Smoking Rates Remain Steady Among the Poor Undiagnosed OSA Can

PULMONOLOGY CARDIOLOGY PEDIATRIC PULMONOLOGY SLEEP MEDICINE AFib is on the rise in COPD patients ODYSSEY trial supports PCSK9 use to Maternal vaccination for RSV was Insomnia is linked with epileptic hospitalized for exacerbation // 11 reduce M1 and M2 risk // 21 found to protect neonates // 28 seizure frequency // 39

VOL. 14 • NO. 6 • JUNE 2019

Smoking rates Undiagnosed remain steady OSA can double among the poor

cardiovascular BY ANDREW D. BOWSER MDedge News

risk after hile an increasing number of U.S. citizens are saying no to cigarettes, current smok- surgery Wing rates are holding steady among people who face multiple forms of socioeconomic or health-related disadvantages, a recent study shows. The odds of current smoking, versus never smoking, declined significantly during 2008- 2017 for individuals with none of six disadvan- Dr. Matthew T.V. Chan and tages tied to cigarette use, including disability, colleagues stated, “General unemployment, poverty, low education, psy- anesthetics, sedatives, and chological distress, and heavy alcohol intake, postoperative analgesics are according to researchers. potent respiratory depressants Individuals with one or two of those disad- that relax the upper airway vantages have also been cutting back, the data dilator muscles and impair suggest. But, by contrast, odds of current versus ventilatory response to never smoking did not significantly change for hypoxemia and hypercapnia.” those with three or more disadvantages, accord-

Courtesy Dr. Matthew T.V. Chan Matthew T.V. Dr. Courtesy ing to Adam M. Leventhal, PhD, of the Univer- sity of Southern California, Los Angeles, and BY BIANCA NOGRADY patients to postoperative cardiovascular compli- coinvestigators. MDedge News cations,” said researchers who conducted the The “How this pattern can inform a cohesive poli- Postoperative vascular complications in unrec- cy agenda is unknown, but it is clear from these nrecognized severe obstructive sleep apnea ognised Obstructive Sleep apnoea (POSA) study findings that the crux of the recently expanding is a risk factor for cardiovascular compli- (NCT01494181). tobacco-related health disparity problem in the Ucations after major noncardiac surgery, They undertook a prospective observational Smoking // continued on page 7 according to a study published in JAMA. cohort study involving 1,218 patients undergo- The findings indicate that perioperative mis- ing major noncardiac surgery, who were already INSIDE HIGHLIGHT management of obstructive sleep apnea can considered at high risk of postoperative cardio- NEWS FROM CHEST lead to serious medical consequences. “Gen- vascular events – having, for example, a history Envisioning the eral anesthetics, sedatives, and postoperative of coronary artery disease, stroke, diabetes, or analgesics are potent respiratory depressants renal impairment. However, none had a prior INSPIRATION: future: The CHEST that relax the upper airway dilator muscles and diagnosis of obstructive sleep apnea. Environmental Pacing the Future impair ventilatory response to hypoxemia and Preoperative sleep monitoring revealed that Scan hypercapnia. Each of these events exacerbates two-thirds of the cohort had unrecognized and Page 44

[obstructive sleep apnea] and may predispose OSA // continued on page 6

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CHANGE SERVICE REQUESTED SERVICE CHANGE Presorted Standard Presorted CHEST PHYSICIAN CHEST Register Today chestmeeting.chestnet.org NEWS Employed physicians now outnumber independents BY ALICIA GALLEGOS survey from the American Medical employed, compared with 46% of percentage points over the same peri- MDedge News Association. doctors who were self-employed that od, according to the study published The AMA’s annual Physician year. The number of employed phy- May 6 on the AMA website. or the first time, employed Practice Benchmark Survey, which sicians has risen 6 percentage points Younger physicians and women physicians outnumber indepen- queried 3,500 doctors, showed that since 2012, while the number of doctors were more likely to be em- Fdent physicians, according to a 47% of all physicians in 2018 were self-employed doctors has fallen by 7 ployed than their counterparts. Nearly

4 • JUNE 2019 • CHEST PHYSICIAN 70% of physicians under age 40 years cian-owned practices in 2018 either 42% who were employees. employed physicians (57%). were employees in 2018, compared as an owner, employee, or contrac- Surgical subspecialists had the A majority of doctors still work in with 38% of physicians 55 years and tor, a decrease from 60% in 2012. highest share of owners (65%) fol- small practices, the analysis found. older, the study found. About 35% of Male physicians were more likely lowed by obstetrician-gynecologists In 2018, 57% of physicians worked physicians worked either directly for a to be practice owners than female (54%) and internal medicine subspe- in practices with 10 or fewer phy- hospital or in a practice at least partly physicians. Among female doctors, cialists (52%). Emergency physicians sicians versus 61% in 2012. How- owned by a hospital in 2018, up from 58% were employees, compared had the lowest share of owners (26%) ever, fewer physicians work in solo 29% in 2012. with 34% who were practice owners, and the highest share of independent practice. Between 2012 and 2018 More than half of physicians while 52% of men physicians were contractors (27%). Family physicians, the percentage of physicians in solo surveyed (54%) worked in physi- practice owners, compared with meanwhile, had the highest share of practice fell from 18% in 2012 to 15% in 2018. The AMA’s Physician Practice Benchmark Survey is a nationally representative survey of post-resi- dency physicians who provide at least 20 hours of patient care per week, are not employed by the federal government, and practice in one of the 50 states or the District of Columbia. The 2018 survey was conducted in September 2018, and the final data included 3,500 physicians. [email protected]

VIEW ON THE NEWS Michael E. Nelson, MD, FCCP, comments: Today one hears of physician early retire- ment and burnout, and now data that reveal that most doctors are choosing employment over ownership. With the hyperbolic expansion of ad- ministrative tasks related to government oversight, the institution of the electronic records, the ever-increasing cost of overhead, among many other pressures, it is not difficult to understand why physicians choose not to “own” a practice. If one transfers those headaches to someone else, the practice of medicine should be sim- plified. But as an employee, physicians are often judged more by their Press-Ganey score than how well they practice medicine. There is also a crowd of corporate clerks whose job it is to count things and tell you why you are not doing your job correctly or efficiently, while knowing nothing of what your job entails. In addition, most employment contracts contain a “termination without cause” clause that allows the employer to fire you without giving you a reason. I believe owning a practice may be less frightening.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 5 NEWS FROM CHEST // 40 Sedation amplies OSA risk // continued from page 1

untreated obstructive sleep apnea, “Despite a substantial decrease in PULMONARY PERSPECTIVES®// 50 including 11.2% with severe ob- ODI [oxygen desaturation index] structive sleep apnea. with oxygen therapy in patients with At 30 days after surgery, patients OSA during the first 3 postoperative CHEST PHYSICIAN with obstructive sleep apnea had a nights, supplemental oxygen did IS ONLINE 49% higher risk of the primary out- not modify the association between CHEST Physician is available at David A. Schulman, MD, come of myocardial injury, cardiac OSA and postoperative cardiovascu- chestphysician.org. FCCP, is Medical Editor in death, heart failure, thromboem- lar event,” wrote Matthew T.V. Chan, Chief of CHEST Physician. bolism, atrial fibrillation, or stroke, MD, of Chinese University of Hong compared with those without ob- Kong, Prince of Wales Hospital, and structive sleep apnea. coauthors. However, this association was Given that the events were as- largely due to a significant 2.23-fold sociated with longer durations of higher risk among patients with se- severe oxyhemoglobin desaturation, American College of Chest CHEST Physician, the newspaper of the American vere obstructive sleep apnea, while more aggressive interventions such Physicians (CHEST) College of Chest Physicians, provides cutting-edge those with only moderate or mild as positive airway pressure or oral EDITOR IN CHIEF reports from clinical meetings, FDA coverage, clinical David A. Schulman, MD, FCCP trial results, expert commentary, and reporting on the sleep apnea did not show a signifi- appliances may be required, they business and politics of chest medicine. Each issue also cant increased risk of cardiovascular noted. PRESIDENT provides material exclusive to CHEST members. Content Clayton Cowl, MD, FCCP for CHEST Physician is provided by Frontline Medical complications. “However, high-level evidence EXECUTIVE VICE PRESIDENT & CEO Communications Inc. Content for News From Chest is Patients in this study with severe demonstrating the effect of these Robert Musacchio provided by the American College of Chest Physicians. PUBLISHER, CHEST® JOURNAL The statements and opinions expressed in CHEST obstructive sleep apnea had a 13- measures on perioperative outcomes Physician Nicki Augustyn do not necessarily reflect those of the fold higher risk of cardiac death, is lacking [and] further clinical trials American College of Chest Physicians, or of its officers, 80% higher risk of myocardial inju- are now required to test if additional MANAGER, EDITORIAL RESOURCES regents, members, and employees, or those of the Pamela L. Goorsky Publisher. The American College of Chest Physicians, ry, more than 6-fold higher risk of monitoring or alternative interven- PUBS & DIGITAL CONTENT EDITOR its officers, regents, members, and employees, and heart failure, and nearly 4-fold high- tions would reduce the risk,” they Martha Zaborowski Frontline Medical Communications Inc. do not assume responsibility for damages, loss, or claims of any kind er risk of atrial fibrillation. wrote. SECTION EDITORS arising from or related to the information contained in Corey Kershaw, MD Researchers also saw an asso- The study was supported by the ® this publication, including any claims related to products, ciation between obstructive sleep Health and Medical Research Fund Pulmonary Perspectives drugs, or services mentioned herein. Angel Coz, MD, FCCP POSTMASTER: Send change of address (with apnea and increased risk of infective (Hong Kong), National Healthcare Critical Care Commentary old mailing label) to CHEST Physician, outcomes, unplanned tracheal intu- Group–Khoo Teck Puat Hospital, Michelle Cao, DO, FCCP Subscription Services, 10255 W Higgins bation, postoperative lung ventila- University Health Network Founda- Sleep Strategies Road, Suite 280, Rosemont, IL 60018-9914. RECIPIENT: To change your address, contact tion, and readmission to the ICU. tion, University of Malaya, Malay- Editorial Advisory Board Subscription Services at 1-800-430-5450. For The majority of patients received sian Society of Anaesthesiologists, G. Hossein Almassi, MD, FCCP, Wisconsin paid subscriptions, single issue purchases, and nocturnal oximetry monitoring Auckland Medical Research Foun- Jennifer Cox, MD, FCCP, Florida missing issue claims, call Customer Service at 1-833-836-2705 or e-mail Jacques-Pierre Fontaine, MD, FCCP, Florida during their first 3 nights after dation, and ResMed. One author de- [email protected] surgery. This revealed that patients clared grants from private industry Eric Gartman, MD, FCCP, Rhode Island Octavian C. Ioachimescu, MD, PhD, FCCP, CHEST PHYSICIAN (ISSN 1558-6200) is without obstructive sleep apnea and a patent pending on an obstruc- Georgia published monthly for the American College had significant increases in oxygen tive sleep apnea risk questionnaire Jason Lazar, MD, FCCP, New York of Chest Physicians by Frontline Medical Communications Inc., 7 Century Drive, Susan Millard, MD, FCCP, Michigan desaturation index during their used in the study. Suite 302, Parsippany, NJ 07054-4609. first night after surgery, while those [email protected] Michael E. Nelson, MD, FCCP, Kansas Subscription price is $244.00 per year. Phone with sleep apnea did not return to Daniel Ouellette, MD, FCCP, Michigan 973-206-3434, fax 973-206-9378. Frank Podbielski, MD, FCCP, Massachusetts EDITORIAL OFFICES 2275 Research Blvd, Suite their baseline oxygen desaturation SOURCE: Chan MTV et al. JAMA. M. Patricia Rivera, MD, FCCP, North Carolina 400, Rockville, MD 20850, 240-221-2400, fax index until the third night after 2019;321(18):1788-98. doi: 10.1001/ Nirmal S. Sharma, MD, California 240-221-2548 Krishna Sundar, MD, FCCP, Utah ADVERTISING OFFICES 7 Century Drive, Suite surgery. jama.2019.4783. 302, Parsippany, NJ 07054-4609 973-206- E-mail: [email protected] 3434, fax 973-206-9378 ©Copyright 2019, by the American College VIEW ON THE NEWS of Chest Physicians Wake-up call on OSA surgery risk This study is large, prospective, and rigorous, and adds import- FRONTLINE MEDICAL COMMUNICATIONS ant new information to the puzzle of the impact of sleep apnea Frontline Medical Corporate on postoperative risk, Dennis Auckley, MD, FCCP, and Stavros Communications PRESIDENT/CEO Alan J. Imhoff Memtsoudis, MD, wrote in an editorial accompanying this study. Society Partners CFO Douglas E. Grose The study focused on predetermined clinically significant and VP/GROUP PUBLISHER; DIRECTOR, SVP, FINANCE Steven J. Resnick measurable events, used standardized and objective sleep apnea FMC SOCIETY PARTNERS Mark Branca VP, OPERATIONS Jim Chicca EDITOR IN CHIEF Mary Jo M. Dales VP, SALES Mike Guire testing, and attempted to control for many of the confounders EXECUTIVE EDITORS Denise Fulton, VP, SOCIETY PARTNERS Mark Branca that might have influenced outcomes. Kathy Scarbeck VP, EDITOR IN CHIEF Mary Jo M. Dales The results suggest that obstructive sleep apnea should be EDITOR Therese Borden VP, EDITORIAL DIRECTOR, CLINICAL CONTENT recognized as a major perioperative risk factor, and it should CREATIVE DIRECTOR Louise A. Koenig Karen Clemments DIRECTOR, PRODUCTION/MANUFACTURING CHIEF DIGITAL OFFICER Lee Schweizer receive the same attention and optimization efforts as comorbidi- Rebecca Slebodnik VP, DIGITAL CONTENT & STRATEGY Amy Pfeiffer ties such as diabetes. DIRECTOR, BUSINESS DEVELOPMENT PRESIDENT, CUSTOM SOLUTIONS JoAnn Wahl Monique Michowski, VP, CUSTOM SOLUTIONS Wendy Raupers 973-206-8015, cell 732-278-4549, VP, MARKETING & CUSTOMER ADVOCACY Dr. Auckley is from the division of pulmonary, critical care and sleep [email protected] medicine at MetroHealth Medical Center, Case Western Reserve University, Jim McDonough DIGITAL ACCOUNT MANAGER VP, HUMAN RESOURCES & FACILITY OPERATIONS Cleveland, and Dr. Memtsoudis is clinical professor of anesthesiology at Rey Valdivia 973-206-8094 Carolyn Caccavelli [email protected] Cornell University, New York. These comments are adapted from an ed- DATA MANAGEMENT DIRECTOR Mike Fritz CLASSIFIED SALES REPRESENTATIVE CIRCULATION DIRECTOR Jared Sonners itorial (JAMA. 2019;231[18]:1775-6). Both declared board and executive Drew Endy 215-657-2319, positions with the Society of Anesthesia and Sleep Medicine. Dr. Auckley cell 267-481-0133 CORPORATE DIRECTOR, RESEARCH & COMMS. [email protected] Lori Raskin declared research funding from Medtronic, and Dr. Memtsoudis declared DIRECTOR, CUSTOM PROGRAMS Patrick Finnegan personal fees from Teikoku and Sandoz. SENIOR DIRECTOR OF CLASSIFIED SALES Tim LaPella, 484-921-5001, In affiliation with Global Academy for Medical Education, LLC [email protected] PRESIDENT David J. Small, MBA

6 • JUNE 2019 • CHEST PHYSICIAN NEWS New guidance on TB screens for health care workers BY BIANCA NOGRADY the previously recommended rou- assessment should have a second risk – for example, pulmonologists or MDedge News tine serial occupational testing. test (either an IGRA or a TST) as respiratory therapists – or for those “In addition, a recent retrospective recommended in the 2017 TB diag- working in settings in which trans- .S. health care personnel no cohort study of approximately 40,000 nostic guidelines of the American mission has happened in the past. longer need to undergo rou- health care personnel at a tertiary Thoracic Society, Infectious Diseases For personnel with latent tuber- Utine tuberculosis testing in U.S. medical center in a low TB-inci- Society of America, and CDC,” they culosis infection, the guidelines the absence of known exposure, dence state found an extremely low wrote. “In this example, the health recommend “encouragement of according to new screening guide- rate of TST conversion (0.3%) during treatment” unless it is contraindicat- lines from the National Tuberculosis 1998-2014, with a limited proportion “In addition, a recent retrospective ed, and annual symptom screening Controllers Association and Centers attributable to occupational expo- in those not undergoing treatment. for Disease Control and Prevention. sure,” they wrote. cohort study of approximately The guideline committee also ad- The revised guidelines The new guidelines recom- 40,000 health care personnel vocated for annual tuberculosis edu- on tuberculosis screening, mend health care personnel cation for all health care workers. testing, and treatment of undergo baseline or preplace- at a tertiary U.S. medical The new recommendations were U.S. health care personnel, ment tuberculosis testing center in a low TB-incidence based on a systematic review of 36 published in Morbidity and with an interferon-gamma studies of tuberculosis screening Mortality Weekly Report, are release assay (IGRA) or a state found an extremely low and testing among health care per- the first update since 2005. tuberculin skin test (TST), as rate of TST conversion (0.3%) sonnel, 16 of which were performed The new recommendations well as individual risk assess- during 1998-2014, with a in the United States. reflect a reduction in concern about ment and symptom evaluation. The authors stressed that recom- U.S. health care personnel’s risk of The individual risk assessment limited proportion attributable mendations from the 2005 CDC occupational exposure to latent and considers whether the person has to occupational exposure.” guidelines – which do not pertain active tuberculosis infection. lived in a country with a high tuber- to health care personnel screening, Lynn E. Sosa, MD, from the culosis rate, whether they are immu- testing, treatment and education – Connecticut Department of Public nosuppressed, or whether they have care personnel should be considered remain unchanged. Health and National Tuberculosis had close contact with someone infected with M. tuberculosis only if One author declared personal Controllers Association, and coau- with infectious tuberculosis. both the first and second tests are fees from the National Tuberculosis thors wrote that rates of tubercu- This risk assessment can help de- positive.” Controllers Association during the losis infection in the United States cide how to interpret an initial posi- After that baseline testing, per- conduct of the study. Two others re- have declined by 73% since 1991, tive test result, the authors said. sonnel do not need to undergo ported unrelated grants and personal from 10.4/100,000 population in “For example, health care person- routine serial testing except in the fees from private industry. No other 1991 to 2.8/100,000 in 2017. This nel with a positive test who are case of known exposure or ongoing conflicts of interest were disclosed. has been matched by similar de- asymptomatic, unlikely to be in- transmission. The guideline authors [email protected] clines among health care workers, fected with M. [Mycobacterium] suggested serial screening might be which the authors said raised ques- tuberculosis, and at low risk for pro- considered for health care workers SOURCE: Sosa LE et al. MMWR. tions about the cost-effectiveness of gression on the basis of their risk whose work puts them at greater 2019;68:439-43.

