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Biologics options for pediatric asthma continue to grow
ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.
That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.
Severe asthma challenges
These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.
Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.
The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta2-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.
It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
Biologics for pediatric asthma
Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.
The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.
Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.
For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV1) and overall quality of life.
Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV1 or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).
Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.
Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.
Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV1. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.
Dupilumab: New kid on the block
The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.
The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.
“It could be potentially better than those currently available due to additional effect on FEV1,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.
As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.
“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”
Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.
ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.
That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.
Severe asthma challenges
These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.
Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.
The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta2-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.
It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
Biologics for pediatric asthma
Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.
The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.
Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.
For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV1) and overall quality of life.
Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV1 or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).
Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.
Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.
Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV1. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.
Dupilumab: New kid on the block
The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.
The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.
“It could be potentially better than those currently available due to additional effect on FEV1,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.
As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.
“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”
Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.
ORLANDO – The goal of treatment is the same for all asthma cases, regardless of severity: “to enable a patient to achieve and maintain control over their asthma,” according to Stanley J. Szefler, MD, a professor of pediatrics at the University of Colorado at Denver, Aurora.
That goal includes “reducing the risk of exacerbations, emergency department visits, hospitalizations, and progression as well as reducing impairments, including symptoms, functional limitations, poor quality of life, and other manifestations of asthma,” Dr. Szefler, also director of the Children’s Hospital of Colorado pediatric asthma research program, told colleagues at the annual meeting of the American Academy of Pediatrics.
Severe asthma challenges
These aims are more difficult with severe asthma, defined by the World Health Organization as “the current level of clinical control and risks which can result in frequent severe exacerbations and/or adverse reactions to medications and/or chronic morbidity,” Dr. Szefler explained. Severe asthma includes untreated severe asthma, difficult-to-treat asthma, and treatment-resistant severe asthma, whether controlled on high-dose medication or not.
Allergen sensitization, viral respiratory infections, and respiratory irritants (such as air pollution and smoking) are common features of severe asthma in children. Also common are challenges specific to management: poor medication adherence, poor technique for inhaled medications, and undertreatment. Poor management can lead to repeated exacerbations, adverse effects from drugs, disease progression, possible development of chronic obstructive pulmonary disease (COPD), and early mortality.
The National Heart, Lung, and Blood Institute EPR-3 guidelines for treatment of pediatric asthma recommend a stepwise approach to therapy, starting with short-acting beta2-agonists as needed (SABA p.r.n.). The clinician then assesses the patient’s symptoms, exacerbations, side effects, quality of life, and lung function to determine whether the asthma is well managed or requires inhaled corticosteroids, or another therapy in moving through the steps. Each step also involves patient education, environmental control, and management of the child’s comorbidities.
It is not until steps 5 and 6 that the guidelines advise considering the biologic omalizumab for patients who have allergies. But other biologic options exist as well. Four biologics currently approved for treating asthma include omalizumab, mepolizumab, benralizumab, and reslizumab, but reslizumab is approved only for patients at least 18 years old.
Biologics for pediatric asthma
Omalizumab, which targets IgE, is appropriate for patients at least 6 years old in whom inhaled corticosteroids could not adequately control the symptoms of moderate to-severe persistent asthma. Dosing of omalizumab is a subcutaneous injection every 2-4 weeks based on pretreatment serum IgE and body weight using a dosing table that starts at 0.016 mg/kg/IgE (IU/mL). Maximum dose is 375 mg every 2 weeks in the United States and 600 mg every 2 weeks in the European Union.
The advantages of an anti-IgE drug are its use only once a month and its substantial effect on reducing exacerbations in a clearly identified population. However, these drugs are costly and require supervised administration, Dr. Szefler noted. They also carry a risk of anaphylaxis in less than 0.2% of patients, requiring the patient to be monitored after first administration and to carry an injectable epinephrine after omalizumab administration as a precaution for late-occurring anaphylaxis.
Mepolizumab is an anti–interleukin (IL)–5 drug used in patients at least 12 years old with severe persistent asthma that’s inadequately controlled with inhaled corticosteroids. Peripheral blood counts of eosinophilia determine if a patient has an eosinophilic phenotype, which has the best response to mepolizumab. People with at least 150 cells per microliter at baseline or at least 300 cells per microliter within the past year have shown a good response to mepolizumab. Dosing is 100 mg subcutaneously every 4 weeks.
For patients with atopic asthma, mepolizumab is effective in reducing the daily oral corticosteroid dose and the number of both annual exacerbations and exacerbations requiring hospitalization or an emergency visit. Other benefits of mepolizumab include increasing the time to a first exacerbation, the pre- and postbronchodilator forced expiratory volume in one second (FEV1) and overall quality of life.
Patient reductions in exacerbations while taking mepolizumab were associated with eosinophil count but not IgE, atopic status, FEV1 or bronchodilator response in the DREAM study (Lancet. 2012 Aug 18;380[9842]:651-9.).
