Chest. 2013;143(3):587-589. doi:10.1378/chest.12-2682

In this issue of CHEST (see page 605), Kahrilas et al1 report the results of their systematic review of clinical trials reporting cough response to antireflux therapy. They identified nine randomized, controlled studies that treated patients with acid suppression. Eight of the nine trials used proton pump inhibitors (PPIs) (daily or bid for 8-16 weeks); one trial used ranitidine (150 mg daily for 8 weeks). The authors report that there was significant study variability in methodology and measured outcome. Although they could not definitively state that acid-suppression therapy benefits patients with chronic cough, they could not dismiss that possibility. Importantly, they found that the therapeutic gain was in favor of PPI therapy if patients had pathologic esophageal acid exposure (range, 12.5% to 35.8%) than if they had normal esophageal acid exposure (range, 0.0% to 8.6%). The authors conclude that “rigorous patient selection is necessary to identify patient populations likely to be responsive” to acid-suppression therapy.

Chest. 2013;143(3):589-590. doi:10.1378/chest.12-1710

Imagine a set of assumptions that proves entirely incorrect. You order a peripherally inserted central catheter (PICC) for your hospitalized patient. False assumption 1: This is a PICC team procedure, and physicians do not really need to give this order much thought. The PICC team will figure out the largest catheter that can be safely inserted. At most, you will specify whether you want a single-, double-, or triple-lumen catheter. If unsure, order double lumen rather than single lumen or order triple lumen rather than double lumen; after all, to minimize the number of procedures, it is better to err on having more rather than fewer sites to infuse medications, blood products, and nutritional support. Eventually, the PICC will stop working. Its duration of function is mostly a matter of luck. The catheter may thrombose, but this is a minor problem. False assumption 2: An upper-extremity line-associated DVT is nothing more than a nuisance. It adds hardly a blip to the length of hospital stay and barely registers on the radar screen for incremental cost of hospitalization.

Chest. 2013;143(3):590-592. doi:10.1378/chest.12-2139

Ventilator-associated pneumonia (VAP), defined as pneumonia occurring >48 h after the initiation of mechanical ventilation, is the most common hospital-acquired infection in the ICU.1 Although the impact of VAP on mortality is controversial in patients dying from or with VAP, most studies demonstrate an increased attributable mortality.2,3 VAP also prolongs mechanical ventilation, increases the duration of ICU and hospital stays, accounts for more antibiotic consumption, and generates more costs related to treatment.4,5 Current methods used to diagnose VAP have limited accuracy, and there is poor agreement among clinical and surveillance methods.6 As a result, the National Healthcare Safety Network, the hospital-acquired infection surveillance system of the US Centers for Disease Control and Prevention, created a new surveillance algorithm for ventilator-associated events.7 This streamlined and objective surveillance system focuses on changes in ventilator parameters indicative of worsening oxygenation (ie, an increase in the fraction of inspired oxygen or the positive end-expiratory pressure after a period of stability) and hopes to identify a broader range of potentially preventable clinical conditions associated with mechanical ventilation.7 However, VAP still represents an important infection requiring prevention, not only due to its associated morbidity and mortality excess, but also due to the increased occurrence of VAP due to antibiotic-resistant bacteria.8,9

Chest. 2013;143(3):592-594. doi:10.1378/chest.13-0058

About a decade ago I received a call from a colleague that I will not soon forget. As background, we had “grown up” in the university together, she an ICU nurse and I a pulmonary attending. She was a grizzled hospital veteran and was knowledgeable about all aspects of clinical care. She had worked her way up into management, and I had not seen her for a while when I received the call. She sounded panicked and asked if she could come by my office to review her medical record with me. When we met, she told me she had recently discovered a breast lump. After mammography and ultrasonography, she had her initial appointment with a surgical oncologist. The surgeon, a trusted colleague, had a reputation for having a good bedside manner. I asked her what he said, and her reply was “After he told me it might be a breast cancer, I completely shut down. I don’t remember a thing for the rest of the visit, and I was too embarrassed to ask.” After a good cry, we reviewed her chart, and I was able to reassure her that his interpretation was that the risk of cancer was <10% and that he believed this was likely a fluid-filled cyst in a patient with preexisting fibrocystic breast disease. He wanted a biopsy to rule out the possibility of cancer, but it was low on his list of possible differential diagnoses. I encouraged her to call him to confirm this prior to the biopsy to help alleviate her fears. All turned out well for this patient, but it left me quite unsettled. If this health care-savvy nurse heard something different (or in this case nothing at all) from what a competent, compassionate physician had told her, then what were my patients hearing when I discussed a newly discovered pulmonary nodule that may or may not be cancer?

Chest. 2013;143(3):594-595. doi:10.1378/chest.12-2710

Strong forces, including health-care payment reform, the changing composition of the health-care workforce, and telemedicine, are sculpting our delivery of critical care. Among the strongest of these forces is the emergence and continued evolution of a role for advanced practice providers (APPs)(including nurse practitioners and physicians’ assistants) in independent practice, as well as team-based intensive care.1 Begun 15 years ago with the Balanced Budget Act of 1997, reimbursement from Medicare for the independent practice of APPs has proliferated to similar reimbursement mechanisms from many other payers.2

Second Opinion

Chest. 2013;143(3):596. doi:10.1378/chest.143.3.596

Point/Counterpoint Editorials

Chest. 2013;143(3):597-600. doi:10.1378/chest.12-2546

Lung cancer is the most common cause of cancer-related death in the United States, with >160,000 new cases per year.1,2 Over the past several years, there have been remarkable developments in the diagnosis, staging, and treatment of lung cancer, including chest CT scan screening for high-risk individuals with proven survival benefit,3 minimally invasive surgical approaches,4 and endobronchial ultrasound (EBUS) as the primary means of mediastinal staging.5 All of these innovations combined will have a dramatic impact on the quality and quantity of life in lung cancer victims.

Chest. 2013;143(3):600-602. doi:10.1378/chest.12-2548

The square one question is why we need to do the epidermal growth factor receptor (EGFR) mutation tests. The answer is that there is corresponding targeted therapy, namely EGFR-tyrosine kinase inhibitor (TKI), for subjects with tumors that bear EGFR mutations at exons 18 to 21. This is in line with the strategy of personalizing therapy for lung cancer with the ultimate goals of making biomarker-based therapeutic decisions to receive EGFR-TKI and to improve treatment outcome in patients with advanced-stage non-small cell lung cancer (NSCLC).1

Chest. 2013;143(3):602-603. doi:10.1378/chest.12-2547

I am indebted to my colleague, Dr Lam,1 for his excellent Counterpoint Editorial arguing against routine testing for epidermal growth factor receptor (EGFR) mutations in patients with lung cancer. I have conceded that EGFR mutations should not be routinely tested for in all patients with lung cancer, nor do I advocate routine testing for EGFR mutations in patients with squamous cell or small cell lung cancer.2 Other mutational testing will, however, likely prove critical for these tumor subtypes in the future.