Economic disadvantages have cumulative impact on smoking risk // continued from page 1

United States is not tied to groups facing mere- 0.98 (95% CI, 0.97-0.99) for two, all represent- ly a single form of disadvantage,” Dr. Leventhal ing significant annual reductions in current and coauthors wrote in a report on the study in versus never smoking, investigators said. By JAMA Internal Medicine. contrast, no such significant changes were ap- The cross-sectional analysis by Dr. Leventhal parent for those with three, four, five, or six and colleagues was based on National Health such disadvantages. Interview Survey (NHIS) data from 2008 to 2017 Tobacco control or regulatory policies that including more than 278,000 respondents aged consider these disadvantages separately may be 25 years or older. overlooking a “broader pattern” showing that the A snapshot of that 10-year period showed that cumulative number of disadvantages correlates current smoking prevalence was successively with the magnitude of disparity, wrote Dr. Leven- higher depending on the number of socioeco- thal and colleagues in their report. nomic or health-related disadvantages. “Successful prevention of smoking initia- The mean prevalence of current smoking over tion and promotion of smoking cessation in that entire time period was just 13.8% for peo- multi-disadvantaged populations would substan- ple with zero of the six disadvantages, 21.4% for tially reduce the smoking-related public health those with one disadvantage, and so on, up to burden in the United States,” they concluded. 58.2% for those with all six disadvantages, ac- Dr. Leventhal and colleagues reported no cording to data in the published report. conflicts related to their research, which was Encouragingly, overall smoking prevalence fell supported in part by a Tobacco Centers of Reg- from 20.8% in 2008-2009 to 15.8% in 2016-2017, ulatory Science award from the National Cancer the researchers found. However, the decreasing Institute and the Food and Drug Administration, trend was not apparent for individuals with many among other sources. disadvantages. [email protected] The odds ratio for change of smoking per year was 0.951 (95% confidence interval, 0.944- SOURCE: Leventhal AM. et al. JAMA Intern 0.958) for those with zero disadvantages, 0.96 Med. 2019 Apr 22. doi: 10.1001/jamaint-

(95% CI, 0.95-0.97) for one disadvantage, and ernmed.2019.0192. Images Terroa/iStock/Getty

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 7 NEWS Eosinophils key to glucocorticoid response in asthma BY WILL PASS The researchers stated that a MDedge News key finding of the study is that VIEW ON THE NEWS three-quarters of the mild, persistent Daniel Ouellette, MD, FCCP, comments: In atients with mild asthma who asthma population had low eosino- my city clinic, I see many patients with difficult rely solely on short-acting phil levels, far fewer than expected -to-treat asthma. They are often young, poor, un- Pbeta2-agonists (SABAs) to con- and that the difference in their re- derinsured, and obese. The obstacles are many: trol their asthma symptoms remain sponse to mometasone compared to co-pays are too high; patients’ health literacy is at increased risk of exacerbations, tiotropium was not significant. low; medications are too often ineffective; and according to investigators. “Our results raise the question of oral corticosteroids are continued indefinitely by Two recent studies presented at whether treatment guidelines should other providers. Novel biologic agents can be un- the American Thoracic Society’s be reevaluated for patients with mild, realistic as a result of denied coverage and patient international conference demon- persistent asthma for whom evidence concerns about injectable medicines. New advanc- strated the benefits of glucocorticoid of type 2 inflammation is lacking,” es may help. Checking sputum eosinophil levels as an outpatient therapy among patients with mild the investigators wrote. “The need and targeting therapy in these patients may lead to improved persistent or intermittent asthma for a change in treatment strategy outcomes from cost-effective strategies. Intermittent, as needed, while highlighting differential re- is further highlighted by a growing combination ICS/LABA may be an effective, sensible, and afford- sponses to steroids among patients body of literature suggesting that able alternative for many with mild disease. with high versus low levels of eosin- mild, persistent asthma can be man- ophils in sputum. Both studies were aged safely without the daily use of simultaneously published in the inhaled glucocorticoids and by data New England Journal of Medicine. showing that patients with a low The first study, SIENA, led by eosinophil level may not have a fa- Stephen C. Lazarus, MD of the Uni- vorable response to inhaled glucocor- versity of California, San Francisco, ticoids” (New Engl J Med. 2019 May and colleagues, involved 295 patients 19. doi: 10.1056/NEJMoa1814917). with mild, persistent asthma. Patients The second study, Novel START, were classified as having either a high conducted by lead author Richard or low level of eosinophils in sputum, Beasley, DSc, of the Medical Research with a low level defined by two spu- Institute of New Zealand, Wellington, tum samples consisting of less than and colleagues, compared the effica- 2% eosinophils. After a single-blind cy of two inhaled glucocorticoid regi- placebo run-in period of 6 weeks, mens and albuterol alone for patients patients were randomized to receive with mild persistent or intermittent either mometasone (an inhaled glu- asthma, measured by annualized ex- cocorticoid), tiotropium (a long-act- acerbation rate. ing muscarinic antagonist [LAMA]), Initial randomization involved or placebo for 12 weeks each, with 675 patients, of whom 668 were subsequent crossover through the included in the final analysis. Pa- two remaining treatments. The pri- tients were randomized into three mary outcome was the response to groups: albuterol as needed (100 each active agent, compared with mcg, two inhalations as needed for placebo among low-eosinophil pa- asthma symptoms), budesonide tients who had a differential response maintenance (200 mcg, one inhala-

to a trial agent. tion twice daily with as-needed al- Images StockPlanets/E+/Getty Out of 295 patients, 221 (75%) buterol), or budesonide/formoterol had low eosinophils and 74 (25%) (budesonide 200 mcg and formoter- had a 56% lower relative risk of se- inhaled glucocorticoid–[long-acting had high eosinophils. In the low-eo- ol 6 mcg, one inhalation as needed). vere pulmonary exacerbation than beta agonist] and as-needed SABA,” sinophil subgroup, 59% of patients Along with annualized exacerbation patients in the budesonide mainte- the investigators concluded. had a differential response to a trial rate, several secondary outcomes nance group and a 60% lower rel- SIENA was funded by National agent; among these, 57% responded assessed symptoms, respiratory ative risk than the albuterol group. Heart, Lung, and Blood Institute, better to mometasone, compared function, and number of severe ex- However, maintenance budesonide with medications provided by with 43% who responded better to acerbations. provided better symptom relief than Boehringer Ingelheim, Merck, and placebo, and 60% responded better Data analysis showed that patients budesonide/formoterol, “which sug- Teva; the investigators reported to tiotropium, compared with 40% in the budesonide groups had simi- gests that for the patient for whom relationships with Sanofi, Vectura, who responded better to placebo. lar rates of annualized exacerbation, asthma symptoms rather than exac- Circassia, DBV Technologies, and Turning to secondary analyses, both of which were significantly erbations are the most bothersome, others. Novel START was funded among patients with high eosino- better than the exacerbation rate maintenance treatment has value,” by AstraZeneca and the Health Re- phil levels who had a differential in the albuterol-only group; the the investigators wrote (New Engl search Council of New Zealand; the response, 74% responded better to absolute rate of exacerbations per J Med. 2019 May 19. doi: 10.1056/ investigators reported relationships mometasone, compared with 26% patient per year was 0.175, 0.195, NEJMoa1901963). with GlaxoSmithKline, Genentech, who responded better to placebo, and 0.400 for budesonide mainte- “The findings of our trial are con- Theravance Biopharma, and others. and 57% responded better to tiotro- nance, budesonide/formoterol, and sistent with evidence regarding the [email protected] pium, compared with 43% who re- albuterol only, respectively. Similar- treatment of moderate and severe sponded better to placebo. ly, the median fraction of exhaled asthma – that maintenance and SOURCES: Beasley R et al. New Engl In an additional exploratory nitric oxide (FENO) was lower in reliever therapy” with inhaled glu- J Med. 2019 May 19. doi: 10.1056/ analysis, adults with low eosinophil the budesonide groups than in the cocorticoid/formoterol “results in NEJMoa1901963; Lazarus SC et al. levels had better responses to tiotro- albuterol-only group. Patients in a lower risk of severe exacerbations New Engl J Med. 2019 May 19. doi: pium than placebo (62% vs 38%). the budesonide/formoterol group than maintenance therapy with an 10.1056/NEJMoa1814917.

8 • JUNE 2019 • CHEST PHYSICIAN PULMONOLOGY AFib on the rise in patients with COPD hospitalized for exacerbations

BY JEFF CRAVEN 1,345,270 weighted hospital admissions of adults 1.09), and acute respiratory failure (OR, 1.09). with end-stage COPD on home oxygen who met The researchers suggested that the reason for FROM THE JOURNAL CHEST® n Atrial fibrilla- the inclusion criteria for the study, 18.2% (244,488 this increased Afib incidence may be an aging tion is being seen with increasing frequency in admissions) of patients had AFib, and the prev- population, advancing AFib diagnostic approach- patients admitted to U.S. hospitals for exacerba- alence of AFib in COPD patients increased over es, increased AFib awareness improving AFib tions of end-stage chronic obstructive pulmonary time from 2003 (12.9%) to 2014 (21.3%; P less detection, an increase in the prevalence of AFib disease, based on a retrospective analysis of data than .0001). during the study period ocurring as a result of re- from the U.S. Nationwide Inpatient Sample. Patients with AFib, compared with patients duced AFib-related mortality, and finally, increas- The prevalence of atrial fibrillation (AFib) without AFib, were older (75.5 years vs. 69.6 years; ing trends in risk factors may also be involved in among patients with end-stage chronic obstruc- P less than .0001) and more likely to be male the increased of AFib. tive pulmonary disease (COPD) on home oxygen (50.7% vs. 59.1%; P less than .0001) and white The researchers noted the database could have who were admitted with COPD exacerbations (80.9% vs. 74.4%; P less than .0001). Patients with potentially overinflated AFib prevalence, as they increased from 12.9% in 2003 to 21.3% in 2014, AFib also had higher stroke risk reflected in high- could not differentiate index admissions and re- according to Xiaochun Xiao of the department of er CHA2DS2-VASc scores (3.26 vs. 2.45; P less admissions. The database also does not contain health statistics at Second Military Medical Uni- than .0001), and higher likelihood of in-hospital information about secondary diagnoses codes versity in Shanghai and colleagues. mortality and readmission reflected in Elixhauser present on admission. Additionally, “we found that comorbid [AFib] scores greater than or equal to 4 (51.2% vs. 35.6%). “Our findings should prompt further efforts to was associated with an increased risk of the need Larger hospitals in terms of number of beds, identify the reasons for increased [AFib] preva- for mechanical ventilation, especially invasive urban environment, and Medicare insurance lence and provide better management strategies mechanical ventilation. Moreover, comorbid status also were associated with a higher AFib for end-stage COPD patients comorbid with [AFib] was associated with adverse clinical out- prevalence. [AFib],” the researchers concluded. comes, including increased in-hospital death, AFib was associated with an increased cost of This study was funded by a grant from the Fourth acute respiratory failure, acute kidney injury, sep- $1,415 and an increased length of stay of 0.6 days Round of the Shanghai 3-Year Action Plan on Pub- sis, and stroke,” the researchers wrote in the study after adjustment for potential confounders. AFib lic Health Discipline and Talent Program. The au- published in the journal CHEST. also predicted risk for several adverse events, in- thors reported no relevant conflict of interest. Patients included in the study were aged at least cluding stroke (odds ratio, 1.80; in-hospital death, [email protected] 18 years, were diagnosed with end-stage COPD [OR, 1.54]), invasive mechanical ventilation (OR, and on home oxygen, and were hospitalized be- 1.37), sepsis (OR, 1.23), noninvasive mechanical SOURCE: Xiao X et al. CHEST. 2019 Jan 23. doi: cause of a COPD-related exacerbation. Based on ventilation (OR, 1.14), acute kidney injury (OR, 10.1016/j.chest.2018.12.021.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 11 PULMONOLOGY No raised risk of cardiovascular events for patients with COPD receiving aclidinium bromide

BY HEIDI SPLETE placebo patients (0.44 vs. 0.57, P less “No patient subgroup demon- MDedge News than .001). strated a difference in efficacy In a secondary analysis with a except when analyzed by baseline clidinium bromide reduced definition of MACE expanded to in- COPD severity, in which the treat- exacerbations in adults with clude heart failure, arrhythmias, or ment benefit was observed only in Achronic obstructive pulmonary disease with no increased risk of major adverse cardiovascular “Outcomes of this trial add data to the long-standing events, compared with placebo, in a controversy over the safety of LAMAs in COPD” randomized trial of more than 3,000 patients. and support the need for additional research. Aclidinium, a long-acting muscarinic antagonist (LAMA), has been shown to reduce COPD ex- cerebrovascular disease, results re- patients with FEV1 [forced expira- acerbation in the short term, but mained similar between the groups; tory volume in 1 second] of 50% long-term effectiveness has not been events occurred in 168 aclidinium predicted or less,” the researchers examined, wrote Robert A. Wise, patients (9.4%) and 160 placebo pa- noted. “This may be explained by MD, FCCP, of Johns Hopkins Uni- tients (8.9%). The rate of COPD ex- the lower exacerbation rate seen in versity, Baltimore, and colleagues. acerbations requiring hospitalization the placebo group in patients with ASCENT-COPD is a multicenter, Dr. Robert A. Wise was significantly lower in aclidinium moderate airway obstruction vs. double-blind, randomized, placebo patients, compared with placebo pa- severe or very severe obstruction,” -controlled, parallel-group noninfe- and the median exposure overall tients (0.07 vs. 0.10, P = .006). they said. riority study conducted at 522 sites was 495 days for aclidinium patients Overall, the most common treat- “Outcomes of this trial add data to in the United States and Canada. and 478 days for placebo patients. ment-emergent adverse events the long-standing controversy over A paper on recent data from AS- Of the 2,537 patients who com- were similar in the aclidinium and the safety of LAMAs in COPD” and CENT-COPD, published in JAMA, pleted the study, 69 (3.9%) in the placebo groups, respectively: pneu- support the need for additional re- supports early findings reported last aclidinium group and 76 (4.2%) in monia (6.1% vs. 5.8%), urinary search, they said. year at the American Thoracic Soci- the placebo group experienced a tract infections (5.2% vs. 5.0%), and The study findings were limited ety meeting. major adverse cardiovascular event upper respiratory tract infections by several factors including insuffi- The researchers randomized (MACE, defined as a composite (4.8% vs. 5.6%). The most common cient power to detect cause-specific adults with COPD to a 400-mg dose of cardiovascular death, nonfatal serious adverse events (in at least mortality and the use of a LAMA of aclidinium bromide twice daily, myocardial infarction, and nonfatal 1% of patients) were pneumonia, with low risk of systemic effects, the or placebo. The average age of the stroke). atrial fibrillation, heart failure, and researchers noted. patients was 67 years; 59% were In addition, annual rates of mod- coronary artery disease. Dry mouth [email protected] men. The median exposure time to erate to severe COPD exacerbations and urinary retention were rare, and aclidinium or placebo was 365 days were significantly lower in the occurred in less than 1% of patients SOURCE: Wise RA et al. JAMA. 2019. during the first year of treatment, aclidinium patients compared with in each group. 321:1693-701. Survey: Americans support regulation of vaping products

BY RICHARD FRANKI 18, 2019 (margin of error, plus or MDedge News minus 4.12%), showed that 69% of adults strongly or somewhat Public opinion on e-cigarette control lmost 70% of adults believe support raising the age limit to Athat the Food and Drug Ad- purchase e-cigarettes and tobacco ministration should raise the legal and 55% support restricting sales Raise the legal age age to purchase e-cigarettes and of flavored e-cigarettes, NORC to purchase tobacco tobacco, according to a new sur- reported. Almost 40% of the 1,004 69% vey by NORC at the University of respondents expressed support for and e-cigarettes Chicago, a nonpartisan research a complete ban on e-cigarettes. institution. Despite FDA efforts under Com- Carpe89/Thinkstock “Americans are particularly missioner Scott Gottlieb, MD, to concerned about teens becoming raise awareness of teen vaping, only newly addicted to e-cigarettes, and 21% of those surveyed correctly re- they support a range of actions the sponded that e-cigarettes generally federal government could take to contain more nicotine that regular Restrict sales of flavored e-cigarettes 55% make vaping products less avail- cigarettes. Dr. Gottlieb announced able, less addictive, and less appeal- his resignation recently, “but he Outlaw e-cigarettes entirely ing,” Caroline Pearson, senior vice indicated that the Trump Admin- 39% president at NORC, said in a writ- istration will continue efforts to Gianluca Rasile/Thinkstock ten statement. increase regulation of e-cigarettes,”

