The patient safety field rightly focuses on identifying and addressing problems with systems of care. From the patient’s perspective, however, underlying systems issues might be less critical than another unspoken question: can I trust the people who are taking care of me? Last year, a popular podcast¹ detailed the shocking story of Dallas neurosurgeon Christopher Duntsch, who was responsible for the death of two patients and severe injuries in dozens of other patients over two years. Although fellow surgeons had raised concerns about his surgical skill and professionalism almost immediately after he entered practice, multiple hospitals allowed him to continue operating until the Texas Medical Board revoked his license. Duntsch was ultimately prosecuted, convicted, and sentenced to life imprisonment, in what is believed to be the first case of a physician receiving criminal punishment for malpractice.

Only a small proportion of clinicians repeatedly harm patients as Duntsch did, and the harm they cause accounts for only a small share of the preventable adverse events that patients experience. Understandably, cases of individual clinicians who directly harm patients tend to capture the public’s attention, as they vividly illustrate how vulnerable patients are when they entrust their health to a clinician. As a result, these cases have a significant effect on the patient’s trust in healthcare institutions.

In this issue of the Journal of Hospital Medicine, Fan and colleagues² describe the problem of controlled-substance diversion in hospitals and review the contributors and potential solutions to this issue. Their thorough and insightful review highlights a growing problem that is probably invisible to most hospitalists. Diversion of controlled substances can happen at any stage of the medication use process, from procurement to disposal and drugs can be diverted by healthcare workers, nonclinical staff, patients, and caregivers. Perhaps most concerning to hospitalists, diversion at the prescribing and administration stages can directly affect patient care. Strategies used to individualize pain control, such as using flexible dose ranges for opioids, can be manipulated to facilitate diversion at the expense of the patient’s suffering.

The review presents a comprehensive summary of safeguards against diversion at each stage of the medication use process and appropriately emphasizes system-level solutions. These include analyzing electronic health record data to identify unusual patterns of controlled substance use and developing dedicated diversion investigation teams. These measures, if implemented, are likely to be effective at reducing the risk of diversion. However, given the complexity of medication use, eliminating this risk is unrealistic. Opioids are used in more than half of all nonsurgical hospital admissions;³ although this proportion may be decreasing due to efforts to curb opioid overprescribing, many hospitalized patients still require opioids or other controlled substances for symptom control. The opportunity to divert controlled substances will always be present.

Eliminating the problem of drug diversion in hospitals will require addressing the individuals who divert controlled substances and strengthening the medication safety system. The term “impaired clinician” is used to describe clinicians who cannot provide competent care due to illness, mental health, or a substance-use disorder. In an influential 2006 commentary,Leape and Fromson made the case that physician performance impairment is often a symptom of underlying disorders, ranging from short-term, reversible issues (eg, an episode of burnout or depression) to long-term problems that can lead to permanent consequences (ie, physical illness or substance-use disorders).⁴ In this framework, a clinician who diverts controlled substances represents a particularly extreme example of the broader problem of physicians who are unable to perform their professional responsibilities.

Leape and Fromson called for proactively identifying clinicians at risk of performance failure and intervening to remediate or discipline them before patients are harmed. To accomplish this, they envisioned a system with three key characteristics:

• Fairness: All physicians should be subject to regular assessment, and the same standards should be applied to all physicians in the same discipline.
• Objectivity: Performance assessment should be based on objective data.
• Responsiveness: Physicians with performance issues should be identified and given feedback promptly, and provided with opportunities for remediation and assistance when underlying conditions are affecting their performance.

Some progress has been made toward this goal, especially in identifying underlying factors that predispose to performance problems.⁵ There is also greater awareness of underlying factors that may predispose to more subtle performance deterioration. The recent focus on burnout and well-being among physicians is long overdue, and the recent Charter on Physician Well-Being⁶ articulates important principles for healthcare organizations to address this epidemic. Substance-use disorder is a recognized risk factor for performance impairment. Physicians have a higher rate of prescription drug abuse and a similar overall rate of substance-use disorders compared to the general population. While there is limited research around the risk factors for drug diversion by physicians, qualitative studies⁷ of physicians undergoing treatment for substance-use disorders found that most began diverting drugs to manage physical pain, emotional or psychiatric distress, or acutely stressful situations. It is plausible that many burned out or depressed clinicians are turning to illicit substances to self-medicate increasing the risk of diversion.

However, 13 years after Leape and Fromson’s commentary was published, it is difficult to conclude that their vision has been achieved. Objectivity in physician performance assessment is still lacking, and most practicing physicians do not receive any form of regular assessment. This places the onus on members of the healthcare team to identify poorly performing colleagues before patients are harmed. Although nearly all states mandate that physicians report impaired colleagues to either the state medical board or a physician rehabilitation program, healthcare professionals are often reluctant⁸ to report colleagues with performance issues, and clinicians are also unlikely⁹ to self-report mental health or substance-use issues due to stigma and fear that their ability to practice may be at risk.

Even when colleagues do raise alarms—as was the case with Dr. Duntsch, who required treatment for a substance-use disorder during residency—existing regulatory mechanisms either lack evidence of effectiveness or are not applied consistently. State licensing boards play a crucial role in identifying problems with clinicians and have the power to authorize remediation or disciplinary measures. However, individual states vary widely¹⁰ in their likelihood of disciplining physicians for similar offenses. The board certification process is intended to ensure that only fully competent physicians can practice medicine independently. However, there is little evidence that the certification process ensures that clinicians maintain their skills, and significant controversy has accompanied efforts to revise the maintenance of certification process. The medical malpractice system aims to improve patient safety by ensuring compensation when patients are injured and by deterring substandard clinicians from practicing. Unfortunately, the system often fails to meet this goal, as malpractice claims are rarely filed even when patients are harmed due to negligent care.¹¹

Given the widespread availability of controlled substances in hospitals, comprehensive solutions must incorporate the systems-based solutions proffered by Fan and colleagues and address individual clinicians (and staff) who divert drugs. These clinicians are likely to share some of the same risk factors as clinicians who cannot perform their professional responsibilities for other reasons. Major system changes are necessary to minimize the risk of short-term conditions that could affect physician performance (such as burnout) and develop robust methods to identify clinicians with longer-term issues affecting their performance (such as substance-use disorders).

Although individual clinician performance problems likely account for a small proportion of adverse events, these issues strike at the heart of the physician-patient relationship and have a profound impact on patients’ trust in the healthcare system. Healthcare organizations must maintain transparent and effective processes for addressing performance failures such as drug diversion by clinicians, even if these processes are rarely deployed.

Disclosures

The author does not have any conflict of interest to report.

The patient safety field rightly focuses on identifying and addressing problems with systems of care. From the patient’s perspective, however, underlying systems issues might be less critical than another unspoken question: can I trust the people who are taking care of me? Last year, a popular podcast¹ detailed the shocking story of Dallas neurosurgeon Christopher Duntsch, who was responsible for the death of two patients and severe injuries in dozens of other patients over two years. Although fellow surgeons had raised concerns about his surgical skill and professionalism almost immediately after he entered practice, multiple hospitals allowed him to continue operating until the Texas Medical Board revoked his license. Duntsch was ultimately prosecuted, convicted, and sentenced to life imprisonment, in what is believed to be the first case of a physician receiving criminal punishment for malpractice.

Only a small proportion of clinicians repeatedly harm patients as Duntsch did, and the harm they cause accounts for only a small share of the preventable adverse events that patients experience. Understandably, cases of individual clinicians who directly harm patients tend to capture the public’s attention, as they vividly illustrate how vulnerable patients are when they entrust their health to a clinician. As a result, these cases have a significant effect on the patient’s trust in healthcare institutions.

In this issue of the Journal of Hospital Medicine, Fan and colleagues² describe the problem of controlled-substance diversion in hospitals and review the contributors and potential solutions to this issue. Their thorough and insightful review highlights a growing problem that is probably invisible to most hospitalists. Diversion of controlled substances can happen at any stage of the medication use process, from procurement to disposal and drugs can be diverted by healthcare workers, nonclinical staff, patients, and caregivers. Perhaps most concerning to hospitalists, diversion at the prescribing and administration stages can directly affect patient care. Strategies used to individualize pain control, such as using flexible dose ranges for opioids, can be manipulated to facilitate diversion at the expense of the patient’s suffering.

The review presents a comprehensive summary of safeguards against diversion at each stage of the medication use process and appropriately emphasizes system-level solutions. These include analyzing electronic health record data to identify unusual patterns of controlled substance use and developing dedicated diversion investigation teams. These measures, if implemented, are likely to be effective at reducing the risk of diversion. However, given the complexity of medication use, eliminating this risk is unrealistic. Opioids are used in more than half of all nonsurgical hospital admissions;³ although this proportion may be decreasing due to efforts to curb opioid overprescribing, many hospitalized patients still require opioids or other controlled substances for symptom control. The opportunity to divert controlled substances will always be present.

Eliminating the problem of drug diversion in hospitals will require addressing the individuals who divert controlled substances and strengthening the medication safety system. The term “impaired clinician” is used to describe clinicians who cannot provide competent care due to illness, mental health, or a substance-use disorder. In an influential 2006 commentary,Leape and Fromson made the case that physician performance impairment is often a symptom of underlying disorders, ranging from short-term, reversible issues (eg, an episode of burnout or depression) to long-term problems that can lead to permanent consequences (ie, physical illness or substance-use disorders).⁴ In this framework, a clinician who diverts controlled substances represents a particularly extreme example of the broader problem of physicians who are unable to perform their professional responsibilities.

Leape and Fromson called for proactively identifying clinicians at risk of performance failure and intervening to remediate or discipline them before patients are harmed. To accomplish this, they envisioned a system with three key characteristics:

• Fairness: All physicians should be subject to regular assessment, and the same standards should be applied to all physicians in the same discipline.
• Objectivity: Performance assessment should be based on objective data.
• Responsiveness: Physicians with performance issues should be identified and given feedback promptly, and provided with opportunities for remediation and assistance when underlying conditions are affecting their performance.

Some progress has been made toward this goal, especially in identifying underlying factors that predispose to performance problems.⁵ There is also greater awareness of underlying factors that may predispose to more subtle performance deterioration. The recent focus on burnout and well-being among physicians is long overdue, and the recent Charter on Physician Well-Being⁶ articulates important principles for healthcare organizations to address this epidemic. Substance-use disorder is a recognized risk factor for performance impairment. Physicians have a higher rate of prescription drug abuse and a similar overall rate of substance-use disorders compared to the general population. While there is limited research around the risk factors for drug diversion by physicians, qualitative studies⁷ of physicians undergoing treatment for substance-use disorders found that most began diverting drugs to manage physical pain, emotional or psychiatric distress, or acutely stressful situations. It is plausible that many burned out or depressed clinicians are turning to illicit substances to self-medicate increasing the risk of diversion.

However, 13 years after Leape and Fromson’s commentary was published, it is difficult to conclude that their vision has been achieved. Objectivity in physician performance assessment is still lacking, and most practicing physicians do not receive any form of regular assessment. This places the onus on members of the healthcare team to identify poorly performing colleagues before patients are harmed. Although nearly all states mandate that physicians report impaired colleagues to either the state medical board or a physician rehabilitation program, healthcare professionals are often reluctant⁸ to report colleagues with performance issues, and clinicians are also unlikely⁹ to self-report mental health or substance-use issues due to stigma and fear that their ability to practice may be at risk.

