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U.S. travelers to Europe need up to date measles immunization
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
researchers at the Centers for Disease Control and Prevention recommend in a Pediatrics special report.
More than 41,000 measles cases and 37 deaths – primarily due to low immunization coverage – were reported in the World Health Organization European Region in the first 6 months of 2018, the highest incidence since the 1990s. Typical case counts since 2010 have ranged from 5,000 to 24,000 in this region, wrote Kristina M. Angelo, DO, MPH, of the Centers for Disease Control and Prevention Travelers’ Health Branch in Atlanta, and associates.
France, Italy and Greece – all particularly popular countries for U.S. vacationers to visit – have particularly high numbers of cases, as do Georgia, Russia, Serbia and, comprising the majority of cases, Ukraine. Italy, for example, is the 10th most popular destination worldwide for Americans, with an estimated 2.5 million American visitors in 2015.
“The large number of measles infections in the WHO European Region ... is a global concern because the European continent is the most common travel destination worldwide,” but is not perceived as a place with infectious disease risk. So travelers may not consider the need of a pretravel health consultation, including vaccination, they said.
But they need to, Dr. Angelo and associates state, and health care providers should be vigilant about checking for symptoms of measles among those who have recently returned from overseas. Given how highly contagious measles is, unvaccinated and under vaccinated travelers to Europe are susceptible to infection, as are any people they encounter back in the United States if the travelers come home sick.
Measles was eliminated in the United States in 2000, but that status is in jeopardy, CDC officials recently warned. The number of domestic measles cases has exceeded 1,000 just halfway through 2019, the highest count since 1992, nearly a decade before elimination.
“Avoiding international travel with nonimmune infants and performing early vaccination at 6 to 12 months of age per the ACIP [Advisory Committee on Immunization Practices] recommendations if travel is unavoidable are of utmost importance,” Dr. Angelo and colleagues advised. “Other at-risk populations (e.g., immunocompromised individuals and pregnant women), for whom vaccination against the measles virus is contraindicated, may consider alternative destinations or delay travel to measles-endemic destinations or areas with known, ongoing measles outbreaks.”
“Presumptive immunity to measles is defined as 1 or more of the following: birth before 1957, laboratory evidence of immunity or infection, 1 or more doses of a measles containing vaccine administered for preschool-aged children and low-risk adults, or 2 doses of measles vaccine among school-aged children and high-risk adults, including international travelers,” they explained.
In Europe, measles remains endemic in Belgium, Bosnia and Herzegovina, France, Georgia, Germany, Italy, Romania, the Russian Federation, Serbia and the Ukraine, the authors wrote.
“As long as measles remains endemic in other countries, the United States will be challenged by measles importations,” the authors wrote. Yet at least one past study in 2017 revealed a third of U.S. travelers to Europe left the country without being fully vaccinated against measles, most often due to vaccine refusal.
“The reason one-third of travelers to Europe missed an opportunity for measles vaccination remains unclear,” the authors wrote. “It may represent a lack of concern or awareness on the part of travelers and the health care providers about acquiring measles in Europe.”
Dr. Angelo and colleagues also emphasized the importance of returning U.S. travelers seeking health care if they have symptoms of measles, including fever and a rash.
Health care providers should ask all patients about recent international travel, they stated. “If measles is suspected, health care providers should isolate travelers immediately, placing them on airborne precautions until day 4 of the rash.” Providers may consider administering immunoglobulin for unvaccinated and undervaccinated travelers and monitor them for 21 days for development of measles symptoms.
The statement was funded by the CDC. The authors reported no relevant financial disclosures.
SOURCE: Angelo KM et al. Pediatrics. 2019 Jun 17. doi: /10.1542/peds.2019-0414.
FROM PEDIATRICS
Eosinophil-guided therapy reduces corticosteroid use in COPD
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
in terms of the number of days out of hospital and alive, new research has found.
Writing in the Lancet Respiratory Medicine, researchers reported the outcomes of a multicenter, controlled, open-label trial comparing eosinophil-guided and standard therapy with systemic corticosteroids in 318 patients with COPD.
Pradeesh Sivapalan, MD, of the respiratory medicine section of Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors wrote that eosinophilic inflammation had been seen in 20%-40% of patients with acute exacerbations of COPD. Patients with higher eosinophilic blood counts were at increased risk of acute exacerbations but were also more likely to benefit from corticosteroid treatment.
In the eosinophil-guided therapy arm of the study, 159 patients received 80 mg of intravenous methylprednisolone on day 1, then from the second day were treated with 37.5 mg of prednisolone oral tablet daily – up to 4 days – only on days when their blood eosinophil count was at least 0.3 x 10⁹ cells/L. In the control arm, 159 patients also received 80 mg of intravenous methylprednisolone on day 1, followed by 37.5 mg of prednisolone tablets daily for 4 days.
After 14 days, there were no significant differences between the two groups for mean days alive and out of hospital.
There were 12 more cases of readmission with COPD, including three fatalities, in the eosinophil-guided group within the first month. However the authors said these differences were not statistically significant, but “because the study was not powered to detect differences in this absolute risk range, we cannot rule out that this was an actual harm effect from the interventional strategy.”
The eosinophil-guided therapy group did show more than a 50% reduction in the median duration of systemic corticosteroid therapy, which was 2 days in the eosinophil-guided group, compared with 5 days in the control group (P less than .0001), and the differences between the two groups remained significant at days 30 and 90.
“The tested strategy was successful in reducing the exposure to systemic corticosteroids, but we cannot exclude the possibility that a more aggressive algorithm, such as a single dose of systemic corticosteroid, might have been more effective,” the authors wrote.
At the 90-day follow-up, there were no differences in the number of infections requiring antibiotic treatment, nor in dyspepsia, ulcer complications, or initiation of new proton-pump inhibitor treatment.
The study was supported by the Danish Regions Medical Fund and the Danish Council for Independent Research. Two authors declared personal fees from pharmaceutical companies outside the submitted work. No other conflicts were declared.
SOURCE: Sivapalan P et al. Lancet Respir Med. 2019, May 20. doi: 10.1016/S2213-2600(19)30176-6.
FROM LANCET RESPIRATORY MEDICINE
Endobronchial valves for lung volume reduction: What can we offer patients with advanced emphysema?