Two safety considerations with mepolizumab include an increased risk of shingles and the risk of a preexisting helminth infection getting worse. Providers should screen for helminth infection and might consider a herpes zoster vaccination prior to starting therapy, Dr. Szefler said.
Benralizumab is an anti-IL5Ra for use in people at least 12 years old with severe persistent asthma and an eosinophilic phenotype (at least 300 cells per microliter). Dosing begins with three subcutaneous injections of 30 mg every 4 weeks, followed by administration every 8 weeks thereafter.
Benralizumab’s clinical effects include reduced exacerbations and oral corticosteroid use, and improved asthma symptom scores and prebronchodilator FEV1. Higher serum eosinophils and a history of more frequent exacerbations are both biomarkers for reduced exacerbations with benralizumab treatment.
Dupilumab: New kid on the block
The newest biologic for asthma is dupilumab, approved Oct. 19, 2018, by the Food and Drug Administration as the only asthma biologic that patients can administer at home. Dupilumab is an anti–IL-4 and anti–IL-13 biologic whose most recent study results showed a severe exacerbations rate 50% lower than placebo (N Engl J Med. 2018 Jun 28;378[26]:2486-96.). Patients with higher baseline levels of eosinophils had the best response, although some patients showed hypereosinophilia following dupilumab therapy.
The study had a low number of adolescents enrolled, however, and more data on predictive biomarkers are needed. Dupilumab also requires a twice-monthly administration.
“It could be potentially better than those currently available due to additional effect on FEV1,” Dr. Szefler said, but cost and safety may determine how dupilumab is recommended and used, including possible use for early intervention.
As development in biologics for pediatric asthma continues to grow, questions about best practices for management remain, such as what age is best for starting biologics, what strategies are most safe and effective, and what risks and benefits exist for each strategy. Questions also remain regarding the risk factors for asthma and what early intervention strategies might change the disease’s natural history.
“Look at asthma in children as a chronic disease that can result in potentially preventable adverse respiratory outcomes in adulthood,” Dr. Szefler said. He recommended monitoring children’s lung function over time and using “measures of clinical outcomes, lung function, and biomarkers to assess potential benefits of biologic therapy.”
Dr. Szefler has served on the advisory board for Regeneron and Sanofi, and he has consulted for AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Novartis, and Propeller Health.
EXPERT ANALYSIS FROM AAP 18
Obesity linked to 10% of childhood asthma
Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.
Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.
The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.
After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.
Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.
“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”
They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.
The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.
SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.
While there has long been recognition of an association between childhood obesity and childhood asthma, the incidence of pediatric obesity–related asthma has not been well known. This study therefore addresses that gap in knowledge, and does so among children with a range of racial and ethnic backgrounds and while addressing potential confounders such as comorbidities and sociodemographic variables.
The findings show how significant a contribution obesity makes to the burden of childhood asthma, and also points to the potential increase in childhood asthma incidence that may arise with the increase in childhood obesity.
However, the good news is that this offers what may be the first modifiable risk factor for childhood asthma, which presents an opportunity for primary prevention of this common childhood condition.
Deepa Rastogi, MBBS, MS, is from the department of pediatrics at the Albert Einstein College of Medicine, New York. These comments are taken from an editorial (Pediatrics. 2018 Dec;142(6):e20182979.). No conflicts of interest were declared.
While there has long been recognition of an association between childhood obesity and childhood asthma, the incidence of pediatric obesity–related asthma has not been well known. This study therefore addresses that gap in knowledge, and does so among children with a range of racial and ethnic backgrounds and while addressing potential confounders such as comorbidities and sociodemographic variables.
The findings show how significant a contribution obesity makes to the burden of childhood asthma, and also points to the potential increase in childhood asthma incidence that may arise with the increase in childhood obesity.
However, the good news is that this offers what may be the first modifiable risk factor for childhood asthma, which presents an opportunity for primary prevention of this common childhood condition.
Deepa Rastogi, MBBS, MS, is from the department of pediatrics at the Albert Einstein College of Medicine, New York. These comments are taken from an editorial (Pediatrics. 2018 Dec;142(6):e20182979.). No conflicts of interest were declared.
While there has long been recognition of an association between childhood obesity and childhood asthma, the incidence of pediatric obesity–related asthma has not been well known. This study therefore addresses that gap in knowledge, and does so among children with a range of racial and ethnic backgrounds and while addressing potential confounders such as comorbidities and sociodemographic variables.
The findings show how significant a contribution obesity makes to the burden of childhood asthma, and also points to the potential increase in childhood asthma incidence that may arise with the increase in childhood obesity.
However, the good news is that this offers what may be the first modifiable risk factor for childhood asthma, which presents an opportunity for primary prevention of this common childhood condition.
Deepa Rastogi, MBBS, MS, is from the department of pediatrics at the Albert Einstein College of Medicine, New York. These comments are taken from an editorial (Pediatrics. 2018 Dec;142(6):e20182979.). No conflicts of interest were declared.
Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.
Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.
The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.
After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.
Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.
“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”
They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.
The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.
SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.
Around one-quarter of new asthma cases in children with obesity may be attributable to their obesity, according to research published in Pediatrics.
Jason E. Lang, MD, MPH, of Duke University, Durham, N.C., and his coauthors used the PEDSnet clinical data research network to conduct a retrospective cohort study of 507,496 children aged 2-17 years from 2009-2015, comparing the incidence of asthma in overweight and obese children to the incidence in healthy weight children.
The overall rate of new diagnoses of asthma was 2.4 per 1,000 patient years among normal-weight children and 3.2 per 1,000 patient years among obese children.
After adjustment for factors such as age, ethnicity, insurance status, sex, allergic rhinitis, food allergy, and proton pump inhibitor use, overweight children had a 17% higher risk of incident asthma, and obese children had a 26% higher risk of asthma, compared with children of normal weight. The relative risk of spirometry-confirmed asthma was 29% higher in obese children compared with normal-weight children, and the association between obesity and asthma persisted even when a second asthma encounter was required for the diagnosis.
Overall, the authors estimated that 23%-25% of clinically diagnosed asthma in children with obesity could be specifically attributed to obesity, and that in the overall population of children 10% of asthma was attributable to obesity.
“Currently, there are few known preventable risk factors that can be used to reduce childhood asthma,” wrote Dr. Lang and his coauthors. “With these data, it is suggested that reducing the onset of obesity in childhood would significantly reduce the public health burden of asthma in children.”
They noted that with current estimates of U.S. pediatric asthma prevalence being around 6-8 million cases, obesity could therefore account for up to 1 million of these cases.
The study was funded by the Patient-Centered Outcomes Research Institute, the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry. The remaining researchers said they had no conflicts of interest.
SOURCE: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119.
FROM PEDIATRICS
Key clinical point: Obesity may be responsible for around 10% of childhood asthma.
Major finding: Obesity in children is associated with a 26% higher risk of asthma compared with normal-weight children.
Study details: A retrospective cohort study of 507,496 children.
Disclosures: The study was funded by the Patient-Centered Outcomes Research Institute and the Nemours Children’s Hospital and Nemours Children’s Health System. One author declared advisory board positions and consultancies with the pharmaceutical industry.
Source: Lang J et al. Pediatrics. 2018 Dec;142(6):e20182119. doi: 10.1542/peds.2018- 2119
Gestational, umbilical cord vitamin D levels don’t predict atopic disease in offspring
according to study results published in the journal Allergy.
Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.
The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).
Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.
Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.
“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.
The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.
SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.
according to study results published in the journal Allergy.
Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.
The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).
Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.
Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.
“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.
The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.
SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.
according to study results published in the journal Allergy.
Áine Hennessy, PhD, from the School of Food and Nutritional Sciences at the University College Cork (Ireland), and her colleagues performed a prospective cohort study of 1,537 women in the Cork BASELINE Birth Cohort Study who underwent measurement of serum 25-hydroxyvitamin D (25[OH]D) from maternal sera followed by measurement of 25(OH)D in umbilical cord blood (1,050 cases). They then measured the prevalence of eczema, food allergy, allergic rhinitis, and asthma in infants at aged 2 and 5 years.
The researchers found at 2 years old, 5% of infants had persistent eczema, 4% of infants had a food allergy and 8% of infants had aeroallergen sensitization. At age 5 years, 15% of infants had asthma, while 5% had allergic rhinitis. Mothers whose children went on to have atopy did not differ in their 25(OH)D levels at 15 weeks’ gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) or in the levels in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L).
Of the women in the cohort, 74% ranged in age from 25 to 34 years; 49% reported a personal history of allergy and 37% reported a paternal allergy. The mean birth weight of the infants was 3,458 g; infants were breastfed for mean 11.9 weeks, 73% of infants were breastfeeding by the time they left the hospital and 45% of infants were breastfeeding by age 2 months.
Limitations of the study included that parental atopy status was self-reported and that the researchers noted they did not examine genetic variants of immunoglobulin E synthesis or vitamin D receptor polymorphisms.
“To fully characterize relationships between intrauterine vitamin D exposure and allergic disease, analysis of well‐constructed, large‐scale prospective cohorts of maternal‐infant dyads, which take due consideration of an individual’s inherited risk, early‐life exposures and environmental confounders, is still needed,” Dr. Hennessy and her colleagues wrote.
The study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.
SOURCE: Hennessy A et al. Allergy. 2018 Aug 7. doi: 10.1111/all.13590.
FROM ALLERGY
Key clinical point: There was no association between prevalence of atopic disease and vitamin D levels measured in maternal sera during pregnancy or in umbilical cord blood.