Even when colleagues do raise alarms—as was the case with Dr. Duntsch, who required treatment for a substance-use disorder during residency—existing regulatory mechanisms either lack evidence of effectiveness or are not applied consistently. State licensing boards play a crucial role in identifying problems with clinicians and have the power to authorize remediation or disciplinary measures. However, individual states vary widely¹⁰ in their likelihood of disciplining physicians for similar offenses. The board certification process is intended to ensure that only fully competent physicians can practice medicine independently. However, there is little evidence that the certification process ensures that clinicians maintain their skills, and significant controversy has accompanied efforts to revise the maintenance of certification process. The medical malpractice system aims to improve patient safety by ensuring compensation when patients are injured and by deterring substandard clinicians from practicing. Unfortunately, the system often fails to meet this goal, as malpractice claims are rarely filed even when patients are harmed due to negligent care.¹¹

Given the widespread availability of controlled substances in hospitals, comprehensive solutions must incorporate the systems-based solutions proffered by Fan and colleagues and address individual clinicians (and staff) who divert drugs. These clinicians are likely to share some of the same risk factors as clinicians who cannot perform their professional responsibilities for other reasons. Major system changes are necessary to minimize the risk of short-term conditions that could affect physician performance (such as burnout) and develop robust methods to identify clinicians with longer-term issues affecting their performance (such as substance-use disorders).

Although individual clinician performance problems likely account for a small proportion of adverse events, these issues strike at the heart of the physician-patient relationship and have a profound impact on patients’ trust in the healthcare system. Healthcare organizations must maintain transparent and effective processes for addressing performance failures such as drug diversion by clinicians, even if these processes are rarely deployed.

Disclosures

The author does not have any conflict of interest to report.

The patient safety field rightly focuses on identifying and addressing problems with systems of care. From the patient’s perspective, however, underlying systems issues might be less critical than another unspoken question: can I trust the people who are taking care of me? Last year, a popular podcast¹ detailed the shocking story of Dallas neurosurgeon Christopher Duntsch, who was responsible for the death of two patients and severe injuries in dozens of other patients over two years. Although fellow surgeons had raised concerns about his surgical skill and professionalism almost immediately after he entered practice, multiple hospitals allowed him to continue operating until the Texas Medical Board revoked his license. Duntsch was ultimately prosecuted, convicted, and sentenced to life imprisonment, in what is believed to be the first case of a physician receiving criminal punishment for malpractice.

Only a small proportion of clinicians repeatedly harm patients as Duntsch did, and the harm they cause accounts for only a small share of the preventable adverse events that patients experience. Understandably, cases of individual clinicians who directly harm patients tend to capture the public’s attention, as they vividly illustrate how vulnerable patients are when they entrust their health to a clinician. As a result, these cases have a significant effect on the patient’s trust in healthcare institutions.

In this issue of the Journal of Hospital Medicine, Fan and colleagues² describe the problem of controlled-substance diversion in hospitals and review the contributors and potential solutions to this issue. Their thorough and insightful review highlights a growing problem that is probably invisible to most hospitalists. Diversion of controlled substances can happen at any stage of the medication use process, from procurement to disposal and drugs can be diverted by healthcare workers, nonclinical staff, patients, and caregivers. Perhaps most concerning to hospitalists, diversion at the prescribing and administration stages can directly affect patient care. Strategies used to individualize pain control, such as using flexible dose ranges for opioids, can be manipulated to facilitate diversion at the expense of the patient’s suffering.

The review presents a comprehensive summary of safeguards against diversion at each stage of the medication use process and appropriately emphasizes system-level solutions. These include analyzing electronic health record data to identify unusual patterns of controlled substance use and developing dedicated diversion investigation teams. These measures, if implemented, are likely to be effective at reducing the risk of diversion. However, given the complexity of medication use, eliminating this risk is unrealistic. Opioids are used in more than half of all nonsurgical hospital admissions;³ although this proportion may be decreasing due to efforts to curb opioid overprescribing, many hospitalized patients still require opioids or other controlled substances for symptom control. The opportunity to divert controlled substances will always be present.

Eliminating the problem of drug diversion in hospitals will require addressing the individuals who divert controlled substances and strengthening the medication safety system. The term “impaired clinician” is used to describe clinicians who cannot provide competent care due to illness, mental health, or a substance-use disorder. In an influential 2006 commentary,Leape and Fromson made the case that physician performance impairment is often a symptom of underlying disorders, ranging from short-term, reversible issues (eg, an episode of burnout or depression) to long-term problems that can lead to permanent consequences (ie, physical illness or substance-use disorders).⁴ In this framework, a clinician who diverts controlled substances represents a particularly extreme example of the broader problem of physicians who are unable to perform their professional responsibilities.

Leape and Fromson called for proactively identifying clinicians at risk of performance failure and intervening to remediate or discipline them before patients are harmed. To accomplish this, they envisioned a system with three key characteristics:

• Fairness: All physicians should be subject to regular assessment, and the same standards should be applied to all physicians in the same discipline.
• Objectivity: Performance assessment should be based on objective data.
• Responsiveness: Physicians with performance issues should be identified and given feedback promptly, and provided with opportunities for remediation and assistance when underlying conditions are affecting their performance.

Some progress has been made toward this goal, especially in identifying underlying factors that predispose to performance problems.⁵ There is also greater awareness of underlying factors that may predispose to more subtle performance deterioration. The recent focus on burnout and well-being among physicians is long overdue, and the recent Charter on Physician Well-Being⁶ articulates important principles for healthcare organizations to address this epidemic. Substance-use disorder is a recognized risk factor for performance impairment. Physicians have a higher rate of prescription drug abuse and a similar overall rate of substance-use disorders compared to the general population. While there is limited research around the risk factors for drug diversion by physicians, qualitative studies⁷ of physicians undergoing treatment for substance-use disorders found that most began diverting drugs to manage physical pain, emotional or psychiatric distress, or acutely stressful situations. It is plausible that many burned out or depressed clinicians are turning to illicit substances to self-medicate increasing the risk of diversion.

However, 13 years after Leape and Fromson’s commentary was published, it is difficult to conclude that their vision has been achieved. Objectivity in physician performance assessment is still lacking, and most practicing physicians do not receive any form of regular assessment. This places the onus on members of the healthcare team to identify poorly performing colleagues before patients are harmed. Although nearly all states mandate that physicians report impaired colleagues to either the state medical board or a physician rehabilitation program, healthcare professionals are often reluctant⁸ to report colleagues with performance issues, and clinicians are also unlikely⁹ to self-report mental health or substance-use issues due to stigma and fear that their ability to practice may be at risk.

Even when colleagues do raise alarms—as was the case with Dr. Duntsch, who required treatment for a substance-use disorder during residency—existing regulatory mechanisms either lack evidence of effectiveness or are not applied consistently. State licensing boards play a crucial role in identifying problems with clinicians and have the power to authorize remediation or disciplinary measures. However, individual states vary widely¹⁰ in their likelihood of disciplining physicians for similar offenses. The board certification process is intended to ensure that only fully competent physicians can practice medicine independently. However, there is little evidence that the certification process ensures that clinicians maintain their skills, and significant controversy has accompanied efforts to revise the maintenance of certification process. The medical malpractice system aims to improve patient safety by ensuring compensation when patients are injured and by deterring substandard clinicians from practicing. Unfortunately, the system often fails to meet this goal, as malpractice claims are rarely filed even when patients are harmed due to negligent care.¹¹

Given the widespread availability of controlled substances in hospitals, comprehensive solutions must incorporate the systems-based solutions proffered by Fan and colleagues and address individual clinicians (and staff) who divert drugs. These clinicians are likely to share some of the same risk factors as clinicians who cannot perform their professional responsibilities for other reasons. Major system changes are necessary to minimize the risk of short-term conditions that could affect physician performance (such as burnout) and develop robust methods to identify clinicians with longer-term issues affecting their performance (such as substance-use disorders).

Although individual clinician performance problems likely account for a small proportion of adverse events, these issues strike at the heart of the physician-patient relationship and have a profound impact on patients’ trust in the healthcare system. Healthcare organizations must maintain transparent and effective processes for addressing performance failures such as drug diversion by clinicians, even if these processes are rarely deployed.

Disclosures

The author does not have any conflict of interest to report.

The field of pediatric hospital medicine has seen tremendous growth in scholarship in the past decade. To obtain a wide view of advancements in the field from the current literature, the authors selected 18 English-language journals (Table 1) across four domains believed to be relevant to the practice of pediatric hospital medicine, including hospital medicine, pediatrics, emergency care, and medical education. The median Hirsch index (h-index) of the selected journals was 131. A goal of 10, a number that could maximally benefit consumers of the finished product, was set as the final number of articles to be selected.

Guiding principles for the initial selection included novelty of hypotheses, study design, significance of results, and likelihood to change pediatric hospital medicine practice from both the community and academic hospital perspectives. Journals were assigned randomly to each author for review and assignments were switched after six months to limit potential bias in coverage. A three-stage review process was employed. The authors initially independently reviewed titles and abstracts from 13,296 articles published between January 2018 and December 2018 and rated them according to their likelihood to be included in the final set of 10 articles and their broad applicability to pediatric hospital medicine. This resulted in 99 studies that were selected for further review. Next, the authors were assigned a subset of the 99 articles for further review; each author rated the articles independently based on their likelihood of inclusion in the final 10-article set. At this stage, 75 articles were excluded. Finally, all remaining 24 articles were reviewed independently and in depth by both authors.

Ten articles were selected by consensus formation, and the authors presented their findings at the 2019 Society for Hospital Medicine annual meeting. From these 10 articles, six were determined to be most impactful to current practice; these articles are presented below. After discussing the study background, an overview, key results, limitations of the study, important findings (Table 2), and implications for practice and future research are presented.

Interventions to Reduce Over-Utilized Tests and Treatments in Bronchiolitis. Tyler A, et al. Pediatrics. 2018;141(6):e20170485. ¹

Background

The American Academy of Pediatrics (AAP) published clinical practice guidelines (CPG) for bronchiolitis in 2014.² However, unnecessary tests and interventions continue to be ordered and used on children with bronchiolitis that are not recommended by the guidelines. In this quality improvement project, the authors sought to increase compliance with the AAP CPG for bronchiolitis by reducing chest x-rays (CXR) to <20%, respiratory viral testing (RVT) to <15%, and use of bronchodilators to <20%.

Study Overview and Results

This project took place at a free-standing children’s hospital and included urgent care locations. Authors obtained pre-intervention data through two bronchiolitis seasons in 2013 and 2014 for patients aged 1-23 months with a primary or secondary diagnosis of bronchiolitis and who did not require admission to the Intensive Care Unit (ICU). The intervention period was from December 2015 to April 2016. All sites simultaneously implemented their interventions, which included education of care team members and families, updated order sets, and electronic health record (EHR)-generated e-mails that provided data looking at peer ranking statistics for each intervention, CXR, RVT, and bronchodilator usage. A data dashboard was created to display real-time utilization of the studied interventions. Providers were also asked to sign a pledge that they would reduce unnecessary testing and treatment. As balancing measures, the numbers of patients presenting to the Emergency Room (ER) or readmitted within seven days of an ED visit or admission for bronchiolitis were tracked; patients who required ICU levels of care during their first admission or on readmission were also tracked. Statistically significant decreases in CXR ordering from 39.5% to 27.2%, RVT ordering from 31.9% to 26.3%, and any bronchodilator usage from 34.2% to 21.5% were noted. No difference pre- and postintervention in patients readmitted to the ICU was found, and length of stay (LOS) between groups was not statistically significant.

Limitations

As all interventions were initiated simultaneously, identifying which individual or subset of interventions was responsible for changing provider behavior was impossible. More patients postintervention were admitted under observation status and under a milder All Patient Refined Diagnosis Related Groups (APR DRGs) severity index, which may indicate a less-sick cohort of patients in this group. Since the LOS and number of patients readmitted to the ICU were similar in both groups, it is unlikely that the postintervention group represented a less-sick cohort.

Important Findings and Implications

This QI project highlighted novel ways to implement and emphasize the importance of compliance to CPG. A provider pledge may be helpful in reinforcing to all providers the idea that the institution is committed to guideline implementation. Comparing individual provider data and having a real-time dashboard with group performance can help reinforce goals and progress toward them at the group, site, and individual patient population levels.

Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children. Shaikh N, et al. JAMA Pediatrics. 2018;172(6):550-556.³

Background

The prevalence of urinary tract infections (UTIs) in children under 2 years of age that present to the emergency department (ED) with fever is about 7%.⁴ After clinical examination, providers obtaining a urinalysis must then determine if empirical antibiotics are warranted for a suspected UTI. This study describes the development of a novel calculator, UTICalc that estimates the pretest probability of a UTI based on clinical findings and the posttest probability of a UTI based on laboratory results.

