increased 19-fold (OR, 19.10; 95% CI, 16.98-21.49), which was more than for men smoking the same quantity (OR, 12.81; 95% CI, 11.52-14.24). There was strong evidence of a difference in effect of quantity smoked on lung cancer between men and women (interaction P < .0001), which remained after adjusting for height (a proxy marker for lung volume).

Conclusions:  Moderate and heavy smoking carry a higher risk of lung cancer in women than in men, and this difference does not seem to be explained by lung volume. The findings suggest that extrapolating risk estimates for lung cancer in men to women will underestimate the adverse impact of smoking in women.

Chest. 2013;143(1):130-137. doi:10.1378/chest.12-0207

Background:  Stereotactic body radiation therapy (SBRT) is standard care for patients with inoperable early-stage non-small cell lung cancer. However, clinicians may hesitate to use SBRT in patients with severe COPD because of potential negative effects on pulmonary function. We quantitatively analyzed long-term declines in pulmonary function after SBRT to ascertain lifelong tolerability to SBRT.

Methods:  Between 2005 and 2010 at Ofuna Chuo Hospital, 292 patients with lung tumors were treated with SBRT. Among them, patients who underwent pulmonary function tests (PFTs) both pretreatment and at ≥ 1 year after SBRT were evaluated in this retrospective analysis. The decline ratio in FEV1 and FVC was assessed (ie, ΔFEV1/preFEV1 and ΔFVC/preFVC). Predictors were identified using univariate and multivariate analyses.

Results:  The 141 eligible patients had follow-up PFTs at a median of 21.0 (range, 12.0-74.8) months after SBRT. Among groups with normal function, or mild to moderate or severe COPD, the median values for ΔFEV1/preFEV1 were 7.9%, 7.9%, and 7.4%, respectively, and for ΔFVC/preFVC, 5.1%, 3.4%, and 0.5%, respectively. Low BMI was the only predictor for ΔFEV1/preFEV1 > 10%. Low BMI, high lung volume receiving ≥ 20 Gy, and high pretreatment FVC were predictors for ΔFVC/preFVC > 10%.

Conclusions:  Declines in FEV1 and FVC were small, but statistically significant in patients with normal function or mild to moderate COPD, but nonsignificant in patients with severe COPD. These declines were primarily due to physiologic aging. SBRT had a limited effect on decline in long-term pulmonary function and may be an acceptable alternative to surgery for patients with comorbid lung cancer and COPD.

Chest. 2013;143(1):138-145. doi:10.1378/chest.12-0964

Background:  Physicians need a specific risk-stratification tool to facilitate safe and cost-effective approaches to the management of patients with cancer and acute pulmonary embolism (PE). The objective of this study was to develop a simple risk score for predicting 30-day mortality in patients with PE and cancer by using measures readily obtained at the time of PE diagnosis.

Methods:  Investigators randomly allocated 1,556 consecutive patients with cancer and acute PE from the international multicenter Registro Informatizado de la Enfermedad TromboEmbólica to derivation (67%) and internal validation (33%) samples. The external validation cohort for this study consisted of 261 patients with cancer and acute PE. Investigators compared 30-day all-cause mortality and nonfatal adverse medical outcomes across the derivation and two validation samples.

Results:  In the derivation sample, multivariable analyses produced the risk score, which contained six variables: age > 80 years, heart rate ≥ 110/min, systolic BP < 100 mm Hg, body weight < 60 kg, recent immobility, and presence of metastases. In the internal validation cohort (n = 508), the 22.2% of patients (113 of 508) classified as low risk by the prognostic model had a 30-day mortality of 4.4% (95% CI, 0.6%-8.2%) compared with 29.9% (95% CI, 25.4%-34.4%) in the high-risk group. In the external validation cohort, the 18% of patients (47 of 261) classified as low risk by the prognostic model had a 30-day mortality of 0%, compared with 19.6% (95% CI, 14.3%-25.0%) in the high-risk group.

Conclusions:  The developed clinical prediction rule accurately identifies low-risk patients with cancer and acute PE.

Chest. 2013;143(1):146-151. doi:10.1378/chest.12-0681

Background:  Small cell lung carcinoma (SCLC) continues to have a poor prognosis, with a 2-year survival of < 20%. Studies have suggested that SCLC may affect the immune system to allow it to evade immunologic responses. We hypothesized that any such effect would be characterized by a decrease in the lymphoid cells associated with the tumor in biopsy specimens and that this might relate to patient outcome.