Major finding: Maternal vitamin D levels at 15 weeks of gestation (mean 58.4 nmol/L vs. 58.5 nmol/L) and concentrations in umbilical cord blood (mean 35.2 nmol/L and 35.4 nmol/L) were not associated with such atopic diseases as eczema, food allergy, asthma, and allergic rhinitis in children.
Study details: A prospective group of 1,537 women and infant pairs from the Cork BASELINE Birth Cohort Study.
Disclosures: This study was funded by grants from the European Commission, Ireland Health Research Board, National Children’s Research Centre, Food Standards Agency and Science Foundation Ireland. The authors report no relevant conflicts of interest.
Source: Hennessy A et al. Allergy 2018 Aug 7. doi:10.1111/all.13590.
Asthma: Guideline-Informed Practice
The powerful virus inflammatory response
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].
Inflammation is a double-edged sword. Controlled and modest proinflammatory responses can enhance host immunity against viruses and decrease bacterial colonization and infection, whereas excessive uncontrolled proinflammatory responses may increase the susceptibility to bacterial colonization and secondary infection to facilitate disease pathogenesis. The immune system produces both proinflammatory and anti-inflammatory cytokines and chemokines. It is a balanced response that is key to maintaining good health.
Viral upper respiratory tract infections (URIs) are caused by rhinoviruses, coronaviruses, enteroviruses, respiratory syncytial viruses, influenza A and B viruses, parainfluenza viruses, adenoviruses, and human metapneumoviruses. Viruses are powerful. In the nose, they induce hypersecretion of mucus, slow cilia beating, up-regulate nasal epithelial cell receptors to facilitate bacterial attachment, suppress neutrophil function, and cause increased release of proinflammatory cytokines and chemokines. All these actions by respiratory viruses promote bacterial overgrowth in the nasopharynx and thereby facilitate bacterial superinfections. In fact, progression in pathogenesis of the common bacterial respiratory infections – acute otitis media, acute sinusitis, acute conjunctivitis, and pneumonia – almost always is preceded by a viral URI. Viruses activate multiple target cells in the upper respiratory tract to produce an array of proinflammatory cytokines and chemokines. The symptoms of a viral URI resolve coinciding with an anti-inflammatory response and adaptive immunity.
In recent work, we found a higher frequency of viral URIs in children who experienced more frequent acute otitis media (AOM). We sought to understand why this might occur by comparing levels of inflammatory cytokines/chemokines in the nose during viral URI that did not precipitate AOM versus when a viral URI precipitated an AOM episode. When a child had a viral URI but did not go on to experience an AOM, the child had higher proinflammatory responses than when the viral URI precipitated an AOM. When differences of levels of proinflammatory cytokines/chemokines were compared in otitis-prone and non–otitis-prone children, lower nasal responses were associated with higher otitis-prone classification frequency (Clin Infect Dis. 2018. doi: 10.1093/cid/ciy750).
The powerful virus and the inflammatory response it can induce also play a major role in allergy and asthma. Viral URIs enhance allergic sensitization to respiratory viruses, such as influenza and respiratory syncytial virus, cause cytopathic damage to airway epithelium, promote excessive proinflammatory cytokine/chemokine production, and increase the exposure of allergens and irritants to antigen-presenting cells. Viral infections also may induce the release of epithelial mediators and cytokines that may propagate eosinophilia. Viral URIs, particularly with respiratory syncytial virus and rhinovirus, are the most common causes of wheezing in children, and they have important influences on the development of asthma. Studies have shown that viral infections trigger up to 85% of asthma exacerbations in school-aged children.
Because this column is being published during the winter, a brief discussion of influenza as a powerful virus is appropriate. Influenza occurs in winter outbreaks of varying extent every year. The severity of the influenza season reflects the changing nature of the antigenic properties of influenza viruses, and their spread depends on susceptibility of the population. Influenza outbreaks typically peak over a 2-3 week period and last for 2-3 months. Most outbreaks have attack rates of 10%-20% in children. There may be variations in disease severity caused by different influenza virus types. The symptoms are caused by excessive proinflammatory cytokine/chemokine production in the nose and lung.
Influenza and other viruses can precipitate the systemic inflammatory response syndrome (SIRS), a manifestation of extreme immune dysregulation resulting in organ dysfunction that clinically resembles bacterial sepsis. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation. SIRS is another example of the double-edged sword of inflammation.
The onset and progression of SIRS occurs because of dysregulation of the normal inflammatory response, usually with an increase in both proinflammatory and anti-inflammatory cytokines and chemokines, initiating a chain of events that leads to organ failure.
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].
FDA approves Primatene Mist return
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
Pneumonia, COPD most common emergency care–sensitive conditions
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
SAN DIEGO – Emergency care–sensitive conditions – those for which timely access to high-quality emergency care impact morbidity and mortality—account for 14% of all ED visits, results from a large analysis of national data showed.