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
The global burden COPD is considerable. In the United States, it is the third most common cause of death and is associated with over $50 billion in annual direct and indirect health-care expenditures (Guarascio AJ, et al. Clinicoecon Outcomes Res. 2013;5:235). For patients with severe emphysema with hyperinflation, dyspnea is often a quality of life (QOL)-limiting symptom (O’Donnell DE, et al. Ann Am Thorac Soc. 2017;14:S30). Few proven palliation options exist, particularly for patients with dyspnea refractory to smoking cessation, medical management with bronchodilators, and pulmonary rehabilitation. The recent Food and Drug Administration (FDA) approval of two endobronchial valves for lung volume reduction has established the increasing importance of bronchoscopy as a management tool in advanced COPD.
Why were these valves developed?
For decades, lung volume reduction has been investigated as a mechanical approach to counter-act the physiologic effects of emphysematous hyperinflation. Its goal is to improve lung elastic recoil, respiratory muscle mechanical advantage and efficiency, and ventilation/perfusion matching. The landmark National Emphysema Treatment Trial (NETT), published in 2001 and 2003, demonstrated that in a select patient population (upper lobe-predominant emphysema and low exercise capacity), lung volume reduction surgery (LVRS) lowers mortality and improves QOL and exercise tolerance (Fishman A et al. N Engl J Med. 2003;348:2059). Despite the encouraging results in this study subpopulation, LVRS is per-formed infrequently (Decker MR, et al. J Thorac Cardiovasc Surg. 2014;148:2651). Concern about its morbidity and the specialized nature of the procedure has hindered widespread adoption. Subsequently, endobronchial techniques have been developed as an alternative to surgical lung volume reduction.
How does bronchoscopic lung volume reduction (BLVR) benefit patients with emphysema?
Valves used for ELVR are removable one-way flow devices placed by flexible bronchoscopy into selected airways supplying emphysematous lung. The valves block air entry but allow the exit of secretions and trapped air. This results in atelectasis of the targeted lobe and a decrease in lung volume.
Which endobronchial valves are available in the United States?
In 2018, two valves were approved by the FDA for bronchoscopic lung volume reduction (BLVR) – the Zephyr® EBV (Pulmonx) ( (Fig 1) and the Spiration® Valve System (Olympus) (IBV) (Fig 2). The Zephyr® EBV is a duckbill-shaped silicone valve mounted within a self-expanding nitinol (nickel titanium alloy) stent. It comes in three sizes for airways with a diameter 4 - 8.5 mm. The Spiration® IBV umbrella-shaped valve is com-posed of six nitinol struts surfaced with polyurethane. Its four sizes accommodate airway diameters 5 - 9 mm.
What’s the evidence behind BLVR?
Zephyr® Valves
The Endobronchial Valve for Emphysema Palliation Trial (VENT), the largest valve trial thus far, randomized patients with severe heterogeneous emphysema to receive unilateral Zephyr® valve placement or standard medical care (Sciurba FC, et al. N Engl J Med. 2010;363:1233). Overall improvement in spirometry and dyspnea scores was modest in the valve group. Post-hoc analysis identified an important subgroup of patients with significant clinical benefit, those with a complete fissure. This finding gave guidance to further EBV studies on patients with severe emphysema and absent collateral ventilation (CV).
Identifying a complete fissure on imaging is now used as a surrogate for assessing CV and is an integral part of the initial profiling of patients for EBV therapy (Koster TD, et al. Respiration. 2016;92(3):150).
In the STELVIO trial, 68 patients were randomized to Zephyr ® EBV placement or standard medical care (Klooster K, et al. N Engl J Med. 2015;373:2325). Those with EBV placement had significantly improved lung function and exercise capacity. TRANSFORM, a multicenter trial evaluating Zephyr® EBV placement in heterogeneous emphysema, showed similar results (Kemp SV, et al. Am J Respir Crit Care Med. 2017;196:1535).
The IMPACT trial compared patients with homogenous emphysema without CV to standard medical therapy alone. It showed improvement in FEV1, QOL scores, and exercise tolerance in the EBV group. This study affirmed that the absence of CV, rather than the pattern of emphysema, correlates with the clinical benefit from EBV therapy (Valipour A, et al. Am J Respir Crit Care Med. 2016;194(9):1073). Finally, LIBERATE, a multicenter study on the Zephyr® EBV, examined its placement in patients with heterogenous emphysema. This study demonstrated improvement in spirometry, QOL, and 6-minute walk test (6-MWT) distance (Criner GJ, et al. Am J Respir Crit Care Med. 2018;198:1151) over a longer period, 12 months, bolstering the findings of prior studies. These results prompted the Zephyr® valve’s FDA approval.
Spiration® Valves
Small trials have shown favorable results with the Spiration® IBV for BLVR, including a pilot multicenter cohort study of 30 patients with heterogeneous, upper-lobe emphysema who underwent valve placement (Wood DE, et al. J Thorac Cardiovasc Surg. 2007;133:65). In this trial, investigators found significant improvement in QOL scores, but no change in FEV1 or other physiologic parameters.
The EMPROVE trial is a multicenter, prospective, randomized, controlled study assessing BLVR with the Spiration® IBV. Six- and twelve-month data from the trial were presented in 2018 at the American Thoracic Society Conference and at the European Respiratory Society International Conference.
Collateral Ventilation
Identifying patients in whom there is no CV between lobes is critical to success with BLVR. Collateral ventilation allows air to bypass the valve occlusion distally, thereby negating the desired effect of valve placement, lobar atelectasis. High-resolution computed tomography (HRCT) scanning combined with quantitative software can be used to assess emphysema distribution and fissure integrity. Additionally, a proprietary technology, the Chartis System®, can be employed intra-procedure to estimate CV by measuring airway flow, resistance, and pressure in targeted balloon-occluded segments. Absence of CV based on Chartis evaluation was an inclusion criterion in the aforementioned valve studies.
Which patients with emphysema should be referred for consideration of valve placement?