Chest. 2013;143(3):603-604. doi:10.1378/chest.12-2549

Having read Dr Sterman’s1 Point Editorial, I remain with my stance that epidermal growth factor receptor (EGFR) mutation testing should be considered, but not done routinely, in all patients with lung cancer.2 It is beyond any debate that EGFR mutation tests should be considered and be done, whenever possible and as early as is possible, for lung adenocarcinoma, which is one major histologic subtype of lung cancer.3

Original Research: Signs and Symptoms of Chest Diseases

Chest. 2013;143(3):605-612. doi:10.1378/chest.12-1788

Background:  Epidemiologic and physiologic studies suggest an association between gastroesophageal reflux disease (GERD) and chronic cough. However, the benefit of antireflux therapy for chronic cough remains unclear, with most relevant trials reporting negative findings. This systematic review aimed to reevaluate the response of chronic cough to antireflux therapy in trials that allowed us to distinguish patients with or without objective evidence of GERD.

Methods:  PubMed and Embase systematic searches identified clinical trials reporting cough response to antireflux therapy. Datasets were derived from trials that used pH-metry to characterize patients with chronic cough.

Results:  Nine randomized controlled trials of varied design that treated patients with acid suppression were identified (eight used proton pump inhibitors [PPIs], one used ranitidine). Datasets from two crossover studies showed that PPIs significantly improved cough relative to placebo, albeit only in the arm receiving placebo first. Therapeutic gain in seven datasets was greater in patients with pathologic esophageal acid exposure (range, 12.5%-35.8%) than in those without (range, 0.0%-8.6%), with no overlap between groups.

Conclusions:  A therapeutic benefit for acid-suppressive therapy in patients with chronic cough cannot be dismissed. However, evidence suggests that rigorous patient selection is necessary to identify patient populations likely to be responsive, using physiologically timed cough events during reflux testing, minimal patient exclusion because of presumptive alternative diagnoses, and appropriate power to detect a modest therapeutic gain. Only then can we hope to resolve this vexing clinical management problem.

Chest. 2013;143(3):613-620. doi:10.1378/chest.12-0441

Background:  The causes of chronic cough in China and its relations with geography, seasonality, age, and sex are largely uncertain.

Methods:  A prospective, multicenter survey was conducted to evaluate patients with chronic cough across five regions in China by using a modified diagnostic algorithm. The effects of geography, seasonality, age, and sex on spectrum of chronic cough were also investigated.

Results:  The current study evaluated 704 adult patients, including 315 men (44.7%) and 389 women (55.3%). The causes of chronic cough were determined in 640 subjects (90.9%). Common causes included cough variant asthma (CVA) (32.6%), upper airway cough syndrome (UACS) (18.6%), eosinophilic bronchitis (EB) (17.2%), and atopic cough (AC) (13.2%). Collectively, these four causes accounted for 75.2% to 87.6% across five different regions without significant difference (P > .05), although there was variation on single causes. Gastroesophageal reflux-related cough was identified in 4.6% of causes. Seasonality, sex, and age were not associated with the spectrum of chronic cough (all P > .05).

Conclusion:  CVA, UACS, EB, and AC were common causes of chronic cough in China. Geography, seasonality, age, and sex were not associated with the spectrum of chronic cough.

Original Research: Interventional Pulmonology

Chest. 2013;143(3):621-626. doi:10.1378/chest.12-2290

Background:  Transbronchial biopsies using standard forceps (FTBBxs) are often limited by crush artifact and their small size. To date, there have been no studies aimed at assessing the safety and efficacy of cryoprobe biopsies (CPBxs) in the population of patients who have undergone lung transplants. We present the safety profile and biopsy results from the first 21 procedures in a pilot study comparing CPBx to FTBBx in patients after lung transplantation.

Methods:  Patients who had undergone lung transplant and who were scheduled for bronchoscopy were sequentially enrolled between November 2011 and September 2012. Inclusion criteria included age > 18 years and bilateral, orthotopic lung transplant. Exclusion criteria were coagulopathy, FEV1 < 0.8 L, diffuse bullous disease, hemodynamic instability, and severe hypoxemia (PaO2 < 55 mm Hg or SpO2 < 92% on room air). Twenty-one procedures were performed, 10 using rigid bronchoscopy followed by 11 via flexible bronchoscopy. Patients were monitored for complications including pneumothorax, hemodynamic instability, and/or respiratory distress. Bleeding was categorized on an adapted grading system.

Results:  Twenty-one procedures in 17 patients (median age: 52 years; 12 male patients) were performed. Specimen area and percent open alveoli were significantly greater using CPBx compared with FTBBx (P < .05). No clinically significant procedural complications occurred and all patients were discharged the day of the procedure.

Conclusions:  The use of the cryoprobe is a safe, alternative technique to FTBBx during post-lung transplant bronchoscopy. Further studies are needed to determine if larger samples obtained with CPBx translate to an increased diagnostic yield.

Trial registry:  ClinicalTrials.gov; No.: NA_00052081; URL: clinicaltrials.gov

Original Research: Procedures

Chest. 2013;143(3):627-633. doi:10.1378/chest.12-0923

Background:  As peripherally inserted central catheter (PICC) use has increased, so has the upper extremity DVT rate. PICC diameter may pose the most modifiable risk for PICC-associated DVT.

Methods:  A 3-year, prospective, observational study of all PICC insertions by a specially trained and certified team using a consistent and replicable approach was conducted at a 456-bed, level I trauma and tertiary referral hospital during January 1, 2008, through December 31, 2010. An intensified effort by the PICC team in 2010 was introduced to discuss and reach interdisciplinary consensus on the need for each lumen of the PICC and a change to smaller diameter 5F triple-lumen PICC.

Results:  Significantly more 4F single-lumen PICCs were used during 2010 (n = 470) compared with 2008 and 2009 (n = 338, 382; P < .0001). DVT rates were similar with the use of 5F triple-lumen PICCs in 2010 as 5F double-lumen PICCs and lower rates than 6F triple-lumen catheters used in 2008 and 2009. The PICC-associated DVT rate was significantly lower (1.9% vs 3.0%, P < .04) in 2010 compared with 2008 and 2009. The cost and length of stay attributable to PICC-associated DVT were $15,973 and 4.6 days.

Conclusions:  A significant increase in the use of single-lumen PICCs in addition to the institutional adoption of smaller 5F triple-lumen PICCs was associated with a significant decrease in the rate of PICC-associated DVT.

Chest. 2013;143(3):634-639. doi:10.1378/chest.12-1285

Background:  It is conventionally taught that the intercostal artery is shielded in the intercostal groove of the superior rib. The continuous course and variability of the intercostal artery, and factors that may influence them, have not been described in a large number of arteries in vivo.

Methods:  Maximal intensity projection reformats in the coronal plane were produced from CT scan pulmonary angiograms to identify the posterolateral course of the intercostal artery (seventh to 11th rib spaces). A novel semiautomated computer segmentation algorithm was used to measure distances between the lower border of the superior rib, the upper border of the inferior rib, and the position of the intercostal artery when exposed in the intercostal space. The position and variability of the artery were analyzed for association with clinical factors.