The AmeriSpeak Spotlight on NORC said. MDedge News Health Poll, conducted Feb. 14- [email protected] Source: NORC at the University of Chicago

12 • JUNE 2019 • CHEST PHYSICIAN PULMONOLOGY In a tight vote, FDA panel backs mannitol for treatment of cystic fibrosis

BY KARI OAKES in forced expiratory volume in 1 group, using an intention-to-treat MDedge News second (FEV1) from baseline to the population (P less than .001). The end of the 26-week study period. In committee heard evidence that in Food and Drug Administra- addition to this primary endpoint, adults with CF, pulmonary function tion Advisory Committee vot- secondary endpoints included other typically decreases by 1%-3% annu- A ed that the benefit-risk profile pulmonary function measures, as ally. of an inhaled treatment for cystic well as the number of protocol-de- The PDPE rate was slightly higher fibrosis merits approval of the drug fined pulmonary exacerbations in the DPM group than in the con- – dry powder mannitol (DPM). (PDPEs). Participants also reported trol group in studies 302 and 303, Mannitol is a naturally occur- quality of life and symptom mea- but the differences were not statis- ring sugar alcohol that is used as a sures on the Cystic Fibrosis Ques- tically significant. These findings low-calorie sweetener; it is generally tionnaire–Revised (CFQ-R). have a backdrop of an overall low recognized as safe when taken en- In study 301, the dropout rate ap- rate of PDPEs ranging from 0.221 to terically. Inhaled DPM, marketed proached one in three participants 0.995 per year, according to Chiesi as Aridol, is currently approved as a with higher discontinuation in the presenter Scott Donaldson, MD, a bronchoprovocation agent. For the intervention than the control arm, pulmonologist who directs the adult current indication, DPM is given as causing significant statistical prob- cystic fibrosis center at the Universi- 10x40-mg capsules twice daily. lems in dealing with missing data. ty of North Carolina at Chapel Hill. In a 9-7 vote, the FDA’s Pul- Dr. John M. Kelso Thus, said the FDA’s Robert Lim, When looking at the subgroup monary-Allergy Drugs Advisory MD, though this study had positive of United States study participants, Committee (PADAC) decided that Some members also noted an results for FEV1, it was not “statisti- the DPM integrated cohort includ- DPM’s modest potential to improve unmet need in CF therapies and cally robust.” ed more patients with a history of pulmonary function in adults with placed confidence in those treat- The second study, 302, did not cystic fibrosis (CF) outweighed a ing CF patients to find ways to use meet its primary endpoint, and potential signal for increased exac- DPM safely and effectively. “I’m there was “no support from second- “This is not a drug for erbations seen in clinical trials. really counting on the cystic fibrosis ary endpoints” for efficacy, said Dr. everybody; but absolutely, it’s a Chiesi USA is seeking approval of clinicians who do this for a living to Lim, a clinical team leader in the DPM for the management of cystic figure out where to use this in their FDA’s Division of Pulmonary, Aller- drug for somebody. Ultimately we fibrosis to improve pulmonary func- armamentarium,” said John M. Kel- gy, and Rheumatology Products. have to make that decision – I do tion in patients 18 years of age and so, MD, an allergist at Scripps Clin- The current submission was also think that we study populations, older in conjunction with standard ic, San Diego. supported by a new post hoc sub- therapies. It plans to market DPM as In 2012, the initial new drug ap- group analysis of adults in studies but we really take care of people.” Bronchitol. plication submitted by Pharmaxis, 301 and 302. A total of 414 patients Some committee members who which then held marketing rights receiving DPM and 347 receiving voted against approval, including to DPM, resulted in a “no” vote for placebo (DPM at a nontherapeutic prior pulmonary exacerbations. In PADAC chair David H. Au, MD, level) were included in the integrat- the DPM group, 45% of U.S. partic- worried that DPM’s ease of use ed analysis of patients from all three ipants had at least one exacerbation might prompt patients and caregiv- The FDA panel decided that studies. Studies 301 and 302 both in the prior year, and 20% had two ers to substitute it for inhaled hy- mannitol’s modest potential to had open-label extension arms, al- or more exacerbations, compared pertonic saline, a medication that’s improve pulmonary function lowing more patients to be included with 38% and 14%, respectively, in more burdensome to use but has a in safety data. the control group. Chiesi argued longer track record for efficacy and in adults with cystic fibrosis The problems caused by the that this imbalance was likely re- safety. While hypertonic saline re- outweighed a potential signal missing data from study 301 were sponsible for the increased exacer- quires cumbersome equipment and addressed in the design of study bation rate. cleaning regimens and takes 20-30 for increased exacerbations 303 by encouraging patients who The sponsor and the FDA used minutes to administer, DPM is ad- seen in clinical trials. discontinued the study drug to different imputation methods to ministered over about 5 minutes via continue data collection efforts for account for missing data from the a series of capsules inserted into a the study. Dropout rates were lower earlier studies, complicating inter- small inhaler device. approval from PADAC, and eventual overall in study 303 and balanced pretation of the potential signal for “I was very impressed by con- FDA denial of approval. The initial between arms. increased exacerbations. versations that we heard from the submission was supported by two Over the 26-week duration of Quality of life data were similar community that this will be viewed phase 3 clinical trials, 301 and 302, study 303, investigators saw a statis- between groups across the studies. as a substitute drug [for hypertonic that included pediatric patients. In tically significant improvement in In the end, the view of the “yes” saline],” said Dr. Au, professor of the pediatric population, there was FEV1 of about 50 mL, according to voters was encapsulated by James medicine at the University of Wash- concern for increased hemoptysis the FDA’s analysis. Post hoc analyses M. Tracy, DO, an allergist in private ington, Seattle. “Before we make with DPM, so the FDA advised the of studies 301 and 302 showed point practice in Omaha, Neb. “This is not that leap of faith ... we have to better drug’s marketers to consider seeking estimate increases of approximately a drug for everybody; but absolutely, understand how it has to be used.” approval for an adult population 80 mL, according to Dr. Lim. it’s a drug for somebody. Ultimately He also acknowledged that making only in its reapplication. The current In its presentations, Chiesi USA we have to make that decision – I do the call for DPM was “challenging.” submission followed a new double presented its integrated analysis of think that we study populations, but Other committee members were -blind, randomized, placebo-con- adult data from the three clinical tri- we really take care of people.” reassured by the fact that DPM is trolled trial, study 303, that included als. The analysis showed an increase The FDA usually follows the approved for adult use in 35 coun- adults with CF aged 18 or over. in FEV1 from baseline of 73 mL for recommendations of its advisory tries; it’s been in use since 2011 in All three studies had similar de- the DPM group, compared with panels. Australia for adults and children. signs, tracking change from baseline an increase of 7 mL for the control [email protected]

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 13 LUNG CANCER Circulating tumor cells predict NSCLC survival, but clinical role uncertain

BY WILL PASS

GENEVA – Circulating tumor cell (CTC) count is an independent pre- dictor of both progression-free and overall survival in patients with advanced non–small cell lung cancer (NSCLC), according to data from 550 patients. This is the largest CTC study to date and the first to compare test results from multiple centers, reported lead author Colin Lindsay, MD, PhD, of the University of Man- chester (England) and colleagues. Among the centers, investigators

found minimal variability in results Will Pass/MDedge News guiding progression-free survival Dr. Colin Lindsay Dr. Juergen Wolf and no significant differences in results predicting overall survival. is still that it is semi-automated,” Dr. that was the basis of this study.” ence. No relationships were detected These findings suggest that CTC Lindsay said at the meeting present- The retrospective study involved between molecular subtypes and testing could be reproducible and ed by the European Society for Med- 550 patients with NSCLC whose CTC profiles. reliable on a large scale, Dr. Lindsay ical Oncology. “The machine will samples were processed at seven “It’s always good to finish a talk said during a presentation at the harvest potential cells and stain po- centers in multiple European coun- with the white elephant in the European Lung Cancer Conference; tential cells, but the end step of the tries, including 209 patients whose room,” Dr. Lindsay said in his con- he added that this conclusion ad- process is that a trained user in each data were previously unpublished. cluding remarks. “Is there room for dresses a previous concern about the laboratory will decide which cell is a The investigators looked for associ- CTCs in non–small cell lung can- process. CTC and which cell isn’t a CTC, and ations between CTC count and sur- cer? I believe they have the potential “A slight problem with the process it’s that potential for user variability vival using Cox regression analysis to complement ctDNA work by of- and evaluated if CTCs could add fering a cellular context, but [CTCs] value to prognostic clinicopatho- aren’t there yet for clinical roll-out.” logic models based on c-indices Invited discussant Juergen Wolf, and likelihood ratio statistics. CTC MD, of the University Hospital count was assessed as a continu- Cologne (Germany) provided a ous variable and, based on previ- similar conclusion, suggesting ous studies, using two categorical that CTCs have a clear place in thresholds: at least 2 cells per 7.5 research, but their clinical value is mL and at least 5 cells per 7.5 mL. debatable. He noted that ctDNA, In addition, the investigators looked the most similar diagnostic and for associations between NSCLC prognostic tool under development, molecular subtypes and CTC levels. has a pragmatic edge because ctD- The results showed that both cut- NA samples are more amenable to off levels were predictive of survival, shipping and handling. Dr. Wolf with the higher threshold carrying noted that ctDNA also has been a poorer prognosis. For progres- shown to have value for treatment Mechanical Ventilation: Advanced Critical sion-free survival, CTC counts of at planning, specifically for the EGFR Care Management | July 25 - 27 least 2 cells per 7.5 mL carried a haz- T790M resistance mutation. This ard ratio of 1.72, whereas the 5-cell latter point tied into a larger issue Join us at CHEST Global Headquarters in Glenview, Illinois, for the upcoming threshold had a hazard ratio of 2.21 described by Dr. Wolf, who sug- live learning course Mechanical Ventilation: Advanced Critical Care (P less than .001 for both). Similarly, gested that in the current treatment Management. Acquire extensive knowledge in advanced techniques and overall survival hazard ratios for the landscape for NSCLC, predictive skills for mechanical ventilation in the critically ill patient—including the latest lower and higher thresholds were testing needs to be actionable. advances in ventilator technology—through lectures, interactive discussion, 2.18 and 2.75, respectively (P less “We cannot draw a consequence hands-on small group workshops, and case-based exercises. than .001 for both). When baseline of a prognostic biomarker,” Dr. Wolf Topics include: CTC count was added to the analysis, said. “In the era of personalized predictive accuracy increased further, medicine, what we need is predic- n Ventilator modes n Management of hypoxemia dropping P values 10-fold, down to tive markers, predictive of the out- n n Ventilator-induced lung injury Patient-ventilator synchrony .0001. C-index models had a more come of specific therapies.” n n Management of obstructive and Noninvasive ventilation modest impact. Although minor het- The investigators disclosed finan- parenchymal lung disease erogeneity was detected among cen- cial relationships with AstraZeneca, ters for prediction of progression-free Novartis, Pfizer, and others. REGISTER TODAY survival, overall survival data were [email protected] http://bit.ly/MechVentJuly2019 broadly reliable. Dr. Lindsay noted that intercenter differences seemed to SOURCE: Lindsay C et al. ELCC 2019, diminish with greater testing experi- Abstract 21O.

20 • JUNE 2019 • CHEST PHYSICIAN CARDIOLOGY Alirocumab reduces both type 1 and 2 MIs BY BRUCE JANCIN mean LDL by 54%, from 93 to 48 Nov 29;379[22]:2097-107). according to the Third Universal MDedge News mg/dL, while the LDL level actually During a median 2.8 years of pro- Definition and determined 66% drifted upward in the control group spective follow-up, there were 1,860 were type 1 MIs, 21% were type 2, NEW ORLEANS – Lowering LDL on placebo plus statin therapy. In and 13% were type 4, with lesser cholesterol with alirocumab to levels the previously reported primary “For type 2 MI, this is the numbers of types 3 and 5 MI. below what’s achievable with inten- results of this landmark randomized Alirocumab reduced the risk of sive statin therapy appears to be an clinical trial, alirocumab on top of first data indicating that any MI by 15%, with a 6.8% inci- important strategy for prevention of background intensive statin therapy a lipid-lowering therapy dence during follow-up, compared type 1 MI – and perhaps even more reduced the primary composite end- can attenuate risk.” with 7.9% on placebo. The risk of impressively, type 2 MI – following point of death attributable to coro- type 1 MI, typically attributable acute coronary syndrome, Harvey nary heart disease, ischemic stroke, to plaque rupture, was reduced by D. White, MD, reported at the an- MI, or unstable angina requiring new MIs in study participants. A 13%, with an incidence of 4.9% with nual meeting of the American Col- hospitalization by 15%, compared blinded clinical events committee alirocumab and 5.6% with placebo. lege of Cardiology. with controls (N Engl J Med. 2018 evaluated the myocardial infarctions Continued on following page What’s so important about the 23% reduction in risk of type 2 MI achieved with alirocumab (Praluent) VIEW ON THE NEWS to be used to obtain a 50% reduction in LDL relative to placebo documented in Jason Lazar, MD, FCCP, comments: This study cholesterol. The updated guidelines recommend- a prespecified secondary analysis represents yet another important milestone in ed the addition of ezetimide and PCSK9 inhibitors from the ODYSSEY Outcomes trial? the broader incorporation of PCSK9 inhibitors to statin therapy in patients not reaching treat- “For type 2 MI, this is the first for cardiovascular risk reduction. ment goals. While PCSK9 inhibitors are general- data indicating that a lipid-lowering While 2013 American Heart As- ly accepted to effectively lower LDL cholesterol therapy can attenuate risk,” accord- sociation/American College of markedly, their use has been limited by high cost ing to Dr. White, a cardiologist at Cardiology guidelines focused on and sparseness of data on clinical event reduc- Auckland (N.Z.) City Hospital. statin dose (high or intermediate tion. Accordingly, more affordable pricing and the The ODYSSEY Outcomes trial intensity) rather than specific demonstration of clinical event reduction such compared the proprotein convertase LDL targets, the 2018 revised as the ODYSSEY Trial will likely lead to expand- subtilisin/kexin type 9 (PCSK9) guidelines re-emphasized LDL ed use of these agents. In addition, lowering of inhibitor alirocumab to placebo in treatment goals as well as the risk for both types 1 and 2 myocardial infarction, 18,924 patients with a recent acute adjunct use of non-statin agents which are felt to result from plaque rupture and coronary syndrome and an LDL to achieve treatment goals. Spe- demand ischemia, respectively, suggest that lipid cholesterol level of at least 70 mg/dL cifically, for patients with atherosclerotic cardio- lowering in general may portend salutary pleio- despite intensive statin therapy. At vascular disease and for those at very high risk, tropic effects that have been previously linked to 4 months, the PCSK9 inhibitor plus high-intensity statin therapy was recommended statin therapy alone. statin therapy reduced participants’ When to transition HF patients to alternative loop diuretic

BY ANDREW D. BOWSER alternative loop diuretic. out-drink any diuretic regi- MDedge News “I think spironolactone is men.’ ” a great medication in heart The next step is to double PHILADELPHIA – While many internists might failure with reduced ejection the dose of the loop diuretic think a switch to spironolactone would be war- fraction, but the doses we and, sometimes, triple the ranted for a heart failure patient with inadequate typically use are generally dose if the double dose is not response to oral furosemide (Lasix), transitioning suboptimal to achieve diure- effective. to an alternative loop diuretic may be the prefer- sis,” he added. “If they’re diuresing but it’s able approach, a cardiologist said at the annual The rationale for consid- just not adequate, then I’ll meeting of the American College of Physicians. ering an alternative loop move to twice-daily dosing,” “Lasix is associated with very high variability diuretic in this patient hing- he said. “A practical tip is I tell in terms of absorption, so torsemide and bu- es on bioavailability, which patients to take their first dose metanide should be considered in patients who is “highly variable” for oral as soon as they wake up and

have a poor response,” said Paul McKie, MD, furosemide, at 10%-100%, Andrew Bowser/MDedge D. News the second dose around 1:00 MPH, a cardiologist and internist with Mayo while by contrast, torsemide Dr. Paul McKie p.m. so that they’re not urinat- Clinic, Rochester, Minn., in a session at the and bumetanide have a very ing all night.” meeting. consistent bioavailability of 80%-100%, according If twice-daily dosing doesn’t help, then that’s When polled, only 22% of attendees at the to Dr. McKie. the point where an alternative loop diuretic session picked “transition to torsemide” as the “For this reason, I think about using torsemide would be warranted, according to Dr. McKie’s best approach for restoring fluid balance with the or bumetanide in patients who are not respond- algorithm. lowest adverse potential in a 74-year-old woman ing to oral Lasix,” he said. “Then I add a thiazide like metolazone, but I with nonischemic cardiomyopathy on furosemide Dr. McKie described an algorithm that he and only do that after I’ve increased the dose of the 80 mg twice daily who has been hospitalized for his colleagues use in clinic to intensify outpatient loop diuretic,” he added. fluid overload three times in the year. therapy for patients not achieving diuresis. If all else fails, then outpatient IV diuretics can The majority of attendees (41%) said they The first step is to ensure adherence and ask be considered, according to the algorithmic ap- would have added spironolactone. Dr. McKie patients whether they are following sodium and proach. disagreed with this approach. Instead, Dr. McKie fluid restriction: “I always ask about that first,” Dr. McKie reported no relevant disclosures. said he would have transitioned this person to an he said. “I tell patients, ‘You can out-eat and [email protected]