In previously published work, an eight-member expert panel identified 51 condition groups as emergency care–sensitive conditions (ECSCs), including asthma, cardiac arrest, cerebral infarction, and pneumonia. The purpose of the current study, published in Annals of Emergency Medicine and presented by Anita Vashi, MD, MPH, at the annual meeting of the American College of Emergency Physicians, was to provide the first national estimates of acute care utilization and the demographic characteristics of adults experiencing ECSCs, compare ECSC and non-ECSC ED visits, and assess patient- and hospital-level characteristics predictive of an ECSC-related ED visit.
Using the Nationwide Emergency Department Sample data set, Dr. Vashi, a physician investigator at the Center for Innovation to Implementation at the VA Palo Alto Health Care System, and her colleagues retrospectively evaluated all ED visits for patients aged 18 years and older from 2009 to 2014. The researchers used summary statistics to compare population characteristics across groups and multivariable logistic regression models to assess the odds of an ECSC-related ED visit with patient- and hospital-level characteristics.
Of the 622,725,542 estimated ED visits evaluated during the study period, 86,577,041 (14%) were ECSCs. Among these ECSC visits, 58% of patients were admitted for an average length of 3.2 days and an average charge of $2,240. The most frequent ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), asthma (7%), heart failure (7%), and sepsis (5%), but varied by age group.
Dr. Vashi and her colleagues found that ECSCs were more common among older adults, males, those who reside in low-income areas, those who reside in the South, and among metropolitan-based hospitals and nontrauma center hospitals. ECSCs also accounted for about 45% of all inpatient admissions.
Multivariate logistic regression analysis revealed that the odds of having an ECSC-related visit was highest among patients aged 65 years and older (odds ratio, 3.84), those on Medicare (OR, 1.37), those who resided in rural counties (OR, 1.21), and those who reside in the Western portion of the United States (OR, 1.11). Significant hospital-related factors related to ECSC visits included trauma centers (OR, 1.09), nonteaching hospitals (OR, 1.04), and EDs located in the wealthiest counties (OR, 1.02).
The researchers also found that 40% of patients who made ECSC-related ED visits were treated and discharged back to the community. “There is evidence of regional variability, suggesting the need for future research,” said Dr. Vashi, who also holds a faculty position in the department of emergency medicine at Stanford (Calif.) University. “We found no consistent relationship between insurance, income, and ED use for ECSC-related conditions. This suggests that ECSCs are not significantly influenced by socioeconomic factor and can serve as a reliable marker for acuity.”
The next steps in this research area, she added, are to create condition-specific measures related to morbidity, mortality, and posthospital events, as well as to analyze regional and hospital variations including correlation across conditions, and to compare performance across conditions and hospitals.
Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
REPORTING FROM ACEP18
Key clinical point: Emergency care–sensitive conditions (ECSCs) make up a significant proportion of ED visits.
Major finding: The most common ECSC-related visits were for pneumonia (9%), chronic obstructive pulmonary disease (9%), and asthma (7%).
Study details: A retrospective cohort study of more than 86.5 million ECSC-related ED visits.
Disclosures: Dr. Vashi reported having no financial disclosures.
Source: Vashi A et al. Ann Emerg Med. 2018 Oct;72;4:S38. doi. 10.1016/j.annemergmed.2018.08.091.
Should you reassess your patient’s asthma diagnosis?
ILLUSTRATIVE CASE
A 45-year-old woman presents to your office for a yearly visit. Two years ago she was started on an inhaled corticosteroid (ICS) and a bronchodilator rescue inhaler after being diagnosed with asthma based on her history and physical exam findings. She has had no exacerbations since then. Should you consider weaning her off the inhalers?
Asthma is a prevalent problem; 8% of adults ages 18 to 64 years have the chronic lung disease.2 Diagnosis can be challenging, partially because it requires measurement of transient airway resistance. And treatment entails significant costs and possible adverse effects. Without some sort of pulmonary function measurements or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication usage is cost effective.3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications, and how they did in the subsequent year.
STUDY SUMMARY
About one-third of adults with asthma are “undiagnosed” within 5 years
The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.1 The researchers focused on people with a recent (<5 years) asthma diagnosis, so as to represent contemporary diagnostic practice and to make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers in Canada. Patients were excluded if they were using long-term oral steroids, pregnant or breastfeeding, unable to tolerate spirometry or methacholine challenges, or had a history of more than 10 pack-years of smoking.
Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.
The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in the first second of expiration (FEV1). If there was no improvement, the patient took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. If the patient did well with another methacholine challenge about 1 month later, maintenance medications were stopped, and the patient underwent a third methacholine challenge 3 weeks later.
Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV1 from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.
Results. Among the adults with physician-diagnosed asthma, 33.1% (95% confidence interval [CI], 29.4%-36.8%) no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. The investigators also found 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma, including ischemic heart disease, subglottic stenosis, and bronchiectasis.
Continue to: During the 1-year follow-up period...