Results:  Two hundred ninety-eight arteries from 47 patients were analyzed. The mean lateral distance from the spine over which the artery was exposed within the intercostal space was 39 mm, with wide variability (SD, 10 mm; 10th-90th centile, 28-51 mm). At 3 cm lateral distance from the spine, 17% of arteries were shielded by the superior rib, compared with 97% at 6 cm. Exposed artery length was not associated with age, sex, rib space, or side. The variability of arterial position was significantly associated with age (coefficient, 0.91; P < .001) and rib space number (coefficient, −2.60; P < .001).

Conclusions:  The intercostal artery is exposed within the intercostal space in the first 6 cm lateral to the spine. The variability of its vertical position is greater in older patients and in more cephalad rib spaces.

Chest. 2013;143(3):640-645. doi:10.1378/chest.12-0863

Background:  The sterile conditions used when inserting a central venous catheter (CVC) might be thought to decrease the contamination rate of blood cultures taken at CVC insertion; however, a previous retrospective study showed the opposite, that such blood cultures are contaminated more frequently than peripheral venipuncture blood cultures. The current study explored whether use of the CVC nonwire hub as a source of blood cultures decreased contamination while maintaining detection of true pathogens.

Methods:  A prospective, observational study was performed from June 2010 to May 2011 in the general ICU of an academic, tertiary referral center. The proportions of blood cultures taken from wire and nonwire CVC hubs growing contaminants and true pathogens were compared. Risk factors for blood culture contamination were identified, and multivariate analysis was used to identify independent predictors of blood culture contamination.

Results:  Among 313 blood cultures taken from 227 CVCs in 139 patients, 27 of 141 wire hub (19%) vs nine of 172 nonwire hub (5%) cultures were contaminated (P < .001). Only hub of blood culture origin was associated with contamination on multivariate analysis (OR, 4.3; 95% CI, 1.9-9.5; P < .001). True pathogens grew in 19 of 141 wire hub (13%) vs 27 of 172 nonwire hub (16%) cultures (P = .581).

Conclusions:  A higher proportion of blood cultures taken from the CVC lumen exposed to the guidewire were contaminated when compared with nonwire hub cultures; detection of true pathogens was equivalent. To limit detrimental sequelae of blood culture contamination, blood cultures obtained at CVC insertion should be taken from the nonwire hub.

Original Research: Critical Care

Chest. 2013;143(3):646-655. doi:10.1378/chest.12-1745

Background:  The objective of this study was to systematically review and quantitatively synthesize all randomized controlled trials (RCTs) that have compared important outcomes in critically ill patients who received an administration of probiotics.

Methods:  A systematic literature search of PubMed, Scopus, and the Cochrane Central Register of Controlled Trials was conducted using specific search terms. Eligible studies were RCTs that compared the effect of prebiotics, probiotics, or synbiotics administration with control on ICU and hospital mortality rates in critically ill adult patients. Weighted mean differences (WMDs), pooled ORs, and 95% CIs were calculated using the Mantel-Haenszel fixed- and random-effects models.

Results:  Thirteen trials with 1,439 patients were analyzed. Probiotics did not significantly reduce ICU (OR, 0.85; 95% CI, 0.63-1.15) or hospital (OR, 0.90; 95% CI, 0.65-1.23) mortality. By contrast, probiotics administration reduced the incidence of ICU-acquired pneumonia (OR, 0.58; 95% CI, 0.42-0.79) and was associated with a shorter stay in the ICU (WMD, −1.49 days; 95% CI, −2.12 to −0.87 days). Finally, probiotics use was not associated with a shorter duration of mechanical ventilation (WMD, −0.18 days; 95% CI, −1.72-1.36 days) or a shorter hospital length of stay (WMD, −0.45 days; 95% CI, −1.41-0.52 days).

Conclusions:  The present meta-analysis suggests that the administration of probiotics did not significantly reduce ICU or hospital mortality rates but did reduce the incidence of ICU-acquired pneumonia and ICU length of stay.

Chest. 2013;143(3):656-663. doi:10.1378/chest.12-1173

Background:  A growing trend is the implementation of 24-h attending physician coverage in the ICU. Our aim was to measure the impact of 24-h, in-house, attending intensivist coverage on the quality of end-of-life care and the timing of end-of-life decision-making.

Methods:  A retrospective cohort study was conducted of all ICU deaths 6 months before and 6 months after the implementation of mandatory 24-h attending intensivist coverage in a medical ICU. Data relevant to end-of-life care per established consensus recommendations were abstracted from the medical record.

Results:  The following changes were observed after implementation of 24-h intensivist coverage: Time from ICU admission to decision to withdraw mechanical ventilation and time to decision to change to do-not-resuscitate code status both were shortened by 2 days (both P = .03). Quality measures, such as increased family presence around time of death (P = .01) also improved. Other findings, which did not reach statistical significance, included the following: Time to family conference was shortened by 2 days (P = .09), time to decision to limit any life support was shortened by 1 day (P = .08), time to death was shortened by 2 days (P = .08), and intubations against patient wishes decreased (from three to none; P = .12).

Conclusions:  The implementation of mandatory 24-h, in-house, attending intensivist coverage was associated with earlier decision-making across a number of domains related to end-of-life care. Positive trends were noted in quality of end-of-life care as reflected in the presence of family at the time of death.

Chest. 2013;143(3):664-671. doi:10.1378/chest.12-1106

Background:  Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients.

Methods:  We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy.

Results:  We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01).

Conclusions:  One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV.

Original Research: Lung Cancer

Chest. 2013;143(3):672-677. doi:10.1378/chest.12-1095

Background:  More than 150,000 Americans each year are found to have a pulmonary nodule. Even more will be affected following the publication of the National Lung Screening Trial. Patient-doctor communication about pulmonary nodules can be challenging. Although most nodules are benign, it may take 2 to 3 years to rule out cancer. We sought to characterize patients’ perceptions of communication with their providers about pulmonary nodules.

Methods:  We conducted four focus groups at two sites with 22 adults with an indeterminate pulmonary nodule. Transcripts were analyzed using principles of grounded theory.

Results:  Patients described conversations with 53 different providers about the pulmonary nodule. Almost all patients immediately assumed that they had cancer when first told about the nodule. Some whose providers did not discuss the actual cancer risk or explain the evaluation plan experienced confusion and distress that sometimes lasted for months. Patients were frustrated when their providers did not address their concerns about cancer or potential adverse effects of surveillance (eg, prolonged uncertainty, radiation exposure), which in some cases led to poor adherence to evaluation plans. Patients found it helpful when physicians used lay terms, showed the CT image, and quantified cancer risk. By contrast, patients resented medical jargon and dismissive language.

Conclusions:  Patients commonly assume that a pulmonary nodule means cancer. What providers tell (or do not tell) patients about their cancer risk and the evaluation plan can strongly influence patients’ perceptions of the nodule and related distress. We describe simple communication strategies that may help patients to come to terms with an indeterminate pulmonary nodule.