The following criteria should be used in selecting patients for referral for BLVR:
• FEV1 15% - 45% of predicted value at baseline
• Evidence of hyperinflation: TLC greater than or equal to 100% and RV greater than or equal to 175%
• Baseline postpulmonary rehabilitation 6-MWT distance of 100 - 500 meters
• Clinically stable on < 20 mg prednisone (or equivalent) daily
• Nonsmoking for at least 4 months
• Integrity of one or both major fissures at least 75%
• Ability to provide informed consent and to tolerate bronchoscopy
Complications
The most common complication after valve placement is pneumothorax – a double-edged sword in that it typically indicates the achievement of atelectasis. In published trials, the frequency of pneumothorax varies. Some studies document rates below 10%. Others report rates of nearly 30% (Gompelmann D, et al. Respiration. 2014;87:485). In landmark trials, death related to pneumothorax occurred rarely. Most severe pneumothoraces occur within the first 72 hours after valve placement. This has prompted many centers to observe postprocedure patients in hospital for an extended period. Pneumonia and COPD exacerbations have also been reported after EBV placement. Therefore, in some trials, patients received prophylactic prednisolone and azithromycin. Other less common complications are hemoptysis, granulation tissue formation, and valve migration.
What’s ahead for ELVR?
Overall, valve technology for BLVR is an exciting option in the management of patients with severe emphysema and is now a staple for any advanced emphysema program. Key areas of future interest include management of patients with partial fissures, minimizing adverse procedural effects, and developing programs to optimize and streamline a multidisciplinary approach to timely and efficient referral, assessment, and intervention. As more patients with COPD undergo ELVR, one goal should be to create multi-institution prospective studies as well as registries to delineate further the optimal use of endobronchial valves for lung volume reduction.
Zephyr® Endobronchial Valve (Pulmonx)
Spiration® Valve System (Olympus)
The American College of Chest Physicians (CHEST) does not endorse or supp
Clinical pulmonary medicine. Cardiovascular medicine and surgery. Chest infections. Interprofessional team.
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member
Clinical Pulmonary Medicine
Pulmonary embolism in pregnancy: A diagnostic conundrum
Pulmonary embolism (PE) is the 6th leading cause of maternal mortality in the United States. The clinical signs and symptoms of PE are usually nonspecific and often overlap with the normal physiologic changes of pregnancy. Due to low specificity and sensitivity of D-dimer test, pregnant patients with suspected PE often undergo CT pulmonary angiography (CTPA) and ventilation-perfusion scanning, both of which can cause radiation exposure to mother and fetus.
To answer whether pregnancy-adapted YEARS algorithm (Van der Hulle T et al. Lancet. 2017;390[10091]:289) can be safely used to avoid diagnostic imaging, Artemis Study Investigators prospectively studied three criteria from YEARS algorithm in combination with a D-dimer level (Van der Pol et al. N Engl J Med. 2019;380[12]:1139. The three criteria included clinical signs of deep-vein thrombosis (DVT), hemoptysis, and PE as the most likely diagnosis. PE was considered ruled out when none of the three criteria were present and D-dimer was less than 1000 ng/mL or if one or more of the criteria were met and D-dimer was less than 500 ng/mL. Patients in whom D-dimer was greater than 1000 ng/mL or in those with D-dimer greater than 500 ng/mL and had 1 or more of the YEARS algorithm criteria present, PE could not be ruled out and underwent CTPA. A modification of the criteria was done only for patients who had clinical signs of DVT at baseline. These patients underwent compression ultrasonography and if a clot was found, CTPA was not performed and patients were started on anticoagulation therapy. Those with negative DVT studies were subclassified based on D-dimer levels as the study population above. Patients in whom pulmonary embolism was not ruled out underwent CTPA. Of these 299 patients, 16 (5.4%) were confirmed to have PE at baseline.
In the remaining 195 patients in whom PE was ruled out on the basis of study protocol, a 3-month follow-up diagnosed one patient (0.51%) with VTE. Using pregnancy-adapted YEARS algorithm, CTPA was avoided in 39% of the patients of which 65% were in their first trimester when the radiation exposure can be most harmful to the fetus.
Muhammad Adrish, MD, FCCP
Steering Committee Member
Munish Luthra, MD, FCCP
Steering Committee Member
Cardiovascular Medicine and Surgery
Physical examination of low cardiac output in the ICU
Rapid evaluation of shock requires identifying signs of tissue hypoperfusion and differentiating between cardiogenic, obstructive, hypovolemic, and vasodilatory etiologies. Cardiac abnormalities may also contribute to mixed shock states in a broad array of critically ill patients. Left ventricular dysfunction in inpatients correlates with physical exam, with a 2.0 positive likelihood ratio and 0.41 negative likelihood ratio (Simel DL, Rennie D, eds. The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. 2009). Accurate clinical assessment of cardiac output, however, is a fraught endeavor. In a recently published large series of patients with unplanned ICU admission, atrial fibrillation, systolic blood pressure (BP) < 90, altered consciousness, capillary refill time >4.5 seconds at the sternum, or skin mottling over the knee predicted low cardiac output with specificity >90%. Of 280 patients with a cardiac index of < 2.2 L/min/m2, less than half had any one of these findings (Hiemstra, et al. Intensive Care Med. 2019;45[2]:190).
Regarding determination of shock etiology, in a small series of patients with systolic blood pressure < 90 mm Hg, physical exam findings of relatively warm skin temperature and rapid capillary refill had 89% sensitivity for vasodilatory shock, and jugular venous pressure ≥8 had 82% sensitivity for cardiogenic etiologies (Vazquez, et al. J Hosp Med. 2010;5[8]:471). Thus, while physical exam findings may inform bedside shock assessment, their accuracy is limited. Critical care physicians should consider additional assessment techniques, such as echocardiography or invasive hemodynamic monitoring, if diagnostic uncertainty persists (Vincent, et al. N Engl J Med. 2013;369[18]:1726).
Benjamin Kenigsberg, MD
Steering Committee Member
Dr. David Bowton and Dr. Steven Hollenberg contributed to the article.
Chest Infections
Lung infections in the transplant recipients
The increase in lung transplantation over the years led to lung transplant recipients presenting to pulmonologists outside of specialized centers. One of the most common presentations is for infections. Infections account for more than 25% of all posttransplant deaths (Yusen, et al. J Heart Lung Transplant. 2014;33[10]:1009.
Multiple factors contribute to this increased infection risk, including donor lung colonization, disruption of local host defenses, constant contact with environmental pathogens, and heavy immunosuppression (Redmund KF, et al. Proc Am Thorac Soc. 2009;6[1]:94).