Study Overview and Results

This study features a single center, nested, case-control design that looked retrospectively at 542 children aged 2-24 months who presented to the ED from January 2007 to April 2013 with fever and had a catheterized urinalysis obtained. Patients were then matched with randomly selected children without a UTI to create a training database. Five models using different variables were developed, including one with only clinical characteristics and four that combined clinical characteristics with differing laboratory values. The area under the curve of the “clinical model” was 0.80, while those of the remaining four models ranged from 0.97 to 0.98. The clinical model showed a sensitivity of 95% and specificity of 35% in the training database, while the four other models showed sensitivities ranging from 93% to 96% and specificities ranging from 91% to 93%. The models were then validated using a cohort of children aged 2-24 months who presented to the ED with fever from July 2015 to December 2016; the UTI prevalence in this cohort was 7.8%. Finally, using a hypothetical cohort of 1,000 children being evaluated for a UTI, the authors showed that UTICalc reduced the numbers of urine samples obtained by 8.1% and missed UTIs from 3 to 0 compared with following AAP guidelines.⁵

Limitations

The training database was created retrospectively at a single institution and is subject to local practice patterns. The proposed calculator creates an algorithm that is meant to be used in a setting where the pretest probability for a UTI is reasonably high based on criteria from the AAP UTI guidelines.

Important Findings and Implications

UTICalc could be a great tool for providers to guide testing for UTIs in children aged 2-24 months presenting with a fever. Given further study at multiple sites and settings, including outpatient clinics, UTICalc could have significant implications for reducing unnecessary testing and treatment in febrile children.

Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations. Chang LV, et al. Pediatrics. 2018;142(3):e20180195.⁶

Background

Although medical expenses related to hospitalization can be significant for many families, nonmedical costs, such as transportation, parking, meals, and lost earnings from missed days at work, are also important to consider. These hardships can lead to challenges in postdischarge follow-up and adherence to discharge instructions, both of which lead to hospital readmissions. This article presents a cross-sectional analysis at a large, free-standing children’s hospital that participated in the Hospital-to-Home Outcomes Study (H2O). The authors sought to determine whether families with more financial or social hardships are affected disproportionately by nonmedical costs related to hospitalizations.

Study Overview and Results

A total of 1,372 children were included and children with lengths of stay >13 days were excluded. Face-to-face parental surveys were conducted and included questions on parental education, employment status, sick leave flexibility, and measures of financial and social hardship. The study authors calculated a total cost burden (TCB) based on nonmedical costs estimated at the time of the survey, including lost wages and expenses during the hospitalization. A daily cost burden (DCB) based on length of hospital stay and daily cost burden as a percentage of daily income (DCBi) were also calculated. The median TCB was $112.80, and the median DCB was $51.40. The median DCBi showed that the median household had 45% of their daily income depleted by nonmedical expenses related to their hospitalization. Those who reported more financial or social hardships had a higher median DCBi; if ≥3 financial hardships were reported, 86% of the daily household income was depleted.

Limitations

The study was conducted at a single institution with a number of existing support systems in place to help unburden families of hospitalized children. Non-English-speaking families were excluded. A face-to-face survey may have influenced parental responses regarding social and financial hardships.

Important Findings and Implications

Nonmedical costs of hospitalized children can be quantified and disproportionately affect those experiencing financial and social hardships. Hospitalists should be aware of these findings and find ways within their hospital systems to provide support for families both during and after hospitalizations.

A Prescription for Note Bloat: An Effective Progress Note Template. Kahn D, et al. Journal of Hospital Medicine. 2018;13(6):378-382.⁷

Background

Although electronic health records (EHRs) have improved the speed and legibility of documentation, the harm of “note bloat,” defined as multiple pages of nonessential information which leaves key aspects buried or lost, is prevalent. In this prospective, quality improvement study across four internal medicine residency programs, the authors investigated a bundled intervention consisting of didactic teaching and an electronic progress note template on note quality, length, and timeliness.

Study overview and results

Notes pre- and postintervention were graded using a tool that considered the general impression of the note, its score on the validated Physician Documentation Quality Instrument (PDQI-9),⁸ and a questionnaire based on the Accreditation Council for Graduate Medical Education competency note checklist.⁹ Analyzing 200 preintervention and 199 postintervention notes, significant improvement was seen in general impression scores, all PDQI-9 domains, and 6 of 13 note competency questionnaire items. The mean number of lines in the note decreased by 25%, and the mean completion time when the note was signed was 1 hour and 15 minutes earlier. The greatest impact on shortening notes involved a reduction in the auto-population of laboratory and imaging studies.

Limitations

The study was unblinded. The authors attempted to minimize bias with an objective questionnaire and employed multiple graders per note; however, poor interrater reliability was obtained. Postintervention, 70% of all residents used the template. At one of the four institutions, evidence of note quality improvement despite low template use was found. At another institution, no improvement in note quality was reported despite relatively high template uptake. Local culture and institutional buy-in may be factors affecting these results. In addition, pre- and postintervention notes were examined in the same academic year; thus, the effects seen may be due, in part, to resident maturation. Generalizability to nonacademic institutions and the durability of the intervention are additional concerns.

Important Findings and Implications

Resident education on documentation and an EHR progress note template incorporating best practices can effectively combat “note bloat” and lead to higher quality and shorter notes that are completed earlier in the day. This solution has significant implications for improving transitions of care, handoffs, and patient safety.

Time to Pathogen Detection for Non-Ill Versus Ill-Appearing Infants ≤60 Days Old with Bacteremia and Meningitis. Aronson PL, et al. Hospital Pediatrics 2018;8 (7):379-384.¹⁰

Background

The routine evaluation of febrile infants aged ≤60 days old often involves blood and cerebrospinal (CSF) fluid evaluations, and many infants are hospitalized while waiting for culture results. A previous study of febrile infants showed that 91% of the pathogenic organisms could be identified on blood culture within 24 hours and that 96% could be identified within 36 hours; 81% of the bacterial pathogens present were detected on CSF culture within 36 hours.¹¹

Study Overview and Results

In this large, multicenter study of infants presenting to the Emergency Departments (EDs) of 10 children’s hospitals over a five-year study period, the authors investigated the time to pathogen detection in blood and CSF for infants aged ≤60 days with bacteremia and/or bacterial meningitis; whether the time to detection differed for non-ill and ill infants was also examined. Ill- versus non-ill-appearance was determined by a medical record review of the physical exam looking for one of 13 key words (eg, “ill-appearing,” “toxic,” “lethargic,” etc.). A total of 381 infants were included. Overall, 88% of the pathogens present were detected in blood culture within 24 hours and 95% were detected within 36 hours. In CSF, 89% of the pathogens present were detected within 24 hours, and 95% were detected within 36 hours. In infants with bacteremia who were non-ill-appearing, 85% of the blood pathogens were detected within 24 hours.

Limitations

The median time to detection for blood culture pathogens for ill-appearing versus non-ill-appearing infants was shorter by just one hour, but 15% of the non-ill infants had a positive blood culture after 24 hours. However, the prevalence of bacteremia and meningitis in non-ill-appearing infants is likely low; the authors did not report the total number of febrile infants evaluated by EDs in the study.

Important Findings and Implications

Most positive blood and/or CSF cultures for infants aged ≤60 days will yield results by 24 hours; 95% of the pathogens present could be detected within 36 hours. Sending a non-ill-appearing febrile infant home at 24 hours may miss 15% of the instances of bacteremia, but the overall low prevalence of invasive bacterial infection in infants should be considered.

The High-Value Care Rounding Tool: Development and Validity Evidence. McDaniel CE, et al. Academic Medicine. 2018;93(2):199-206.¹²

Background

Providing high-value care (HVC) to patients is a struggle for physicians and healthcare systems. Although physicians teaching trainees HVC practices could be an effective way to increase cost-conscious care, the best practices for teaching HVC remain unknown. To fill this gap, the authors developed a tool to measure the frequency and content of observable HVC teaching and evaluated the validity of the tool within a pediatric inpatient setting.

Study Overview and Results

The HVC rounding tool was developed through several phases from conception to validation. The research group used a modified Delphi method to construct the tool using a consensus building process based on opinions from content experts in the field of HVC, from a variety of specialties, experience levels, and geographic areas of the United States. Each item of the HVC instrument was rated by these experts, and, from their evaluations and surveys, an 11-item HVC tool was constructed. A pilot of the tool was performed to establish internal validity and interrater reliability based on observations of 148 patient encounters. From this process, a final 10-item HVC rounding tool emerged, including domains in quality, cost, and patient values. A few items included giving positive feedback for not doing an unnecessary test, discussing whether a patient needs to stay inpatient or meets discharge criteria, and customizing a care plan to align with family values and goals. The final iteration of the tool had no rater disagreements within the quality and patient values domain and only one disagreement within the cost domain.

Limitations

This tool was validated at a single pediatric institution, and, thus, the generalizability of the tool has not been established. The authors note that the Delphi panelists used for the construction of the tool were from a medical subspecialty background and not surgical backgrounds, which limits its applicability from a surgical perspective. The tool does not allow for differentiation between lengthy discussions or brief comments presented during rounds.

Important Findings and Implications

The HVC rounding tool is both innovative and timely. Pediatric hospitalists are leaders in family-centered care, and this tool allows assessment of whether important concepts of high-value care are discussed at the bedside. A multisite educational study using this tool would be welcome.

Disclosures

The authors have no conflicts of interest to declare.

The field of pediatric hospital medicine has seen tremendous growth in scholarship in the past decade. To obtain a wide view of advancements in the field from the current literature, the authors selected 18 English-language journals (Table 1) across four domains believed to be relevant to the practice of pediatric hospital medicine, including hospital medicine, pediatrics, emergency care, and medical education. The median Hirsch index (h-index) of the selected journals was 131. A goal of 10, a number that could maximally benefit consumers of the finished product, was set as the final number of articles to be selected.

Guiding principles for the initial selection included novelty of hypotheses, study design, significance of results, and likelihood to change pediatric hospital medicine practice from both the community and academic hospital perspectives. Journals were assigned randomly to each author for review and assignments were switched after six months to limit potential bias in coverage. A three-stage review process was employed. The authors initially independently reviewed titles and abstracts from 13,296 articles published between January 2018 and December 2018 and rated them according to their likelihood to be included in the final set of 10 articles and their broad applicability to pediatric hospital medicine. This resulted in 99 studies that were selected for further review. Next, the authors were assigned a subset of the 99 articles for further review; each author rated the articles independently based on their likelihood of inclusion in the final 10-article set. At this stage, 75 articles were excluded. Finally, all remaining 24 articles were reviewed independently and in depth by both authors.

Ten articles were selected by consensus formation, and the authors presented their findings at the 2019 Society for Hospital Medicine annual meeting. From these 10 articles, six were determined to be most impactful to current practice; these articles are presented below. After discussing the study background, an overview, key results, limitations of the study, important findings (Table 2), and implications for practice and future research are presented.

Interventions to Reduce Over-Utilized Tests and Treatments in Bronchiolitis. Tyler A, et al. Pediatrics. 2018;141(6):e20170485. ¹

Background

The American Academy of Pediatrics (AAP) published clinical practice guidelines (CPG) for bronchiolitis in 2014.² However, unnecessary tests and interventions continue to be ordered and used on children with bronchiolitis that are not recommended by the guidelines. In this quality improvement project, the authors sought to increase compliance with the AAP CPG for bronchiolitis by reducing chest x-rays (CXR) to <20%, respiratory viral testing (RVT) to <15%, and use of bronchodilators to <20%.