Original Research: Copd

Chest. 2013;143(3):678-686. doi:10.1378/chest.12-0228

Background:  Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2R) techniques have not been systematically evaluated in these patients.

Methods:  This is a pilot study of a novel ECCO2R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean.

Results:  The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; PaCO2 decreased significantly (P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization.

Conclusions:  This single-catheter, low-flow ECCO2R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure.

Trial registry:  ClinicalTrials.gov; No.: NCT00987740 and 01021605; URL: www.clinicaltrials.gov

Chest. 2013;143(3):687-693. doi:10.1378/chest.12-0039

Background:  In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA).

Methods:  We analyzed CT scan segmental and subsegmental WA% (WA% = 100 × wall area/TBA) of six bronchial paths and corresponding lobar emphysema, lung function, and clinical data in 983 smokers with COPD.

Results:  Compared with segmental WA%, the subsegmental WA% had a greater effect on FEV1% predicted (−0.8% to −1.7% vs −1.9% to −2.6% per 1-unit increase in WA%, respectively; P < .05 for most bronchial paths). After adjusting for emphysema, the association between subsegmental WA% and FEV1 % predicted was weakened in two bronchial paths. Increases in WA% between bronchial segments correlated directly with emphysema in all bronchial paths (P < .05). In multivariate regression models, emphysema was directly related to subsegmental WA% in most bronchial paths and inversely related to subsegmental TBA in all bronchial paths.

Conclusion:  The greater effect of subsegmental WA% on airflow obstruction is mitigated by emphysema. Part of the emphysema effect might be due to loss of airway tethering, leading to a reduction in TBA and an increase in WA%.

Trial registry:  ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov

Chest. 2013;143(3):694-702. doi:10.1378/chest.12-1053

Background:  The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update includes airflow limitation, history of COPD exacerbations, and symptoms to classify and grade COPD severity. We aimed to determine their distribution in 11 well-defined COPD cohorts and their prognostic validity up to 10 years to predict time to death.

Methods:  Spirometry in all 11 cohorts was postbronchodilator. Survival analysis and C statistics were used to compare the two GOLD systems by varying time points.

Results:  Of 3,633 patients, 1,064 (33.6%) were in new GOLD patient group A (low risk, less symptoms), 515 (16.3%) were B (low risk, more symptoms), 561 (17.7%) were C (high risk, less symptoms), and 1,023 (32.3%) were D (high risk, more symptoms). There was great heterogeneity of this distribution within the cohorts (χ2, P < .01). No differences were seen in the C statistics of old vs new GOLD grading to predict mortality at 1 year (0.635 vs 0.639, P = .53), at 3 years (0.637 vs 0.645, P = .21), or at 10 years (0.639 vs 0.642, P = .76).

Conclusions:  The new GOLD grading produces an uneven split of the COPD population, one-third each in A and D patient groups, and its prognostic validity to predict time to death is no different than the old GOLD staging based in spirometry only.

Chest. 2013;143(3):703-710. doi:10.1378/chest.12-0535

Objective:  Our objective was to evaluate the validity of the COPD Assessment Test (CAT), translated locally, for measuring the health status of patients in Asian countries.

Methods:  A pooled analysis of cross-sectional studies from Indonesia, Korea, Vietnam, and Hong Kong was performed. Smokers or ex-smokers, aged ≥ 40 years, with a smoking history of ≥ 10 pack-years and a COPD diagnosis in the past 6 months or more were recruited. Demographic, smoking, and COPD history and spirometry data were collected from patients who completed the CAT or St. George’s Respiratory Questionnaire (SGRQ) and had their dyspnea assessed.

Results:  The study included 333 patients with mean age of 69 ± 9 years and smoking history of 38 ± 25 pack-years; 82% had ceased smoking. One-third suffered from cardiovascular comorbidities, 72% reported at least one exacerbation in the past year, and 82% recorded at least moderate health impairment (CAT scores ≥ 10 units). The CAT score was positively correlated with the SGRQ score (r = 0.72, P < .001) and Medical Research Council (MRC) dyspnea score (r = 0.50, P < .001) and poorly correlated with the FEV1 (r = −0.23, P < .001) and number of exacerbations in the past year (r = 0.11, P = .04). The relationships between the CAT score and SGRQ score, MRC dyspnea score, or FEV1 did not differ between countries (P value for interaction term = 0.76, 0.75, and 0.06, respectively).

Conclusions:  The CAT correlated well with the SGRQ and MRC dyspnea score in all countries, and the relationship did not differ between countries despite varying patient characteristics. This suggests that a CAT score in one of these countries has the same clinical significance as the same score in another.

Chest. 2013;143(3):711-719. doi:10.1378/chest.12-1277

Background:  There is still a lack of data on the seasonality of exacerbations of COPD based on large randomized studies using COPD exacerbations as primary end points. The objective of this study was to assess the seasonal pattern of moderate and severe exacerbations and analyze the influence of associated baseline factors. We also determined the timing of second exacerbations and the potential impact of the 2009 influenza A(H1N1) pandemic on exacerbations.

Methods:  Analyses of exacerbation rates across treatment groups were adjusted for differing times on treatment by means of descriptive statistics based on the 1-year Prevention of Exacerbations with Tiotropium in COPD (POET-COPD) trial, in which exacerbations were the primary end point.

Results:  Of the 7,376 patients who were randomized, a total of 4,411 exacerbations were reported in 2,691 patients. Mean monthly exacerbation rates during winter were 2.16-fold higher than during summer, regardless of baseline characteristics (age, sex, COPD severity, smoking status, BMI, inhaled corticosteroid use, cardiovascular comorbidity, concomitant cardiovascular medication). Second exacerbations after a previous event in October to March occurred 1 month earlier than during the warmer half of the season. The portion of exacerbation-related hospitalizations remained constant throughout the year. Most exacerbations were treated with antibiotics and reached a peak in the colder season. All-cause mortality showed a seasonal pattern similar to exacerbations. The 2009 A(H1N1) pandemic was not associated with an increase in exacerbation rates or deaths.

Conclusions:  This analysis presented a marked impact of season on exacerbation outcomes, antibiotic treatment, timing of second exacerbations, and all-cause mortality.

Trial Registry:  ClinicalTrials.gov; No.: NCT00563381; URL: www.clinicaltrials.gov

Original Research: Sleep Disorders

Chest. 2013;143(3):720-728. doi:10.1378/chest.12-0338

Background:  Dyslipidemia is often comorbid with obstructive sleep apnea (OSA), but few population-based studies have investigated their relationship. Short sleep duration is associated with hypertension and diabetes; however, its association with dyslipidemia is not well known. We investigated relationships among OSA, sleep duration, and the lipid profile in a community-based study.

Methods:  We measured the respiratory disturbance index (RDI) and sleep duration by a type 3 portable device and actigraph in 275 men in a Japanese company. Fasting blood parameters were obtained from periodic inspection data.