The onset of infectious manifestations, from the time of transplantation, is variable, depending on the organism. Based on the time of onset, infections can be categorized into within the first month posttransplant, 1 to 6 months, and beyond 6 months, posttransplant. During the first month, because of allograft colonization, preexisting infections in the recipient, and surgical- and hospital-acquired nosocomial infections are more common. The first 6 months are where the patients are at the highest risk for opportunistic infections. As the immunosuppression is lowered after 6 months, the causative organisms tend to be more common pathogens (Green M. Am J Transplant. 2013;13 [suppl 4]:3-8).
An early, aggressive, empiric antimicrobial therapy initiation and proactive, invasive diagnostic approach with needed testing to identify the potential pathogen, is imperative in these patients. Early bronchoscopy with bronchoalveolar lavage remains the most sensitive test to identify pathogens. Therapy can then be tailored toward the identified pathogen.
As part of the Chest Infections NetWork, we would like to raise awareness of lung infections in unique subgroups, such as lung transplant recipients. Treating infections in such patients requires a high index of suspicion in the setting of an atypical presentation.
Raed Alalawi, MD, FCCP
Steering Committee Member
Interprofessional Team
Extracorporeal Membrane Oxygenation (ECMO) in Near Fatal Asthma
Near fatal asthma (NFA) is defined as acute severe asthma characterized by acute respiratory failure with hypercapnia and/or respiratory acidosis requiring ventilator support. NFA refractory to conventional medical management and ventilator therapy can lead to fatal outcomes. Near fatal asthma also carries substantial mortality if invasive ventilation is needed (Marquette CH, et al. Am Rev Respir Dis. 1992;146[1]:76). Use of sedatives can exacerbate bronchospasm, and positive pressure ventilation can exacerbate dynamic hyperinflation, impairing hemodynamics, and gas exchange, and leading to barotrauma. This approach seems contrary to the goals of management. Outside of conventional therapies, such as IV steroids and inhaled beta-agonists, the data supporting other therapies such as IV beta-agonists, MgSO4, methylxanthines, mucolytics, heliox, and volatile anesthetics are scant. In contrast, venovenous ECMO can provide adequate gas exchange and prevent lung injury induced by mechanical ventilation and may be an effective bridging strategy to avoid aggressive ventilation in refractory NFA (Hye Ju Yeo, et al. Critical Care. 2017;21[1]:297).
Use of early ECMO to permit spontaneous breathing while the circuit accomplishes required ventilation and oxygenation seems more ideal. Avoidance of mechanical ventilation not only prevents complications like barotrauma but also may reduce delirium, malnutrition, and neuromuscular dysfunction. Performing “awake” ECMO has successfully been described for obstructive airway disease (Langer T, et al. Critical Care. 2016;20[1]:150). Factors limiting this approach are the invasive nature of ECMO and the inherent risks of large cannula dislodgement; however, the safety of this has been demonstrated with ambulation of ECMO patients to receive physical therapy (Abrams D, et al. Ann Cardiothorac Surg. 2019;8[1]:44). Alternatively, extracorporeal carbon dioxide removal (ECCO2R) systems utilize smaller catheters to satisfactorily remove CO2 while oxygen supplementation could be achieved via nasal cannula (Pisani L, et al. Respiratory Care. 2018;63[9]:1174). Incorporation of ECMO in select cases of NFA, especially ECCO2R, should be considered as an early rather than rescue therapy for acute severe asthma refractory to conventional medical therapy.
Robert Baeten, DMSc, PA-C, FCCP
Steering Committee Member
Munish Luthra MD, FCCP
Steering Committee Member
Reducing pediatric RSV burden is top priority
LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).
RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).
“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So
Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.
The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.
“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.
He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).
These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.
The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).
RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.
Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.
Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.
He reported serving as a consultant to a half-dozen pharmaceutical companies, as well as having received research funding from Janssen, GlaxoSmithKline, and Novavax.
LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).
RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).
“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So
Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.
The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.
“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.
He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).
These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.
The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).
RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.
Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.
Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.
He reported serving as a consultant to a half-dozen pharmaceutical companies, as well as having received research funding from Janssen, GlaxoSmithKline, and Novavax.
LJUBLJANA, SLOVENIA – Prevention or early effective treatment of respiratory syncytial virus (RSV) infection in infants and small children holds the promise of sharply reduced burdens of both acute otitis media (AOM) and pneumonia, Terho Heikkinen, MD, PhD, predicted in the Bill Marshall Award Lecture presented at the annual meeting of the European Society for Paediatric Infectious Diseases (ESPID).
RSV is by far the hottest virus in the world,” declared Dr. Heikkinen, professor of pediatrics at the University of Turku (Finland).
“A lot of progress is being made with respect to RSV. This increased understanding holds great promise for new interventions,” he explained. “Lots of different types of vaccines are being developed, monoclonal antibodies, antivirals. So
Today influenza is the only respiratory viral infection that’s preventable via vaccine or effectively treatable using antiviral drugs. That situation has to change, as Dr. Heikkinen demonstrated early in his career; RSV is the respiratory virus that’s most likely to invade the middle ear during AOM. It’s much more ototropic than influenza, parainfluenza, enteroviruses, or adenoviruses (N Engl J Med. 1999 Jan 28;340[4]:260-4), he noted.
The Bill Marshall Award and Lecture, ESPID’s most prestigious award, is given annually to an individual recognized as having significantly advanced the field of pediatric infectious diseases. Dr. Heikkinen was singled out for his decades of work establishing that viruses, including RSV, play a key role in AOM, which had traditionally been regarded as a bacterial infection. He and his coinvestigators demonstrated that in about two-thirds of cases, AOM is actually caused by a combination of bacteria and viruses, which explains why patients’ clinical response to antibiotic therapy for AOM often is poor. They also described the chain of events whereby viral infection of the upper airway epithelium triggers an inflammatory response in the nasopharynx, with resultant Eustachian tube dysfunction and negative middle ear pressure, which in turn encourages microbial invasion of the middle ear. Moreover, they showed that the peak incidence of AOM isn’t on day 1 after onset of upper respiratory infection symptoms, but on day 3 or 4.
“What this tells us is that, once a child has a viral respiratory infection, there is a certain window of opportunity to try to prevent the development of the complication if we have the right tools in place,” Dr. Heikkinen said.
He and his colleagues put this lesson to good use nearly a decade ago in a randomized, double-blind trial in which they showed that giving oseltamivir (Tamiflu) within 12 hours after onset of influenza symptoms in children aged 1-3 years reduced the subsequent incidence of AOM by 85%, compared with placebo (Clin Infect Dis. 2010 Oct 15;51[8]:887-94).