Methods:  Sixty-four SCLC biopsy specimens were immunohistochemically stained with anti-CD45 antibody to identify immune cells associated with the tumor. A mean CD45 count per high-power field for each case was obtained, and the results were correlated with age, sex, stage, performance status (PS), treatment with chemotherapy/radiotherapy, and overall survival.

Results:  The median CD45 count for all cases was taken as 40 (CD4540). Kaplan-Meier plots demonstrated better survival for patients with a CD4540 > 40 (P < .009). No relationship between CD4540 and age, sex, stage, or treatment by chemotherapy or radiotherapy was identified. Although PS was a significant predictor of survival (P = .014), it did not correlate with CD4540. In patients with better Eastern Cooperative Oncology Group PS (≤ 2), the CD4540 demonstrated a highly significant survival advantage for those with CD4540 > 40 (P < .0001).

Conclusions:  The data indicate that (1) simple immunohistochemical assessment of immune cell infiltrates in routinely processed and stained biopsy specimens of primary tumors can provide prognostic information in SCLC and (2) tumor-associated CD45+ cells in SCLC biopsy specimens may be a good clinical marker to identify patients with poor prognosis despite good PS.

Original Research: Chest Infections

Chest. 2013;143(1):152-157. doi:10.1378/chest.12-0623

Background:  Protracted bacterial bronchitis is a major cause of persistent cough in childhood. The organisms most commonly isolated are nontypable Haemophilus influenzae and Streptococcus pneumoniae. There are no studies addressing typing of these organisms when recovered from the lower airways.

Methods:  Isolates of these two organisms (identified in BAL samples from children undergoing routine investigation of a chronic cough thought to be attributable to a protracted bacterial bronchitis) were subject to typing. Samples were collected in Sheffield, England, and Athens, Greece. The majority of the children from Sheffield had received pneumococcal-conjugate vaccines 7 or 13 (PCV-7 or PCV-13) conjugate vaccine but only a minority of Greek children had received PCV-7.

Results:  All 18 S pneumoniae isolates from Greek BAL samples are serotypes contained in PCV-13 while 10 are contained in PCV-7. In contrast, 28 of the 39 samples from Sheffield contained serotypes that are not included in PCV-13. All 26 of the nontypable H influenzae samples obtained in Sheffield produced distinct multilocus variable-number tandem repeat analysis profiles. There was a significant difference between children from Athens and Sheffield in the distribution of serotypes contained or not contained in the pneumococcal vaccine (P = .04). More specifically, immunization with pneumococcal vaccine was related with isolation of S pneumoniae serotypes not included in the vaccine (OR, 0.021; CI, 0.003-0.115; P < .001).

Conclusions:  The data suggest that both vaccine and nonvaccine Spneumoniae serotypes may play a role in protracted bacterial bronchitis and provide some hints that serotype replacement may occur in response to the introduction of conjugate vaccines.

Original Research: Disorders of the Pleura

Chest. 2013;143(1):158-163. doi:10.1378/chest.12-0526

Background:  Thoracic duct embolization (TDE) is an acceptable alternative procedure for treating traumatic chylothorax. The purpose of this study is to demonstrate efficacy of TDE in treating nontraumatic chylous effusions.

Methods:  A retrospective review of 34 patients was conducted assessing technical and clinical success of TDE for nontraumatic chylous effusions.

Results:  Thirty-four patients (mean age, 59 years; 27 female patients) with nontraumatic chylous effusions underwent TDE. Presentations included 21 unilateral chylothoraces (61.8%), nine bilateral chylothoraces (26.5%), two isolated chylopericardiums (5.9%), and two pleural effusions with chylopericardium (5.9%). TDE was technically successful in 24 of 34 patients (70.6%). The thoracic duct could not be catheterized in four of 34 (11.8%). Cisterna chyli was not visualized in six of 34 patients (17.6%), and, thus, TDE was not attempted. Follow-up was available for 32 patients. Four lymphangiographic patterns were observed: (1) normal thoracic duct in 17.6% of patients (six of 34), (2) occlusion of thoracic duct in 58.8% (20 of 34), (3) failure to opacify thoracic duct in 17.6% (six of 34), and (4) extravasation of chyle in 5.9% (two of 34). Clinical success varied with the lymphangiographic pattern. The clinical success rate was 16% (one of six) in cases of normal thoracic duct, 75% (15 of 20 patients) in occlusions of the thoracic duct, 16% (one of six) in cases of failure to opacify the thoracic duct, and 50% in two cases of chyle extravasation. Lymphangiography alone cured two patients (6.5%).