Study Overview and Results

This project took place at a free-standing children’s hospital and included urgent care locations. Authors obtained pre-intervention data through two bronchiolitis seasons in 2013 and 2014 for patients aged 1-23 months with a primary or secondary diagnosis of bronchiolitis and who did not require admission to the Intensive Care Unit (ICU). The intervention period was from December 2015 to April 2016. All sites simultaneously implemented their interventions, which included education of care team members and families, updated order sets, and electronic health record (EHR)-generated e-mails that provided data looking at peer ranking statistics for each intervention, CXR, RVT, and bronchodilator usage. A data dashboard was created to display real-time utilization of the studied interventions. Providers were also asked to sign a pledge that they would reduce unnecessary testing and treatment. As balancing measures, the numbers of patients presenting to the Emergency Room (ER) or readmitted within seven days of an ED visit or admission for bronchiolitis were tracked; patients who required ICU levels of care during their first admission or on readmission were also tracked. Statistically significant decreases in CXR ordering from 39.5% to 27.2%, RVT ordering from 31.9% to 26.3%, and any bronchodilator usage from 34.2% to 21.5% were noted. No difference pre- and postintervention in patients readmitted to the ICU was found, and length of stay (LOS) between groups was not statistically significant.

Limitations

As all interventions were initiated simultaneously, identifying which individual or subset of interventions was responsible for changing provider behavior was impossible. More patients postintervention were admitted under observation status and under a milder All Patient Refined Diagnosis Related Groups (APR DRGs) severity index, which may indicate a less-sick cohort of patients in this group. Since the LOS and number of patients readmitted to the ICU were similar in both groups, it is unlikely that the postintervention group represented a less-sick cohort.

Important Findings and Implications

This QI project highlighted novel ways to implement and emphasize the importance of compliance to CPG. A provider pledge may be helpful in reinforcing to all providers the idea that the institution is committed to guideline implementation. Comparing individual provider data and having a real-time dashboard with group performance can help reinforce goals and progress toward them at the group, site, and individual patient population levels.

Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children. Shaikh N, et al. JAMA Pediatrics. 2018;172(6):550-556.³

Background

The prevalence of urinary tract infections (UTIs) in children under 2 years of age that present to the emergency department (ED) with fever is about 7%.⁴ After clinical examination, providers obtaining a urinalysis must then determine if empirical antibiotics are warranted for a suspected UTI. This study describes the development of a novel calculator, UTICalc that estimates the pretest probability of a UTI based on clinical findings and the posttest probability of a UTI based on laboratory results.

Study Overview and Results

This study features a single center, nested, case-control design that looked retrospectively at 542 children aged 2-24 months who presented to the ED from January 2007 to April 2013 with fever and had a catheterized urinalysis obtained. Patients were then matched with randomly selected children without a UTI to create a training database. Five models using different variables were developed, including one with only clinical characteristics and four that combined clinical characteristics with differing laboratory values. The area under the curve of the “clinical model” was 0.80, while those of the remaining four models ranged from 0.97 to 0.98. The clinical model showed a sensitivity of 95% and specificity of 35% in the training database, while the four other models showed sensitivities ranging from 93% to 96% and specificities ranging from 91% to 93%. The models were then validated using a cohort of children aged 2-24 months who presented to the ED with fever from July 2015 to December 2016; the UTI prevalence in this cohort was 7.8%. Finally, using a hypothetical cohort of 1,000 children being evaluated for a UTI, the authors showed that UTICalc reduced the numbers of urine samples obtained by 8.1% and missed UTIs from 3 to 0 compared with following AAP guidelines.⁵

Limitations

The training database was created retrospectively at a single institution and is subject to local practice patterns. The proposed calculator creates an algorithm that is meant to be used in a setting where the pretest probability for a UTI is reasonably high based on criteria from the AAP UTI guidelines.

Important Findings and Implications

UTICalc could be a great tool for providers to guide testing for UTIs in children aged 2-24 months presenting with a fever. Given further study at multiple sites and settings, including outpatient clinics, UTICalc could have significant implications for reducing unnecessary testing and treatment in febrile children.

Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations. Chang LV, et al. Pediatrics. 2018;142(3):e20180195.⁶

Background

Although medical expenses related to hospitalization can be significant for many families, nonmedical costs, such as transportation, parking, meals, and lost earnings from missed days at work, are also important to consider. These hardships can lead to challenges in postdischarge follow-up and adherence to discharge instructions, both of which lead to hospital readmissions. This article presents a cross-sectional analysis at a large, free-standing children’s hospital that participated in the Hospital-to-Home Outcomes Study (H2O). The authors sought to determine whether families with more financial or social hardships are affected disproportionately by nonmedical costs related to hospitalizations.

Study Overview and Results

A total of 1,372 children were included and children with lengths of stay >13 days were excluded. Face-to-face parental surveys were conducted and included questions on parental education, employment status, sick leave flexibility, and measures of financial and social hardship. The study authors calculated a total cost burden (TCB) based on nonmedical costs estimated at the time of the survey, including lost wages and expenses during the hospitalization. A daily cost burden (DCB) based on length of hospital stay and daily cost burden as a percentage of daily income (DCBi) were also calculated. The median TCB was $112.80, and the median DCB was $51.40. The median DCBi showed that the median household had 45% of their daily income depleted by nonmedical expenses related to their hospitalization. Those who reported more financial or social hardships had a higher median DCBi; if ≥3 financial hardships were reported, 86% of the daily household income was depleted.

Limitations

The study was conducted at a single institution with a number of existing support systems in place to help unburden families of hospitalized children. Non-English-speaking families were excluded. A face-to-face survey may have influenced parental responses regarding social and financial hardships.

Important Findings and Implications

Nonmedical costs of hospitalized children can be quantified and disproportionately affect those experiencing financial and social hardships. Hospitalists should be aware of these findings and find ways within their hospital systems to provide support for families both during and after hospitalizations.

A Prescription for Note Bloat: An Effective Progress Note Template. Kahn D, et al. Journal of Hospital Medicine. 2018;13(6):378-382.⁷

Background

Although electronic health records (EHRs) have improved the speed and legibility of documentation, the harm of “note bloat,” defined as multiple pages of nonessential information which leaves key aspects buried or lost, is prevalent. In this prospective, quality improvement study across four internal medicine residency programs, the authors investigated a bundled intervention consisting of didactic teaching and an electronic progress note template on note quality, length, and timeliness.

Study overview and results

Notes pre- and postintervention were graded using a tool that considered the general impression of the note, its score on the validated Physician Documentation Quality Instrument (PDQI-9),⁸ and a questionnaire based on the Accreditation Council for Graduate Medical Education competency note checklist.⁹ Analyzing 200 preintervention and 199 postintervention notes, significant improvement was seen in general impression scores, all PDQI-9 domains, and 6 of 13 note competency questionnaire items. The mean number of lines in the note decreased by 25%, and the mean completion time when the note was signed was 1 hour and 15 minutes earlier. The greatest impact on shortening notes involved a reduction in the auto-population of laboratory and imaging studies.

Limitations

The study was unblinded. The authors attempted to minimize bias with an objective questionnaire and employed multiple graders per note; however, poor interrater reliability was obtained. Postintervention, 70% of all residents used the template. At one of the four institutions, evidence of note quality improvement despite low template use was found. At another institution, no improvement in note quality was reported despite relatively high template uptake. Local culture and institutional buy-in may be factors affecting these results. In addition, pre- and postintervention notes were examined in the same academic year; thus, the effects seen may be due, in part, to resident maturation. Generalizability to nonacademic institutions and the durability of the intervention are additional concerns.

Important Findings and Implications

Resident education on documentation and an EHR progress note template incorporating best practices can effectively combat “note bloat” and lead to higher quality and shorter notes that are completed earlier in the day. This solution has significant implications for improving transitions of care, handoffs, and patient safety.

Time to Pathogen Detection for Non-Ill Versus Ill-Appearing Infants ≤60 Days Old with Bacteremia and Meningitis. Aronson PL, et al. Hospital Pediatrics 2018;8 (7):379-384.¹⁰

Background

The routine evaluation of febrile infants aged ≤60 days old often involves blood and cerebrospinal (CSF) fluid evaluations, and many infants are hospitalized while waiting for culture results. A previous study of febrile infants showed that 91% of the pathogenic organisms could be identified on blood culture within 24 hours and that 96% could be identified within 36 hours; 81% of the bacterial pathogens present were detected on CSF culture within 36 hours.¹¹

Study Overview and Results

In this large, multicenter study of infants presenting to the Emergency Departments (EDs) of 10 children’s hospitals over a five-year study period, the authors investigated the time to pathogen detection in blood and CSF for infants aged ≤60 days with bacteremia and/or bacterial meningitis; whether the time to detection differed for non-ill and ill infants was also examined. Ill- versus non-ill-appearance was determined by a medical record review of the physical exam looking for one of 13 key words (eg, “ill-appearing,” “toxic,” “lethargic,” etc.). A total of 381 infants were included. Overall, 88% of the pathogens present were detected in blood culture within 24 hours and 95% were detected within 36 hours. In CSF, 89% of the pathogens present were detected within 24 hours, and 95% were detected within 36 hours. In infants with bacteremia who were non-ill-appearing, 85% of the blood pathogens were detected within 24 hours.

Limitations

The median time to detection for blood culture pathogens for ill-appearing versus non-ill-appearing infants was shorter by just one hour, but 15% of the non-ill infants had a positive blood culture after 24 hours. However, the prevalence of bacteremia and meningitis in non-ill-appearing infants is likely low; the authors did not report the total number of febrile infants evaluated by EDs in the study.

Important Findings and Implications

Most positive blood and/or CSF cultures for infants aged ≤60 days will yield results by 24 hours; 95% of the pathogens present could be detected within 36 hours. Sending a non-ill-appearing febrile infant home at 24 hours may miss 15% of the instances of bacteremia, but the overall low prevalence of invasive bacterial infection in infants should be considered.

The High-Value Care Rounding Tool: Development and Validity Evidence. McDaniel CE, et al. Academic Medicine. 2018;93(2):199-206.¹²

Background

Providing high-value care (HVC) to patients is a struggle for physicians and healthcare systems. Although physicians teaching trainees HVC practices could be an effective way to increase cost-conscious care, the best practices for teaching HVC remain unknown. To fill this gap, the authors developed a tool to measure the frequency and content of observable HVC teaching and evaluated the validity of the tool within a pediatric inpatient setting.

Study Overview and Results

The HVC rounding tool was developed through several phases from conception to validation. The research group used a modified Delphi method to construct the tool using a consensus building process based on opinions from content experts in the field of HVC, from a variety of specialties, experience levels, and geographic areas of the United States. Each item of the HVC instrument was rated by these experts, and, from their evaluations and surveys, an 11-item HVC tool was constructed. A pilot of the tool was performed to establish internal validity and interrater reliability based on observations of 148 patient encounters. From this process, a final 10-item HVC rounding tool emerged, including domains in quality, cost, and patient values. A few items included giving positive feedback for not doing an unnecessary test, discussing whether a patient needs to stay inpatient or meets discharge criteria, and customizing a care plan to align with family values and goals. The final iteration of the tool had no rater disagreements within the quality and patient values domain and only one disagreement within the cost domain.

Limitations

This tool was validated at a single pediatric institution, and, thus, the generalizability of the tool has not been established. The authors note that the Delphi panelists used for the construction of the tool were from a medical subspecialty background and not surgical backgrounds, which limits its applicability from a surgical perspective. The tool does not allow for differentiation between lengthy discussions or brief comments presented during rounds.

Important Findings and Implications

The HVC rounding tool is both innovative and timely. Pediatric hospitalists are leaders in family-centered care, and this tool allows assessment of whether important concepts of high-value care are discussed at the bedside. A multisite educational study using this tool would be welcome.

Disclosures

The authors have no conflicts of interest to declare.

The field of pediatric hospital medicine has seen tremendous growth in scholarship in the past decade. To obtain a wide view of advancements in the field from the current literature, the authors selected 18 English-language journals (Table 1) across four domains believed to be relevant to the practice of pediatric hospital medicine, including hospital medicine, pediatrics, emergency care, and medical education. The median Hirsch index (h-index) of the selected journals was 131. A goal of 10, a number that could maximally benefit consumers of the finished product, was set as the final number of articles to be selected.