These observations paved the way for the ongoing intensive research effort exploring ways of preventing AOM through interventions at two different levels: by developing viral vaccines to prevent a healthy child from contracting the viral upper respiratory infection that precedes AOM and by coming up with antiviral drugs or bacterial vaccines to prevent a upper respiratory infection from evolving into AOM.
The same applies to pneumonia. Other investigators showed years ago that both respiratory viruses and bacteria were present in two-thirds of sputum samples obtained from children with community-acquired pneumonia (Clin Microbiol Infect. 2012 Mar;18[3]:300-7).
RSV is the top cause of hospitalization for acute respiratory infection – pneumonia and bronchiolitis – in infants. Worldwide, it’s estimated that RSV accounts for more than 33 million episodes of pneumonia annually, with 3.2 million hospitalizations and 118,200 deaths.
Beyond the hospital, however, Dr. Heikkinen and colleagues conducted a prospective cohort study in Turku over the course of two consecutive respiratory infection seasons in which they captured the huge burden of RSV as an outpatient illness. It hit hardest in children younger than 3 years, in whom the average annual incidence of RSV infection was 275 cases per 1,000 children. In that youngest age population, RSV upper respiratory infection was followed by AOM 58% of the time, with antibiotics prescribed in 66% of the cases of this complication of RSV illness. The mean duration of RSV illness was greatest in this young age group, at 13 days, and it was associated with parental absenteeism from work at a rate of 136 days per 100 children with RSV illness.
Moreover, while AOM occurred less frequently in children aged 3-6 years, 46% of the cases were attributed to a preceding RSV infection, which led to antibiotic treatment nearly half of the time (J Infect Dis. 2017 Jan 1;215[1]:17-23). This documentation has spurred further efforts to develop RSV vaccines and antivirals.
He reported serving as a consultant to a half-dozen pharmaceutical companies, as well as having received research funding from Janssen, GlaxoSmithKline, and Novavax.
EXPERT ANALYSIS FROM ESPID 2019
Waning pertussis immunity may be linked to acellular vaccine
A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.
Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.
“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”
The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).
The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.
In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).
Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.
“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”
But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).
The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).
The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.
“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”
The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.
SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.
Fixing one problem with the pertussis vaccine seemed to have created another, Kathryn M. Edwards, MD, wrote in an accompanying editorial.
The current acellular vaccine was approved in 1997. It was considered a less reactive substitute for the previous whole-cell vaccine, which was associated with injection site pain, swelling, fever, and febrile seizures, Dr. Edwards wrote. “For about a decade, all seemed to be going well with pertussis control. Serological methods were employed to diagnose pertussis infections in adolescents and adults, and polymerase chain reaction methods were devised to more accurately detect pertussis organisms. Thus, the burden of pertussis disease was increasingly appreciated as the diagnostic methods improved.”
But things soon changed. There were pertussis outbreaks, some of them quite large. The increasing disease rates showed that protection conferred by the acellular vaccine waned much more quickly than that conferred by the whole-cell vaccine. “In the current study, Zerbo et al. add to the body of evidence documenting the increase in pertussis risk with time after DTaP vaccination,” she noted.
This has several practical implications, Dr. Edwards wrote.
“First, given the markedly increased risk of pertussis in unvaccinated and undervaccinated children, universal DTaP vaccination should be strongly recommended. Second, the addition of maternal Tdap vaccination administered during pregnancy has been shown to significantly reduce infant disease before primary immunization and should remain the standard,” Dr. Edwards wrote.
More problematic is how to address the waning DTaP immunity now seen. “One option presented [at an international meeting] was a live-attenuated pertussis vaccine administered intranasally that would stimulate local immune responses and prevent colonization with pertussis organisms. This vaccine is currently being studied in adults and might provide a solution for waning immunity seen with DTaP vaccine,” she noted.
Another possibility is adding the live vaccine to the current DTaP, which should, in theory, stimulate more long-lasting immunity. But numerous safety studies in young children would be necessary before adopting such an approach, Dr. Edwards wrote.
Adding more antigens to the acellular vaccine also might work, and investigational vaccines like this are in development.
Studies in animals and humans show that acellular vaccines “generate functionally different T-cell responses than those seen after whole-cell vaccines, with the whole cell vaccines generating more protective T-cell responses. Studies are ongoing to determine if adjuvants can be added to acellular vaccines to modify their T-cell responses to a more protective immune response or whether the T-cell response remains fixed once primed with DTaP vaccine,” she wrote.
Dr. Edwards is a pediatric infectious disease specialist at Vanderbilt University, Nashville, Tenn. She wrote an editorial to accompany Zerbo et al (Pediatrics. 2019. doi: 10.1542/peds.2019-1276). She reported no financial disclosures, and received no funding to write the editorial.
Fixing one problem with the pertussis vaccine seemed to have created another, Kathryn M. Edwards, MD, wrote in an accompanying editorial.
The current acellular vaccine was approved in 1997. It was considered a less reactive substitute for the previous whole-cell vaccine, which was associated with injection site pain, swelling, fever, and febrile seizures, Dr. Edwards wrote. “For about a decade, all seemed to be going well with pertussis control. Serological methods were employed to diagnose pertussis infections in adolescents and adults, and polymerase chain reaction methods were devised to more accurately detect pertussis organisms. Thus, the burden of pertussis disease was increasingly appreciated as the diagnostic methods improved.”
But things soon changed. There were pertussis outbreaks, some of them quite large. The increasing disease rates showed that protection conferred by the acellular vaccine waned much more quickly than that conferred by the whole-cell vaccine. “In the current study, Zerbo et al. add to the body of evidence documenting the increase in pertussis risk with time after DTaP vaccination,” she noted.
This has several practical implications, Dr. Edwards wrote.
“First, given the markedly increased risk of pertussis in unvaccinated and undervaccinated children, universal DTaP vaccination should be strongly recommended. Second, the addition of maternal Tdap vaccination administered during pregnancy has been shown to significantly reduce infant disease before primary immunization and should remain the standard,” Dr. Edwards wrote.
More problematic is how to address the waning DTaP immunity now seen. “One option presented [at an international meeting] was a live-attenuated pertussis vaccine administered intranasally that would stimulate local immune responses and prevent colonization with pertussis organisms. This vaccine is currently being studied in adults and might provide a solution for waning immunity seen with DTaP vaccine,” she noted.