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 21 Continued from previous page 1 MI, with a 10.2% rate as com- ways for the benefit of alirocumab “I think that’s the probable mecha- The risk reduction conferred by the pared to 13.4% with placebo; that’s a in preventing type 2 MI, Dr. White nism. And we also know that statins PCSK9 inhibitor was even more ro- 31% relative risk reduction. Yet the noted that, in a Scottish study of improve endothelial function,” he bust for type 2 MI, the type caused PCSK9 inhibitor had no impact on the PCSK9 inhibitor evolocumab said. by an oxygen supply/demand imbal- the risk of death after a type 2 MI: (Repatha), over the course of 72 He reported receiving research ance most commonly attributable 24.8% in the alirocumab group and months the drug appeared to reduce grant support and consultant fees to coronary artery spasm, coronary 25.9% in controls. atherosclerotic progression and from Sanofi and Regeneron, funders embolism, arrhythmias, anemia, Asked for his thoughts as to pos- induce plaque stabilization and per- of the ODYSSEY Outcomes trial. hypertension, or hypotension: a 23% sible explanatory mechanistic path- haps even regression. [email protected] relative risk reduction as reflected in a 1.3% incidence in the alirocumab group, compared with a 1.7% rate in controls. In contrast, alirocumab had no impact on the incidence of type 4 MI, a category that includes peri– Bruce Jancin/MDedge News Dr. Harvey D. White

The beneficial effect of alirocumab on MI risk mostly * involved a reduction in larger MIs – those with a biomarker peak greater than three times the upper limit of normal. percutaneous coronary intervention MIs as well as those attributable to stent thrombosis or restenosis. The beneficial effect of alirocumab on MI risk mostly involved a reduction in larger MIs – those with a biomarker peak greater than three times the upper limit of normal. An emphatic difference was found in the risk of death following type 1 as opposed to type 2 MI. Patients who experienced a type 1 MI during the study had an 11.9% mortality rate during an average of 1.6 years of post-MI follow-up, as compared with a 25.4% rate during 1.3 years of follow-up after a type 2 MI. Alirocumab significantly reduced the risk of mortality following a type

22 • JUNE 2019 • CHEST PHYSICIAN CARDIOLOGY High coronary artery calcium score points to CV risk BY JIM KLING diovascular disease and all-cause “Our data argues for consider- (or more) have both a higher area mortality than those with CAC scores ation of CAC 1000 (or more) as a and density of calcification, a more symptomatic patients with of 400-999, based on data from a large distinct group with CVD mortality dispersed pattern of calcification in coronary artery calcium (CAC) retrospective study presented by Alli- greater than that of contemporary their coronary artery tree (the ma- Ascores of 1,000 or higher should son W. Peng at the annual meeting of secondary prevention trials. ... We jority with 4-vessel disease), with a be considered at higher risk for car- the American College of Cardiology. showed that those with CAC 1000 Continued on following page

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 23 Continued from previous page group that might gain the most ben- patients with CAC (Agatston) scores apparent upper CAC threshold. markedly more diffuse distribution efit from targeted, aggressive pre- of 1,000 or more, indicate patients Patients with a CAC score of at of extra-coronary calcification com- ventive therapy, the researchers said. with CAC scores of 1000 or more least 1,000 were 66.3 years old, on pared to the other CAC groups,” Ms. Current guidelines identify indi- have nearly a two-fold higher risk of average; 86.3% were male, 52.4% Peng and her colleagues wrote in the viduals with CAC scores over 400 as CVD mortality compared to those had 4-vessel CAC, and they had a study, which was published online the highest risk group. With a mean with CAC scores of 400-999. While larger total CAC area. in the Journal of the American Col- follow-up time of 12.3 years, the the mortality risk levels off slight- Compared with patients with lege of Cardiology. results from 66,636 asymptomatic ly in those with scores exceeding CAC scores of 400-999, those with Future guidelines should address individuals in the CAC consortium 1,000, all-cause and cause-specific a CAC score of 1,000 or more had these patients as a distinct risk study, which included over 2,800 mortality risk still increases with no a greater risk of cardiovascular dis-

24 • JUNE 2019 • CHEST PHYSICIAN ease (hazard ratio, 1.71; 95% confi- mortality, respectively. But those subset of CVD mortality, constituted fits of such treatment in this unique dence interval, 1.41-2.08), coronary with CAC scores of 1,000 of more 21.1% of deaths in the CAC 400-999 group,” the authors wrote. They also heart disease (HR, 1.84; 95% CI, had a 5.1, 8.0, 4.6, and 18.8 mortal- group and 27.1% of deaths in the urged updating current guidelines. 1.43-2.36), cancer (HR, 1.36; 95% ity rate per 1,000 person-years for CAC 1,000 or more group. The study was funded by the CI, 1.07-1.73), and all-cause mor- CHD, CVD, cancer, and all-cause “Future randomized controlled National Institutes of Health. The tality (HR, 1.51; 95% CI, 1.33-1.70). mortality, respectively. trials of aggressive preventative ther- authors have no relevant financial Those with CAC scores of 400- The leading cause of death was apies, for example PCSK9-inhibitors disclosures. 999 had a 2.1, 3.6, 2.7, and 9.8 mor- CVD; 36.5% in the CAC 400-999 and anti-inflammatory drugs, in tality rate per 1,000 person-years for group and 42.6% in the CAC 1,000 patients with CAC ≥ 1,000, may SOURCE: Peng AW et al. JACC 2019. CHD, CVD, cancer, and all-cause or more group. CHD mortality, as a prove helpful to evaluate the bene- doi: 10.1016/S0735-1097(19)31894-7.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 25 PEDIATRIC PULMONOLOGY PCV13 vaccine reduces frequency of otitis media visits BY HEIDI SPLETE significantly after the introduction Previous studies have shown that York, and colleagues. MDedge News of the 13-valent pneumococcal more than half of children with oti- To assess the impact of PCV13, conjugate vaccine, according to tis media (OM) have serotypes in- with the additional serotypes 1, 3, he mean number of office vis- findings published in the Interna- cluded in the PCV7 vaccine (4, 6B, 5, 6A, 7F, and 19A, the researchers its for otitis media in children tional Journal of Pediatric Otorhi- 9V, 14, 18C, 19F, and 23F), wrote analyzed data from the U.S. Nation- Tyounger than 5 years dropped nolaryngology. Xiaofeng Zhou, MD, of Pfizer, New al Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001- 2009), and after the introduction of PCV13 (2011-2013). Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. For the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, from 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years. The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted. The investigators are employed by Pfizer, which funded the study. [email protected]

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96- 102.

VIEW ON THE NEWS Susan Millard, MD, FCCP, comments: In the present era of vaccination skepticism by non-medical parent groups, Dr. Zhou’s study is welcome news. Acute otitis media and recurrent otitis media cause missed days from school for children and work for parents, potential hearing issues, and frequent antibiotic use that has risk of emer- gence of resistant bacterial strains. Parents, pediatricians, and pediatric subspecialists will be excited to get this information.

26 • JUNE 2019 • CHEST PHYSICIAN PEDIATRIC PULMONOLOGY Combo respiratory pathogen tests miss pertussis BY M. ALEXANDER OTTO assay, and to use comprehensive respiratory MDedge News pathogen testing only if there are other, specific VIEW ON THE NEWS targets that will change your clinical manage- Susan Millard, MD, FCCP, comments: Swab- BALTIMORE – Comprehensive respiratory patho- ment,” such as mycoplasma or the flu, Dr. May- bing the nose to screen for infectious eti- gen panels (RPAN) cannot be relied on to detect hew said. ologies of respiratory infections such as pertussis, according to an investigation from the In the study, 102 nasopharyngeal swabs posi- pertussis, mycoplasma, respiratory syn- University of Michigan, Ann Arbor. tive for pertussis on standalone PCR testing – the cytial virus, etc. is expensive but can be Respiratory pathogen panels university uses an assay from extremely helpful for specific populations are popular because they test Focus Diagnostics – were thawed at risk, such as immunocompromised for many things at once, but and tested with RPAN. patients, for example. I appreciate the providers have to know their RPAN was negative for pertus- information that using a panel to confirm limits, said lead investigator sis on 45 swabs (44%). “These pertussis may be inaccurate. Microbiolo- Colleen Mayhew, MD, a pe- are the potential missed pertus- gy lab directors may block certain “extra diatric emergency medicine sis cases if RPAN is used alone,” tests” so we need more research on this fellow at the University of Dr. Mayhew said. RPAN de- topic to review sensitivity and specificity Michigan. tected other pathogens, such as for different age groups tested. “Should [the Respiratory coronavirus, about half the time, Viruses Pathogen Panel] be whether or not it tested positive used to diagnosis pertussis? for pertussis. “Those additional aged 1 month to 73 years, so “it’s important for No,” she said at the Pediatric pathogens might represent coin- all of us to keep pertussis on our differential Academic Societies annual fection, but might also represent diagnose” no matter how old patients are, Dr. meeting. RPAN was negative asymptomatic carriage.” It’s im- Mayhew said. for confirmed pertussis 44% Dr. Colleen Mayhew possible to differentiate between Freezing and thawing the swabs shouldn’t have of the time in the study. the two, she noted. degraded the genetic material, but it might have; “In our cohort, [it] was no better than a coin In short, “neither positive testing for other that was one of the limits of the study. flip for detecting pertussis,” she said. Also, even respiratory pathogens, nor negative testing for The team hopes to run a quality improvement when it missed pertussis, it still detected other pertussis by RPAN, is reliable for excluding the project to encourage the use of standalone per- pathogens, which raises the risk that symptoms diagnosis of pertussis. Dedicated pertussis PCR tussis PCR in Ann Arbor. It might save money, might be attributed to a different infection. “This testing should be used for diagnosis,” she and her because the tests cost the university around $400 has serious public health implications.” team concluded. each, instead of $700 for RPAN. “The bottom line is, if you are concerned RPAN also is a PCR test, but with a different, There was no industry funding. Dr. Mayhew about pertussis, it’s important to use a dedicat- perhaps less robust, genetic target. didn’t report any disclosures. ed pertussis PCR [polymerase chain reaction] The 102 positive swabs were from patients [email protected] Role of mucin further delineated in CF pathogenesis

BY CALEB RANS over 62 study visits and subsequently “Elevated total mucin concentrations MDedge News cultured for detection and quantifica- and inflammatory markers were ob- VIEW ON THE NEWS tion of pathogens. The children with served in children with CF despite a Susan Millard, ucin in children with cystic fi- CF were enrolled in the Australian Re- low incidence of pathogens identified MD, FCCP, com- brosis precedes airway chang- spiratory Early Surveillance Team for by culture or molecular microbiology. ments: We Mes and infections, according to Cystic Fibrosis (AREST CF) program. This muco-inflammatory state also have known a cross-sectional cohort study. “We analyzed the relationships be- characterized our CF population with for a long It has been difficult for research- tween airway mucus, inflammation, the earliest lung disease in the setting time that ers to pinpoint the mechanisms of little or no pathogen infection,” even healthy that initiate lung disease in people “Elevated total mucin they wrote. cystic fibrosis with CF, because it is challenging to Based on the findings, the investi- infants have concentrations and study young people with the disease gators postulated that the airways of inflammation and “CF animal models often fail to inflammatory markers were children with CF may show distinct in their lungs. More basic recapitulate aspects of human CF observed in children with CF defects in the clearance of recently science research in mucin disease and yield disparate findings,” created mucins, which could con- clearance is needed. wrote Charles R. Esther Jr., MD, of despite a low incidence of tribute to early CF lung disease. the division of pediatric pulmonolo- pathogens identified by culture A key limitation of the study was gy at the University of North Caroli- the prophylactic use of intermittent Institute; the North Carolina na at Chapel Hill and his colleagues or molecular microbiology.” antibiotics. As a result, bacterial Translational and Clinical Sciences in Science Translational Medicine. infection could have contributed to Institute; the National Health and They studied 46 clinically stable and bacterial culture/microbiome,” the the development of early CF lung Medical Research Council; and the young children (aged 3.3 years, plus researchers wrote. BALF total mucin disease. “Agents designed to remove Cystic Fibrosis Foundation. Two or minus 1.7 years) with CF and 16 levels were higher in CF samples ver- permanent mucus covering airway coauthors reported financial affilia- age-matched controls who did not sus non-CF controls. In addition, Dr. surfaces of young children with CF tions with Parion Sciences. have CF, but had respiratory symp- Esther and his colleagues found that appear to be rational strategies to [email protected] toms (aged 3.2 years, plus or minus these results were the same regardless prevent bacterial infection and dis- 2.0 years) using chest CT imaging and of infection status and that increased ease progression,” they concluded. SOURCE: Esther CR et al. Sci Transl bronchoalveolar lavage fluid. BALF densities of mucus flakes were also The study was supported by the Med. 2019 Apr 3. doi: 10.1126/sci- samples in CF patients were collected seen in samples from the CF patients. National Heart, Lung, and Blood translmed.aav3488.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 27 PEDIATRIC PULMONOLOGY Maternal immunization protects infants from RSV BY BRUCE JANCIN PREPARE included 4,636 women MDedge News with low-risk pregnancies who were VIEW ON THE NEWS randomized 2:1 to a single intramus- Susan Millard, MD, FCCP, comments: This is such an LJUBLJANA, SLOVENIA – Passive cular injection of the investigational exciting trial! The risks of severe RSV infection, protection of infants from severe RSV vaccine or placebo during ges- though, are often highest in extremely premature respiratory syncytial virus lower tational weeks 28-36, with efficacy infants & premature infants with bronchopulmo- respiratory tract infection during assessed through the first 180 days nary dysplasia (chronic lung disease of infancy) the first 6 months of life has con- of life. The study took place at 87 but in the trial, mothers got the placebo or the vincingly been achieved through sites in 11 countries during 4 years vaccine later in pregnancy. The vaccine would maternal immunization using a worth of RSV seasons. Roughly half certainly help susceptible patient populations such novel nanoparticle vaccine in the of participants were South African, as complex congenital heart disease infants born landmark PREPARE trial. one-quarter were in the United at term or close to term. “I think it’s important for everyone, States, and the rest were drawn from especially people like myself who’ve nine other low-, middle-, or high-in- been working on maternal immuni- come countries in the Northern and tions, with zero impact on pregnan- centers around the fact that RSV zation for about 20 years, to realize Southern Hemispheres. The median cy and delivery. seasons were generally milder there, that this is a historic study,” Flor M. gestational age at vaccination was 32 An intriguing finding in an ex- and American women were vacci- Munoz, MD, declared in reporting weeks. ploratory analysis was that the nated at a later gestational age, with the study results at the annual meet- The primary efficacy endpoint vaccine appeared to have ancillary a corresponding shorter interval to ing of the European Society for Pae- specified by the Food and Drug benefits beyond prevention of med- delivery. diatric Infectious Diseases. Administration – but not other ically significant RSV disease in the The novel recombinant nanoparti- regulatory agencies – was the pla- young infants. For example, the rate cle vaccine tested in PREPARE con- cebo-subtracted rate of RSV lower of all lower respiratory tract infec- tains a nearly full-length RSV fusion respiratory tract infection as defined tions with severe hypoxemia – with protein produced in insect cells. The by RSV detected by reverse tran- no requirement for demonstration nanoparticles express both prefusion scription polymerase chain reac- of RSV infection – was reduced by epitopes and epitopes common to tion, along with at least one clinical 46% during the first 90 days of life pre- and postfusion conformations. manifestation of lower respiratory in the immunized group. Similarly, Aluminum phosphate is employed tract infection, oxygen saturation the rate of all-cause lower respirato- as the adjuvant. below 95%, and/or tachypnea. The ry tract infection resulting in hospi- Novavax’s stock price has been risk of this outcome was reduced talization was reduced by 28%. kicked to the curb since the compa- by 39% during the first 90 days of “This is actually quite interesting, ny earlier reported that a large phase life and by 27% through 180 days in because these are unexpected ben- 3 trial of the vaccine failed to meet infants in the maternal immuniza- efits in terms of all-cause effects,” its primary endpoint for prevention tion group, a difference which didn’t the pediatrician commented, adding of RSV lower respiratory tract infec- achieve statistical significance. that she and her coinvestigators are tion in older adults. Now the vac-

