Pulmonary Health Hub

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

The number of lung injury cases caused by e-cigarettes or vaping now stands at 1,299 as of Oct. 8, according to a statement released by the Centers for Disease Control and Prevention.

mauro grigollo/Thinkstock

These cases have been reported to the CDC from 49 states, the District of Columbia, and the U.S. Virgin Islands. The increase in lung injury cases from Oct. 1 (reported to be 1,080) represents both new patients and recent reporting of patients previously identified to the CDC.

Twenty-six deaths have been confirmed in 21 states and more deaths are currently being reviewed.

The causes of the injuries are still under investigation. The CDC stated, “The latest findings from the investigation into lung injuries associated with e-cigarette use, or vaping, suggest products containing THC play a role in the outbreak. All patients have a reported history of e-cigarette product use, or vaping, and no consistent evidence of an infectious cause has been discovered. Therefore, the suspected cause is a chemical exposure.” The specific chemical causing the lung injuries associated with vaping remains unknown at this time.

The CDC has created information hubs and resources for the public, for health care providers, and for state and local health department officials. The CDC has also provided additional resources to address the outbreak of vaping-associated lung injuries.

[email protected]

The number of lung injury cases caused by e-cigarettes or vaping now stands at 1,299 as of Oct. 8, according to a statement released by the Centers for Disease Control and Prevention.

mauro grigollo/Thinkstock

These cases have been reported to the CDC from 49 states, the District of Columbia, and the U.S. Virgin Islands. The increase in lung injury cases from Oct. 1 (reported to be 1,080) represents both new patients and recent reporting of patients previously identified to the CDC.

Twenty-six deaths have been confirmed in 21 states and more deaths are currently being reviewed.

The causes of the injuries are still under investigation. The CDC stated, “The latest findings from the investigation into lung injuries associated with e-cigarette use, or vaping, suggest products containing THC play a role in the outbreak. All patients have a reported history of e-cigarette product use, or vaping, and no consistent evidence of an infectious cause has been discovered. Therefore, the suspected cause is a chemical exposure.” The specific chemical causing the lung injuries associated with vaping remains unknown at this time.

The CDC has created information hubs and resources for the public, for health care providers, and for state and local health department officials. The CDC has also provided additional resources to address the outbreak of vaping-associated lung injuries.

[email protected]

The number of lung injury cases caused by e-cigarettes or vaping now stands at 1,299 as of Oct. 8, according to a statement released by the Centers for Disease Control and Prevention.

mauro grigollo/Thinkstock

These cases have been reported to the CDC from 49 states, the District of Columbia, and the U.S. Virgin Islands. The increase in lung injury cases from Oct. 1 (reported to be 1,080) represents both new patients and recent reporting of patients previously identified to the CDC.

Twenty-six deaths have been confirmed in 21 states and more deaths are currently being reviewed.

The causes of the injuries are still under investigation. The CDC stated, “The latest findings from the investigation into lung injuries associated with e-cigarette use, or vaping, suggest products containing THC play a role in the outbreak. All patients have a reported history of e-cigarette product use, or vaping, and no consistent evidence of an infectious cause has been discovered. Therefore, the suspected cause is a chemical exposure.” The specific chemical causing the lung injuries associated with vaping remains unknown at this time.

The CDC has created information hubs and resources for the public, for health care providers, and for state and local health department officials. The CDC has also provided additional resources to address the outbreak of vaping-associated lung injuries.

[email protected]

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

Influenza vaccination modestly reduces the risk of hospitalizations associated with laboratory-confirmed influenza in people with chronic obstructive pulmonary disease (COPD), according to data published in the Journal of Infectious Diseases.

Cynthia Goldsmith/CDC photo #10073

“To the best of our knowledge, this is the first large, real-world population study to examine vaccine effectiveness in people with COPD using the test-negative design and influenza-specific study outcomes,” wrote Andrea S. Gershon, MD, of Sunnybrook Health Sciences Center in Toronto and colleagues. “These findings emphasize the need for more effective influenza vaccines for older COPD patients and other preventive strategies.”
 

A test-negative study design

Data suggest that 70% of COPD exacerbations are caused by infection, and influenza often is identified as the cause. Although all major COPD practice guidelines recommend seasonal influenza vaccination, the evidence indicating that vaccination reduces hospitalizations and death is limited. The inherent or corticosteroid-induced decrease in immune response to vaccination and respiratory infection among patients with COPD may reduce the effectiveness of influenza vaccination, wrote Dr. Gershon and colleagues.