Conclusion:  TDE was most successful in cases of thoracic duct occlusion and extravasation. Lymphangiography is important for identifying the cause of chylous effusions and selecting patients who benefit most from TDE.

Chest. 2013;143(1):164-171. doi:10.1378/chest.11-2727

Background:  Ophiolites, a special sequence of geologic rock units, are known sources of naturally occurring asbestos. The aim of this study was to test whether the occurrence of malignant mesothelioma (MM) or pleural plaques (PPs) in the province of Sivas, Turkey, is determined by the proximity of the patient’s birthplace to ophiolites and, if so, to establish the magnitude of the risk.

Methods:  The birthplaces of patients with MM or PPs (cases) and patients with prostate or breast cancer (control subjects), diagnosed between 2000 and 2010 and identified through a mandatory cancer registry or from hospital records (PPs), were located on a geologic map, and the nearest distance to ophiolites was measured. The relation of MM or PPs with distance to ophiolites was analyzed by logistic regression. Samples of soil and house plaster were determined by x-ray diffraction.

Results:  Patients with MM (n = 100) or PPs (n = 133) were born significantly nearer to ophiolites (median distance, 4.5 km for men, 0 km for women) than were patients with prostate cancer (n = 161) or breast cancer (n = 139) (median distance, 20 km for both). ORs were 1.6 (men) (P < .001) and 2.0 (women) (P < .001) for every 5-km decrease in the distance of birthplace to ophiolites for MM, compared with prostate and breast cancer, respectively.

Conclusion:  In this area without substantial industrial asbestos use, there is an association between the occurrence of mesothelioma (and of PPs) and the proximity of the subject’s birthplace to ophiolites.

Original Research: IMAGING

Chest. 2013;143(1):172-178. doi:10.1378/chest.11-2501

Background:  Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course of screening-detected pure GGO lung nodules in patients with no history of malignancy.

Methods:  We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening.

Results:  Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer.

Conclusions:  About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.

Original Research: Cardiovascular Disease

Chest. 2013;143(1):179-184. doi:10.1378/chest.12-0608

Background:  Despite the clear net clinical benefit of oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF), the occurrence of major bleeding events may be devastating. The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding risk score was first described in 2010 and is recommended in European and Canadian guidelines to estimate major bleeding risk. In 2011, the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study group described a new bleeding risk scheme for AF, which includes five weighted risk factors: anemia, severe renal disease, age ≥ 75 years, previous hemorrhage, and diagnosed hypertension. We assessed the predictive value of the ATRIA bleeding score in a large cohort of patients with AF receiving anticoagulant therapy, compared with the well-validated HAS-BLED score.

Methods:  We recruited consecutive patients with AF receiving anticoagulant therapy from our outpatient anticoagulation clinic with an INR between 2.0 and 3.0 during the previous 6 months’ clinic visits. During follow-up, major bleeding events were assessed. We assessed both bleeding risk scores as quantitative variables or as dichotomized variables (low-moderate risk vs high risk). Model performance was evaluated by calculating C statistics, and the improvement in predictive accuracy was evaluated by calculating the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).

Results:  We included 937 patients (49% men; median age, 76 years). Median (interquartile range) follow-up was 952 (785-1,074) days, during which 79 (8%) suffered a major bleeding event (annual rate, 3.2%). The HAS-BLED score had a model performance (based on C statistics) similar to that of the ATRIA score as a quantitative variable (C statistic, 0.71 vs 0.68; P = .356) but was superior to the ATRIA score when analyzed as a dichotomized variable (C statistic, 0.68 vs 0.59; P = .035). Both NRI and IDI analyses demonstrated that the HAS-BLED score more accurately predicted major bleeding episodes than did the ATRIA risk score, as reflected in the percentage of events reclassified correctly.

Conclusion:  The HAS-BLED score shows significantly better prediction accuracy than the weighted (and more complex) ATRIA score. Our findings reinforce the incremental usefulness of the simple HAS-BLED score over other published bleeding risk scores in patients with AF receiving anticoagulant therapy.