Guiding principles for the initial selection included novelty of hypotheses, study design, significance of results, and likelihood to change pediatric hospital medicine practice from both the community and academic hospital perspectives. Journals were assigned randomly to each author for review and assignments were switched after six months to limit potential bias in coverage. A three-stage review process was employed. The authors initially independently reviewed titles and abstracts from 13,296 articles published between January 2018 and December 2018 and rated them according to their likelihood to be included in the final set of 10 articles and their broad applicability to pediatric hospital medicine. This resulted in 99 studies that were selected for further review. Next, the authors were assigned a subset of the 99 articles for further review; each author rated the articles independently based on their likelihood of inclusion in the final 10-article set. At this stage, 75 articles were excluded. Finally, all remaining 24 articles were reviewed independently and in depth by both authors.

Ten articles were selected by consensus formation, and the authors presented their findings at the 2019 Society for Hospital Medicine annual meeting. From these 10 articles, six were determined to be most impactful to current practice; these articles are presented below. After discussing the study background, an overview, key results, limitations of the study, important findings (Table 2), and implications for practice and future research are presented.

Interventions to Reduce Over-Utilized Tests and Treatments in Bronchiolitis. Tyler A, et al. Pediatrics. 2018;141(6):e20170485. ¹

Background

The American Academy of Pediatrics (AAP) published clinical practice guidelines (CPG) for bronchiolitis in 2014.² However, unnecessary tests and interventions continue to be ordered and used on children with bronchiolitis that are not recommended by the guidelines. In this quality improvement project, the authors sought to increase compliance with the AAP CPG for bronchiolitis by reducing chest x-rays (CXR) to <20%, respiratory viral testing (RVT) to <15%, and use of bronchodilators to <20%.

Study Overview and Results

This project took place at a free-standing children’s hospital and included urgent care locations. Authors obtained pre-intervention data through two bronchiolitis seasons in 2013 and 2014 for patients aged 1-23 months with a primary or secondary diagnosis of bronchiolitis and who did not require admission to the Intensive Care Unit (ICU). The intervention period was from December 2015 to April 2016. All sites simultaneously implemented their interventions, which included education of care team members and families, updated order sets, and electronic health record (EHR)-generated e-mails that provided data looking at peer ranking statistics for each intervention, CXR, RVT, and bronchodilator usage. A data dashboard was created to display real-time utilization of the studied interventions. Providers were also asked to sign a pledge that they would reduce unnecessary testing and treatment. As balancing measures, the numbers of patients presenting to the Emergency Room (ER) or readmitted within seven days of an ED visit or admission for bronchiolitis were tracked; patients who required ICU levels of care during their first admission or on readmission were also tracked. Statistically significant decreases in CXR ordering from 39.5% to 27.2%, RVT ordering from 31.9% to 26.3%, and any bronchodilator usage from 34.2% to 21.5% were noted. No difference pre- and postintervention in patients readmitted to the ICU was found, and length of stay (LOS) between groups was not statistically significant.

Limitations

As all interventions were initiated simultaneously, identifying which individual or subset of interventions was responsible for changing provider behavior was impossible. More patients postintervention were admitted under observation status and under a milder All Patient Refined Diagnosis Related Groups (APR DRGs) severity index, which may indicate a less-sick cohort of patients in this group. Since the LOS and number of patients readmitted to the ICU were similar in both groups, it is unlikely that the postintervention group represented a less-sick cohort.

Important Findings and Implications

This QI project highlighted novel ways to implement and emphasize the importance of compliance to CPG. A provider pledge may be helpful in reinforcing to all providers the idea that the institution is committed to guideline implementation. Comparing individual provider data and having a real-time dashboard with group performance can help reinforce goals and progress toward them at the group, site, and individual patient population levels.

Development and Validation of a Calculator for Estimating the Probability of Urinary Tract Infection in Young Febrile Children. Shaikh N, et al. JAMA Pediatrics. 2018;172(6):550-556.³

Background

The prevalence of urinary tract infections (UTIs) in children under 2 years of age that present to the emergency department (ED) with fever is about 7%.⁴ After clinical examination, providers obtaining a urinalysis must then determine if empirical antibiotics are warranted for a suspected UTI. This study describes the development of a novel calculator, UTICalc that estimates the pretest probability of a UTI based on clinical findings and the posttest probability of a UTI based on laboratory results.

Study Overview and Results

This study features a single center, nested, case-control design that looked retrospectively at 542 children aged 2-24 months who presented to the ED from January 2007 to April 2013 with fever and had a catheterized urinalysis obtained. Patients were then matched with randomly selected children without a UTI to create a training database. Five models using different variables were developed, including one with only clinical characteristics and four that combined clinical characteristics with differing laboratory values. The area under the curve of the “clinical model” was 0.80, while those of the remaining four models ranged from 0.97 to 0.98. The clinical model showed a sensitivity of 95% and specificity of 35% in the training database, while the four other models showed sensitivities ranging from 93% to 96% and specificities ranging from 91% to 93%. The models were then validated using a cohort of children aged 2-24 months who presented to the ED with fever from July 2015 to December 2016; the UTI prevalence in this cohort was 7.8%. Finally, using a hypothetical cohort of 1,000 children being evaluated for a UTI, the authors showed that UTICalc reduced the numbers of urine samples obtained by 8.1% and missed UTIs from 3 to 0 compared with following AAP guidelines.⁵

Limitations

The training database was created retrospectively at a single institution and is subject to local practice patterns. The proposed calculator creates an algorithm that is meant to be used in a setting where the pretest probability for a UTI is reasonably high based on criteria from the AAP UTI guidelines.

Important Findings and Implications

UTICalc could be a great tool for providers to guide testing for UTIs in children aged 2-24 months presenting with a fever. Given further study at multiple sites and settings, including outpatient clinics, UTICalc could have significant implications for reducing unnecessary testing and treatment in febrile children.

Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations. Chang LV, et al. Pediatrics. 2018;142(3):e20180195.⁶

Background

Although medical expenses related to hospitalization can be significant for many families, nonmedical costs, such as transportation, parking, meals, and lost earnings from missed days at work, are also important to consider. These hardships can lead to challenges in postdischarge follow-up and adherence to discharge instructions, both of which lead to hospital readmissions. This article presents a cross-sectional analysis at a large, free-standing children’s hospital that participated in the Hospital-to-Home Outcomes Study (H2O). The authors sought to determine whether families with more financial or social hardships are affected disproportionately by nonmedical costs related to hospitalizations.

Study Overview and Results

A total of 1,372 children were included and children with lengths of stay >13 days were excluded. Face-to-face parental surveys were conducted and included questions on parental education, employment status, sick leave flexibility, and measures of financial and social hardship. The study authors calculated a total cost burden (TCB) based on nonmedical costs estimated at the time of the survey, including lost wages and expenses during the hospitalization. A daily cost burden (DCB) based on length of hospital stay and daily cost burden as a percentage of daily income (DCBi) were also calculated. The median TCB was $112.80, and the median DCB was $51.40. The median DCBi showed that the median household had 45% of their daily income depleted by nonmedical expenses related to their hospitalization. Those who reported more financial or social hardships had a higher median DCBi; if ≥3 financial hardships were reported, 86% of the daily household income was depleted.

Limitations

The study was conducted at a single institution with a number of existing support systems in place to help unburden families of hospitalized children. Non-English-speaking families were excluded. A face-to-face survey may have influenced parental responses regarding social and financial hardships.

Important Findings and Implications

Nonmedical costs of hospitalized children can be quantified and disproportionately affect those experiencing financial and social hardships. Hospitalists should be aware of these findings and find ways within their hospital systems to provide support for families both during and after hospitalizations.

A Prescription for Note Bloat: An Effective Progress Note Template. Kahn D, et al. Journal of Hospital Medicine. 2018;13(6):378-382.⁷

Background

Although electronic health records (EHRs) have improved the speed and legibility of documentation, the harm of “note bloat,” defined as multiple pages of nonessential information which leaves key aspects buried or lost, is prevalent. In this prospective, quality improvement study across four internal medicine residency programs, the authors investigated a bundled intervention consisting of didactic teaching and an electronic progress note template on note quality, length, and timeliness.

Study overview and results

Notes pre- and postintervention were graded using a tool that considered the general impression of the note, its score on the validated Physician Documentation Quality Instrument (PDQI-9),⁸ and a questionnaire based on the Accreditation Council for Graduate Medical Education competency note checklist.⁹ Analyzing 200 preintervention and 199 postintervention notes, significant improvement was seen in general impression scores, all PDQI-9 domains, and 6 of 13 note competency questionnaire items. The mean number of lines in the note decreased by 25%, and the mean completion time when the note was signed was 1 hour and 15 minutes earlier. The greatest impact on shortening notes involved a reduction in the auto-population of laboratory and imaging studies.

Limitations

The study was unblinded. The authors attempted to minimize bias with an objective questionnaire and employed multiple graders per note; however, poor interrater reliability was obtained. Postintervention, 70% of all residents used the template. At one of the four institutions, evidence of note quality improvement despite low template use was found. At another institution, no improvement in note quality was reported despite relatively high template uptake. Local culture and institutional buy-in may be factors affecting these results. In addition, pre- and postintervention notes were examined in the same academic year; thus, the effects seen may be due, in part, to resident maturation. Generalizability to nonacademic institutions and the durability of the intervention are additional concerns.

Important Findings and Implications

Resident education on documentation and an EHR progress note template incorporating best practices can effectively combat “note bloat” and lead to higher quality and shorter notes that are completed earlier in the day. This solution has significant implications for improving transitions of care, handoffs, and patient safety.

Time to Pathogen Detection for Non-Ill Versus Ill-Appearing Infants ≤60 Days Old with Bacteremia and Meningitis. Aronson PL, et al. Hospital Pediatrics 2018;8 (7):379-384.¹⁰

Background

The routine evaluation of febrile infants aged ≤60 days old often involves blood and cerebrospinal (CSF) fluid evaluations, and many infants are hospitalized while waiting for culture results. A previous study of febrile infants showed that 91% of the pathogenic organisms could be identified on blood culture within 24 hours and that 96% could be identified within 36 hours; 81% of the bacterial pathogens present were detected on CSF culture within 36 hours.¹¹

Study Overview and Results

In this large, multicenter study of infants presenting to the Emergency Departments (EDs) of 10 children’s hospitals over a five-year study period, the authors investigated the time to pathogen detection in blood and CSF for infants aged ≤60 days with bacteremia and/or bacterial meningitis; whether the time to detection differed for non-ill and ill infants was also examined. Ill- versus non-ill-appearance was determined by a medical record review of the physical exam looking for one of 13 key words (eg, “ill-appearing,” “toxic,” “lethargic,” etc.). A total of 381 infants were included. Overall, 88% of the pathogens present were detected in blood culture within 24 hours and 95% were detected within 36 hours. In CSF, 89% of the pathogens present were detected within 24 hours, and 95% were detected within 36 hours. In infants with bacteremia who were non-ill-appearing, 85% of the blood pathogens were detected within 24 hours.

Limitations

The median time to detection for blood culture pathogens for ill-appearing versus non-ill-appearing infants was shorter by just one hour, but 15% of the non-ill infants had a positive blood culture after 24 hours. However, the prevalence of bacteremia and meningitis in non-ill-appearing infants is likely low; the authors did not report the total number of febrile infants evaluated by EDs in the study.

Important Findings and Implications

Most positive blood and/or CSF cultures for infants aged ≤60 days will yield results by 24 hours; 95% of the pathogens present could be detected within 36 hours. Sending a non-ill-appearing febrile infant home at 24 hours may miss 15% of the instances of bacteremia, but the overall low prevalence of invasive bacterial infection in infants should be considered.

The High-Value Care Rounding Tool: Development and Validity Evidence. McDaniel CE, et al. Academic Medicine. 2018;93(2):199-206.¹²

Background

Providing high-value care (HVC) to patients is a struggle for physicians and healthcare systems. Although physicians teaching trainees HVC practices could be an effective way to increase cost-conscious care, the best practices for teaching HVC remain unknown. To fill this gap, the authors developed a tool to measure the frequency and content of observable HVC teaching and evaluated the validity of the tool within a pediatric inpatient setting.