Another possibility is adding the live vaccine to the current DTaP, which should, in theory, stimulate more long-lasting immunity. But numerous safety studies in young children would be necessary before adopting such an approach, Dr. Edwards wrote.
Adding more antigens to the acellular vaccine also might work, and investigational vaccines like this are in development.
Studies in animals and humans show that acellular vaccines “generate functionally different T-cell responses than those seen after whole-cell vaccines, with the whole cell vaccines generating more protective T-cell responses. Studies are ongoing to determine if adjuvants can be added to acellular vaccines to modify their T-cell responses to a more protective immune response or whether the T-cell response remains fixed once primed with DTaP vaccine,” she wrote.
Dr. Edwards is a pediatric infectious disease specialist at Vanderbilt University, Nashville, Tenn. She wrote an editorial to accompany Zerbo et al (Pediatrics. 2019. doi: 10.1542/peds.2019-1276). She reported no financial disclosures, and received no funding to write the editorial.
Fixing one problem with the pertussis vaccine seemed to have created another, Kathryn M. Edwards, MD, wrote in an accompanying editorial.
The current acellular vaccine was approved in 1997. It was considered a less reactive substitute for the previous whole-cell vaccine, which was associated with injection site pain, swelling, fever, and febrile seizures, Dr. Edwards wrote. “For about a decade, all seemed to be going well with pertussis control. Serological methods were employed to diagnose pertussis infections in adolescents and adults, and polymerase chain reaction methods were devised to more accurately detect pertussis organisms. Thus, the burden of pertussis disease was increasingly appreciated as the diagnostic methods improved.”
But things soon changed. There were pertussis outbreaks, some of them quite large. The increasing disease rates showed that protection conferred by the acellular vaccine waned much more quickly than that conferred by the whole-cell vaccine. “In the current study, Zerbo et al. add to the body of evidence documenting the increase in pertussis risk with time after DTaP vaccination,” she noted.
This has several practical implications, Dr. Edwards wrote.
“First, given the markedly increased risk of pertussis in unvaccinated and undervaccinated children, universal DTaP vaccination should be strongly recommended. Second, the addition of maternal Tdap vaccination administered during pregnancy has been shown to significantly reduce infant disease before primary immunization and should remain the standard,” Dr. Edwards wrote.
More problematic is how to address the waning DTaP immunity now seen. “One option presented [at an international meeting] was a live-attenuated pertussis vaccine administered intranasally that would stimulate local immune responses and prevent colonization with pertussis organisms. This vaccine is currently being studied in adults and might provide a solution for waning immunity seen with DTaP vaccine,” she noted.
Another possibility is adding the live vaccine to the current DTaP, which should, in theory, stimulate more long-lasting immunity. But numerous safety studies in young children would be necessary before adopting such an approach, Dr. Edwards wrote.
Adding more antigens to the acellular vaccine also might work, and investigational vaccines like this are in development.
Studies in animals and humans show that acellular vaccines “generate functionally different T-cell responses than those seen after whole-cell vaccines, with the whole cell vaccines generating more protective T-cell responses. Studies are ongoing to determine if adjuvants can be added to acellular vaccines to modify their T-cell responses to a more protective immune response or whether the T-cell response remains fixed once primed with DTaP vaccine,” she wrote.
Dr. Edwards is a pediatric infectious disease specialist at Vanderbilt University, Nashville, Tenn. She wrote an editorial to accompany Zerbo et al (Pediatrics. 2019. doi: 10.1542/peds.2019-1276). She reported no financial disclosures, and received no funding to write the editorial.
A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.
Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.
“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”
The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).
The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.
In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).
Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.
“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”
But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).
The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).
The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.
“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”
The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.
SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.
A large Kaiser Permanente study paints a nuanced picture of the acellular pertussis vaccine, with more cases occurring in fully vaccinated children, but the highest risk of disease occurring among the under- and unvaccinated.
Among nearly half a million children, the unvaccinated were 13 times more likely to develop pertussis than fully vaccinated children, Ousseny Zerbo, PhD, of Kaiser Permanente Northern California in Oakland and colleagues wrote in Pediatrics. But 82% of cases occurred in fully vaccinated children and just 5% in undervaccinated children – and rates increased in both groups the farther they were in time from the last vaccination.
“Within our study population, greater than 80% of pertussis cases occurred among age-appropriately vaccinated children,” the team wrote. “Children who were further away from their last DTaP dose were at increased risk of pertussis, even after controlling for undervaccination. Our results suggest that, in this population, possibly in conjunction with other factors not addressed in this study, suboptimal vaccine efficacy and waning [immunity] played a major role in recent pertussis epidemics.”
The results are consistent with several prior studies, including one finding that the odds of the disease increased by 33% for every additional year after the third or fifth DTaP dose (Pediatrics. 2015;135[2]:331-43).
The current study comprised 469,982 children aged between 3 months and 11 years, who were followed for a mean of 4.6 years. Over the entire study period, there were 738 lab-confirmed pertussis cases. Most of these (515; 70%) occurred in fully vaccinated children. Another 99 (13%) occurred in unvaccinated children, 36 (5%) in undervaccinated children, and 88 (12%) in fully vaccinated plus one dose.
In a multivariate analysis, the risk of pertussis was 13 times higher among the unvaccinated (adjusted hazard ratio, 13) and almost 2 times higher among the undervaccinated (aHR, 1.9), compared with fully vaccinated children. Those who had been fully vaccinated and received a booster had the lowest risk, about half that of fully vaccinated children (aHR, 0.48).
Risk varied according to age, but also was significantly higher among unvaccinated children at each time point. Risk ranged from 4 times higher among those aged 3-5 months to 23 times higher among those aged 19-84 months. Undervaccinated children aged 5-7 months and 19-84 months also were at significantly increased risk for pertussis, compared with fully vaccinated children. Children who were fully vaccinated plus one dose had a significantly reduced risk at 7-19 months and at 19-84 months, compared with the fully vaccinated reference group.
“Across all follow-up and all age groups, VE [vaccine effectiveness] was 86% ... for undervaccinated children, compared with unvaccinated children,” Dr. Zerbo and associates wrote. “VE was even higher for fully vaccinated children [93%] and for those who were fully vaccinated plus one dose [96%].”