Original Research: Pulmonary Vascular Disease

Chest. 2013;143(1):185-195. doi:10.1378/chest.11-1387

Background:  The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL Registry) is a multicenter, US-based, observational study of patients diagnosed with group 1 pulmonary hypertension enrolled consecutively from March 2006 to December 2009. Of 3,128 patients in this analysis, inclusion criteria permitted enrollment of 268 patients with mean pulmonary capillary wedge pressure (PCWP) 16 to 18 mm Hg at diagnostic right-sided heart catheterization (RHC) (above currently accepted pulmonary arterial hypertension [PAH] diagnostic criteria). This study compared the demographics and outcomes of those 268 patients with an elevated mean PCWP to patients with a mean PCWP ≤ 15 mm Hg.

Methods:  Demographic characteristics and outcomes were compared for patients with mean PCWP ≤ 12, 13 to 15, and 16 to 18 mm Hg at diagnostic and follow-up RHC.

Results:  At diagnostic RHC, patients with PCWP 16 to18 mm Hg were older, had more severe hemodynamic impairments, and were more likely to be obese and have other comorbidities than patients with PCWP ≤ 15 mm Hg. There were no clinically relevant differences in 5-year survival rates from diagnostic RHC regardless of PCWP at diagnosis (≤15 mm Hg vs 16-18 mm Hg, P = .07). Two-year survival rates of 108 patients with PAH whose PCWP increased to ≥ 19 mm Hg (regardless of PCWP at diagnosis) were significantly lower than that of patients with PAH with PCWP ≤ 18 mm Hg at subsequent RHC.

Conclusion:  Patients with PCWP 16 to 18 mm Hg who were diagnosed and treated for PAH were older, heavier, and more likely to have comorbidities associated with left ventricular diastolic dysfunction at diagnosis than those with PCWP ≤ 15 mm Hg. Five-year survival rates were similarly low for all PCWP subgroups.

Trial registry:  ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov

Translating Basic Research Into Clinical Practice

Chest. 2013;143(1):196-206. doi:10.1378/chest.12-0930

COPD is a complex syndrome that poses a serious health threat to >1.1 billion smokers worldwide. The stable disease is punctuated by episodes of acute exacerbation, which are predominantly the result of viral and bacterial infections. Despite their devastating health impact, mechanisms underlying disease exacerbations remain poorly understood. Mounting evidence suggests that cigarette smoke profoundly affects the immune system, compromising the host’s ability to mount appropriate immune and inflammatory responses against microbial agents. This review highlights recent advances in our understanding of the impact of cigarette smoke on type 1 interferon and IL-1 signaling cascades. The immune defects caused by cigarette smoke on these two key pathways contribute to the seemingly contradictory nature of cigarette smoke as both a damaging and a proinflammatory factor as well as an immunosuppressive factor. Understanding the impact of cigarette smoke on the immune system may unravel novel targets for therapies that could affect acute exacerbations and COPD pathogenesis.

Ahead of the Curve

Chest. 2013;143(1):207-213. doi:10.1378/chest.12-1639

A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco.

Recent Advances in Chest Medicine

Chest. 2013;143(1):214-221. doi:10.1378/chest.12-1531

The evidence regarding physician staffing of ICUs does not yet provide a consistent view of the best model to use. Most studies have significant limitations, and this subject is complicated by the fact that optimal ICU staffing may depend on ICU characteristics. The topic with the most data regarding patient outcomes is the intensity of intensivist involvement in care, particularly the value of closed- vs open-model ICUs; however, the evidence is inconsistent here as well. Even if closed-model ICUs produce better outcomes, we do not know which specific elements of that multifaceted organizational paradigm are responsible for improvement. Also, studies of around-the-clock intensivist presence have not consistently shown that it is associated with superior outcomes. Increasingly, nonphysician providers are playing innovative roles in the ICU, and care provided by teams including nurse practitioners or physician assistants appears to be safe and comparable to that provided by other staffing models. Although we do not know the best way to staff ICUs, the conditions of ICU physician coverage will continue to change under the stresses of shortages of intensivists and increasing duty hour limitations for trainees. Nonphysician providers, innovative physician staffing models, telemedicine, and other technologies will be increasingly used to cope with these realities. This evolution makes it more important than ever to study how staffing affects outcomes. Only quantitative evaluation can tell us whether one staffing model is better than another. Accordingly, we need more research from multiple sites to develop a consistent and integrated understanding of this complex topic.