Bruce Bruce Jancin/MDedge News However, prespecified major delving into this phenomenon in or- cine’s failure to meet its prespecified Dr. Flor M. Munoz secondary endpoints arguably of der to gain better understanding. FDA-mandated primary endpoint greater clinical relevance were con- Additional analyses of the recently in the maternal immunization study “We have here for the first time sistently positive. Notably, maternal completed PREPARE study are on- will doubtless spawn further finan- a phase-3, global, randomized, pla- vaccination reduced infant hospi- going but already have yielded some cially dismissive headlines in the cebo-controlled, observer-blinded talization for RSV lower respiratory important findings. For example, business press as well. clinical trial looking at an experi- tract infection by 44% during the women immunized before 33 weeks’ But pediatricians are famously ad- mental vaccine in pregnant women first 90 days of life, when levels of gestation had significantly greater vocates for children, and PREPARE for the protection of infants from transplacentally transferred neutral- transplacental antibody transfer received a warm welcome from the a disease for which we really don’t izing antibodies against RSV A and than those immunized later in pediatric infectious disease commu- have other potential solutions quite B were highest, with events occur- pregnancy, with resultant markedly nity, regardless of investor response. yet, and in a period of high vulner- ring in 57 of 2,765 evaluable infants greater vaccine efficacy in their off- Indeed, PREPARE was the only ability,” said Dr. Munoz, a pediatric in the active treatment arm and in spring as well: a placebo-subtracted clinical trial deemed of sufficient infectious disease specialist at Baylor 53 of 1,430 controls. Similarly, there 70% reduction in RSV lower respi- import to be featured in the opening College of Medicine, Houston. was a 40% reduction through day ratory tract infection with severe hy- plenary session of ESPID 2019. Indeed, respiratory syncytial virus 180. Moreover, rates of another key poxemia through 90 days, compared Ulrich Heininger, MD, professor (RSV) is the No. 2 cause of mor- secondary endpoint – RSV lower re- with a 44% reduction associated of pediatrics at the University of Ba- tality worldwide during the first spiratory tract infection plus severe with immunization at gestational sel (Switzerland), who cochaired the year of life. Moreover, most cases of hypoxemia with an oxygen satura- week 33 or later. And when the in- session, jointly sponsored by ESPID severe RSV lower respiratory tract tion below 92% – were reduced by terval between immunization and and the Pediatric Infectious Diseases infection occur in otherwise healthy 48% and 42% through days 90 and delivery was at least 30 days, the Society, declared, “These findings, I infants aged less than 5 months, 180, respectively. Thus, the vaccine’s risk of this endpoint was reduced by think, are a great step forward.” when active immunization presents protective effect was greatest against 65%; in contrast, there was no sig- Dr. Munoz reported receiving daunting challenges. the most severe outcomes of RSV nificant difference between vaccine research grants from Janssen, the “While certainly mortality is un- infection in infancy, according to and placebo groups when time from National Institutes of Health, the common in high-income countries, Dr. Munoz. immunization to delivery was less Centers for Disease Control and we do see significant hospitalization No safety signals related to this than 30 days. Prevention, and Novavax, which there due to severe RSV lower re- immunization strategy were seen Also noteworthy was that mater- sponsored the PREPARE trial, as- spiratory tract infection in the first during 1 year of follow-up of infants nal immunization afforded no infant sisted by an $89 million grant from year of life, sometimes more than and 6 months for the mothers. Side protection in the United States. This the Bill and Melinda Gates Founda- other common diseases, like influ- effects were essentially limited to unanticipated finding is still under tion. enza,” she noted. mild, self-limited injection site reac- investigation, although suspicion [email protected]

28 • JUNE 2019 • CHEST PHYSICIAN SLEEP MEDICINE Interaction of sleep and opioid use disorder is complex BY KARI OAKES past 3 months, with 10 or more days said, 58% of all patient-days had those newly abstinent from cocaine, MDedge News per month of pain. at least one momentary report of Dr. Finan said, adding that it’s pos- Pain ratings were captured via pain greater than zero. On average, sible individuals with substance use MILWAUKEE – Individuals with a smartphone app that prompted participants recorded a pain score disorder who are new to treatment chronic pain frequently have dis- participants to enter a pain rating at of 2.27. simply feel better than they have in rupted sleep and also may be at risk three random times during each day. Brief Pain Inventory scores at base- some time along many dimensions, for opioid use disorder. However, Each evening, patients also complet- line showed a mean severity of 5, and with sleep being one such domain. even with advanced monitoring, it’s ed a sleep diary giving information a pain interference score of 5.07. Pain on a given day didn’t predict not clear how sleep modulates pain about bedtime, sleep-onset latency, Participants with OUD and poor sleep on that night, except that and opioid cravings. waking after sleep onset, and wake chronic pain did not differ across sleep onset took slightly longer (P = Sleep has an impact on positive time for the preceding day. any EEG-recorded sleep measures, .01), said Dr. Finan. He noted that and negative affect, but new re- A self-applied ambulatory elec- compared with those with OUD “there was no substantive effect on search shows that the link between troencephalogram applied to the alone. However, subjective reports other sleep continuity parameters.” sleep and mood states that may forehead was used for up to 7 con- of sleep were actually better overall Looking at how negative affect me- contribute to opioid use disorder is not straightforward. At the scientific meeting of the American Pain So- ciety, Patrick Finan, PhD, of Johns Hopkins University, Baltimore, discussed how sleep and mood affect cravings for opioids among those in treatment for opioid use disorder (OUD). Affective function, mesolimbic system function, and pain mod- ulation are all adversely affected by poor sleep, said Dr. Finan, who told attendees that one key question he and his colleagues were seeking to answer was whether those with OUD and chronic pain had more disturbed sleep than those with OUD alone. Also, the researchers wanted to know whether the ups and downs of sleep on a day-to-day basis were reflected in pain scores among those with OUD, as would be predicted by prevailing models. Finally, two “proximal indicators” of relapse risk, affect, and heroin craving, might be affected by both

sleep and pain, and Dr. Finan and Images Mladen Zivkovic/iStock/Getty collaborators sought to explore that association. secutive nights to capture sleep for those with chronic pain than the diated craving for heroin, Dr. Finan The work was part of a larger continuity estimates; the device has objective EEG reports. The EEG re- and colleagues found that negative study looking at the natural history been validated against polysomnog- cordings captured an average of 9.11 affect–related craving was signifi- of OUD and OUD with comorbid raphy data in other work. Partici- minutes more of waking after sleep cantly greater for those with chronic chronic pain. To participate in this pants were given incentives to use onset (P less than .001). Also, total pain (P less than .001). parent study, adults with OUD had the device, and this “yielded strong sleep time was 10.37 minutes short- Unlike findings in patients with- to be seeking treatment or currently adherence,” with an average of 5 er as recorded by the EEG than by out OUD, having disrupted sleep enrolled in methadone or buprenor- nights of use per participant, Dr. self-report (P less than .001). Over- continuity was more associated phine maintenance treatment, and Finan said. all sleep efficiency was also worse by with increased daily negative affect, without current major depressive Patients were an average age of 5.96 minutes according to the EEG, rather than decreased positive affect. disorder. Also, patients could not about 49 years, and were 75% male. compared with self-report (P less And this increased negative affect have a history of significant mental African American participants made than .001). was associated with heroin cravings, illness, cognitive impairment, or a up just over half of the cohort, and “Sleep is objectively poor but said Dr. Finan. “In the past few medical condition that would inter- 43% were white. Participants were subjectively ‘normal’ and variable years, we’ve seen quite a few studies fere with study participation. A total roughly evenly divided in the type in opioid use disorder patients,” Dr. that have found some abnormalities of 56 patients participated, and 20 of maintenance therapy they were Finan said. In aggregate, however, in the reward system in patients of these individuals also had chronic taking. Overall, 39% of participants neither diary-based subjective nor with chronic pain.” Whether poor pain. had a positive urine toxicology EEG-based objective sleep mea- sleep is a mediator of these abnor- Those with OUD and chronic screen. sures differed between those with malities deserves further study. pain qualified if they had pain (not For patients with chronic pain, and without chronic pain in the re- The study was supported by the related to opioid withdrawal) aver- 45% of all momentary pain reports search cohort. This phenomenon of National Institutes of Health. Dr. aging above 3 on a 0-10 pain rating had a pain score over zero, with a sleep efficiency being self-reported Finan reported no outside sources scale over the past week; additional mean of 32 days of pain. Looking as higher than objective measures of funding. criteria included pain for at least the at the data another way, Dr. Finan capture sleep has also been seen in [email protected]

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 37 SLEEP MEDICINE Trial finds no link between CPAP and weight gain BY ANDREW D. BOWSER adults enrolled at 89 centers in sev- cluded that CPAP promoted signif- found in women with good CPAP MDedge News en countries. icant increases in BMI and weight. adherence. FROM THE JOURNAL CHEST® n In a subanalysis, there was a However, the median study duration It’s not exactly clear why this Continuous positive airway pressure small but statistically significant was only 3 months. SAVE analysis would find no evi- (CPAP) over several years did not weight gain of less than 400 g in In contrast, the analysis of the dence of CPAP promoting weight lead to clinically concerning levels men who used CPAP at least 4 SAVE trial included adults who had gain over the long term, in contrast of weight gain among patients with hours per night as compared to regular body measurements over a to the earlier meta-analysis of short- obstructive sleep apnea and comor- matched controls. However, there mean follow-up of nearly 4 years. term studies finding a significant bid cardiovascular disease enrolled were no differences in BMI or neck That long-term follow-up provid- risk of weight gain. in a large international trial, findings and waist circumferences for these ed an “ideal opportunity” to assess However, it is possible that dif- from a large, multicenter trial show. men, and no such changes were whether CPAP treatment promotes ferences in study populations such No differences in weight, body observed in women, according to weight gain in OSA patients over the as ethnicity, age, or comorbidities mass index, or other body mea- the investigators, led by Qiong Ou, course of several years, the authors of contributed to the differences, said surements were found when com- MD, of Guangdong (China) Gen- the SAVE trial analysis wrote. investigators. paring CPAP and control groups eral Hospital and R. Doug McEvoy, For men in the SAVE trial, the For example, results of regression in a post hoc analysis of the Sleep MD, of the Adelaide Institute for difference in weight change for the analysis in the present study showed Apnea Cardiovascular Endpoints Sleep Health at Flinders University, CPAP group vs. the control group that, compared with recruitment (SAVE) trial, which included 2,483 Adelaide, Australia. was just 0.07 kg (95% confidence in- in Australia, recruitment in China “Such a small change in weight, terval, –0.40 to 0.54; P = .773) while and India was significantly linked to even with good adherence over sev- in women, the difference for CPAP weight loss, while recruitment in New eral years, is highly unlikely to have vs. controls was –0.14 kg (95% CI, Zealand was linked to weight gain. any serious clinical ramifications,” –0.37 to 0.09; P = .233), the investi- Dr. Ou had no disclosures relat- wrote the investigators of the study gators reported. ed to the study, while Dr. McEvoy published in Chest. Weight gain was significantly reported disclosures related to “Taken together, these results higher among men with good CPAP Philips Respironics, ResMed, Fisher indicate that long-term CPAP treat- adherence, defined as use for at least & Paykel, Air Liquide, and the Na- ment is unlikely to exacerbate the 4 hours per night, investigators said, tional Health and Medical Research problems of overweight and obesity noting a mean difference of 0.38 Council of Australia. that are common among patients kg (95% CI, 0.04-0.73; P = .031), [email protected] with OSA,” they added. though no other differences were In a previous meta-analysis of found in body measurements for SOURCE: Ou Q et al. Chest. 2019

Courtesy ResMed Courtesy randomized trials, investigators con- men, and no such associations were Apr;155(4):720-9. Insomnia meds get boxed at CHEST Annual NEW Meeting 2019—An warning from FDA Inaugural Event BY CHRISTOPHER PALMER these behaviors with any of these MDedge News medications. Complex sleep behaviors have he Food and Drug Adminis- been seen with these medications in tration will now require that patients with and without a history Tcertain medications prescribed of them, at low doses, and even after for insomnia carry a boxed warning one dose of the medication. They’ve because of associated complex sleep also been observed with and with- behaviors. out concomitant use of These behaviors, in- alcohol or other CNS de- cluding sleep walking, pressants. sleep driving, and en- Health care profession- Do you have an innovative idea pertaining to gaging in other activities als should advise patients pulmonary, critical care, or sleep medicine while not fully awake, about these risks, even technology or education? Submit your pitch are more common with though they are rare. Pa- between June 15 and July 31 to be considered eszopiclone (Lunesta), tients should contact health for presentation at the inaugural FISH Bowl event at CHEST 2019 in New Orleans, Louisiana. zaleplon (Sonata), and zolpidem care professionals if they either (Ambien, Ambien CR, Edluar, experience a complex sleep behav- Finalists will receive complimentary Intermezzo, Zolpimist) than they ior while not fully awake on one of CHEST 2019 registration. are with other prescription med- these medicines or have performed icines used for sleep. Although activities they don’t remember while chestmeeting.chestnet.org/fish-bowl these complex sleep behaviors taking the medicine. are rare, they are potentially very More information about these dangerous. Boxed warnings are the risks and the safety warnings can be FDA’s most prominent warning, found in the FDA’s safety announce- but the agency will also require ment. Other information is also a contraindication – its strongest available in a press announcement warning – to avoid use in patients from the agency. who’ve previously experienced [email protected]

38 • JUNE 2019 • CHEST PHYSICIAN SLEEP MEDICINE Insomnia correlated with epilepsy seizure frequency

BY JAKE REMALY 2019 Education Calendar MDedge News

PHILADELPHIA – Nearly a quarter of adults with epilepsy have moderate or severe insomnia, and insomnia symptoms are associated with depression, anxiety, worse seizure control, and poorer quality of life, according to a prospective analysis presented at the annual meeting of Dr. Thapanee Somboon CHEST Innovation, Simulation, and Training Center in Glenview, Illinois the American Academy of Neurol- ogy. Insomnia symptoms are not “Given the potential benefits Learn More livelearning.chestnet.org associated with epilepsy type, num- of sleep therapies on ber of antiepileptic drugs (AEDs), or June 28 - 29 Therapeutic Bronchoscopy for Airway AED standardized dose, however. epilepsy outcomes, routine Obstruction “Given the potential benefits of screening of insomnia sleep therapies on epilepsy outcomes, July 25 - 27 Mechanical Ventilation: Advanced Critical routine screening of insomnia symp- symptoms is warranted.” toms is warranted,” said lead study Care Management author Thapanee Somboon, MD, a lepsy Center for an initial evaluation August 8 - 10 Cardiopulmonary Exercise Testing (CPET) researcher at the sleep disorders cen- between January and August 2018. ter at Cleveland Clinic Neurological The patients completed the Insomnia September 5 - 7 Difficult Airway Management Institute and at Prasat Neurological Severity Index (ISI). An ISI score of 8 September 12 - 14 Ultrasonography: Essentials in Critical Care Institute in Bangkok. or greater indicated clinical insomnia Insomnia is common and associ- symptoms, and an ISI score of 15 or September 19 - 21 Comprehensive Bronchoscopy With ated with depression in patients with greater indicated moderate or severe Endobronchial Ultrasound epilepsy, but prior studies that looked insomnia symptoms. at the relationship between insomnia The researchers used Spearman’s November 7-9 Extracorporeal Support for Respiratory and and epilepsy-related characteristics correlation and the Kruskal-Wallis Cardiac Failure in Adults yielded limited and conflicting re- test to evaluate associations among sults, according to Dr. Somboon. insomnia symptoms and AED November 14 - 16 Critical Care Ultrasound: Integration into To evaluate potential associations standardized dose, monthly seizure Clinical Practice between insomnia and epilepsy, Dr. frequency, Patient Health Question- Somboon and colleagues conducted naire (PHQ-9), Generalized Anxiety November 22 - 23 Comprehensive Pleural Procedures a prospective analysis of data from Disorder Questionnaire (GAD-7), December 5 - 7 Ultrasonography: Essentials in Critical Care 270 patients with epilepsy who pre- and Quality of Life in Epilepsy-10 sented to the Cleveland Clinic Epi- (QOLIE10). December 13 - 14 Advanced Critical Care Echocardiography Among the 270 patients, the av- Board Review Exam Course erage age was 43.5 years, 58% were female, 74% had focal epilepsy, and 26% had one or more seizures per month. The population’s median ISI score was 7. Nearly half had an ISI score of 8 or greater, and 23% had an ISI score of 15 or greater. “A positive correlation was found between ISI and PHQ-9 (r = CHEST Board Review 2019 P 0.64, less than .001), GAD-7 (r = August 16-24 | Phoenix, Arizona 0.68, P less than .001), QOLIE (r = 0.55, P less than .001), and month- SLEEP CRITICAL CARE PULMONARY ly seizure frequency (r = 0.31, P less than .001),” the researchers reported. Insomnia symptoms had a significantly stronger correlation with PHQ-9 and GAD-7 than with seizure frequency. Dr. Somboon had no disclo- 2019 sures. A coinvestigator has received research support from Jazz October 19-23 | New Orleans, LA Pharmaceuticals. [email protected] Calendar subject to change. For most current course list and more information, visit livelearning.chestnet.org. SOURCE: Somboon T et al. AAN

demaerre/Getty Images demaerre/Getty 2019, Abstract P3.6-026.