During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well off all asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.
WHAT’S NEW?
Asthma meds are of no benefit for about one-third of patients taking them
This study found that one-third of patients with asthma diagnosed in the last 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, there appears to be no benefit to using asthma medications. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.5 While patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study, over 40% of patients who no longer had asthma were objectively proven to have had asthma at their original diagnosis.
CAVEATS
High level of rigor and the absence of a randomized trial
This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests, most including methacholine challenges, as well as oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.
Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. The results here are consistent with those of a study that looked at asthma disappearance in groups of patients with and without obesity. In that study, approximately 30% of both groups of patients no longer had a diagnosis of asthma.6
Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
“Undiagnosis” is unusual
Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a physician’s typical work, and it may take some time and effort to educate and monitor patients through the process.
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. Aaron SD, Vandemheen KL, FitzGerald JM, et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.
2. QuickStats: percentage of adults aged 18-64 years with current asthma,* by state - National Health Interview Survey,† 2014-2016. MMWR Morb Mortal Wkly Rep. 2018;67:590.
3. Pakhale S, Sumner A, Coyle D, et al. (Correcting) misdiagnoses of asthma: a cost effectiveness analysis. BMC Pulm Med. 2011;11:27.
4. Rank MA, Liesinger JT, Branda ME, et al. Comparative safety and costs of stepping down asthma medications in patients with controlled asthma. J Allergy Clin Immunol. 2016;137:1373-1379.
5. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2018. https://ginasthma.org. Accessed June 15, 2018.
6. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.
ILLUSTRATIVE CASE
A 45-year-old woman presents to your office for a yearly visit. Two years ago she was started on an inhaled corticosteroid (ICS) and a bronchodilator rescue inhaler after being diagnosed with asthma based on her history and physical exam findings. She has had no exacerbations since then. Should you consider weaning her off the inhalers?
Asthma is a prevalent problem; 8% of adults ages 18 to 64 years have the chronic lung disease.2 Diagnosis can be challenging, partially because it requires measurement of transient airway resistance. And treatment entails significant costs and possible adverse effects. Without some sort of pulmonary function measurements or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication usage is cost effective.3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications, and how they did in the subsequent year.
STUDY SUMMARY
About one-third of adults with asthma are “undiagnosed” within 5 years
The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.1 The researchers focused on people with a recent (<5 years) asthma diagnosis, so as to represent contemporary diagnostic practice and to make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers in Canada. Patients were excluded if they were using long-term oral steroids, pregnant or breastfeeding, unable to tolerate spirometry or methacholine challenges, or had a history of more than 10 pack-years of smoking.
Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.
The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in the first second of expiration (FEV1). If there was no improvement, the patient took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. If the patient did well with another methacholine challenge about 1 month later, maintenance medications were stopped, and the patient underwent a third methacholine challenge 3 weeks later.
Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV1 from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.
Results. Among the adults with physician-diagnosed asthma, 33.1% (95% confidence interval [CI], 29.4%-36.8%) no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. The investigators also found 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma, including ischemic heart disease, subglottic stenosis, and bronchiectasis.
Continue to: During the 1-year follow-up period...
During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well off all asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.
WHAT’S NEW?
Asthma meds are of no benefit for about one-third of patients taking them
This study found that one-third of patients with asthma diagnosed in the last 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, there appears to be no benefit to using asthma medications. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.5 While patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study, over 40% of patients who no longer had asthma were objectively proven to have had asthma at their original diagnosis.
CAVEATS
High level of rigor and the absence of a randomized trial
This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests, most including methacholine challenges, as well as oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.
Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. The results here are consistent with those of a study that looked at asthma disappearance in groups of patients with and without obesity. In that study, approximately 30% of both groups of patients no longer had a diagnosis of asthma.6
Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
“Undiagnosis” is unusual
Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a physician’s typical work, and it may take some time and effort to educate and monitor patients through the process.
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
A 45-year-old woman presents to your office for a yearly visit. Two years ago she was started on an inhaled corticosteroid (ICS) and a bronchodilator rescue inhaler after being diagnosed with asthma based on her history and physical exam findings. She has had no exacerbations since then. Should you consider weaning her off the inhalers?
Asthma is a prevalent problem; 8% of adults ages 18 to 64 years have the chronic lung disease.2 Diagnosis can be challenging, partially because it requires measurement of transient airway resistance. And treatment entails significant costs and possible adverse effects. Without some sort of pulmonary function measurements or trials off medication, there is no clinical way to differentiate patients with well-controlled asthma from those who are being treated unnecessarily. Not surprisingly, studies have shown that ruling out active asthma and reducing medication usage is cost effective.3,4 This study followed a cohort of patients to see how many could be weaned off their asthma medications, and how they did in the subsequent year.