Results:  According to Japanese criteria, 143 subjects had dyslipidemia. Percent sleep time of oxygen saturation as measured by pulse oximetry (SpO2) < 90% and prevalence of severe OSA were greater and sleep duration and mean SpO2 during sleep were lower in subjects with dyslipidemia than in those without. Univariate analysis showed that the RDI was positively correlated with serum triglyceride (TG) levels (ρ = 0.20, P < .01), and sleep duration was negatively correlated with serum total cholesterol (TC) levels (γ = −0.13, P = .03) and serum low-density lipoprotein cholesterol levels (γ = −0.12, P = .04). Stepwise multiple regression analysis revealed that TG was correlated with RDI (β = 0.14, P = .02), BMI (β = 0.20, P < .01), and alcohol intake (β = 0.20, P < .01), and that TC was correlated with sleep duration (β = −0.13, P = .03), age (β = 0.15, P = .02), and waist/hip ratio (β = 0.15, P = .02).

Conclusions:  Short sleep duration was associated with TC levels and RDI was positively associated with TG levels among working-aged men in an urban Japanese company. Correcting the status of OSA and/or short sleep duration might improve the lipid profile and cardiovascular consequences.

Chest. 2013;143(3):729-735. doi:10.1378/chest.12-1224

Background:  The objective of this study was to examine the natural history of childhood primary snoring (PS) and to identify predictive clinical symptoms and risk factors associated with PS progression to obstructive sleep apnea (OSA).

Methods:  Children aged 6 to 13 years old who received a diagnosis of PS in our previous community-based OSA prevalence study were invited to undergo repeat polysomnography (PSG) at 4-year follow-up. Subjects with an obstructive apnea hypopnea index (OAHI) ≥ 1 were classified as having OSA at follow-up.

Results:  Seventy children (60% boys) with a mean age of 14.7 ± 1.8 years were analyzed in this follow-up study. The mean duration of follow-up was 4.6 ± 0.6 years. At follow-up, 26 subjects (37.1%) progressed to OSA, of whom five (7.1%) had moderate to severe disease (OAHI ≥ 5). Twenty-two (31.4%) remained at PS, and 18 (25.7%) had complete resolution of their snoring with normal PSG. Persistent snoring had a positive predictive value of 47.7% and a negative predictive value of 86.4% for progression from PS to OSA. Multivariate logistic regression analysis showed that persistent overweight/obesity was a significant risk factor for the development of OSA at follow-up, with an OR of 7.95 (95% CI, 1.43-44.09).

Conclusions:  More than one-third of school-aged children with PS progressed to OSA over a 4-year period, although only 7.1% developed moderate to severe disease. Weight control may be an important component in the management of PS because obesity was found to be a significant risk factor for PS progression.

Original Research: Transplantation

Chest. 2013;143(3):736-743. doi:10.1378/chest.12-0830

Background:  The provision of effective palliative care is of great importance to patients awaiting lung transplantation. Although the prospect of lung transplantation provides hope to patients and their families, these patients are usually very symptomatic from their underlying disease.

Methods:  An e-mail questionnaire was sent to members of the American College of Chest Physicians’ Transplant NetWork and the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT). The survey included questions about barriers to providing palliative care, the availability of palliative care services, and recommended strategies to improve palliative care for lung transplant candidates.

Results:  The 158 respondents represented approximately 65% of transplant programs in the ISHLT registry. Respondents were in practice a mean of 11.3 (± 9) years, 70% were pulmonologists, 17% were surgeons, and 13% were other care providers. Barriers were classified into domains including patient factors, family factors, physician factors, and institutional/transplant program/lung allocation system factors. Significant patient/family barriers included unrealistic patient/family expectations about survival, unwillingness to plan end-of-life care, concerns about abandonment or inappropriate care after enrollment in a palliative care program, and family disagreements about care goals. For institutional/program/allocation system barriers, only the requirement for weight loss or gain to meet program-specific BMI requirements was identified. Significant physician barriers included competing time demands and the seemingly contradictory goals of transplant vs palliative care. Strategies recommended to improve palliative care included routine advance care planning for patients awaiting transplantation, access to palliative care specialists, training of transplant physicians in symptom management, and regular meetings among transplant physicians, nurses, patients, and families.

Conclusions:  Physicians providing care to lung transplant candidates reported considerable barriers to the delivery and acceptance of palliative care and identified specific strategies to improve palliative care for lung transplant candidates.

Chest. 2013;143(3):744-750. doi:10.1378/chest.12-0971

Background:  Quality of life (QOL) is an important but understudied outcome after lung transplantation. Previous cross-sectional, single-center studies suggest improved QOL, but few prior longitudinal multicenter data exist regarding the effect of transplantation on the patient’s QOL.

Methods:  We hypothesized that lung transplantation confers a 1-year QOL benefit in both physical and psychologic well-being; we further hypothesized that the magnitude of benefit would vary by sex, native disease, age, or type of transplant operation. To test these hypotheses, we conducted a secondary analysis using QOL data prospectively and serially measured with the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36) in a multicenter cytomegalovirus prevention clinical trial. Linear mixed-effects models were used to assess the impact of transplantation on the recipient’s QOL.

Results:  Over the first year after lung transplantation, the SF-36 Physical Component Score significantly increased an average of 10.9 points from baseline levels (P < .0001). A positive benefit was observed for all native diseases; however, the magnitude varied slightly by native disease (P = .04) but not by sex (P = .35), age (P = .06), or transplant type (P = .30). In contrast, the SF-36 Mental Component Score did not change from baseline (P = .36) and remained well below population norms.

Conclusions:  Our results demonstrate that lung transplantation confers clinically important QOL benefits in physical domains but not in psychologic well-being. A better understanding of the barriers to psychologic well-being after transplant is critical to enhancing the benefits of lung transplantation.

Original Research: Antithrombotic Therapy

Chest. 2013;143(3):751-757. doi:10.1378/chest.12-1119

Background:  Among patients receiving oral anticoagulation, a gap of > 56 days between international normalized ratio tests suggests loss to follow-up that could lead to poor anticoagulation control and serious adverse events.

Methods:  We studied long-term oral anticoagulation care for 56,490 patients aged 65 years and older at 100 sites of care in the Veterans Health Administration. We used the rate of gaps in monitoring per patient-year to predict percentage time in therapeutic range (TTR) at the 100 sites.

Results:  Many patients (45%) had at least one gap in monitoring during an average of 1.6 years of observation; 5% had two or more gaps per year. The median gap duration was 74 days (interquartile range, 62-107). The average TTR for patients with two or more gaps per year was 10 percentage points lower than for patients without gaps (P < .001). Patient-level predictors of gaps included nonwhite race, area poverty, greater distance from care, dementia, and major depression. Site-level gaps per patient-year varied from 0.19 to 1.78; each one-unit increase was associated with a 9.2 percentage point decrease in site-level TTR (P < .001).