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 39 NEWS FROM CHEST Shared decision-making in action: Real data on biopsy risk and how to mitigate it

BY MATT ABOUDARA, MD, risk may be generalizable, it may be tube. Hemorrhage occurred in 2.5% institutional expertise. Specifically FCCP institutionally specific, and knowl- of all patients, with 1.5% having a speaking for the pulmonologist, this edge of local skill and outcomes common terminology criteria for translates into identifying specific n a study highlighted in a re- data can help guide discussions. adverse events (CTCAE) ≥ 2. Grade procedural “champions” who are cent issue of CHEST Physician, With that said, some general infor- 4 respiratory failure occurred in 1 dedicated to performing these pro- IHou and colleagues analyzed mation can inform decisions. The patient. There were no ENB procedures and are members of a mul- complications from biopsies of lung NAVIGATE study investigators cedure-related deaths. It should be tidisciplinary thoracic team. These abnormalities seen on CT scans by recently published their 1-year fol- noted that individuals performing individuals should have dedicated conducting a large retrospective low-up results using a navigational these procedures were, by and large, training in advanced diagnostic study with data gleaned from na- bronchoscopy system (superDimen- high-volume and experienced users. procedures to achieve the aforemen- tional databases of patients under- sion™). While inherent limitations In comparison, the overall pooled tioned goals.5 The same should hold going CT-guided biopsy, surgery, to this study exist, it does provide sensitivity for CT scan-guided bi- true for transthoracic, CT-guided or bronchoscopy.1 While it should some useful information as to pro- opsy is 90% for pulmonary nodules biopsies. Interventional pulmonolo- not be interpreted as representative cedure-related complications from and masses. The yield is lower, gy fellowships are structured to pro- of a lung cancer screening popu- a large sample of patients who ap- however, for smaller lesions (≤2.0) vide exposure to multidisciplinary lation (for excellent comments by proximate a lung cancer screening and ranges from 74% to 77%.3 The nodule clinics and tumor boards, Drs. Rivera and Silvestri regarding population. This group was com- average pneumothorax rate is 20%, establishing quality improvement the study, see: https://tinyurl.com/ posed of both academic and com- with 1% to 3% requiring chest tube initiatives, as well as developing pro- y52ucb94), it does raises two im- munity centers and prospectively placement. Risk factors for pneu- cedural expertise.6 portant questions when performing followed 1,215 patients for 1 year.2 mothorax vary between studies, but, It is apparent that shared deci- shared decision-making for low The average age of the population generally speaking, have been asso- sion-making can become complex. dose CT (LDCT) scanning: (1) was 67.6 (± 11.3), and 80% were ciated with nodules ≤ 2 cm, those These details will likely be lost to a What information should clinicians current or former smokers. The within 2 cm of the pleura (but not primary care provider simply due discuss with patients regarding vari- median nodule size was 2 cm. The abutting the pleura), and emphyse- to time constraints and information ous biopsy methods until more data diagnostic yield was 73% at 1 year ma in the track of needle trajectory. overload. As such, pulmonologists are available? (2) How do we miti- follow-up (data will be re-analyzed Pulmonary hemorrhage occurs 30% should be at the forefront of lung gate complications from biopsies? at 2 years). The pneumothorax rate of the time but is mild in most cas- cancer screening – in programmatic While procedure-specific biopsy was 4%, with 3% requiring chest es. Hemoptysis and severe hemor- development, implementation, and rhage occur at rates of 4% and <1%, providing education to providers respectively. Risk factors for devel- directly involved with shared deci- opment of pulmonary hemorrhage sion-making discussions. include small lesion size (< 2 cm) and lesions > 2 cm from the pleura. Dr. Aboudara is with the Division When considering surgical lung of Allergy, Pulmonary, and Critical biopsies and resection, recent data Care; Vanderbilt University Medical suggest every effort should be made Center; Nashville, Tennessee. to encourage smoking cessation in order to mitigate postoperative References morbidity. In a retrospective study 1. Huo J, Xu Y, Sheu T, et al. Complication by Fukui and colleagues,4 respira- rates and downstream medical costs associ- tory morbidity (defined as hypoxia, ated with invasive diagnostic procedures for lung abnormalities in the community setting: pneumonia, atelectasis, and uncon- Complications and medical costs associated trolled sputum production) was with diagnostic procedures for lung abnormal- 22% in smokers vs 3.5% in never ities. JAMA Intern Med. 2019;179:324-32. smokers. The rate of complications 2. Folch EE, Pritchett MA, Nead MA, et al. Electromagnetic navigation bronchoscopy for Join Us in the Big Easy decreased as the time from smok- peripheral pulmonary lesions: One-year re- ing cessation to date of surgery in- sults of the prospective, multicenter NAVIGATE Visit New Orleans, Louisiana, for the premier event in clinical chest medicine. The CHEST Annual study. J Thorac Oncol. 2019;14(3):445-58. Meeting has a long-standing history of featuring learning opportunities in pulmonary, critical care, creased. The goal for each patient who is 3. Ohno Y, Hatabu H, Takenaka D, et al. and sleep medicine—we strive to deliver that education in a way that will make lessons learned CT-guided transthoracic needle aspiration long lasting and clinically relevant. Some of those educational sessions include: counseled should be to limit the biopsy of small (< or = 20 mm) solitary pul- n Literature review sessions n Original investigations n Simulation number of procedures and achieve monary nodules. AJR Am J Roentgenol. 2003;180(6):1665-69. n Bite-sized teaching and case reports n Games for Augmenting the greatest diagnostic confidence n Case-based discussions n Pro-con debates Medical Education (CHEST with the lowest complication rate. 4. Fukui M, Suzuki K, Matsunaga T, et al. n Case puzzlers n Problem-based learning Games) Importance of smoking cessation on surgical With these risks and diagnostic yield outcome in primary lung cancer. Ann Thorac in mind, the decision to recommend Surg. 2019;107(4):1005-09. In addition to these exciting educational opportunities, CHEST 2019 will feature new ways to make your life easier while you are away from home, including: a particular biopsy strategy (or no 5. Mahajan A, Khandhar S, Folch EE. Pulmo- biopsy at all) should be based on nary Perspectives®: Ensuring quality for EBUS n Childcare option at the headquarters hotel current guideline recommendations: bronchoscopy with varying levels of practi- n Professional headshot booth tioner experience. CHEST Physician. April 6, n Designated wellness area to recharge and relax during a busy day of learning (1) patient co-morbidities and pref- 2017. https://tinyurl.com/y3hwlc4g. . erences; (2) size of index nodule or 6. Mullon JJ, Burkart KM, Silvestri G, et al. Interventional Pulmonology Fellowship Ac- Registration now open mass; (3) presence of pathologically enlarged mediastinal and/or hilar creditation Standards: Executive summary of chestmeeting.chestnet.org the Multisociety Interventional Pulmonology lymphadenopathy; (4) evidence of Fellowship Accreditation Committee. Chest. extrathoracic metastasis; and (5) 2017;151(5):1114-21.

40 • JUNE 2019 • CHEST PHYSICIAN Timing is critical.

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CHPH_41.indd 1 5/29/2019 11:50:23 AM NEWS FROM CHEST Addressing current asthma management: What clinicians told us A Medscape/CHEST Survey

BY MEGAN BROOKS Medscape/CHEST Survey here are differences in how Use of Asthma Evaluation Guidelines pulmonologists and other Biomarkers for Moderate to Severe Asthma Allergy* Considered Most Important Among Clinicians clinicians approach the diag- 80% T 2% nosis and management of patients 9% 12% 20% NP/PA/RN 60% Critical Care with moderate to severe asthma, 36% 31% 45% 34% 40% according to a survey conducted 11% 38% 44% 20% by Medscape in collaboration with 72% 10% CHEST, the American College of 8% 33% 14% 24% Chest Physicians. Despite some of 24% PCP EM these differences, those surveyed do 14% 5% predominantly favor similar treat- 50% 47% 36% 10% 32% 35% ment options, including inhaled 26% corticosteroids and biologics. Bio- 13% logics in particular are perceived as Allergy* Critical EM Ped Pulm PCP NP/PA/ Pulm Ped a promising therapeutic approach Care RN National Asthma Education Guidelines for moderate to severe asthma by Immunoglobulin E (IgE) levels Fraction of exhaled nitric oxide (FENO) clinicians overall, and many are also Global Initiative for Asthma (GINA) Eosinophils comfortable prescribing them. Don't know European Respiratory Society/American Thoracic Society Guidelines Medscape and CHEST asked 763 clinicians about their views on mod- Inhaled Corticosteroid With Long-Acting Clinicians Comfortable With Prescribing Biologics erate to severe asthma. Responses Bronchodilator Favored as Treatment came from 100 pulmonologists; 102 Percentage of Specialists Ranking This Medication As #1 Allergy* 91% allergists/immunologists; 102 crit- 83% Pulm 59% ical care medicine physicians; 100 NP/PA/RN 34% emergency medicine (EM) physi- 62% 63% 60% 62% cians; 104 pediatricians; 100 prima- 54% 52% Critical Care 20% ry care physicians (PCPs); and 155 PCP 16% nurse practitioners (NPs), physician Ped 7% assistants (PAs), or registered nurses (RNs). EM 2% Allergy* Critical EM Ped Pulm PCP NP/PA/ Inhaled steroids top Care RN *Includes allergy and immunology treatment choice Source: Medscape/CHEST Survey of 763 clinicians; August 29 to October 11, 2018. Survey respondents ranked an inhaled corticosteroid with a long-acting bronchodilator as the favored prescribing them. This percentage rage is to personalize treatment by treatments available, and they don’t medication for patients with mod- drops to 59% for pulmonologists, “phenotyping” asthma, with the necessarily respond well to conven- erate to severe asthma; 83% of aller- 34% for NP/PA/RNs, 20% for crit- thought being that certain asthma tional inhaler therapy,” said Holley. gists/immunologists feel this way, ical care medicine physicians, 16% phenotypes will respond well to And for patients with severe, poorly as do between 52% and 63% of the for PCPs, 7% for pediatricians, and some treatments, but not to others. responsive asthma, it’s hard to say pre- other clinicians, including pulmon- just 2% of EM physicians. “This sounds good in academic and cisely what percentage is being treated ologists. inappropriately for their phenotype, Inhaled corticosteroids alone are When it comes to biologic agents for moderate to severe asthma, it is versus what percentage is noncompli- generally preferred by 23%-28% of allergists/immunologists (91%) who say they are most comfortable ant, versus what percentage is due to clinicians surveyed, with the ex- socioeconomic status and behavioral ception of allergists/immunologists prescribing them. This percentage drops to 59% for pulmonologists, health issues, he noted. (12%). EM physicians (19%) and 34% for NP/PA/RNs, 20% for critical care medicine physicians, 16% The solution? “There is no easy pediatricians (16%) tend to more for PCPs, 7% for pediatricians, and just 2% of EM physicians. solution,” said Holley. “More special- often favor an inhaled corticosteroid ized, severe asthma clinics? Greater and leukotriene-modifying agent education on inhaler use and disease than do other clinicians, but notably, severity? Concomitant management none of the allergists/immunologists Aaron B. Holley, MD, FCCP, pro- scientific papers, but remains diffi- of behavioral health complaints? All felt this way. gram director at the Pulmonary and cult to operationalize in the clinic,” these are necessary, but they’re also Critical Care Medical Fellowship, said Holley. resource-intensive.” Biologics are an important Department of Medicine, Walter He also noted that the new biolog- Still, in his view, the glass is half- step forward Reed National Military Medical ics all target one specific phenotype: full. “The biologics are an import- When it comes to biologic agents Center, Bethesda, Maryland, and a eosinophilic asthma. “This pheno- ant step forward, and we’re getting for moderate to severe asthma, it member of the Moderate to Severe type makes up approximately 50% better at phenotyping. Compared is allergists/immunologists (91%) Asthma Center of Excellence steer- of all patients with asthma; however, with 5-10 years ago, we’re in a much who say they are most comfortable ing committee, noted that the latest the other 50% have no targeted better place.”

42 • JUNE 2019 • CHEST PHYSICIAN NEWS FROM CHEST

Preferred biomarkers if someone else sees my patient for link poor asthma control to poor MD, clinical assistant professor Familiarity with biomarkers for some reason, one look at the ACT medication adherence and social or of medicine at the Department of moderate or severe asthma is uni- score will summarize their disease environmental risk irritants, such as Clinical Sciences, Geisinger Com- versal among pulmonologists. Only control, as opposed to them having smoking, secondhand smoke expo- monwealth School of Medicine, 2% of allergists/immunologists are to pull it out of a running narrative sure, vaping, and pollutants. Scranton, Pennsylvania, who is also not familiar with biomarkers, com- history,” said Holley. a member of the Moderate to Severe pared with nearly three quarters of ACTs are also favored by 39% of ‘We know from Asthma Center of Excellence steer- EM physicians, 45% of pediatricians, NP/PA/RNs, 34% of pediatricians, data that poor ing committee, said the biggest bar- 36% of PCPs, 31% of NP/PA/RNs, 27% of PCPs, 16% of critical care control is related riers to treatment, in her experience, and 20% of critical care medicine medicine physicians, and just 6% of to socioeconomic are “poor health literacy, medication physicians. EM physicians. About one third of status and nonadherence, poor social support, Immunoglobulin E (IgE) lev- EM physicians and PCPs (34% each) behavioral health.’ and tobacco use.” els ranked as the most important favor the ACQ, as do 30% of NP/ The survey was conducted Au- biomarker for moderate or severe PA/RNs, 29% of pediatricians, 20% Dr. Holley gust 29, 2018, to October 11, 2018. asthma, favored by 47% of pulmon- of pulmonologists, 17% of allergists/ Pulmonologists were recruited from ologists and 50% of allergists/immu- immunologists, and 8% of EM phy- CHEST, and all other clinicians nologists, followed by eosinophils, sicians. “No surprise here,” said Holley. were recruited from Medscape preferred by 44% of pulmonologists Thirty-six percent of all clinicians “In my experience, medication ad- members. Patients with moderate and 38% of allergists/immunolo- said they don’t use any assessment herence and environmental risks or to severe asthma account for at irritants are big factors in patients least half of all patients with asthma with moderate to severe asthma seen by pulmonologists, allergists/ Clinicians tend to see a lack of appropriate treatment as the greatest who don’t respond to conventional, immunologists, and critical care barrier for patients with moderate to severe asthma; 63% of standard asthma treatment and con- medicine physicians; this proportion pulmonologists feel this way, as do 60% of allergists/immunologists, tinue to progress.” falls to about 30% among pediatri- “We know from data that poor cians and PCPs. Of the clinicians 52% of PCPs, 50% of pediatricians, and 45% of NP/PA/RNs, control is related to socioeconomic surveyed, patients with moderate to compared with just 32% of EM and critical care medicine physicians. status and behavioral health. We severe asthma are overwhelmingly also know that proper inhaler use referred to pulmonologists. Among and compliance are a big problem. the reasons for referral are multiple gists. Between 26% and 36% of oth- tool to gauge asthma control in pa- Does this account for most ‘progres- emergency department visits, poor er clinicians rank IgE tops, except tients with moderate to severe asth- sion’? That’s hard to say, I suppose, control, failure on first-line therapy, for EM physicians (13%). About one ma, including 86% of EM physicians but certainly these are big factors,” and confounding factors. third of critical care medicine phy- and 42% of PCPs – the specialties Holley added. Follow Medscape on Facebook, sicians and one quarter of PCPs and most apt to report no use. Echoing Holley, Navitha Ramesh, Twitter, Instagram, and YouTube. NP/PA/RNs think eosinophils are As for guideline use, 83% of al- the most important biomarker, com- lergists/immunologists and 81% pared with only 14% of pediatricians of pediatricians surveyed use the and 10% of EM physicians. National Asthma Education and Fraction of exhaled nitric ox- Prevention Program (NAEPP) ide (FeNO) is least favored by all guidelines. Pulmonologists tend clinicians surveyed. Just 9% of to use these guidelines less often pulmonologists, 12% of allergists/ (37%), as they also rely on the Glob- immunologists, and 5% of EM al Initiative for Asthma (GINA) physicians like this biomarker. (54%) and European Respiratory Pediatricians ranked FeNO the Society (ERS)/American Thoracic highest among those surveyed, but Society (ATS) guidelines (43%). only at 14%. About two thirds (62%) of NP/PA/ RNs favor the NAEPP guidelines, Assessment tools as do 49% of PCPs and critical care and guidelines medicine physicians and 31% of EM One “interesting” finding is the dif- physicians. Sixty percent of EM phy- ference between specialties in use sicians don’t use guidelines at all. CHEST SEEK™ Library of the Asthma Control Test (ACT) Sleep Medicine Content—CME/MOC Available and Asthma Control Question- Chief culprits behind naire (ACQ), commented Holley. poor asthma control Most pulmonologists (57%) and Clinicians tend to see a lack of ap- Recently reviewed sleep content is now eligible for up to 57.5 CME/MOC in allergists/immunologists (79%) fa- propriate treatment as the greatest the CHEST SEEK™ Library Sleep Medicine - CME/MOC collection. This reviewed vor ACTs for adults and children, barrier for patients with moderate content includes more than 200 questions—all eligible for CME/MOC. whereas other clinicians seem to to severe asthma; 63% of pulmon- Use CHEST SEEK education to test and improve your clinical skills in recall, favor the ACQ. ologists feel this way, as do 60% of interpretation, and problem-solving. Case-based questions reflect the content Both the ACT and ACQ have allergists/immunologists, 52% of of board certification exams. decent literature to support their PCPs, 50% of pediatricians, and 45% * CME/MOC-eligible SEEK sleep medicine collection questions are only available in the use, he noted. “I use the ACT, but of NP/PA/RNs, compared with just online library. personally, I don’t think it makes a 32% of EM and critical care medi- difference which you use. I do think cine physicians. EM (67%) and crit- it’s important to get an objective ical care medicine (54%) physicians score for their subjective symptoms are also more apt to think that the to facilitate tracking over time, and patient not seeing a provider is the CHEST SEEK™ Library | seeklibrary.chestnet.org to ensure that clinicians are speak- greatest barrier. ing the same language. For example, Overall, most clinicians surveyed