STUDY SUMMARY
About one-third of adults with asthma are “undiagnosed” within 5 years
The researchers recruited participants from the general population of the 10 largest cities and surrounding areas in Canada by randomly dialing cellular and landline phone numbers and asking about adult household members with asthma.1 The researchers focused on people with a recent (<5 years) asthma diagnosis, so as to represent contemporary diagnostic practice and to make it easier to collect medical records. Participants lived within 90 minutes of 10 medical centers in Canada. Patients were excluded if they were using long-term oral steroids, pregnant or breastfeeding, unable to tolerate spirometry or methacholine challenges, or had a history of more than 10 pack-years of smoking.
Of the 701 patients enrolled, 613 (87.4%) completed all study assessments. Patients progressed through a series of spirometry tests and were then tapered off their asthma-controlling medications.
The initial spirometry test confirmed asthma if bronchodilators caused a significant improvement in forced expiratory volume in the first second of expiration (FEV1). If there was no improvement, the patient took a methacholine challenge 1 week later; if they did well, their maintenance medications were reduced by half. If the patient did well with another methacholine challenge about 1 month later, maintenance medications were stopped, and the patient underwent a third methacholine challenge 3 weeks later.
Asthma was confirmed at any methacholine challenge if there was a 20% decrease in FEV1 from baseline at a methacholine concentration of ≤8 mg/mL; these patients were restarted on appropriate medications. If current asthma was ruled out, follow-up bronchial challenges were repeated at 6 and 12 months.
Results. Among the adults with physician-diagnosed asthma, 33.1% (95% confidence interval [CI], 29.4%-36.8%) no longer met criteria for an asthma diagnosis. Of those who no longer had asthma, 44% had previously undergone objective testing of airflow limitation. The investigators also found 12 patients (2%) had other serious cardiorespiratory conditions instead of asthma, including ischemic heart disease, subglottic stenosis, and bronchiectasis.
Continue to: During the 1-year follow-up period...
During the 1-year follow-up period, 22 (10.8%) of the 203 patients who were initially judged to no longer have asthma had a positive bronchial challenge test; 16 had no symptoms and continued to do well off all asthma medications. Six (3%) presented with respiratory symptoms and resumed treatment with asthma medications, but only 1 (0.5%) required oral corticosteroid therapy.
WHAT’S NEW?
Asthma meds are of no benefit for about one-third of patients taking them
This study found that one-third of patients with asthma diagnosed in the last 5 years no longer had symptoms or spirometry results consistent with asthma and did well in the subsequent year. For those patients, there appears to be no benefit to using asthma medications. The Global Institute for Asthma recommends stepping down treatment in adults with asthma that is well controlled for 3 months or more.5 While patients with objectively confirmed asthma diagnoses were more likely to still have asthma in this study, over 40% of patients who no longer had asthma were objectively proven to have had asthma at their original diagnosis.
CAVEATS
High level of rigor and the absence of a randomized trial
This study used a very structured protocol for tapering patients off their medications, including multiple spirometry tests, most including methacholine challenges, as well as oversight by pulmonologists. It is unclear whether this level of rigor is necessary for weaning in other clinical settings.
Also, this study was not a randomized trial, which is the gold standard for withdrawal of therapy. However, a cohort study is adequate to assess diagnostic testing, and this could be considered a trial of “undiagnosing” asthma in adults. The results here are consistent with those of a study that looked at asthma disappearance in groups of patients with and without obesity. In that study, approximately 30% of both groups of patients no longer had a diagnosis of asthma.6
Using random dialing is likely to have broadened the pool of patients this study drew upon. Also, there is a possibility that the patients who were lost to follow-up in this study represented those who had worsening symptoms. Some patients with mild asthma may have a waxing and waning course; it is possible that the study period was not long enough to capture this. In this study, only about 3% of patients who had their medications stopped reported worsening of symptoms.
Continue to: CHALLENGES TO IMPLEMENTATION
CHALLENGES TO IMPLEMENTATION
“Undiagnosis” is unusual
Using objective testing may provide some logistical or financial challenges for patients. Furthermore, “undiagnosing” a chronic disease like asthma is not a physician’s typical work, and it may take some time and effort to educate and monitor patients through the process.
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. Aaron SD, Vandemheen KL, FitzGerald JM, et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.
2. QuickStats: percentage of adults aged 18-64 years with current asthma,* by state - National Health Interview Survey,† 2014-2016. MMWR Morb Mortal Wkly Rep. 2018;67:590.
3. Pakhale S, Sumner A, Coyle D, et al. (Correcting) misdiagnoses of asthma: a cost effectiveness analysis. BMC Pulm Med. 2011;11:27.
4. Rank MA, Liesinger JT, Branda ME, et al. Comparative safety and costs of stepping down asthma medications in patients with controlled asthma. J Allergy Clin Immunol. 2016;137:1373-1379.
5. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2018. https://ginasthma.org. Accessed June 15, 2018.
6. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.