Study Overview and Results

The HVC rounding tool was developed through several phases from conception to validation. The research group used a modified Delphi method to construct the tool using a consensus building process based on opinions from content experts in the field of HVC, from a variety of specialties, experience levels, and geographic areas of the United States. Each item of the HVC instrument was rated by these experts, and, from their evaluations and surveys, an 11-item HVC tool was constructed. A pilot of the tool was performed to establish internal validity and interrater reliability based on observations of 148 patient encounters. From this process, a final 10-item HVC rounding tool emerged, including domains in quality, cost, and patient values. A few items included giving positive feedback for not doing an unnecessary test, discussing whether a patient needs to stay inpatient or meets discharge criteria, and customizing a care plan to align with family values and goals. The final iteration of the tool had no rater disagreements within the quality and patient values domain and only one disagreement within the cost domain.

Limitations

This tool was validated at a single pediatric institution, and, thus, the generalizability of the tool has not been established. The authors note that the Delphi panelists used for the construction of the tool were from a medical subspecialty background and not surgical backgrounds, which limits its applicability from a surgical perspective. The tool does not allow for differentiation between lengthy discussions or brief comments presented during rounds.

Important Findings and Implications

The HVC rounding tool is both innovative and timely. Pediatric hospitalists are leaders in family-centered care, and this tool allows assessment of whether important concepts of high-value care are discussed at the bedside. A multisite educational study using this tool would be welcome.

Disclosures

The authors have no conflicts of interest to declare.

A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

A 22-year-old man presented to a Canadian community hospital emergency department complaining of 2-3 weeks of abdominal pain and bloating associated with early satiety. He also noted weight loss of 20 pounds over the preceding months, leg and abdominal swelling with increased girth, and 1-2 loose, nonbloody stools per day.

Early satiety and bloating are nonspecific symptoms that can be due to gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal obstruction, or gastroparesis. Weight loss in a young person, particularly if >5% of body weight, is concerning for a serious underlying medical issue. It could reflect reduced intake due to anorexia, odynophagia, or dysphagia or increased energy expenditure due to an inflammatory state such as infection or rheumatic disease. The etiology of the swelling needs to be elucidated. It may be due to increased hydrostatic forces as in heart failure, venous or lymphatic obstruction, or from lowered oncotic pressure resulting from hepatic disease, nephrotic syndrome, severe malnutrition (nonbloody loose stools), or a protein losing enteropathy.

The patient was transferred to a tertiary care center for closer access to specialty consultation. He described generalized abdominal pain increasing in intensity over three weeks; bilateral lower extremity, scrotal, abdominal wall, and sacral edema; and mild dyspnea on exertion. The early satiety was not associated with dysphagia, odynophagia, nausea, or vomiting. He denied fevers, chills, night sweats, nausea, vomiting, jaundice, easy bruising, orthopnea, paroxysmal nocturnal dyspnea (PND), or chest pain. His past medical history included asthma treated with fluticasone/salmeterol and albuterol. He was a Canadian of East Asian descent working as a plumber. He previously smoked three to four cigarettes per day for six years. He stopped smoking one month before presentation. He had one alcoholic beverage per week and smoked marijuana weekly. He denied any family history of similar symptoms or malignancy.The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

The differential diagnosis for weight loss and anasarca is broad and includes malignancies, infectious diseases, rheumatic or inflammatory disorders, malabsorption, and advanced cardiac, renal, or liver disease. His history does not classically point in one direction. The mild dyspnea on exertion may be due to cardiac disease, but it is unlikely in the absence of orthopnea and PND. The dyspnea could be due to increased abdominal pressure if ascites are present, his underlying asthma, or another etiology such as anemia. Fevers, chills, and/or night sweats can be expected in infections and some malignancies, but their absence does not exclude infections and malignancies from the differential diagnoses. Particular attention should be paid to lymphadenopathy on the physical examination. The presence of an umbilical nodule (Sister Mary Joseph sign) could indicate a malignancy (gastrointestinal or lymphoma).

On physical examination, his temperature was 38.1°C, heart rate was 138 beats per minute, blood pressure was 123/86 mm Hg, respiratory rate was 20 breaths per minute, and oxygen saturation was 97% on room air. He appeared uncomfortable and diaphoretic. No scleral icterus or jaundice was appreciated. There were no palpable cervical, axillary, or inguinal lymph nodes. Cardiac examination revealed tachycardia and no murmurs, rubs, gallops, or jugular venous distention. Abdominal examination revealed abdominal distention, diffuse tenderness to deep palpation, bulging flanks, and a positive fluid wave. Liver and spleen could not be palpated or percussed secondary to abdominal distention. He had pitting bilateral lower extremity edema that extended to and included the scrotum. Neurologic and pulmonary examinations were unremarkable.

His examination reveals low-grade fever, tachycardia, and diaphoresis. Whether this represents progression of his primary disease or he has acutely developed a superimposed infection is uncertain at this point. He has notable anasarca but no jugular venous distention, crackles, or S3 gallop. The lack of evidence of pulmonary edema or increased central venous pressure on physical examination increases the likelihood of cirrhosis, hypoalbuminemia, or obstruction (lymphatic or venous) and decreases the likelihood of heart failure as the etiology of his peripheral edema and likely ascites. Despite the prominence of gastrointestinal symptoms, he has neither jaundice nor stigmata of chronic liver disease. Periorbital edema, which may be present in nephrotic syndrome, is also absent. Although he has no palpable peripheral lymphadenopathy, malignancy remains a concern.

Testing should include urinalysis for proteinuria and coagulation studies to assess synthetic function of the liver. Abdominal ultrasound is indicated to confirm ascites. If present, a diagnostic paracentesis should be performed to rule out spontaneous bacterial peritonitis and determine whether the ascites is from portal hypertension, hypoalbuminemia, or peritoneal disease. If the transaminases are elevated or if the ascitic fluid is concerning for malignancy, he will need a computed tomography (CT) of the abdomen and pelvis. A protein losing enteropathy due to malignancies (gastric cancer or lymphoma), rheumatic disease (systemic lupus erythematosus [SLE]), or infiltrative disease (amyloid) is also a possibility. If the other studies are unrevealing, stool should be sent for alpha-1 antitrypsin.

Laboratory studies revealed hemoglobin 7.8 g/dL, platelets 53 k/mm³, white blood cell count (WBC) 10.6 k/mm³, alkaline phosphatase (ALP) 217 U/L, albumin 2.7 g/dL, reticulocyte count 3 k/mm³ (reference range, 30-110 k/mm³), and ferritin 1,310 ng/mL (reference range, 20-400 ng/L). Serum aminotransferase levels, bilirubin, coagulation panel, electrolytes, and creatinine were normal. Urinalysis was negative for blood, leukocytes, and protein. Diagnostic paracentesis demonstrated a serum-ascites-albumin gradient (SAAG) of two and macrophage predominance (WBC 250 U/L). Ascitic fluid cytology and culture were negative. Blood cultures, human immunodeficiency virus (HIV)-1 and 2, cytomegalovirus (CMV), and Epstein–Barr virus (EBV) serologies were negative. Viral serologies for hepatitis A, B, and C were negative. Antinuclear antibody (ANA), anti-ds DNA, antineutrophilic cytoplasmic antibody (ANCA), serum angiotensin-converting enzyme (ACE) level, and quantitative immunoglobulin levels were all within the normal range. Chest, abdomen, and pelvis CT with contrast revealed large-volume abdominal and pelvic ascites, diffuse subcutaneous edema (Figure 1), modest hepatosplenomegaly, small bilateral pleural effusions, and mediastinal, axillary, mesenteric, periportal, peripancreatic, and retroperitoneal lymphadenopathy (Figure 2).

Some of the more common viral etiologies of generalized lymphadenopathy and cytopenias are unlikely because serologies for HIV, hepatitis B and C, EBV, and CMV are negative. Tuberculosis fits with the insidious nature of his presentation and remains on the differential although a low SAAG would be expected. From a rheumatologic standpoint, the lack of characteristic findings on history and physical examination and the negative ANA and anti-ds DNA results make SLE unlikely. Although elevated in the majority of untreated sarcoid patients, a normal ACE level is not sufficient to rule out this diagnosis. IgG, IgA, and IgM levels would be low if there was significant gastrointestinal protein loss and elevated in MCD. The markedly increased ferritin level, an acute-phase reactant often elevated in the setting of inflammation or malignancy, raises suspicion for adult Still’s disease (despite the lack of characteristic arthralgias and/or rash) and hemophagocytic lymphohistiocytosis (HLH).

A SAAG greater than or equal to 1.1 indicates the presence of portal hypertension. Portal hypertension most often results from cirrhosis for which this patient has no apparent clinical findings. Etiologies of noncirrhotic portal hypertension are classified as prehepatic, intrahepatic, and posthepatic. There is no clinical or radiologic evidence of portal or splenic vein thrombosis (prehepatic) or heart failure (posthepatic). Possible intrahepatic etiologies include malignancy and sarcoid. Although uncommon, patients with malignancy-related ascites may have a high SAAG without coexisting cirrhosis. This occurs if there is portal hypertension due to extensive metastases in the liver or involvement of the portal venous system. The cytology of the ascitic fluid is negative. However, cytology is <80% sensitive in the absence of peritoneal carcinomatosis.

Hematology was consulted for evaluation of the lymphadenopathy, anemia, and thrombocytopenia and recommended bone marrow and excisional lymph node biopsies. Bone marrow biopsy showed trilineage hypercellularity (Figure 3A) with reduced erythropoiesis and reticulin fibrosis (Figure 3B). An axillary lymph node biopsy with flow cytometry was nondiagnostic for a lymphoproliferative disorder or malignancy.

Five days after discharge, he was readmitted with worsening anasarca, massive ascites, and acute kidney injury. Admission laboratory studies revealed creatinine 1.66 mg/dL, hemoglobin 11.5 g/dL, and platelets 94 k/mm³. In addition, his ferritin level was 1,907 ng/L (reference range, 20-400 ng/L), erythrocyte sedimentation rate (ESR) was 50 mm/h (reference range, 0-20 mm/h), and C-reactive protein concentration (CRP) was 12.1 mg/dL (reference range, 0-0.5 mg/dL).

Steroids are used to treat a wide variety of illnesses, some of which are still under consideration in this patient including lymphoma, MCD, adult Still’s disease, and HLH. His symptoms recurred quickly after discontinuation of steroids in the setting of elevated ferritin, ESR, and CRP levels reflecting marked ongoing inflammation. Serologic testing for soluble IL-2 receptor, often elevated in MCD and HLH, should be performed. Excisional biopsy of an accessible node should be performed urgently.

His acute kidney injury resolved; however, he continued to have intermittent fevers, anemia, thromobocytopenia, lymphadenopathy, and hepatosplenomegaly. A hematology case-conference recommended testing for HLH, including soluble IL-2 receptor (CD25), soluble CD163, and natural killer cell degranulation assay, all of which were negative. A right inguinal lymph node biopsy revealed reactive lymphoid tissue and stained negative for HHV-8. Based on the lack of an alternative diagnosis (particularly lymphoma), the presence of multiple areas of lymphadenopathy, anemia, fevers, organomegaly, weight loss, reactive lymphoid tissue on lymph node biopsy, and elevated CRP and ESR, a working diagnosis of MCD was made. The negative HHV-8 testing was consistent with idiopathic MCD (iMCD); however, features inconsistent with iMCD included lack of polyclonal hypergammaglobulinemia and the presence of significant anasarca and thrombocytopenia. Therefore, an internet search was performed using the patient’s salient symptoms and findings. The search revealed a few recently published case reports of a rare variant of iMCD, TAFRO syndrome. TAFRO syndrome, characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly, fully explained the patient’s presentation. He was started on prednisone, rituximab (anti-CD20 antibody), and furosemide. After one month of treatment, he showed complete resolution of cytopenias, lymphadenopathy, organomegaly, anasarca, and ascites. Therapy continued for approximately three months, and he has remained symptom-free.