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 43 NEWS FROM CHEST Envisioning the future: The The Top 6 Drivers of Change CHEST Environmental Scan s a leader in education for on the organization’s work. Healthcare Economy and Technology pulmonary, critical care, and The 2019 CHEST Environmental Workforce A sleep medicine, staying ahead Scan is a synthesis of work that took of trends in its professional fields and place in January 2019 at the CHEST Education, Content Social, Political, across educational delivery, in gen- Environmental Summit, a special Delivery and Career Regulatory and Philanthropy eral, is critical to remaining relevant joint session of the Board of Regents Advancement the Environment and to best serve the membership. (BOR) and the CHEST Founda- MDedge News The leadership of the American Col- tion Board of Trustees (BOT). In lege of Chest Physicians (CHEST) that session attendees attempted findings prior to the Environmental in CHEST Physician, with each in- developed a multifaceted program to free themselves from the usual Summit. Then, in the in-person stallment addressing one of the driv- this year entitled, concentrated focus BOT/BOR summit meeting, the ers of change. Most of the content is “CHEST Inspira- on the College and consultant’s research findings were confirming rather than revolutionary tion,” a series of Foundation missions, discussed and debated and were ad- in nature. Each installment will be programmatic INSPIRATION: goals, and strategies, dressed with the following questions: accompanied by comments from one initiatives aimed recognizing that a • How will this trend impact mem- of four leading physician experts who at stimulating and Pacing the Future possible (even likely) bers? How will it change their will put the content into perspective. encouraging inno- unintended conse- work environment and what they The two other components of the vation within the association and rec- quence of a narrow focus is losing need to know? CHEST Inspiration program are to ognizing individuals with great ideas sight of the outside world and the • How will this trend impact engage a group of experts from out- that streamline current processes or forces there that—like it or not—in- CHEST? What are the challenges side the field of medicine and health disrupt ways of traditional thinking fluence and could even disrupt the and opportunities? care who are innovative and success- about everyday problems. programs and strategies of CHEST • What responses or actions should ful in their own professions. This The CHEST Board of Regents and the CHEST Foundation. CHEST take? focus group of professionals from recently completed one of the first To facilitate the process, CHEST • Does this insight require changes outside of our association will be held components of the CHEST Inspi- engaged a market research and to our strategic plan? in conjunction with the June Board ration program – the 2019 CHEST consulting agency with expertise The consultant synthesized the of Regents meeting. An additional Environmental Scan. This article de- in environmental scans and a cli- debates and discussions and pre- component to stimulate innovative scribes the development of the 2019 ent base of nonprofit organizations pared a draft document that shaped thinking and celebrate great ideas will CHEST Environmental Scan and and associations. The consultant this year’s document. be a new competitive event at the an- its fit with the other components of conducted secondary research orga- The 2019 CHEST Environmental nual meeting. Dubbed “CHEST FISH CHEST Inspiration program. nized around six drivers of change Scan, which will be updated period- BOWL (Furthering Innovation and Environmental scanning is a for- selected by CHEST leadership: ically, will be used to: Science for Health),” this event will mal process for tracking trends and • Health Care • Inform members about external launch this month, with contestants occurrences in an organization’s • Economy and Workforce developments and put each in per- submitting video applications that internal and external environment • Technology spective feature their great idea, and winners that bear on its success--currently • Education, Content Delivery, and • Help leadership and staff deter- in select categories will be selected and in the future. The environ- Career Advancement mine future directions and pro- at CHEST 2019 in New Orleans. mental scanning process examines • Social, Political, Regulatory, and gram opportunities CHEST Physician will be your source both quantitative and qualitative the Environment • Keep the 5-year strategic plan for information about all the CHEST factors and identifies a set of key • Philanthropy fresh and relevant Inspiration programs through a new environmental indicators believed The leadership had the opportuni- The environmental scan will be series of articles called “CHEST Inspi- to have the most important impact ty to review the consultant’s research explored in six monthly installments ration: Pacing the Future.” Are you up for the challenge? Dr. Salim Surani is!

ecently, the CHEST Foundation had the plea- makes sense to be involved in an institution that of satisfaction, and it is that satisfaction which Rsure of sitting down with Salim Surani, MD, is passionate about taking care of patients and drives you – which gives you a feeling of purpose. FCCP, to get his perspective on the NetWorks clinicians. The CHEST Foundation has given tens I want others to get involved and participate. If Challenge and its impact. Dr. Surani initially got of millions of dollars in fund- you feel passionate about something, put your involved with CHEST at the Board level and is ing for grants to help shape money where your mouth is. This is why I will be now a leader within the Council of NetWorks. the future of education, the matching any gift of $500 or greater by 10% made “My hope was that I could work within my Net- future of research, and the fu- to any NetWork during the NetWorks Challenge. Work to help them become more involved with ture of better patient care.” This is an opportunity to multiply your dona- CHEST and the CHEST Foundation. Through this Dr. Surani has always tion before it goes to the CHEST Foundation so involvement, I believe we can help shape changes been a strong advocate for that grants and other awards can be larger in the in chest medicine practice dynamics. In the Prac- the NetWorks Challenge. coming years. The NetWorks Challenge helps tice Operations NetWork, we strive to educate “There is nothing that has fund our Diversity Travel Grants Program and physicians in practice to ensure they are up to date been more satisfying in my provides additional travel grants to each partic- with government regulations and how to navigate Dr. Surani life than the opportunity to ipating NetWork.” Last year, Dr. Surani gave an changes in a positive way, ultimately with the goal give. I have always believed additional $2,365.17 through his challenge match. of impacting our patients’ lives for the better.” that the biggest winner is the person who gives a Are you up for the challenge this year? When asked about his involvement with gift. When you give something to the right cause, Visit chestfoundation.org/donate today to help CHEST and the Foundation, he said “It just what you get in return is a tremendous amount shape the future of our discipline!

44 • JUNE 2019 • CHEST PHYSICIAN CHPH_45.indd 1 5/23/2019 10:55:12 AM NEWS FROM CHEST

PULMONARY PERSPECTIVES® Endobronchial valves for lung volume reduction: What can we offer patients with advanced emphysema?

BY CATHERINE L. OBERG, MD; perfusion matching. The landmark but allow the exit of secretions and the largest valve trial thus far, ran- JASON A. BEATTIE, MD; AND National Emphysema Treatment trapped air. This results in atelec- domized patients with severe het- ERIK E. FOLCH, MD, MSC Trial (NETT), published in 2001 tasis of the targeted lobe and a de- erogeneous emphysema to receive and 2003, demonstrated that in a crease in lung volume. unilateral Zephyr® valve placement or he global burden of COPD is select patient standard medical care (Sciurba FC, considerable. In the United population et al. N Engl J Med. 2010;363:1233). TStates, it is the third most com- (upper lobe-pre- Overall improvement in spirometry mon cause of death and is associated dominant em- and dyspnea scores was modest in with over $50 billion in annual direct physema and the valve group. Post-hoc analysis and indirect health-care expenditures low exercise ca- identified an important subgroup (Guarascio AJ, et al. Clinicoecon Out- pacity), lung vol- of patients with significant clinical comes Res. 2013;5:235). For patients ume reduction benefit, those with a complete fissure. with severe emphysema with hyper- surgery (LVRS) This finding gave guidance to further inflation, dyspnea is often a quality lowers mortality EBV studies on patients with severe of life (QOL)-limiting symptom and improves Dr. Oberg Dr. Beattie Dr. Folch emphysema and absent collateral (O’Donnell DE, et al. Ann Am Tho- QOL and ex- ventilation (CV). rac Soc. 2017;14:S30). Few proven ercise tolerance (Fishman A, et Which endobronchial valves are Identifying a complete fissure on palliation options exist, particularly al. N Engl J Med. 2003;348:2059). available in the United States? imaging is now used as a surrogate for patients with dyspnea refractory Despite the encouraging results in In 2018, two valves were approved for assessing CV and is an integral to smoking cessation, medical man- this study subpopulation, LVRS is by the FDA for bronchoscopic lung part of the initial profiling of pa- agement with bronchodilators, and performed infrequently (Decker volume reduction (BLVR) – the Zeph- tients for EBV therapy (Koster TD, pulmonary rehabilitation. The re- MR, et al. J Thorac Cardiovasc Surg. yr® EBV (Pulmonx) ( (Fig 1) and the et al. Respiration. 2016;92[3]:150). cent Food and Drug Administration 2014;148:2651). Concern about its Spiration® Valve System (Olympus) In the STELVIO trial, 68 patients (FDA) approval of two endobronchi- morbidity and the specialized na- (IBV) (Fig 2). The Zephyr® EBV is a were randomized to Zephyr ® EBV al valves for lung volume reduction ture of the procedure has hindered duckbill-shaped silicone valve mount- placement or standard medical care has established the increasing impor- widespread adoption. Subsequently, ed within a self-expanding nitinol (Klooster K, et al. N Engl J Med. tance of bronchoscopy as a manage- endobronchial techniques have been (nickel titanium alloy) stent. It comes 2015;373:2325). Those with EBV ment tool in advanced COPD. developed as an alternative to surgi- in three sizes for airways with a diam- placement had significantly improved cal lung volume reduction. eter 4 - 8.5 mm. The Spiration® IBV lung function and exercise capacity. Why were these valves umbrella-shaped valve is composed of TRANSFORM, a multicenter trial developed? How does bronchoscopic six nitinol struts surfaced with poly- evaluating Zephyr® EBV placement in For decades, lung volume reduction lung volume reduction urethane. Its four sizes accommodate heterogeneous emphysema, showed has been investigated as a mechan- (BLVR) benefit patients airway diameters 5 - 9 mm. similar results (Kemp SV, et al. Am J ical approach to counteract the with emphysema? Respir Crit Care Med. 2017;196:1535). physiologic effects of emphysem- Valves used for ELVR are remov- What’s the evidence The IMPACT trial compared pa- atous hyperinflation. Its goal is to able one-way flow devices placed behind BLVR? tients with homogenous emphysema improve lung elastic recoil, respira- by flexible bronchoscopy into select Zephyr® valves without CV to standard medical tory muscle mechanical advantage airways supplying emphysematous The Endobronchial Valve for Em- therapy alone. It showed improve- and efficiency, and ventilation/ lung. The valves block air entry physema Palliation Trial (VENT), Continued on following page Five traditional New Orleans dishes to try

hat makes the traditional New Orleans Crawfish étoufee vegetables, spices, and rice, combined in a variety Wfood so special? The flair and broad his- The word étouffée (pronounced eh-too-fey) of ways. tory for these dishes unite the city and the love comes from the French word “to smother.” This for all things tasty with its seafood, Creole, dish is a very thick stew full of crawfish (or Po-Boys Cajun, and many other types of food options. shrimp) served over rice. It is also similar in This classic French bread sandwich is stuffed and We’ve picked five famous New Orleans dishes some way to gumbo – same types of Creole sea- slathered with sauce. Filled with lettuce, tomato, that you should try while you attend CHEST sonings, served over rice, and made with a roux – and pickles, it’s usually whatever filled with what- 2019. but it is often made with a “blonde” roux, which ever meat you choose – roast beef, fried shrimp, is lighter in color and gives an almost sweet oysters. This allows for many types of po-boy Gumbo flavor. It’s a taste that’s worth trying and claimed sandwiches. You tend to see very creative po-boys As one of Louisiana’s quintessential dishes, you you won’t forget. at the Oak Street Po-Boy Festival each year. can find gumbo in restaurants, at events, and homes all over the state. Claiming both French Jambalaya Beignets and West African roots, there’s no one way to Another famous and traditional New Orleans These pastries are more than just a doughnut make gumbo, but it is usually served over rice dish is jambalaya. This is a rice dish that is a cu- and are famous for being a doughnut without the and with a wide variety of other ingredients. linary staple of the city with a history from the hole. As the city’s most popular sweet treat and With so many different recipes that each family time when colonial Spanish settlers tried recon- staple, locals and visitors can enjoy beignets all and cook has perfected to be the “best,” most structing their native paella from locally sourced year long, available 24-hours a day in New Orle- cooks tend to guard their recipes closely. ingredients. It typically contains a mix of meat, ans at more than one coffee hotspot.

50 • JUNE 2019 • CHEST PHYSICIAN NEWS FROM CHEST photos courtesy Dr. courtesy photos L. Catherine Oberg Zephyr® valve Spiration® valve

Continued from previous page High-resolution computed tomog- an extended period. Pneumonia and fissures, minimizing adverse proce- ment in FEV1, QOL scores, and raphy (HRCT) scanning combined COPD exacerbations have also been dural effects, and developing pro- exercise tolerance in the EBV group. with quantitative software can be reported after EBV placement. There- grams to optimize and streamline a This study affirmed that the absence used to assess emphysema distribu- fore, in some trials, patients received multidisciplinary approach to timely of CV, rather than the pattern of em- tion and fissure integrity. Addition- prophylactic prednisolone and azith- and efficient referral, assessment, physema, correlates with the clinical ally, a proprietary technology, the romycin. Other less common compli- and intervention. As more patients benefit from EBV therapy (Valipour Chartis System®, can be employed cations are hemoptysis, granulation with COPD undergo ELVR, one A, et al. Am J Respir Crit Care Med. intra-procedure to estimate CV tissue formation, and valve migration. goal should be to create multi- 2016;194[9]:1073). Finally, LIBER- by measuring airway flow, resis- institution prospective studies, as ATE, a multicenter study on the tance, and pressure in targeted bal- What’s ahead for ELVR? well as registries to delineate further Zephyr® EBV, examined its placement loon-occluded segments. Absence Overall, valve technology for BLVR the optimal use of endobronchial in patients with heterogenous em- of CV based on Chartis evaluation is an exciting option in the man- valves for lung volume reduction. physema. This study demonstrated was an inclusion criterion in the agement of patients with severe improvement in spirometry, QOL, aforementioned valve studies. emphysema and is now a staple for Zephyr® Endobronchial Valve and 6-minute walk test (6-MWT) Which patients with emphysema any advanced emphysema program. (Pulmonx) distance (Criner GJ, et al. Am J Respir should be referred for consideration Key areas of future interest include Crit Care Med. 2018;198:1151) over a of valve placement? management of patients with partial Spiration® Valve System (Olympus) longer period, 12 months, bolstering The following criteria should be the findings of prior studies. These used in selecting patients for referral results prompted the Zephyr® valve’s for BLVR: FDA approval. • FEV1 15% - 45% of predicted value at baseline Spiration® valves • Evidence of hyperinflation: TLC Small trials have shown favorable greater than or equal to 100% and results with the Spiration® IBV for RV greater than or equal to 175% BLVR, including a pilot multicenter • Baseline postpulmonary rehabilita- cohort study of 30 patients with het- tion 6-MWT distance of 100 - 500 erogeneous, upper-lobe emphysema meters who underwent valve placement • Clinically stable on < 20 mg pred- (Wood DE, et al. J Thorac Cardio- nisone (or equivalent) daily REGISTRATION IS NOW OPEN vasc Surg. 2007;133:65). In this trial, • Nonsmoking for at least 4 months 2019 Board Review Courses investigators found significant im- • Integrity of one or both major fis- provement in QOL scores, but no sures at least 75% in Phoenix, AZ change in FEV1 or other physiologic • Ability to provide informed con- parameters. sent and to tolerate bronchoscopy Let CHEST help you prepare CHEST Board Review offers: live and in person for this n The EMPROVE trial is a multi- Board-exam focused courses, emphasizing the same year’s pulmonary, critical care, content as ABIM. center, prospective, randomized, Complications and sleep medicine exams n Presentations, including smaller tutorial sessions, focusing controlled study assessing BLVR The most common complication with our comprehensive on key topics. ® review courses in Phoenix, with the Spiration IBV. Six- and after valve placement is pneumotho- n Valuable study tools such as complimentary Board Review Arizona. twelve-month data from the trial rax – a double-edged sword in that On Demand audio files. were presented in 2018 at the Amer- it typically indicates the achievement n The opportunity to network with renowned faculty and ican Thoracic Society Conference of atelectasis. In published trials, the experts in the pulmonary, critical care, and sleep medicine and at the European Respiratory So- frequency of pneumothorax varies. fields such as David Schulman, MD, MPH, FCCP, and Gerard Silvestri, MD, FCCP. ciety International Conference. Some studies document rates below 10%. Others report rates of nearly As always, CHEST Board Review courses offer thorough Collateral ventilation 30% (Gompelmann D, et al. Respi- exam prep you can put to the test. Identifying patients in whom there ration. 2014;87:485). In landmark is no CV between lobes is critical trials, death related to pneumothorax SLEEP CRITICAL CARE PULMONARY to success with BLVR. Collateral occurred rarely. Most severe pneu- August 16-18 August 16-19 August 21-24 ventilation allows air to bypass mothoraces occur within the first 72 Reserve Your Seat the valve occlusion distally, there- hours after valve placement. This has boardreview.chestnet.org by negating the desired effect of prompted many centers to observe valve placement, lobar atelectasis. postprocedure patients in hospital for

MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 51 NEWS FROM CHEST

CRITICAL CARE COMMENTARY Not another burnout article

BY ROOZEHRA KHAN, DO, FCCP you hear the same old solutions: be We can talk about the symptoms more positive, find balance, do some of burnout all day, but what does Does this sound like your day? yoga, take this resilience module, that really look like? It looks like the You show up to work after a terri- be mindful (what on earth does this day we described at the beginning. ble night’s sleep. Your back is tense, mean anyways?), get some more You know, the day that resonated and you do some kind of walking/ sleep. Basically, it’s our problem. with you and caused you to keep stretching combo as you walk It’s our burden. If all of these were reading. through the doors. Your focus fades easy to understand and implement, during the mind-numbing routine don’t you think doctors and health- Why should we all be of the morning shift sign out. As the care providers would have done it discussing this important topic? day moves forward, you begin to already? I think you and I are a lot Being burned out not only affects feel resentful as you sign orders, see alike. These were my exact feelings. us on a soul level (achingly de- patients, and address your ICU team But stick with me on this one. I scribed above), but, more impor- needs. You know that’s not right, have a solution for you, albeit a little tantly, this can trickle down to our that it’s not in line with who you different. I’ll show you a more “posi- personal lives, family relationships, want to be, but the irritation doesn’t tive” spin on the DIY. and how we care for our patients, go away. I burned out early. After fellow- with some studies showing that it Your lunchtime is filled with com- ship, I didn’t want to be a doctor affects our performance and, gulp, puter screens, notes, billing, and anymore. I desperately sought to Dr. Khan patient outcomes. That’s scary more billing. The previous feelings alter my career somehow. I looked (Moss M et al. Crit Care Med. of irritation begin to boil into anger into website development, some- est rate of burnout among all physi- 2016;44[7]:1414). because more of your day is filled thing I had been good at in high cian subspecialties at >55%, and it is with bureaucratic demands and school. I took a few refresher classes even higher in pediatric critical care. Causes of burnout insurance reports rather than actu- on my days off and started coding (Sessler C. https://www.mdedge. There are many causes of burnout, ally helping people. This isn’t what my own sites, but I had bills to pay. com/chestphysician/article/160951/ and several studies have identified you signed up for. Years and years Big bills. Student loan bills. Luck- society-news/turning-heat-icu- risk factors. A lack of control, con- of training so you could be a paper ily, my first job out of fellowship burnout). The main difference be- flicts with colleagues and leadership, pusher? The thought leads to rage accepted many of my schedule de- tween stress and burnout is hope. and performing menial tasks can ... or sometimes apathy on days you mands, such as day shifts only, and With stress, you still feel like things add to the irritation of a workday. give in to the inevitable. after about a year, I recovered and can get better and you can get it all This doesn’t even include the nature You finish your shift with admis- remembered why I had loved medi- under control. Burnout feels hope- of our actual job as critical care doc- sions, procedures, code blues, and cine to begin with. less. tors. We care for the sickest and are an overwhelming and exhausting frequently involved in end-of-life night shift sign out. You feel like a What is burnout? What are the three core care. Over time, the stress morphs hamster in a wheel. You’re going Mind-body-soul exhaustion caused symptoms of burnout? into burnout. Female gender is also nowhere. What’s the point of all of by excessive stress. Stress and burn- • Irritability and impatience with an independent risk factor for doc- this? You find yourself questioning out are closely related, but they’re patients (depersonalization) tors (Pastores SM, et al. Crit Care why you went into medicine anymore like distant cousins. Stress • Cynicism and difficulty concen- Med. 2019;47[4]:550). ways ... yeah, that’s burnout. can be (and is) a normal part of our trating (emotional exhaustion) We’ve identified it. We’ve quan- I know what you’re thinking. You jobs. I bet you think you’re stressed, • What’s the point of all of this? tified it. But we’re not fixing it. In keep hearing about this, and it’s when you’re probably burned out. Nothing I do matters or is appreci- fact, there are only a few studies important to recognize, but then Critical care doctors have the high- ated (decreased self-efficacy) that have incorporated a needs assessment of doctors, paired with appropriate environmental intervention. A study done with primary care doctors in New York City clinics found that surveying a doctor’s “wish list” of interventions can help identify gaps in workflow, such as pairing one medical assistant with each attending (Linzer M, et al. J Gen Intern Med. 2015;30[8]:1105). Without more data like these, we’re hamsters in a wheel. Lucki- ly, organizations like CHEST have joined together with others to create the Critical Care Societies Collabo- rative and have an annual summit to discuss research strategies.