The investigators used a test-negative design to evaluate how effectively influenza vaccination prevents laboratory-confirmed influenza–associated hospitalizations in community-dwelling older patients with COPD. They chose this design because it attenuates biases resulting from misclassification of infection and from differences in health care–seeking behavior between vaccinated and unvaccinated patients.

Dr. Gershon and colleagues examined health care administrative data and respiratory specimens collected from patients who had been tested for influenza during the 2010-2011 to 2015-2016 influenza seasons. Eligible patients were aged 66 years or older, had physician-diagnosed COPD, and had been tested for influenza within 3 days before and during an acute care hospitalization. The researchers determined influenza vaccination status using physician and pharmacist billing claims. They obtained demographic information through linkage with the provincial health insurance database. Multivariable logistic regression allowed Dr. Gershon and colleagues to estimate the adjusted odds ratio of influenza vaccination in people with laboratory-confirmed influenza, compared with those without.
 

Effectiveness did not vary by demographic factors

The investigators included 21,748 patients in their analysis. Of this population, 3,636 (16.7%) patients tested positive for influenza. Vaccinated patients were less likely than unvaccinated patients to test positive for influenza (15.3% vs. 18.6%). Vaccinated patients also were more likely to be older; live in an urban area; live in a higher income neighborhood; have had more outpatient visits with a physician in the previous year; have received a prescription for a COPD medication in the previous 6 months; have diabetes, asthma, or immunocompromising conditions; have a longer duration of COPD; and have had an outpatient COPD exacerbation in the previous year.

The overall unadjusted estimate of vaccine effectiveness against laboratory-confirmed influenza–associated hospitalizations was 21%. Multivariable adjustment yielded an effectiveness of 22%. When Dr. Gershon and colleagues corrected for misclassification of vaccination status among people with COPD, the effectiveness was estimated to be 43%. Vaccine effectiveness did not vary significantly according to influenza season, nor did it vary significantly by patient-specific factors such as age, sex, influenza subtype, codiagnosis of asthma, duration of COPD, previous outpatient COPD exacerbations, previous COPD hospitalization, previous receipt of inhaled corticosteroids, and previous pneumonia.

One limitation of the study was the possibility that COPD was misclassified because not all participants underwent pulmonary function testing. In addition, the estimates of vaccine effectiveness in the present study are specific to the outcome of influenza hospitalization and may not be generalizable to vaccine effectiveness estimates of outpatient outcomes, said the investigators. Finally, Dr. Gershon and colleagues could not identify the type of vaccine received.

“Given that a large pragmatic randomized controlled trial evaluating influenza vaccination would be unethical, this is likely the most robust estimate of vaccine effectiveness for hospitalizations in the COPD population to guide influenza vaccine recommendations for patients with COPD,” wrote Dr. Gershon and colleagues.

An Ontario Ministry of Health and Long-Term Care Health Systems Research Fund Capacity Grant and a Canadian Institutes of Health Research operating grant funded this research. One investigator received grants from the Canadian Institutes of Health Research during the study, and others received grants from pharmaceutical companies that were unrelated to this study.

[email protected]

SOURCE: Gershon AS et al. J Infect Dis. 2019 Sep 24. doi: 10.1093/infdis/jiz419.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

Children with eosinophilic esophagitis often experience respiratory and motor disturbances during sleep, which appear related to dysregulated sleep architecture, Rasintra Siriwat, MD, and colleagues have ascertained.

©Alex Vasilev/Fotolia.com

Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.

The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m². A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.

Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.

Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).

All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.

“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.

The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).

Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.

“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”

Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.

[email protected]

SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.

Children with eosinophilic esophagitis often experience respiratory and motor disturbances during sleep, which appear related to dysregulated sleep architecture, Rasintra Siriwat, MD, and colleagues have ascertained.

©Alex Vasilev/Fotolia.com

Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.

The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m². A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.

Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.

Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).

All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.

“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.

The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).

Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.

“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”

Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.

[email protected]

SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.

Children with eosinophilic esophagitis often experience respiratory and motor disturbances during sleep, which appear related to dysregulated sleep architecture, Rasintra Siriwat, MD, and colleagues have ascertained.