Medical Ethics

Chest. 2013;143(1):222-227. doi:10.1378/chest.12-1916

We identify five myths of medical malpractice that have wide currency in medical circles. The myths are as follows: (1) Malpractice crises are caused by spikes in medical malpractice litigation (ie, sudden rises in payouts and claim frequency), (2) the tort system delivers “jackpot justice,” (3) physicians are one malpractice verdict away from bankruptcy, (4) physicians move to states that adopt damages caps, and (5) tort reform will lower health-care spending dramatically. We test each assertion against the available empirical evidence on the subject and conclude by identifying various nonmythical problems with the medical malpractice system.

Topics in Practice Management

Chest. 2013;143(1):228-235. doi:10.1378/chest.12-0949

Electronic health record (EHR) order sets are common. Order sets represent one clinical decision support (CDS) tool within computerized provider order entry systems that may promote safe, efficient, and evidence-based patient care. A small number of order sets account for the vast majority of use, suggesting that some order sets have a higher value to clinicians than others. While EHR order sets can save time and improve processes of care, it remains less clear that EHR order sets have shown definite patient outcome benefits. There are general guidelines on CDS and usability that can be applied to the development of EHR order sets. Order set success requires leadership, planning, and resources as well as ongoing maintenance and evaluation. This article describes one academic medical center’s experience in developing an EHR order set embedded with evidence-based principles and lessons learned for future order set development.

Selected Reports

Chest. 2013;143(1):236-238. doi:10.1378/chest.12-0226

Bullous pemphygoid is the most common blistering skin disease, characterized by an autoantibody response against two major hemidesmosomal antigens within the dermo-epidermal junction. We describe a proven case of bullous pemphigoid with extensive tracheobronchial involvement and with the only bronchoscopic images available in the published literature, to our knowledge. The patient, a 73-year-old woman with a medical history of bullous pemphigoid, was admitted to our hospital for dyspnea, productive cough, and blood-streaked sputum. She underwent bronchoscopy, which showed ulcerative tracheitis with fibrinous exudates. After antibiotic therapy, a repeat bronchoscopy revealed hemorrhagic vesciculobullous lesions in the subglottic area and at the level of the main bronchi. Pathologic evaluation, direct immunofluorescence microscopy examination, and enzyme-linked immunosorbent assay led to a definitive diagnosis of bullous pemphigoid. Due to the potential confounding presence of bacterial superinfection, the real prevalence of such manifestation of this disease is still unknown. Our experience should alert clinicians about this possible localization of bullous pemphigoid.

Chest. 2013;143(1):238-241. doi:10.1378/chest.12-0400

Pulmonary aspergilloma is a chronic fungal infection that has a high mortality when hemoptysis occurs. Surgery is the treatment of choice, but patients often have severe physiologic impairment putting them at risk for significant surgical morbidity and mortality. We present the case of a 63-year-old woman with a large aspergilloma, unfit for surgery due to medical reasons. The aspergilloma was enlarging, with progression of the patient’s symptoms of anorexia, cough, chest discomfort, and hemoptysis. Bronchoscopy revealed an airway leading into a cavity with a large fungal ball. Biopsy confirmed Aspergillus fumigatus. Using flexible and rigid bronchoscopy, the aspergilloma was mechanically removed. Eighteen months later the patient reported no hemoptysis, reduced pain and cough, significant weight gain, and improved appetite, with no recurrence of the aspergilloma on repeat imaging. To our knowledge, this is the first reported case of bronchoscopic removal of a large cavitary aspergilloma. This important new treatment modality provides a viable alternative therapy for this potentially life-threatening problem.

Postgraduate Education Corner: Contemporary Reviews in Sleep Medicine

Chest. 2013;143(1):242-251. doi:10.1378/chest.12-0561

Over the past 10 years, significant strides have been made in therapeutics for sleep disorders. In this second installment of a two-part review series, we discuss the current evidence surrounding the mechanisms of actions, indications, efficacy, and adverse side effects associated with the current over-the-counter and pharmacotherapeutics for hypersomnia, parasomnias, and movement disorders of sleep.