Conclusions:  Site-level gap rates varied widely within an integrated care system. Sites with more gaps per patient-year had worse anticoagulation control. Strategies to address and reduce gaps in monitoring may improve anticoagulation control.

Original Research: Pulmonary Vascular Disease

Chest. 2013;143(3):758-766. doi:10.1378/chest.12-1653

Background:  Left-sided heart disease (LHD) is the most common cause of pulmonary hypertension (PH). In patients with LHD, elevated left atrial pressure causes a passive increase in pulmonary vascular pressure by hydrostatic transmission. In some patients, an active component caused by pulmonary arterial vasoconstriction and/or vascular remodeling superimposed on left-sided pressure elevation is observed. This “reactive” or “out-of-proportion” PH, defined as PH due to LHD with a transpulmonary gradient (TPG) > 12 mm Hg, confers a worse prognosis. However, TPG is sensitive to changes in cardiac output and left atrial pressure. Therefore, we tested the prognostic value of diastolic pulmonary vascular pressure gradient (DPG) (ie, the difference between invasive diastolic pulmonary artery pressure and mean pulmonary capillary wedge pressure) to better prognosticate death in “out-of-proportion” PH.

Methods:  A large database of consecutive cases was analyzed. One thousand ninety-four of 2,351 complete data sets were from patients with PH due to LHD. For proof of concept, available lung histologies were reviewed.

Results:  In patients with postcapillary PH and a TPG > 12 mm Hg, a worse median survival (78 months) was associated with a DPG ≥ 7 mm Hg compared with a DPG < 7 mm Hg (101 months, P = .010). Elevated DPG was associated with more advanced pulmonary vascular remodeling.

Conclusions:  DPG identifies patients with “out-of-proportion” PH who have significant pulmonary vascular disease and increased mortality. We propose a diagnostic algorithm, using pulmonary capillary wedge pressure, TPG, and DPG in sequence to diagnose pulmonary vascular disease superimposed on left-sided pressure elevation.

Original Research: Chest Infections

Chest. 2013;143(3):767-775. doi:10.1378/chest.12-1235

Background:  Thrombocytosis, often considered a marker of normal inflammatory reaction of infections, has been recently associated with increased mortality in hospitalized patients with community-acquired pneumonia (CAP). We assessed the characteristics and outcomes of patients with CAP and thrombocytosis (platelet count ≥ 4 × 105/mm3) compared with thrombocytopenia (platelet count < 105/mm3) and normal platelet count.

Methods:  We prospectively analyzed 2,423 consecutive, hospitalized patients with CAP. We excluded patients with immunosuppression, neoplasm, active TB, or hematologic disease.

Results:  Fifty-three patients (2%) presented with thrombocytopenia, 204 (8%) with thrombocytosis, and 2,166 (90%) had normal platelet counts. Patients with thrombocytosis were younger (P < .001); those with thrombocytopenia more frequently had chronic heart and liver disease (P < .001 for both). Patients with thrombocytosis presented more frequently with respiratory complications, such as complicated pleural effusion and empyema (P < .001), whereas those with thrombocytopenia presented more often with severe sepsis (P < .001), septic shock (P = .009), need for invasive mechanical ventilation (P < .001), and ICU admission (P = .011). Patients with thrombocytosis and patients with thrombocytopenia had longer hospital stays (P = .004), and higher 30-day mortality (P = .001) and readmission rates (P = .011) than those with normal platelet counts. Multivariate analysis confirmed a significant association between thrombocytosis and 30-day mortality (OR, 2.720; 95% CI, 1.589-4.657; P < .001). Adding thrombocytosis to the confusion, respiratory rate, and BP plus age ≥65 years score slightly improved the accuracy to predict mortality (area under the receiver operating characteristic curve increased from 0.634 to 0.654, P = .049).

Conclusions:  Thrombocytosis in patients with CAP is associated with poor outcome, complicated pleural effusion, and empyema. The presence of thrombocytosis in CAP should encourage ruling out respiratory complication and could be considered for severity evaluation.

Chest. 2013;143(3):776-781. doi:10.1378/chest.12-1312

Background:  In a patient with positive serum serology for coccidioidomycosis, the differential diagnosis of concurrent pleural effusions can be challenging. We, therefore, sought to clarify the performance characteristics of biochemical, serologic, and nucleic-acid-based testing in an attempt to avoid invasive procedures. The utility of adenosine deaminase (ADA), coccidioidal serology, and polymerase chain reaction (PCR) in the evaluation of pleuropulmonary coccidioidomycosis has not been previously reported.

Methods:  Forty consecutive patients evaluated for pleuropulmonary coccidioidomycosis were included. Demographic data, pleural fluid values, culture results, and clinical diagnoses were obtained from patient chart review. ADA testing was performed by ARUP Laboratories, coccidioidal serologic testing was performed by the University of California-Davis coccidioidomycosis serology laboratory, and PCR testing was performed by the Translational Genomics Research Institute using a previously published methodology.

Results:  Fifteen patients were diagnosed with pleuropulmonary coccidioidomycosis by European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria. Pleural fluid ADA concentrations were <40 IU/L in all patients (range, < 1.0-28.6 IU/L; median, 4.7). The sensitivity and specificity of coccidioidal serologic testing was 100% in this study. The specificity of PCR testing was high (100%), although the overall sensitivity remained low, and was comparable to the experience of others in the clinical use of PCR for coccidioidal diagnostics.

Conclusion:  Contrary to prior speculation, ADA levels in pleuropulmonary coccidioidomycosis were not elevated in this study. The sensitivity and specificity of coccidioidal serologic testing in nonserum samples remained high, but the clinical usefulness of PCR testing in pleural fluid was disappointing and was comparable to pleural fluid culture.

Original Research: Genetic and Developmental Disorders

Chest. 2013;143(3):782-790. doi:10.1378/chest.12-0954

Background:  Rhinovirus (RV)-induced pulmonary exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium in vitro. Here, we assess in vivo the association of RV prevalence and load with antiviral defense mechanisms, airway inflammation, and lung function parameters in children with CF compared with a control group and children with other chronic respiratory diseases.

Methods:  RV presence and load were measured by real-time reverse transcription-polymerase chain reaction in BAL samples and were related to antiviral and inflammatory mediators measured in BAL and to clinical parameters.

Results:  BAL samples were obtained from children with CF (n = 195), non-CF bronchiectasis (n = 40), or asthma (n = 29) and from a control group (n = 35) at a median (interquartile range [IQR]) age of 8.2 (4.0-11.7) years. RV was detected in 73 samples (24.4%). RV prevalence was similar among groups. RV load (median [IQR] × 103 copies/mL) was higher in children with CF (143.0 [13.1-1530.0]), especially during pulmonary exacerbations, compared with children with asthma (3.0 [1.3-25.8], P = .006) and the control group (0.5 [0.3-0.5], P < .001), but similar to patients with non-CF bronchiectasis (122.1 [2.7-4423.5], P = not significant). In children with CF, RV load was negatively associated with interferon (IFN)-β and IFN-λ, IL-1ra levels, and FEV1, and positively with levels of the cytokines CXCL8 and CXCL10.