Solutions Even millennials are sick of the mindful “chore” list. Yoga pants, yoga mats, crystals, chakras, medi-

Kupicoo Kupicoo / E+ tation, and the list goes on and on.

52 • JUNE 2019 • CHEST PHYSICIAN NEWS FROM CHEST

What millennials want are work-life books, religious symbols, your which leads to a more productive girl. When crossing the street, you integrations that are easy; work- child’s toy car, anything can work if conversation. always look twice, oftentimes thrice. spaces that invite mindful behavior it has meaning for you, so when you Lastly, I started what I call a new Why be so careful? It’s the pedestri- and daily rituals that excite and see it or touch it during your day, Pavlov home routine. When I’m an’s right of way after all. “Well..” he relax them. Co-working spaces like you remember your big why. Why done with work, I light a candle and replied, “If a car hits you, nothing WeWork have designated self-care you’re serving people. Why you’re write out three things I’m grateful much happens to them, but your en- spaces. a doctor. I prefer the crystals over for. Retrain your brain. Retrain your tire life will be destroyed, forever.” Self-care is now essential, not an triggers. What’s your Pavlov’s bell Stop walking into traffic thinking indulgence. I wasn’t sure how to going to be? Many of us come home everything will be okay. Take control create this space in my ICU, so I Luckily, my first job out of hungry and stressed. Food then be- of what you can. started small, with things I could fellowship accepted many of comes linked to stress. This is not Look, I get it. As health-care carry with myself. The key is to find my schedule demands, such good. Link it with something else. providers, we are an independent small rituals with big meanings. Light a candle, count to 3, then blow group. But just because you can do What could this look like for you? as day shifts only, and after it out. Use your kids to incorpo- it alone, doesn’t mean you have to. I began doing breathwork. Frankly, about a year, I recovered and rate something fun. Use a toy with Choose one thing. Whether it be the idea came to me from my Apple® “super powers” to “beam” the bad something I mentioned or some- watch. It just started giving me these remembered why I had loved feelings away. Taking a few extra thing that came to your mind as you reminders one day, and I decided medicine to begin with. minutes to shift gears has created a read this. Then, drop me a line at to take it seriously. I found that my much happier home for me. my personal email at roozehra.khan. mind and muscles eased after only There are things that we can’t [email protected]. I will send you a 1 minute of breathing in and out jewelry because it’s something un- control. That’s called circumstances. reply to let you know I hear you and slowly. This elevated my mood and usual that I don’t expect to be sitting We can’t control other people; we I’m in your corner. was the refresher I needed in the in my pocket. It’s always a nice gen- can’t control the hospital system; we Burnout happens. afternoons. My body ached less after tle reminder of the love I have for can’t control our past. But the rest But, so does joy, job satisfaction, procedures. my patients, my job, and humanity. of everything we can control: our and balance. Those things just take I also got a little woo-woo (stay When I put my hands in my pocket thoughts, feelings, and daily self- more effort. with me now) and began carrying as I’m talking to yet another frus- care rituals. around crystal stones. You don’t trated family member, my responses It reminds me of something my Dr. Khan is Assistant Editor, Web have to carry around crystals. Prayer are more patient and more calm, dad always said when I was a little and Multimedia, CHEST® journal. CLASSIFIEDS Also available at MedJobNetwork.com

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MDEDGE.COM/CHESTPHYSICIAN • JUNE 2019 • 53 NEWS FROM CHEST

CHEST NetWorks Pulmonary medicine. Cardiovascular medicine and surgery. Chest infections. Interprofessional team.

Clinical Pulmonary Medicine algorithm (Van der Hulle T et al. who had clinical signs of DVT at ratio (Simel DL, Rennie D, eds. Pulmonary embolism Lancet. 2017;390[10091]:289) can baseline. These patients under- The Rational Clinical Examination: in pregnancy: A be safely used to avoid diagnostic went compression ultrasonography Evidence-Based Clinical Diagnosis. diagnostic conundrum imaging, Artemis Study Investi- and, if a clot was found, CTPA was 2009). Accurate clinical assess- Pulmonary embolism (PE) is the gators prospectively studied three not performed, and patients were ment of cardiac output, however, 6th leading cause of maternal criteria from YEARS algorithm in started on anticoagulation therapy. is a fraught endeavor. In a recently mortality in the United States. The combination with a D-dimer level Those with negative DVT studies published large clinical signs (Van der Pol et al. N Engl J Med. were subclassified based on D-di- series of patients and symptoms 2019;380[12]:1139). The three with unplanned of PE are usually criteria included clinical signs of ICU admission, nonspecific and deep-vein thrombosis (DVT), he- Due to low specificity and atrial fibrillation, often overlap moptysis, and PE as the most likely systolic blood with the nor- diagnosis. PE was considered ruled sensitivity of D-dimer test, pressure (BP) < mal physiologic out when none of the three criteria pregnant patients with suspected 90, altered con- changes of preg- were present and D-dimer was less PE often undergo CT pulmonary sciousness, cap- nancy. Due to than 1000 ng/mL or if one or more illary refill time low specificity of the criteria were met and D-di- angiography and ventilation- > 4.5 seconds Dr. Kenigsberg Dr. Adrish and sensitivity mer was less than 500 ng/mL. Pa- perfusion scanning, both of at the sternum, of D-dimer test, tients in whom D-dimer was greater or skin mottling over the knee pre- pregnant patients with suspected than 1000 ng/mL or in those with which can cause radiation dicted low cardiac output with spec- PE often undergo CT pulmonary D-dimer greater than 500 ng/mL exposure to mother and fetus. ificity >90%. Of 280 patients with angiography (CTPA) and ventila- and had one or more of the YEARS a cardiac index of < 2.2 L/min/m2, tion-perfusion scanning, both of algorithm criteria present, PE could less than half had any one of these which can cause radiation exposure not be ruled out and underwent findings (Hiemstra, et al. Intensive to mother and fetus. To answer CTPA. A modification of the cri- mer levels as the study population Care Med. 2019;45[2]:190). whether pregnancy-adapted YEARS teria was done only for patients above. Patients in whom pulmonary Regarding determination of shock embolism was not ruled out under- etiology, in a small series of patients went CTPA. Of these 299 patients, with systolic blood pressure < 90 16 (5.4%) were confirmed to have mm Hg, physical exam findings of FOUNDATION FOCUS PE at baseline. In the remaining relatively warm skin temperature 195 patients in whom PE was ruled and rapid capillary refill had 89% Are YOU ready for the Round up the members of your NetWork and get ready out on the basis of study protocol, a sensitivity for vasodilatory shock, for the annual NetWorks Challenge – a philanthropic 2019 NetWorks competition that encourages members of NetWorks 3-month follow-up diagnosed one and jugular venous pressure ≥8 had Challenge? to give back to their community and improve patient outpatient (0.51%) with VTE. Using 82% sensitivity for cardiogenic eti- April 1 to June 30 comes by donating to the CHEST Foundation in honor of pregnancy-adapted YEARS algo- ologies (Vazquez, et al. J Hosp Med. their NetWork. This year, EVERY NetWork is eligible to win rithm, CTPA was avoided in 39% of 2010;5[8]:471). Thus, while physical travel grants for their members to attend CHEST 2019 in the patients, of which 65% were in exam findings may inform bedside New Orleans! their first trimester when the radia- shock assessment, their accuracy NETWORKS CHALLENGE Contributions made between April 1 and June 30 will count tion exposure can be most harmful is limited. Critical care physicians toward your NetWork’s fundraising total. Be sure to watch to the fetus. should consider additional assess- our social media profiles to find out each month’s unique Muhammad Adrish, MD, FCCP ment techniques, such as echocardi- CHEST theme and to engage during the challenge! Steering Committee Member ography or invasive hemodynamic Visit chestfoundation.org/nc Munish Luthra, MD, FCCP monitoring, if diagnostic uncertain- to learn more about travel grants for CHEST 2019! Steering Committee Member ty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726). Cardiovascular Medicine Benjamin Kenigsberg, MD and Surgery Steering Committee Member DID YOU Physical examination Dr. David Bowton and Dr. Steven of low cardiac Hollenberg contributed to the article. ? output in the ICU KNOW Rapid evaluation of shock requires Chest Infections identifying signs of tissue hypoper- Lung infections in Angel Coz Yataco, MD, FCCP, one of the first winners of a CHEST Foundation Diversity Travel Grant fusion and differentiating between transplant recipients in 2016, has since stepped into leadership positions within the CHEST Foundation and CHEST, joining our Diversity and Inclusion Roundtable, chairing the Critical Care NetWork, becoming the elected cardiogenic, obstructive, hypovo- The increase in lung transplan- Vice-Chair of the Council of NetWorks, and assuming the Section Editor position for Critical Care lemic, and vasodilatory etiologies. tation over the years led to lung Commentary in CHEST Physician. Cardiac abnormalities may also transplant recipients presenting to Your giving during the NetWorks Challenge brings early career clinicians to the CHEST Annual Meeting contribute to mixed shock states pulmonologists outside of special- and provides winners with mentorship opportunities from experts in the chest medicine space! in a broad array of critically ill pa- ized centers. One of the most com- Donate today to help frame the future of chest medicine! tients. Left ventricular dysfunction mon presentations is for infections. chestfoundation.org/donate in inpatients correlates with physical Infections account for more than exam, with a 2.0 positive likelihood 25% of all posttransplant deaths ratio and 0.41 negative likelihood (Yusen, et al. J Heart Lung

54 • JUNE 2019 • CHEST PHYSICIAN NEWS FROM CHEST

Transplant. 2014;33[10]:1009. and proactive, invasive diagnostic impairing hemodynamics, and gas fully been described for obstructive Multiple factors contribute to this approach with needed testing to exchange, and leading to barotrau- airway disease (Langer T, et al. Crit- increased infection risk, including identify the potential pathogen, is ma. This approach seems contrary ical Care. 2016;20[1]:150). Factors donor lung colonization, disruption imperative in these patients. Early to the goals of management. Outside limiting this approach are the inva- of local host defenses, constant con- bronchoscopy with bronchoalveolar of conventional sive nature of tact with environmental pathogens, lavage remains the most sensitive therapies, such as ECMO and the and heavy immunosuppression test to identi- IV steroids and inherent risks (Redmund KF, et al. Proc Am Tho- fy pathogens. inhaled beta-ag- of large cannula rac Soc. 2009;6[1]:94). Therapy can onists, the data dislodgement; The onset of infectious manifes- then be tailored supporting other however, the tations, from the time of transplan- toward the iden- therapies such safety of this has tation, is variable, depending on tified pathogen. as IV beta-ag- been demon- As part of the onists, MgSO4, strated with Chest Infections methylxanthines, ambulation of Multiple factors contribute NetWork, we mucolytics, he- Dr. Baeten Dr. Luthra ECMO patients to this increased infection would like to liox, and volatile to receive phys- risk, including donor lung raise awareness Dr. Alalawi anesthetics are scant. In contrast, ical therapy (Abrams D, et al. Ann of lung infec- venovenous ECMO can provide Cardiothorac Surg. 2019;8[1]:44). colonization, disruption of local tions in unique subgroups, such as adequate gas exchange and prevent Alternatively, extracorporeal carbon host defenses, constant contact lung transplant recipients. Treating lung injury induced by mechanical dioxide removal (ECCO2R) systems infections in such patients requires ventilation and may be an effective utilize smaller catheters to satisfac- with environmental pathogens, a high index of suspicion in the set- bridging strategy to avoid aggres- torily remove CO2 while oxygen and heavy immunosuppression. ting of an atypical presentation. Raed Alalawi, MD, FCCP Performing “awake” ECMO has successfully been described for Steering Committee Member the organism. Based on the time obstructive airway disease. Factors limiting this approach are the of onset, infections can be catego- Interprofessional Team invasive nature of ECMO and the inherent risks of large cannula rized into within the first month Extracorporeal membrane posttransplant, 1 to 6 months, and oxygenation (ECMO) dislodgement; however, the safety of this has been demonstrated beyond 6 months, posttransplant. in near fatal asthma with ambulation of ECMO patients to receive physical therapy. During the first month, because of Near fatal asthma (NFA) is defined allograft colonization, preexisting as acute severe asthma characterized infections in the recipient, and sur- by acute respiratory failure with hy- sive ventilation in refractory NFA supplementation could be achieved gical- and hospital-acquired nosoco- percapnia and/or respiratory acidosis (Hye Ju Yeo, et al. Critical Care. via nasal cannula (Pisani L, et al. Re- mial infections are more common. requiring ventilator support. NFA 2017;21[1]:297). spiratory Care. 2018;63[9]:1174). In- The first 6 months are where the refractory to conventional medical Use of early ECMO to permit corporation of ECMO in select cases patients are at the highest risk for management and ventilator therapy spontaneous breathing while the of NFA, especially ECCO2R, should opportunistic infections. As the im- can lead to fatal outcomes. Near fatal circuit accomplishes required venti- be considered as an early rather than munosuppression is lowered after asthma also carries substantial mor- lation and oxygenation seems more rescue therapy for acute severe asth- 6 months, the causative organisms tality if invasive ventilation is needed ideal. Avoidance of mechanical ma refractory to conventional medi- tend to be more common pathogens (Marquette CH, et al. Am Rev Respir ventilation not only prevents com- cal therapy. (Green M. Am J Transplant. 2013;13 Dis. 1992;146[1]:76). Use of seda- plications like barotrauma but also Robert Baeten, DMSc, PA-C, FCCP [suppl 4]:3-8). tives can exacerbate bronchospasm, may reduce delirium, malnutrition, Steering Committee Member An early, aggressive, empiric and positive pressure ventilation can and neuromuscular dysfunction. Per- Munish Luthra MD, FCCP antimicrobial therapy initiation exacerbate dynamic hyperinflation, forming “awake” ECMO has success- Steering Committee Member This month in the journal CHEST® INDEX OF Editor’s Picks ADVERTISERS

Biomerieux BY RICHARD S. IRWIN, MD, MASTER FCCP BioFire 41 COMMENTARY A Novel Algorithm to Analyze Boehringer Ingelheim Pharmaceuticals, Inc. On Being the Editor in Chief of Epidemiology and Outcomes of Ofev 22-26 the Journal CHEST: 14 Memorable Carbapenem Resistance Among Years. Patients With Hospital-Acquired Genentech USA, Inc. Esbriet 2-5 By Dr. Richard S. Irwin and Ventilator-Associated Pneu- monia: A Retrospective Cohort GSK ORIGINAL RESEARCH Study. Trelegy 29-36, 56 Breo 45-49 Procalcitonin-Guided Antibiotic By Dr. M. D. Zilberberg, et al. Discontinuation and Mortality in Pfizer Inc. Critically Ill Adults: A Systematic Raw Bioelectrical Impedance Revatio 9-11 Review and Meta-analysis. Analysis Variables Are Indepen- Sanofi and Regeneron Pharmaceuticals, By Dr. B. J. Pepper, et al. dent Predictors of Early Inc. All-Cause Mortality in Patients Dupixent 14-19 With COPD. By Dr. Francesca de Blasio, et al.

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