But VE waned as time progressed farther from the last DTaP dose. The multivariate model found more than a 100% increased risk for those whose last DTaP was at least 3 years past, compared with less than 1 year past (aHR, 2.58).
The model also found time-bound risk increases among fully vaccinated children, with a more than 300% increased risk among those at least 6 years out from the last DTaP dose, compared with 3 years out (aHR, 4.66).
The results indicate that other factors besides adherence to the recommended vaccine schedule may be at work in recent pertussis outbreaks.
“Although waning immunity is clearly an important factor driving pertussis epidemics in recent years, other factors that we did not evaluate in this study might also contribute to pertussis epidemics individually or in synergy,” Dr. Zerbo and associates wrote. “Results from studies in baboons suggest that the acellular pertussis vaccines are unable to prevent colonization, carriage, and transmission. If this is also true for humans, this could contribute to pertussis epidemics. The causes of recent pertussis epidemics are complex, and we were only able to address some aspects in our study.”
The study was funded by Kaiser Permanente Northern California, the National Institutes of Health, and in part by a National Institute of Allergy and Infectious Diseases grant. One coauthor reported receiving research grant support from Sanofi Pasteur, Novartis, GlaxoSmithKline, Merck, MedImmune, Pfizer, and Dynavax for unrelated studies; the other authors reported no relevant financial disclosures.
SOURCE: Zerbo O et al. Pediatrics. 2019 Jun 10. doi: 10.1542/peds.2018-3466.
FROM PEDIATRICS
United States now over 1,000 measles cases this year
The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.
Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.
Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.
The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.
Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.
Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.
The 41 new cases reported for the week ending June 6 bring the total for the year to 1,022, the CDC reported June 10, and that is more than any year since 1992, when there were 2,237 cases.
Idaho and Virginia reported their first cases of 2019, which makes a total of 28 states with measles cases this year. The Idaho case was reported in Latah County and is the state’s first since 2001. In Virginia, health officials are investigating possible contacts with an infected individual at Dulles International Airport and two other locations on June 2 and 4.
Outbreaks in Georgia, Maryland, and Michigan have ended, while seven others continue in California (Butte, Los Angeles, and Sacramento Counties), New York (Rockland County and New York City), Pennsylvania, and Washington, the CDC said. New York City has the largest outbreak this year with 509 cases through June 3, most of them occurring in Brooklyn.
A better approach to the diagnosis of PE
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
Penny E is a 48-year-old woman with a history of asthma who presents with wheezing and respiratory distress. There are no clinical signs of deep vein thrombosis or hemoptysis. Pulmonary embolism (PE) is not your most likely diagnosis, but it is included in the differential, so you order a D-dimer concentration and it returns at 700 ng/mL. Should you order computed tomography pulmonary angiography (CTPA) to evaluate for PE?
PE is the third most common type of cardiovascular disease after coronary artery disease and stroke, with an estimated incidence in the United States of 1-2 people/1000 population and a 30-day mortality rate between 10% and 30%.2 Improved adherence to a clinical decision support system has been shown to significantly decrease the number of diagnostic tests performed and the number of diagnostic failures.3
The use of a diagnostic algorithm that includes the Wells’ criteria and a
Further, it is common for a
Three items of the original Wells’ criteria—clinical signs of deep vein thrombosis, hemoptysis, and whether PE is the most likely diagnosis—are the most predictive for PE.8 The development of a more efficient algorithm based on these 3 items that uses differential D
STUDY SUMMARY
Simplified algorithm diagnoses PE with fewer CTPAs
The YEARS study was a prospective cohort study conducted in 12 hospitals in the Netherlands that included 3616 patients with clinically suspected PE.1 After excluding 151 patients who met exclusion criteria (life expectancy < 3 months, ongoing anticoagulation treatment, pregnancy, and contraindication to CTPA), investigators managed 3465 study patients according to the YEARS algorithm. This algorithm called for obtaining a
Of the 1743 patients who had none of the 3 YEARS items, 1320 had a
Continue to: Eighteen of the 2964 patients...
Eighteen of the 2964 patients who had PE ruled out by the YEARS algorithm at baseline were found to have symptomatic VTE during the follow-up period (0.61%; 95% CI, 0.36-0.96), with 6 patients (0.20%; 95% CI, 0.07-0.44) sustaining a fatal PE. The 3-month incidence of VTE in patients who did not have CTPA was 0.43% (95% CI, 0.17-0.88), which is similar to the 0.34% (0.036-0.96) reported in a previous meta-analysis of the Wells’ rule algorithm.13 Overall, fatal PE occurred in 0.3% (95% CI, 0.12-0.78) of patients in the YEARS cohort vs 0.6% (0.4-1.1) in a meta-analysis of studies using standard algorithms.14
Using an intention-to-diagnose analysis, 1611 (46%) patients did not have a CTPA indicated by the YEARS algorithm compared with 1174 (34%) using the Wells’ algorithm, for an absolute difference of 13% (95% CI, 10-15) and estimated cost savings of $283,176 in this sample. The per-protocol analysis also had a decrease of CTPA examinations in favor of the YEARS algorithm, ruling out 1651 (48%) patients—a decrease of 14% (95% CI, 12-16) and an estimated savings of $309,096.
WHAT’S NEW
High-level evidence says 14% fewer CTPAs
The YEARS study provides a high level of evidence that a new, simple diagnostic algorithm can reliably and efficiently exclude PE and decrease the need for CTPA by 14% (absolute difference; 95% CI, 12-16) when compared with using the Wells’ rule and fixed
CAVEATS
No adjusting D -dimer for age
The YEARS criteria does not consider an age-adjusted
CHALLENGES TO IMPLEMENTATION
None to speak of
We see no challenges to the implementation of this recommendation.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
1. van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38:S495-S501.
3. Douma RA, Mos ICM, Erkens PMG, et al. Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism. Ann Intern Med. 2011;154:709-718.
4. van Es N, van der Hulle T, van Es J, et al. Wells Rule and D-dimer testing to rule out pulmonary embolism. Ann Intern Med. 2016;165:253-261.
5. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of diagnostic management and outcomes of suspected pulmonary embolism. Ann Intern Med. 2006;144:157-164.
6. Newnham M, Stone H, Summerfield R, et al. Performance of algorithms and pre-test probability scores is often overlooked in the diagnosis of pulmonary embolism. BMJ. 2013;346:f1557.
7. Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. JAMA. 2014;311:1117-1124.
8. van Es J, Beenen LFM, Douma RA, et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost. 2015;13:1428-1435.
9. Kooiman J, Klok FA, Mos ICM, et al. Incidence and predictors of contrast-induced nephropathy following CT-angiography for clinically suspected acute pulmonary embolism. J Thromb Haemost. 2010;8:409-411.
10. Sarma A, Heilbrun ME, Conner KE, et al. Radiation and chest CT scan examinations: what do we know? Chest. 2012;142:750-760.
11. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009;169:2071-2077.
12. Verma K, Legnani C, Palareti G. Cost-minimization analysis of venous thromboembolism diagnosis: comparison of standalone imaging with a strategy incorporating D-dimer for exclusion of venous thromboembolism. Res Pract Thromb Haemost. 2017;1:57-61.
13. Pasha SM, Klok FA, Snoep JD, et al. Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: a meta-analysis. Thromb Res. 2010;125:e123-e127.
14. Mos ICM, Klok FA, Kroft LJM, et al. Safety of ruling out acute pulmonary embolism by normal computed tomography pulmonary angiography in patients with an indication for computed tomography: systematic review and meta-analysis. J Thromb Haemost. 2009;7:1491-1498.
PRACTICE CHANGER
Do not order computed tomography pulmonary angiography when evaluating patients for suspected pulmonary embolism unless: (1) the patient has a
STRENGTH OF RECOMMENDATION
A: Based on a prospective, multicenter, cohort study of 3616 patients with clinically suspected pulmonary embolism.1
van der Hulle T, Cheung WY, Kooij S, et al. Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390:289-297.
FDA approves Nucala’s new at-home formulations
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
Pediatricians report low knowledge, comfort discussing e-cigarettes
BALTIMORE – according to a recent study.
“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.
A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.
Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.
Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.
The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.
Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.
Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.
Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).
Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).
Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).
Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).
The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).
Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).
More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).
The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.
The researchers noted no external funding or disclosures.
BALTIMORE – according to a recent study.
“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.
A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.
Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.
Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.
The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.
Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.
Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.
Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).
Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).
Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).
Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).
The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).
Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).
More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).
The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.
The researchers noted no external funding or disclosures.
BALTIMORE – according to a recent study.
“Providers are aware of the increased prevalence, harms [of e-cigs] and [the] positive impact of counseling teens about e-cigs,” said Allison Heinly, MD, of Hasbro Children’s Hospital in Providence, R.I., and her colleagues. But, “providers are less likely to ask, advise, or assist parents [and teens] regarding e-cig use, compared to tobacco, and are less comfortable doing so.” The researchers presented their findings at the Pediatric Academic Societies annual meeting.
A variety of concerns exist regarding ingredients in e-cigarettes, Dr. Heinly noted, including nicotine, volatile organic compounds, carcinogenic chemicals, flavorings, and ultra-fine particles.
Dr. Heinly and her associates aimed to assess pediatricians’ knowledge, attitudes, and behaviors toward both teens’ and parents’ use of e-cigarettes, as well as the barrier pediatricians perceived when it came to screening and counseling those who use e-cigarettes.
Among 69 providers at a large Northeastern urban academic primary care clinic who received surveys, 62 responded, primarily residents (84%). The respondents included 44 pediatric residents, eight triple-board residents, and 10 attending physicians.
The researchers collapsed “most of the time”/“always” and “some of the time”/“never” responses into two categories.
Most of the respondents (82%) knew e-cigarettes are the most common tobacco product that youth use, and nearly all (97%) believed e-cigarettes were addictive and harmful to users’ health. In addition, most (79%) believed using e-cigarettes could be a pathway toward students beginning to use other drugs.
Even though respondents believed counseling teens about use of tobacco or e-cigarettes can reduce the likelihood that they will start using them, providers were much less likely to discuss e-cigarettes than tobacco with teens.
Nearly all the doctors (97%) reported asking teens about their use of tobacco, but only about half (52%) asked about e-cigarette use (P less than .001). And only about one in five doctors (21%) reported counseling teens about using e-cigarettes, compared with 47% of those who advised teens regarding tobacco use (P = .002).
Over a third of responding physicians (37%) reported helping adolescent patients quit using tobacco, but just 7% reported doing so with e-cigarettes (P less than .001).
Doctors overwhelmingly reported feeling comfortable talking about tobacco with teens (98%), but fewer felt comfortable discussing e-cigarettes (77%; P less than .001). Respondents similarly were less comfortable discussing e-cigarettes (55%) than tobacco (87%) with parents (P less than .001).
Very few pediatricians asked parents about their use of e-cigarettes (5%) or advised them about e-cigarettes’ harms (7%), and even fewer reported helping parents quit using them (2%). By contrast, more than half of pediatricians (60%) asked parents about smoking or advised them about tobacco use harms (52%), and nearly one-third (31%) reported helping parents quit smoking (P less than .001 for all comparisons).
The biggest barrier to discussing e-cigarettes with families was, as with discussing tobacco, not having enough time. But about twice as many respondents cited insufficient knowledge as a barrier for e-cigarettes as for tobacco (P = .003). A small percentage of respondents (less than 20%) also reported feeling unsure about the harm of e-cigarettes (P = .001).
Lack of training was a significant barrier to physicians’ discussion of e-cigarettes as well. Many more physicians reported receiving training in medical school on tobacco and traditional cigarettes (78%) than on e-cigarettes (13%), possibly because of how recently e-cigarettes have become widely available (P less than .001).
More physicians reported receiving training related to e-cigarettes during residency (36%), but it still fell well short of how many reported other tobacco and smoking training during residency (61%; P = .001).
The findings “emphasize the importance of increasing training about e-cig counseling,” Dr. Heinly and her associates concluded.
The researchers noted no external funding or disclosures.
REPORTING FROM PAS 2019
Key clinical point: Physicians report less training and less comfort when discussing e-cigarettes with teens and parents than when discussing tobacco products.
Major finding: 7% of physicians reported helping adolescent patients quit using e-cigarettes, compared with 37% helping with quitting tobacco use (P less than .001).
Study details: The findings are based on a cross-sectional survey of 62 pediatric residents and attendings at a large urban academic primary care clinic in the Northeast.
Disclosures: The researchers noted no external funding or disclosures.