Conclusions:  RV load in CF BAL is high, especially during exacerbated lung disease. Impaired production of antiviral mediators may lead to the high RV burden in the lower airways of children with CF. Whether high RV load is a cause or a consequence of inflammation needs further investigation in longitudinal studies.

Original Research: Occupational and Environmental Lung Diseases

Chest. 2013;143(3):791-797. doi:10.1378/chest.12-0675

Background:  Few longitudinal studies characterize firefighters’ pulmonary function. We sought to determine whether firefighters have excessive FEV1 decline rates compared with control subjects.

Methods:  We examined serial measurements of FEV1 from about 6 months prehire to about 5 years posthire in newly hired male, never smoking, non-Hispanic black and white firefighters, hired between 2003 and 2006, without prior respiratory disease or World Trade Center exposure. Similarly defined Emergency Medical Service (EMS) workers served as control subjects.

Results:  Through June 30, 2011, 940 firefighters (82%) and 97 EMS workers (72%) who met study criteria had four or more acceptable posthire spirometries. Prehire FEV1% averaged higher for firefighters than EMS workers (99% vs 95%), reflecting more stringent job entry criteria. FEV1 (adjusted for baseline age and height) declined by an average of 45 mL/y both for firefighters and EMS workers, with Fire − EMS decline rate differences averaging 0.2 mL/y (CI, −9.2 to 9.6). Four percent of each group had FEV1 less than the lower limit of normal before hire, increasing to 7% for firefighters and 17.5% for EMS workers, but similar percentages of both groups had adjusted FEV1 decline rates ≥ 10%. Mixed effects modeling showed a significant influence of weight gain but not baseline weight: FEV1 declined by about 8 mL/kg gained for both groups. Adjusting for weight change, FEV1 decline averaged 38 mL/y for firefighters and 34 mL/y for EMS workers.

Conclusions:  During the first 5 years of duty, firefighters do not show greater longitudinal FEV1 decline than EMS control subjects, and fewer of them develop abnormal lung function. Weight gain is associated with a small loss of lung function, of questionable clinical relevance in this fit and active population.

Translating Basic Research into Clinical Practice

Chest. 2013;143(3):798-807. doi:10.1378/chest.12-0938

It is now well established that cardiovascular disease contributes significantly to both morbidity and mortality in COPD. Shared risk factors for cardiovascular disease and COPD, such as smoking, low socioeconomic class, and a sedentary lifestyle contribute to the natural history of each of these conditions. However, it is now apparent that alternative, novel mechanisms are involved in the pathogenesis of cardiovascular disease, and these may play an important role in driving the increased cardiovascular risk associated with COPD. In this article, we discuss the potential mechanisms that link COPD to an increased risk of cardiovascular disease.

Ahead of the Curve

Chest. 2013;143(3):808-813. doi:10.1378/chest.12-2287

The United States Critical Illness and Injury Trials (USCIIT) Group is an inclusive, grassroots “network of networks” with the dual missions of fostering investigator-initiated hypothesis testing and developing recommendations for strategic plans at a national level. The USCIIT Group’s transformational approach enlists multidisciplinary investigative teams across institutions, critical illness and injury professional organizations, federal agencies that fund clinical and translational research, and industry partners. The USCIIT Group is endorsed by all major critical illness and injury professional organizations spanning the specialties of anesthesiology, emergency medicine, internal medicine, neurology, nursing, pediatrics, pharmacy and nutrition, surgery and trauma, and respiratory and physical therapy. Recent successes provide the opportunity to significantly increase the dialogue necessary to advance clinical and translational research on behalf of our community. More than 200 investigators are now involved across > 30 academic and community hospitals. Collectively, USCIIT Group investigators have enrolled > 10,000 patients from academic and community hospitals in studies during the last 3 years. To keep our readership “ahead of the curve,” this article provides a vision for critical illness and injury research based on (1) programmatic organization of large-scale, multicentered collaborative studies and (2) annual strategic planning at a national scale across disciplines and stakeholders.

Recent Advances in Chest Medicine

Chest. 2013;143(3):814-824. doi:10.1378/chest.12-0741

Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD.

Special Features

Chest. 2013;143(3):840-846. doi:10.1378/chest.12-1487

In this second part of a two-part series, we describe an algorithmic approach to the diagnosis of the solitary pulmonary nodule (SPN). An essential aspect of the evaluation of SPN is determining the pretest probability of malignancy, taking into account the significant medical history and social habits of the individual patient, as well as morphologic characteristics of the nodule. Because pretest probability plays an important role in determining the next step in the evaluation, we describe various methods the physician may use to make this determination. Subsequently, we outline a simple yet comprehensive algorithm for diagnosing a SPN, with distinct pathways for the solid and subsolid SPN.

Special Features: Chest Imaging

Chest. 2013;143(3):825-839. doi:10.1378/chest.12-0960

The solitary pulmonary nodule (SPN) is frequently encountered on chest imaging and poses an important diagnostic challenge to clinicians. The differential diagnosis is broad, ranging from benign granulomata and infectious processes to malignancy. Important concepts in the evaluation of SPNs include the definition, morphologic characteristics via appropriate imaging modalities, and the calculation of pretest probability of malignancy. Morphologic differentiation of SPN into solid or subsolid types is important in the choice of follow-up and further management. In this first part of a two-part series, we describe the morphologic characteristics and various imaging modalities available to further characterize SPN. In Part 2, we will describe the determination of pretest probability of malignancy and an algorithmic approach to the diagnosis of SPN.

Topics in Practice Management

Chest. 2013;143(3):847-850. doi:10.1378/chest.12-0722

Because there is increasing demand for critical care providers in the United States, many medical ICUs for adults have begun to integrate nurse practitioners and physician assistants into their medical teams. Studies suggest that such advanced practice providers (APPs), when appropriately trained in acute care, can be highly effective in helping to deliver high-quality medical critical care and can be important elements of teams with multiple providers, including those with medical house staff. One aspect of building an integrated team is a practice model that features appropriate coding and billing of services by all providers. Therefore, it is important to understand an APP’s scope of practice, when they are qualified for reimbursement, and how they may appropriately coordinate coding and billing with other team providers. In particular, understanding when and how to appropriately code for critical care services (Current Procedural Terminology [CPT] code 99291, critical care, evaluation and management of the critically ill or critically injured patient, first 30-74 min; CPT code 99292, critical care, each additional 30 min) and procedures is vital for creating a sustainable program. Because APPs will likely play a growing role in medical critical care units in the future, more studies are needed to compare different practice models and to determine the best way to deploy this talent in specific ICU settings.