©Alex Vasilev/Fotolia.com

Children with eosinophilic esophagitis (EoE) also were found to have a high prevalence of atopic diseases, including allergic rhinitis and eczema – findings that could be driving the breathing problems, said Dr. Siriwat, a neurology fellow at the Cleveland Clinic, and coauthors.

The retrospective study comprised 81 children with a diagnosis of EoE who were referred to sleep clinics. In this group, 46 of the children had active EoE (having gastrointestinal symptoms, including feeding difficulties, dysphagia, reflux, nausea/vomiting, or epigastric pain at presentation). The other 35 had an EoE diagnosis but no symptoms on presentation and were categorized as having inactive EoE. Most were male (71.6%) and white (92.5%). The mean age in the cohort was 10 years and the mean body mass index for all subjects was 22 kg/m². A control group of 192 children without an EoE diagnosis who had overnight polysomnography were included in the analysis.

Allergic-type comorbidities were common among those with active EoE, including allergic rhinitis (55.5%), food allergy (39.5%), and eczema (26%). In addition, a quarter had attention-deficit/hyperactivity disorder, 22% an autism spectrum disorder, 21% a neurological disease, and 29% a psychiatric disorder.

Several sleep complaints were common in the entire EoE cohort, including snoring (76.5 %), restless sleep (66.6%), legs jerking or leg discomfort (43.2%), and daytime sleepiness (58%).

All children underwent an overnight polysomnography. Compared with controls, the children with EoE had significantly higher non-REM2 sleep, significantly lower non-REM3 sleep, lower REM, increased periodic leg movement disorder, and increased arousal index.

“Of note, we found a much higher percentage of [periodic leg movement disorder] in active EoE compared to inactive EoE,” the authors said.

The most common sleep diagnosis for the children with EoE was sleep-disordered breathing. Of 62 children with EoE and sleep disordered breathing, 37% had obstructive sleep apnea (OSA). Two patients had central sleep apnea and five had nocturnal hypoventilation. Children with EoE also reported parasomnia symptoms such as sleep talking (35.8%), sleepwalking (16%), bruxism (23.4%), night terrors (28.4%), and nocturnal enuresis (21.2%).

Of the 59 children with leg movement, 20 had periodic limb movement disorder and 5 were diagnosed with restless leg syndrome. Two were diagnosed with narcolepsy and three with hypersomnia. Four children had a circadian rhythm disorder.

“Notably, the majority of children with EoE had symptoms of sleep-disordered breathing, and more than one-third of total subjects were diagnosed with OSA,” the authors noted. “However, most of them were mild-moderate OSA. It should be noted that the prevalence of OSA in the pediatric population is 1%-5% mostly between the ages of 2-8 years, while the mean age of our subjects was 10 years old. The high prevalence of mild-moderate OSA in the EoE population might be explained by the relationship between EoE and atopic disease.”

Dr. Siriwat had no financial disclosures. The study was supported by Cincinnati Children’s Hospital Research Fund.

[email protected]

SOURCE: Siriwat R et al. Sleep Med. 2019 Sep 11. doi: 10.1016/j.sleep.2019.08.018.

The Food and Drug Administration has approved a prefilled, single-use autoinjector of benralizumab (Fasenra) for self-administration in adults with eosinophilic asthma, according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.

Olivier Le Moal/Getty Images

The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.

The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.

Full prescribing information can be found on the AstraZeneca website.

[email protected]

The Food and Drug Administration has approved a prefilled, single-use autoinjector of benralizumab (Fasenra) for self-administration in adults with eosinophilic asthma, according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.

Olivier Le Moal/Getty Images

The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.

The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.

Full prescribing information can be found on the AstraZeneca website.

[email protected]

The Food and Drug Administration has approved a prefilled, single-use autoinjector of benralizumab (Fasenra) for self-administration in adults with eosinophilic asthma, according to a press release from AstraZeneca. Benralizumab is already approved as add-on maintenance for this form of asthma, but not for other eosinophilic conditions or for acute bronchospasm or status asthmaticus.