Postgraduate Education Corner: Chest Imaging and Pathology for Clinicians

Chest. 2013;143(1):252-257. doi:10.1378/chest.11-2379

Postgraduate Education Corner: Pulmonary, Critical Care, and Sleep Pearls

Chest. 2013;143(1):258-261. doi:10.1378/chest.12-0547
Chest. 2013;143(1):262-265. doi:10.1378/chest.11-2841

Postgraduate Education Corner: Ultrasound Corner

Chest. 2013;143(1):e1-e3. doi:10.1378/chest.12-2878

A 66-year-old woman had a brief syncopal episode after standing up from the toilet. She awoke in seconds and noted no chest pain or shortness of breath. On presentation to the ED, she had a BP of 90/60 mm Hg, a regular heart rate of 115 beats/min, temperature of 37.2°C, and a respiratory rate of 26 breaths/min. Her oxygen saturation on 4 L nasal cannula was 91%. The physical examination was otherwise unremarkable. Her chest radiograph was clear, and the ECG showed sinus tachycardia without other abnormality. Laboratory values were as follows: WBC count, 12.7 K/μL; lactate, 3.4 mmol/L; and creatinine, 2.2 mg/dL; urinalysis results were 25 WBC per high-powered field. She was given antibiotics for presumed septic shock with a urinary tract infection, and over the next few hours, per sepsis bundle protocol, she was given a total of 3 L of normal saline. The patient remained hypotensive. Norepinephrine was started at 0.5 μg/kg/min while fluid resuscitation with normal saline was continued. The patient was admitted to the medical ICU with a diagnosis of septic shock. The intensivist performed an immediate bedside ultrasound examination to diagnose and guide management of her hypotension and hypoxemia (Videos 1-3).


Chest. 2013;143(1):266-267. doi:10.1378/chest.12-0439

Wind . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spray . . . . . . . . . . . . . . . . . . . . . . Foam
Thought              Plan             Hair
Working at the Repat, helping old diggers.
Physiology, oncology, bronchoscopy, polysomnography.
Giving talks with overheads, hand-drawn figures.
OSA, asthma, CSA, fibrosis, COPD, BUAD.
              an old wooden yacht
             sails sheet rope with knot
             ocean blue and spray in hair
                sail along without a care
                 boat untidy
                mobile in sea
A seed, a thought, a dream
In a fertile mind
Planning, discussing, worrying
Writing grants, ideas are flowing
Working hard, long nights at Bowen
Triumph at last
A new grey suit
IBAS is born.
A Party for the Winter Soltice.
  Up the Bald Spur Road, St Andrew, a rough road, a bit erratic, and wandering,
      a bit like its resident.
  Mud brick house with a free spirit, generous welcome and warm hearth,
      just like its owner.
  Bottles of wine, simple food, carefree music,
      like its host.
Grey Jaguar
      wooden steering wheel
            leather seats
                   proudly conveying its owner
               proudly carrying its coat of fine brown dust.
Now on the James Craig; waves crash; hold on fast.
Ship’s doctor? There’s more for me.
On the rigging, grab the winch, up the mast.
Obey the captain when at sea.
                 We need more free thinking.”
                   RIP   RJP

Chest. 2013;143(1):268. doi:10.1378/chest.12-0487

In Plato’s epistemology, cast iron Truth
floats about in the sky. Aristotle believed
we are addicted to knowledge, and David
Hume proved the crowing of a rooster caused
the sun to rise. I live simply by the numbers, unzip
the little black bag my doctor gave me, load
a disposable needle in the spring driven lancet,
tell myself it can’t hurt anymore than last night,
and I’m ready for the first wounding of the day.
Sometimes my blood needs encouragement
to leave it’s happy home, so I squeeze and rub,
squeeze and rub, a drop on the meter, and viola,
my blood sugar level stacked, straightened and
counted, a posteriori, like Oreo Cookie packages
inventoried on a supermarket shelf.
I’d like to get rid of the meter, stop the twice
daily testing, but I’ve got to be sure my numbers
are low, and besides after all these years I’ve come
to love my feet and toes, don’t want to lose them. So-
I’ve given up candy, take mine black, and I’ll pass
on the apple pie a la mode.


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Chest. 2013;143(1):279a. doi:10.1378/chest.12-2187

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    Print ISSN: 0012-3692
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