Castleman’s disease (CD) is a rare lymphoproliferative disorder divided into unicentric (solitary enlarged lymph node) and multicentric (multifocal enlarged lymph nodes).¹ MCD typically presents with systemic inflammation, reactive proliferation of benign lymphocytes, multifocal lymphadenopathy, elevated inflammatory markers, anemia, hypoalbuminemia, and polyclonal gammaglobulinemia.¹ It is hypothesized that HHV-8 drives the systemic inflammation of MCD via high levels of interleukin-6 (IL-6) activity.¹ iMCD is an HHV-8-negative variant of MCD.¹

TAFRO syndrome was first described in 2010 in three Japanese patients demonstrating high fever, anasarca, hepatosplenomegaly, lymphadenopathy, severe thrombocytopenia, and reticulin fibrosis.² In 2015, the All Japan TAFRO Syndrome Research Group recognized TAFRO syndrome as a variant of iMCD and created diagnostic criteria and a severity classification system.³ Major criteria consist of anasarca, including pleural effusion and/or ascites identified on CT scan and general edema, thrombocytopenia (platelet count <100 k/mm³), and systemic inflammation (fever >37.5°C and/or serum CRP greater than or equal to 2 mg/dL).³ Two of four minor criteria must be met, which include (1) lymph node histology consistent with CD, (2) reticulin myelofibrosis and/or increased number of megakaryocytes in bone marrow, (3) mild organomegaly, including hepatomegaly, splenomegaly, and lymphadenopathy <1.5 cm in diameter identified on CT scan, and (4) progressive renal insufficiency (serum creatinine >1.2 mg/dL in males or >1.0 mg/dL in females).³ In addition, several patients with TAFRO syndrome demonstrate elevated ALP, low-normal LDH, elevated vascular endothelial growth factor, elevated IL-6, microcytic anemia, and slight polyclonal hypergammopathy.³ Malignancies such as lymphoma and myeloma, autoimmune diseases such as SLE and ANCA-associated vasculitis, infectious diseases such as those caused by mycobacteria, and POEMS (polyneuropathy, organomegaly, endocrine diseases, M-protein, and skin lesions) syndrome must be excluded to diagnose TAFRO syndrome.^3,4

The pathophysiology of TAFRO syndrome is unknown, and it is unclear whether the syndrome is truly a variant of iMCD or a distinct entity.³ IL-6 is typically only mildly elevated in TAFRO syndrome, without the consequent thrombocytosis and polyclonal hypergammaglobulinemia seen in MCD, which is associated with higher levels of IL-6.¹ Multiple non-HHV-8 mechanisms for TAFRO syndrome have been proposed, including (1) systemic inflammation, autoimmune/autoinflammatory mechanisms, (2) neoplastic, ectopic cytokine secretion by malignant or benign tumor cells, and/or (3) infectious, such as non-HHV-8 virus.⁵

Immunosuppression is the mainstay of treatment for TAFRO syndrome based on recommendations from the 2015 TAFRO Research Group.³ Glucocorticoids are considered first-line therapy.³ Cyclosporin A is recommended for individuals refractory to glucocorticoids.³ In patients with a contraindication to cyclosporin A, anti-IL-6 receptor antibodies such as tocilizumab (approved for treatment of iMCD in Japan) and siltuximab (approved for treatment of iMCD in North America and Europe) or the anti-CD20 antibody rituximab should be prescribed.³ There is evidence for the thrombopoietin receptor agonists romiplostim and eltrombopag to treat persistent thrombocytopenia.³ Additional treatments for refractory TAFRO syndrome include IVIG and plasma exchange, chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), and thalidomide.^3,6

Little is known about the epidemiologic characterization of TAFRO syndrome as less than 40 cases of TAFRO syndrome have been reported in the United States, Asia, and Europe.

• Key clinical and pathologic features of TAFRO syndrome include thrombocytopenia, anasarca, fever, reticulin fibrosis and/or renal insufficiency, and organomegaly.
• TAFRO syndrome may be under-recognized due to very recent characterization and no previous ICD code for CD.
• TAFRO syndrome experts recommend immunosuppression for treatment of TAFRO syndrome, including glucocorticoids as first-line treatment.
• Internet searches can be helpful in the diagnosis of challenging cases, particularly with rare, unusual, and emerging diseases that have not yet been described in reference texts and only infrequently reported in the medical literature.

Disclosures

Jonathan S. Zipursky, Keri T. Holmes-Maybank, Steven L. Shumak, and Ashley A. Ducketthave none to declare.

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

There are differences in how pulmonologists and other clinicians approach the diagnosis and management of patients with moderate to severe asthma, according to a survey conducted by Medscape in collaboration with CHEST, the American College of Chest Physicians. Despite some of these differences, those surveyed do predominantly favor similar treatment options, including inhaled corticosteroids and biologics. Biologics in particular are perceived as a promising therapeutic approach for moderate to severe asthma by clinicians overall, and many are also comfortable prescribing them.

Medscape and CHEST asked 763 clinicians about their views on moderate to severe asthma. Responses came from 100 pulmonologists; 102 allergists/immunologists; 102 critical care medicine physicians; 100 emergency medicine (EM) physicians; 104 pediatricians; 100 primary care physicians (PCPs); and 155 nurse practitioners (NPs), physician assistants (PAs), or registered nurses (RNs).

Inhaled Steroids Top Treatment Choice

Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored medication for patients with moderate to severe asthma; 83% of allergists/immunologists feel this way, as do between 52% and 63% of the other clinicians, including pulmonologists.

Inhaled corticosteroids alone are generally preferred by 23%-28% of clinicians surveyed, with the exception of allergists/immunologists (12%). EM physicians (19%) and pediatricians (16%) tend to more often favor an inhaled corticosteroid and leukotriene-modifying agent than do other clinicians, but notably, none of the allergists/immunologists felt this way.

 

Biologics Are an Important Step Forward

When it comes to biologic agents for moderate to severe asthma, it is allergists/immunologists (91%) who say they are most comfortable prescribing them. This percentage drops to 59% for pulmonologists, 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% for PCPs, 7% for pediatricians, and just 2% of EM physicians

Aaron B. Holley, MD, FCCP, program director at the Pulmonary and Critical Care Medical Fellowship, Department of Medicine, Walter Reed National Military Medical Center, Bethesda, Maryland, and a member of the Moderate to Severe Asthma Center of Excellence steering committee, noted that the latest rage is to personalize treatment by “phenotyping” asthma, with the thought being that certain asthma phenotypes will respond well to some treatments, but not to others. “This sounds good in academic and scientific papers, but remains difficult to operationalize in the clinic,” said Holley.

He also noted that the new biologics all target one specific phenotype: eosinophilic asthma. “This phenotype makes up approximately 50% of all patients with asthma; however, the other 50% have no targeted treatments available, and they don’t necessarily respond well to conventional inhaler therapy,” said Holley.

And for patients with severe, poorly responsive asthma, it’s hard to say precisely what percentage is being treated inappropriately for their phenotype, versus what percentage is noncompliant, versus what percentage is due to socioeconomic status and behavioral health issues, he noted.

The solution? “There is no easy solution,” said Holley. “More specialized, severe asthma clinics? Greater education on inhaler use and disease severity? Concomitant management of behavioral health complaints? All these are necessary, but they’re also resource-intensive.”

Still, in his view, the glass is half-full. “The biologics are an important step forward, and we’re getting better at phenotyping. Compared with 5-10 years ago, we’re in a much better place.”

Preferred Biomarkers

Familiarity with biomarkers for moderate or severe asthma is universal among pulmonologists. Only 2% of allergists/immunologists are not familiar with biomarkers, compared with nearly three quarters of EM physicians, 45% of pediatricians, 36% of PCPs, 31% of NP/PA/RNs, and 20% of critical care medicine physicians.

Immunoglobulin E (IgE) levels ranked as the most important biomarker for moderate or severe asthma, favored by 47% of pulmonologists and 50% of allergists/immunologists, followed by eosinophils, preferred by 44% of pulmonologists and 38% of allergists/immunologists. Between 26% and 36% of other clinicians rank IgE tops, except for EM physicians (13%). About one third of critical care medicine physicians and one quarter of PCPs and NP/PA/RNs think eosinophils are the most important biomarker, compared with only 14% of pediatricians and 10% of EM physicians.

Fraction of exhaled nitric oxide (FeNO) is least favored by all clinicians surveyed. Just 9% of pulmonologists, 12% of allergists/immunologists, and 5% of EM physicians like this biomarker. Pediatricians ranked FeNO the highest among those surveyed, but only at 14%.

 

Assessment Tools and Guidelines

One “interesting” finding is the difference between specialties in use of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ), commented Holley. Most pulmonologists (57%) and allergists/immunologists (79%) favor ACTs for adults and children, whereas other clinicians seem to favor the ACQ.

Both the ACT and ACQ have decent literature to support their use, he noted. “I use the ACT, but personally, I don’t think it makes a difference which you use. I do think it’s important to get an objective score for their subjective symptoms to facilitate tracking over time, and to ensure that clinicians are speaking the same language. For example, if someone else sees my patient for some reason, one look at the ACT score will summarize their disease control, as opposed to them having to pull it out of a running narrative history,” said Holley.

ACTs are also favored by 39% of NP/PA/RNs, 34% of pediatricians, 27% of PCPs, 16% of critical care medicine physicians, and just 6% of EM physicians. About one third of EM physicians and PCPs (34% each) favor the ACQ, as do 30% of NP/PA/RNs, 29% of pediatricians, 20% of pulmonologists, 17% of allergists/immunologists, and 8% of EM physicians.
 

Thirty-six percent of all clinicians said they don’t use any assessment tool to gauge asthma control in patients with moderate to severe asthma, including 86% of EM physicians and 42% of PCPs – the specialties most apt to report no use.

As for guideline use, 83% of allergists/immunologists and 81% of pediatricians surveyed use the National Asthma Education and Prevention Program (NAEPP) guidelines. Pulmonologists tend to use these guidelines less often (37%), as they also rely on the Global Initiative for Asthma (GINA) (54%) and European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines (43%).

About two thirds (62%) of NP/PA/RNs favor the NAEPP guidelines, as do 49% of PCPs and critical care medicine physicians and 31% of EM physicians. Sixty percent of EM physicians don’t use guidelines at all.

 

Chief Culprits Behind Poor Asthma Control

Clinicians tend to see a lack of appropriate treatment as the greatest barrier for patients with moderate to severe asthma; 63% of pulmonologists feel this way, as do 60% of allergists/immunologists, 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, compared with just 32% of EM and critical care medicine physicians. EM (67%) and critical care medicine (54%) physicians are also more apt to think that the patient not seeing a provider is the greatest barrier.

Overall, most clinicians surveyed link poor asthma control to poor medication adherence and social or environmental risk irritants, such as smoking, secondhand smoke exposure, vaping, and pollutants.

“No surprise here,” said Holley. “In my experience, medication adherence and environmental risks or irritants are big factors in patients with moderate to severe asthma who don’t respond to conventional, standard asthma treatment and continue to progress.”

“We know from data that poor control is related to socioeconomic status and behavioral health. We also know that proper inhaler use and compliance are a big problem. Does this account for most ‘progression’? That’s hard to say, I suppose, but certainly these are big factors,” Holley added.

Echoing Holley, Navitha Ramesh, MD, clinical assistant professor of medicine at the Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, who is also a member of the Moderate to Severe Asthma Center of Excellence steering committee, said the biggest barriers to treatment, in her experience, are “poor health literacy, medication nonadherence, poor social support, and tobacco use.”

The survey was conducted August 29, 2018, to October 11, 2018. Pulmonologists were recruited from CHEST, and all other clinicians were recruited from Medscape members. Patients with moderate to severe asthma account for at least half of all patients with asthma seen by pulmonologists, allergists/immunologists, and critical care medicine physicians; this proportion falls to about 30% among pediatricians and PCPs. Of the clinicians surveyed, patients with moderate to severe asthma are overwhelmingly referred to pulmonologists. Among the reasons for referral are multiple emergency department visits, poor control, failure on first-line therapy, and confounding factors.