Chest. 2013;143(3):851-855. doi:10.1378/chest.09-0359

This article explores the rules and regulations from Current Procedural Terminology (CPT) code set and US Medicare and Medicaid Services (Medicare) regarding multiple physicians reporting critical care services during the global period. The article takes into account the critical care definitions, regulations, documentation requirements, and services each provider can report to Medicare. A clinical scenario based on literature supporting the types of complications and care that might typically be included in the post-operative period for a patient who is surgically treated for a type A aortic dissection was analyzed. It was determined that multiple physicians may provide critical care services to a single patient during the global period. The physician who performed the primary procedure cannot report critical care separately unless documentation supporting use of modifier 25 (significant, separately identifiable services) or 24 (unrelated services) supports that critical care is unrelated to the global period. Other physicians may report critical care services separately if specific criteria are met. To report critical care services to Medicare, the patient’s condition must meet the Medicare definition of critical care and the physicians should generally represent different specialties providing different aspects of care to the critically ill or injured patient as defined by Medicare. There should be no overlap in time of services provided by each physician. Each physician’s documentation should clearly support medical necessity with the diagnosis demonstrating the critical nature of the patients’ illness, the total time spent providing critical care, the critical care service provided, and other contributing factors.

Selected Reports

Chest. 2013;143(3):856-858. doi:10.1378/chest.12-0859

Airway inflammation is considered a central component of asthma and, therefore, international guidelines recommend antiinflammatory medications. We describe the clinical history of a 34-year-old woman with airway hyperresponsiveness and asthma who had a reduced ability to mount an inflammatory response due to two unrelated and rare genetic conditions: Fanconi anemia and incontinentia pigmenti. Absence of eosinophils in blood and sputum led to a successful reduction in the dose of corticosteroids without loss of asthma control demonstrating the clinical utility of monitoring treatment using biomarkers and the importance of recognizing the components of airway diseases that contribute to symptoms.

Chest. 2013;143(3):858-861. doi:10.1378/chest.12-1467

Ipilimumab is one of the newly developed human monoclonal antibodies used in the treatment of metastatic melanoma. Its primary mechanism of action is a specific blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a T-cell receptor responsible for inhibition of lymphocyte activation. By blocking CTLA-4, ipilimumab enhances immune responses against tumor cells, but also exposes normal tissues to an increased risk of autoimmune phenomena as a potential side effect. In this report, we describe the case of a 58-year-old woman with metastatic melanoma who was treated with ipilimumab in the weeks prior to the onset of severe nonresolving dyspnea and cough. Extensive workup revealed organizing pneumonia as the cause of her hypoxemic respiratory failure and treatment with steroids led to a resolution of her pulmonary disease. To our knowledge, this is the first report of pulmonary toxicity caused by ipilimumab, which manifested on pathology as organizing pneumonia.

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

Chest. 2013;143(3):862-865. doi:10.1378/chest.12-1130

A 67-year-old woman presented to the ED of a tertiary hospital with sudden onset of difficulty expressing words, associated with a frontal headache. She reported general malaise, muscle weakness, and a persistent abnormal sensation in her legs in the preceding couple of weeks. These symptoms presented on a background of refractory asthma, which had been diagnosed in early childhood. She had been on maintenance therapy of 10 mg prednisolone daily (which she titrated based on her exacerbations), in addition to fluticasone/salmeterol 250 μg/50 μg metered-dose inhaler, two puffs bid. There was no history of rhinosinusitis or nasal polyposis. Two years prior, she had an episode of amaurosis fugax, which was treated as temporal arteritis (no histology was undertaken), with oral steroids.

Chest. 2013;143(3):866-869. doi:10.1378/chest.12-1651


Chest. 2013;143(3):870. doi:10.1378/chest.12-0943

        -for David
You ask me to tell you a story from GodsMan,
but I can’t take my eyes off your thick, wavy hair.
It drifts & twirls, lands like fresh snow onto your dark
brown sofa cushions. Onto your red wool sweater.
Remember how you & I danced at weddings &
bar mitzvahs? The first woodcut shows an artist
struggling in a storm at sea. Remember our balding
uncles, their tight shoes & shiny striped three-piece
suits from Zachary All? The artist gives his last coin
to a one-legged beggar, but I keep looking at your stark
white hair. Remember how our balding uncles danced
with platinum blond aunts in dark flowery polyester:
to every single platter from Elvis to the Stones,
the Beatles to the Bee-Gees? I watch your hair float
& swirl, watch it drift like ash onto your dark brown
sofa cushions. Onto your red wool sweater. The artist
strikes a bargain with a masked stranger, an auctioneer.
Further on, it seems the artist finds fame & gold-digging
women. Remember how you & I danced at weddings?
How our aunts went crazy over your wild mustache
& voluminous dark brown Afro sphere. Who knew
about illness then, about the toll of treatment—
this astonishing dance of your hair? Near the end
of the graphic novel, the so-called auctioneer removes
his mask for a portrait; I realize he’s the devil but
don’t want to tell you. So here’s real & poetic justice:
The artist pushes the auctioneer-devil into an abyss
between the shadowed, pointy cliffs of Lynd Ward’s
final woodcut. Then you & I dance like we used to—
rock ‘n’ roll, cha-cha-cha, & maybe some Tango Nuevo.

Chest. 2013;143(3):871. doi:10.1378/chest.12-1352

It is a minor miracle
that I have learned to see—
in a collection of numbers,
  and letters—
a patient that moves
 and breathes
  and has his or her being
among us.
Through these complex numbers
I prescribe
and I dictate action.
Through these trends
I decide which diseases this person has,
and I demarcate their progress or descent.
The once impersonal
has evolved legs and hair and heartbeats.
The postulate has become
It is real.


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Chest. 2013;143(3):873-874. doi:10.1378/chest.12-2544
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Chest. 2013;143(3):874-875. doi:10.1378/chest.12-2717
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Chest. 2013;143(3):876. doi:10.1378/chest.12-2783
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Chest. 2013;143(3):878-879. doi:10.1378/chest.12-2780


Chest. 2013;143(3):880. doi:10.1378/chest.13-0043

The article entitled, “The Genetics of Innate Immunity” published in the supplement to the March 2002 issue of CHEST (2002;121[3][suppl]:62S-68S) repurposed portions of text and figures from previous publications without attribution. Figures 1, 2, and 3 should have referenced two earlier publications by Schwartz shown below. Figures 3 and 4 should have also referenced the same articles as well as Arbour et al,21 cited in the article. Figure 5 should have referenced Lorenz et al, 24, cited in the article.

Chest. 2013;143(3):880. doi:10.1378/chest.13-0227

The article: “High Risk of Malignant Mesothelioma and Pleural Plaques in Subjects Born Close to Ophiolites” published in the January 2013 issue of CHEST (2013;143[1]:164-171) contained errors in the text and Figure 2.

Ultrasound Corner

Chest. 2013;143(3):e1-e4. doi:10.1378/chest.13-0079

A 29-year-old man with type 1 diabetes mellitus presented to our ED complaining of malaise, nausea, abdominal pain, and persistently elevated glucometer readings. This was his third visit to the ED within a week for similar complaints despite reporting full compliance with his outpatient medication. He had not had an episode of diabetic ketoacidosis (DKA) in >10 years. Review of systems was negative for productive cough, fevers, dyspnea, dysuria, or headache.

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