Olivier Le Moal/Getty Images

The autoinjector “pen” was tested for usability and pharmacokinetic exposure in two studies, the phase 3 GRECO trial and the phase 1 AMES trial, respectively. The multicenter, open-label GRECO trial was designed to assess patient- or caregiver-reported functionality, and it found that 97% of at-home administrations were successful at week 12 and week 16. The multicenter, randomized, open-label, parallel-group AMES trial compared pharmacokinetic exposure with the subcutaneous administration using either prefilled syringe or prefilled autoinjector; it found that the eosinophils were rapidly depleted in patients with use of either device.

The safety profiles in both trials were comparable to those seen in previous trials. Hypersensitivity reactions have been sometimes observed in the hours following administration of benralizumab; discontinuation is advised in case of any hypersensitivity reaction. The therapy should not be used to treat acute asthma symptoms, such as exacerbations, or bronchospasm, and any reduction in corticosteroid therapy should be gradual and performed under careful supervision of a health care professional. Although benralizumab’s effects on helminth infections are currently unknown, care should be taken with preexisting or incident infections.

Full prescribing information can be found on the AstraZeneca website.

[email protected]

Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.

VlaDee/Getty Images

Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.

While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.

“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.

No conflicts of interest were reported.

[email protected]

SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.

Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.

VlaDee/Getty Images

Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.

While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.

“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.

No conflicts of interest were reported.

[email protected]

SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.

Vaping-associated lung injury is likely a form of airway-centered chemical pneumonitis, not exogenous lipoid pneumonia, according to Yasmeen M. Butt, MD, of the University of Texas Southwestern Medical Center, Dallas, and associates.

VlaDee/Getty Images

Dr. Butt and associates performed a review of lung biopsies from 17 patients (13 men; median age, 35 years) with a history of vaping and either suspected or confirmed vaping-associated lung injury. All cases showed patterns of acute lung injury, including acute fibrinous pneumonitis, diffuse alveolar damage, or organizing pneumonia, the authors noted in a letter to the editor published in the New England Journal of Medicine.

While no histologic findings were specific, foamy macrophages and pneumocyte vacuolization were seen in all cases, the authors added. Pigmented macrophages were occasionally present but not dominant, neutrophils were often prominent, eosinophils were rare, and granulomas were not seen. Two patients eventually died, despite treatment with glucocorticoids and maximum supportive care.

“None of our cases showed histologic evidence of exogenous lipoid pneumonia and no radiologic evidence thereof has been found; this calls into question the diagnostic utility of identifying lipid-laden macrophages or performing oil red O staining on bronchioloalveolar lavage fluid as a marker of vaping-associated lung injury, as has been proposed,” Dr. Butt and associates wrote.

No conflicts of interest were reported.

[email protected]

SOURCE: Butt YM et al. N Engl J Med. 2019 Oct 2. doi: 10.1056/NEJMc1913069.

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

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Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

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Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

[email protected]

Vaccination policy in the United States is set largely at the state level, and no state does a better job at vaccinating than Massachusetts, according to a new analysis from personal finance website WalletHub.

The Bay State’s top finish in the “children and teenagers immunization rates” category moved it ahead of Vermont in the overall rankings, which had the highest score in each of the other two broad categories – “adult and elderly vaccination rates” and “immunization uptake disparities and influencing factors” – but only finished 15th in child/teen immunization, Wallethub reported.

The state that ranked 51st in child/teen immunization – Mississippi – also finished 51st overall, behind every other state and Washington, D.C. The rest of the bottom five consisted of Texas (50th); Florida (49th), which ranked last in the adult/elderly category; Georgia (48th); and Indiana (47th). New Mexico, however, managed to show that last is not always least by earning a mid-pack overall rank of 30 despite its last-place showing in the disparities/influencing factors category, the WalletHub analysis showed.

Scores for the three broad categories were determined using 18 relevant metrics, including influenza vaccination rate in children aged 6 months to 17 years (1st, Rhode Island; 51st, Wyoming), share of adults aged 60 years and older with zoster vaccination (1st, Vermont; 51st, Mississippi), and share of population without health insurance coverage (1st, Massachusetts; 51st, Texas), WalletHub said.

“Each state should tailor its vaccines policy to its need, with an understanding that those needs may change,” Dorit Rubinstein Reiss of the University of California Hastings College of the Law, San Francisco, told WalletHub. When parents refuse to have their children vaccinated, it’s important to remember that “the state is not denying these children schooling. It is requiring that they be protected from disease first.”

[email protected]