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In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

In a study highlighted in a recent issue of CHEST Physician, Hou and colleagues analyzed complications from biopsies of lung abnormalities seen on CT scans by conducting a large retrospective study with data gleaned from national databases of patients undergoing CT- guided biopsy, surgery, or bronchoscopy.¹ While it should not be interpreted as representative of a lung cancer screening population (for excellent comments by Drs. Rivera and Silvestri regarding the study, see: https://tinyurl.com/y52ucb94), it does raises two important questions when performing shared decision-making for low dose CT (LDCT) scanning: (1) What information should clinicians discuss with patients regarding various biopsy methods until more data are available? (2) How do we mitigate complications from biopsies?

While procedure-specific biopsy risk may be generalizable, it may be institutionally specific, and knowledge of local skill and outcomes data can help guide discussions. With that said, some general information can inform decisions. The NAVIGATE study investigators recently published their 1-year follow-up results using a navigational bronchoscopy system (superDimension^™). While inherent limitations to this study exist, it does provide some useful information as to procedure-related complications from a large sample of patients who approximate a lung cancer screening population. This group was composed of both academic and community centers and prospectively followed 1,215 patients for 1 year.² The average age of the population was 67.6 (± 11.3), and 80% were current or former smokers. The median nodule size was 2 cm. The diagnostic yield was 73% at 1 year follow-up (data will be re-analyzed at 2 years). The pneumothorax rate was 4%, with 3% requiring chest tube. Hemorrhage occurred in 2.5% of all patients, with 1.5% having a common terminology criteria for adverse events (CTCAE) ≥ 2. Grade 4 respiratory failure occurred in 1 patient. There were no ENB procedure-related deaths. It should be noted that individuals performing these procedures were, by and large, high-volume and experienced users.

In comparison, the overall pooled sensitivity for CT scan-guided biopsy is 90% for pulmonary nodules and masses. The yield is lower, however, for smaller lesions (≤2.0) and ranges from 74% to 77%.³ The average pneumothorax rate is 20%, with 1% to 3% requiring chest tube placement. Risk factors for pneumothorax vary between studies, but, generally speaking, have been associated with nodules ≤ 2 cm, those within 2 cm of the pleura (but not abutting the pleura), and emphysema in the track of needle trajectory. Pulmonary hemorrhage occurs 30% of the time but is mild in most cases. Hemoptysis and severe hemorrhage occur at rates of 4% and <1%, respectively. Risk factors for development of pulmonary hemorrhage include small lesion size (< 2 cm) and lesions > 2 cm from the pleura.

When considering surgical lung biopsies and resection, recent data suggest every effort should be made to encourage smoking cessation in order to mitigate postoperative morbidity. In a retrospective study by Fukui and colleagues,⁴ respiratory morbidity (defined as hypoxia, pneumonia, atelectasis, and uncontrolled sputum production) was 22% in smokers vs 3.5% in never smokers. The rate of complications decreased as the time from smoking cessation to date of surgery increased.

The goal for each patient who is counseled should be to limit the number of procedures and achieve the greatest diagnostic confidence with the lowest complication rate. With these risks and diagnostic yield in mind, the decision to recommend a particular biopsy strategy (or no biopsy at all) should be based on current guideline recommendations: (1) patient co-morbidities and preferences; (2) size of index nodule or mass; (3) presence of pathologically enlarged mediastinal and/or hilar lymphadenopathy; (4) evidence of extrathoracic metastasis; and (5) institutional expertise. Specifically speaking for the pulmonologist, this translates into identifying specific procedural “champions” who are dedicated to performing these procedures and are members of a multidisciplinary thoracic team. These individuals should have dedicated training in advanced diagnostic procedures to achieve the aforementioned goals.⁵ The same should hold true for transthoracic, CT-guided biopsies. Interventional pulmonology fellowships are structured to provide exposure to multidisciplinary nodule clinics and tumor boards, establishing quality improvement initiatives, as well as developing procedural expertise.⁶

It is apparent that shared decision-making can become complex. These details will likely be lost to a primary care provider simply due to time constraints and information overload. As such, pulmonologists should be at the forefront of lung cancer screening – in programmatic development, implementation, and providing education to providers directly involved with shared decision-making discussions.
 

Dr. Aboudara is with the Division of Allergy, Pulmonary, and Critical Care; Vanderbilt University Medical Center; Nashville, Tennessee.

References

1. Huo J, Xu Y, Sheu T, et al. Complication rates and downstream medical costs associated with invasive diagnostic procedures for lung abnormalities in the community setting: Complications and medical costs associated with diagnostic procedures for lung abnormalities. JAMA Intern Med. 2019;179:324-32.

2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for peripheral pulmonary lesions: One-year results of the prospective, multicenter NAVIGATE study. J Thorac Oncol. 2019;14(3):445-58.

3. Ohno Y, Hatabu H, Takenaka D, et al. CT-guided transthoracic needle aspiration biopsy of small (< or = 20 mm) solitary pulmonary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69.

4. Fukui M, Suzuki K, Matsunaga T, et al. Importance of smoking cessation on surgical outcome in primary lung cancer. Ann Thorac Surg. 2019;107(4):1005-09.

5. Mahajan A, Khandhar S, Folch EE. Pulmonary Perspectives^®: Ensuring quality for EBUS bronchoscopy with varying levels of practitioner experience. CHEST Physician. April 6, 2017. https://tinyurl.com/y3hwlc4g. .

6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Accreditation Standards: Executive summary of the Multisociety Interventional Pulmonology Fellowship Accreditation Committee. Chest. 2017;151(5):1114-21.

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
 

Why were these valves developed?

Courtesy of Dr. Catherine L. Oberg

For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
 

How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?

Courtesy of Dr. Catherine L. Oberg

Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
 

Which endobronchial valves are available in the United States?

In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr^® EBV (Pulmonx) ( (Fig 1) and the Spiration^® Valve System (Olympus) (IBV) (Fig 2). The Zephyr^® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration^® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
 

What’s the evidence behind BLVR?

Zephyr^® Valves

The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr^® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).

Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).

In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr^® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).

The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr^® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr^® valve’s FDA approval.
 

Spiration^® Valves

Small trials have shown favorable results with the Spiration^® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV₁ or other physiologic parameters.

The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration^® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
 

Collateral Ventilation

Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System^®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.

Which patients with emphysema should be referred for consideration of valve placement?

The following criteria should be used in selecting patients for referral for BLVR:

• FEV₁ 15% - 45% of predicted value at baseline

• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%

• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters

• Clinically stable on < 20 mg prednisone (or equivalent) daily

• Nonsmoking for at least 4 months

• Integrity of one or both major fissures at least 75%

• Ability to provide informed consent and to tolerate bronchoscopy
 

Complications

The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.


 

What’s ahead for ELVR?

Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.



Zephyr^® Endobronchial Valve (Pulmonx)

Spiration^® Valve System (Olympus)

The American College of Chest Physicians (CHEST) does not endorse or supp


 

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Editor’s Picks


COMMENTARY
On Being the Editor in Chief of the Journal CHEST: 14 Memorable Years.
By Dr. Richard S. Irwin

ORIGINAL RESEARCH
Procalcitonin-Guided Antibiotic Discontinuation and Mortality in Critically Ill Adults: A Systematic Review and Meta-analysis.
By Dr. B. J. Pepper, et al.

A Novel Algorithm to Analyze Epidemiology and Outcomes of Carbapenem Resistance Among Patients With Hospital-Acquired and Ventilator-Associated Pneumonia: A Retrospective Cohort Study.
By Dr. M. D. Zilberberg, et al.

Raw Bioelectrical Impedance Analysis Variables Are Independent Predictors of Early All-Cause Mortality in Patients With COPD.
By Dr. Francesca de Blasio, et al.

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Recently, the CHEST Foundation had the pleasure of sitting down with Salim Surani, MD, FCCP to get his perspective on the NetWorks Challenge and its impact. Dr. Surani initially got involved with CHEST at the Board level and is now a leader within the Council of NetWorks. “My hope was that I could work within my NetWork to help them become more involved with CHEST and the CHEST Foundation. Through this involvement, I believe we can help shape changes in chest medicine practice dynamics. In the Practice Operations NetWork, we strive to educate physicians in practice to ensure they are up to date with government regulations and how to navigate changes in a positive way, ultimately with the goal of impacting our patients’ lives for the better.”

When asked about his involvement with CHEST and the Foundation, he said “It just makes sense to be involved in an institution that is passionate about taking care of patients and clinicians. The CHEST Foundation has given tens of millions of dollars in funding for grants to help shape the future of the education, the future of research, and the future of better patient care.”

Dr. Surani has always been a strong advocate for the NetWorks Challenge. “There is nothing that has been more satisfying in my life than the opportunity to give. I have always believed that the biggest winner is the person who gives a gift. When you give something to the right cause, what you get in return is a tremendous amount of satisfaction, and it is that satisfaction which drives you – which gives you a feeling of purpose. I want others to get involved and participate. If you feel passionate about something, put your money where your mouth is. This is why I will be matching any gift of $500 or greater by 10% made to any NetWork during the NetWorks Challenge. This is an opportunity to multiply your donation before it goes to the CHEST Foundation so that grants and other awards can be larger in the coming years. The NetWorks Challenge helps fund our Diversity Travel Grants Program and provides additional travel grants to each participating NetWork.” Last year, Dr. Surani gave an additional $2,365.17 through his challenge match. Are you up for the challenge this year?

Visit chestfoundation.org/donate today to help shape the future of our discipline!

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

Clinical Pulmonary Medicine

Pulmonary embolism in pregnancy: A diagnostic conundrum

Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.

To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.

In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.

Muhammad Adrish, MD, FCCP
Steering Committee Member

Munish Luthra, MD, FCCP
Steering Committee Member
 

Cardiovascular Medicine and Surgery

Physical examination of low cardiac output in the ICU

Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).

Benjamin Kenigsberg, MD
Steering Committee Member

Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
 

Chest Infections

Lung infections in the transplant recipients

Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).

The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).

An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.

As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.

Raed Alalawi, MD, FCCP
Steering Committee Member
 

Interprofessional Team

Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma

Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO₂ while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.

Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member

Munish Luthra MD, FCCP
Steering Committee Member
 

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.

What makes the traditional New Orleans food so special? The flair and broad history for these dishes unite the city and the love for all things tasty with its seafood, Creole, Cajun, and many other types of food options. We’ve picked five famous New Orleans dishes that you should try while you attend CHEST 2019.

GUMBO

As one of Louisiana’s quintessential dishes, you can find gumbo in restaurants, at events, and homes all over the state. Claiming both French and West African roots, there’s no one way to make gumbo, but it is usually served over rice and with a wide variety of other ingredients. With so many different recipes that each family and cook has perfected to be the “best,” most cooks tend to guard their recipes closely.

CRAWFISH ETOUFFEE

The word étouffée (pronounced eh-too-fey) comes from the French word “to smother.” This dish is a very thick stew full of crawfish (or shrimp) served over rice. It is also similar in some way to gumbo – same types of Creole seasonings, served over rice, and made with a roux – but it is often made with a “blonde” roux, which is lighter in color and gives an almost sweet flavor. It’s a taste that’s worth trying and claimed you won’t forget.

JAMBALAYA

Another famous and traditional New Orleans dish is jambalaya. This is a rice dish that is a culinary staple of the city with a history from the time when colonial Spanish settlers tried reconstructing their native paella from locally sourced ingredients. It typically contains a mix of meat, vegetables, spices, and rice, combined in a variety of ways.

PO-BOYS

This classic French bread sandwich is stuffed and slathered with sauce. Filled with lettuce, tomato, and pickles, it’s usually whatever filled with whatever meat you choose – roast beef, fried shrimp, oysters. This allows for many types of po-boy sandwiches. You tend to see very creative po-boys at the Oak Street Po-Boy Festival each year.

BEIGNETS

These pastries are more than just a doughnut and are famous for being a doughnut without the hole. As the city’s most popular sweet treat and staple, locals and visitors can enjoy beignets all year long, available 24-hours a day in New Orleans at more than one coffee hotspot.