1. Aaron SD, Vandemheen KL, FitzGerald JM, et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.
2. QuickStats: percentage of adults aged 18-64 years with current asthma,* by state - National Health Interview Survey,† 2014-2016. MMWR Morb Mortal Wkly Rep. 2018;67:590.
3. Pakhale S, Sumner A, Coyle D, et al. (Correcting) misdiagnoses of asthma: a cost effectiveness analysis. BMC Pulm Med. 2011;11:27.
4. Rank MA, Liesinger JT, Branda ME, et al. Comparative safety and costs of stepping down asthma medications in patients with controlled asthma. J Allergy Clin Immunol. 2016;137:1373-1379.
5. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2018. https://ginasthma.org. Accessed June 15, 2018.
6. Aaron SD, Vandemheen KL, Boulet LP, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008;179:1121-1131.
PRACTICE CHANGER
Consider tapering medications and retesting spirometry in adults with well-controlled asthma, as many may no longer have the disease.1
STRENGTH OF RECOMMENDATION
A: Based on a high-quality prospective cohort study and consistent findings in other studies.
Aaron SD, Vandemheen KL, FitzGerald JM, et al. Reevaluation of diagnosis in adults with physician-diagnosed asthma. JAMA. 2017;317:269-279.
Two-thirds of COPD patients not using inhalers correctly
SAN ANTONIO – Two-thirds of U.S. adults with (MDIs), according to new research. About half of patients failed to inhale slowly and deeply to ensure they received the appropriate dose, and about 40% of patients failed to hold their breath for 5-10 seconds afterward so that the medication made its way to their lungs, the findings show.
“There’s a need to educate patients on proper inhalation technique to optimize the appropriate delivery of medication,” Maryam Navaie, DrPH, of Advance Health Solutions in New York told attendees at the annual meeting of the American College of Chest Physicians. She also urged practitioners to think more carefully about what devices to prescribe to patients based on their own personal attributes.
“Nebulizer devices may be a better consideration for patients who have difficulty performing the necessary steps required by handheld inhalers,” Dr. Navaie said.
She and fellow researchers conducted a systematic review to gain more insights into the errors and difficulties experienced by U.S. adults using MDIs for COPD or asthma. They combed through PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar databases for English language studies about MDI-related errors in U.S. adult COPD or asthma patients published between January 2003 and February 2017.
The researchers included only randomized controlled trials and cross-sectional and observational studies, and they excluded studies with combined error rates across multiple devices so they could better parse out the data. They also used baseline rates only in studies that involved an intervention to reduce errors.
The researchers defined the proportion of overall MDI errors as “the percentage of patients who made errors in equal to or greater than 20% of inhalation steps.” They computed pooled estimates and created forest plots for both overall errors and for errors according to each step in using an MDI.
The eight studies they identified involved 1,221 patients, with ages ranging from a mean 48 to 82 years, 53% of whom were female. Nearly two-thirds of the patients had COPD (63.6%) while 36.4% had asthma. Most of the devices studied were MDIs alone (68.8%), while 31.2% included a spacer.
The pooled weighted average revealed a 66.5% error rate, that is, two-thirds of all the patients were making at least two errors during the 10 steps involved in using their device. The researchers then used individual error rates data in five studies to calculate the overall error rate for each step in using MDIs. The most common error, made by 73.8% of people in those five studies, was failing to attach the inhaler to the spacer. In addition, 68.7% of patients were failing to exhale fully and away from the inhaler before inhaling, and 47.8% were inhaling too fast instead of inhaling deeply.
“So these [findings] actually give you [some specific] ideas of how we could help improve patients’ ability to use the device properly,” Dr. Navaie told attendees, adding that these data can inform patient education needs and interventions.
Based on the data from those five studies, the error rates for all 10 steps to using an MDI were as follows:
- Failed to shake inhaler before use (37.9%).
- Failed to attach inhaler to spacer (73.8%).
- Failed to exhale fully and away from inhaler before inhalation (68.7%).
- Failed to place mouthpiece between teeth and sealed lips (7.4%).
- Failed to actuate once during inhalation (24.4%).
- Inhalation too fast, not deep (47.8%).
- Failed to hold breath for 5-10 seconds (40.1%).
- Failed to remove the inhaler/spacer from mouth (11.3%).
- Failed to exhale after inhalation (33.2%).
- Failed to repeat steps for second puff (36.7%).
Dr. Navaie also noted the investigators were surprised to learn that physicians themselves sometimes make several of these errors in explaining to patients how to use their devices.
“I think for the reps and other people who go out and visit doctors, it’s important to think about making sure the clinicians are using the devices properly,” Dr. Navaie said. She pointed out the potential for patients to forget steps between visits.
“One of the things a lot of our clinicians and key opinion leaders told us during the course of this study is that you shouldn’t just educate the patient at the time you are scripting the device but repeatedly because patients forget,” she said. She recommended having patients demonstrate their use of the device at each visit. If patients continue to struggle, it may be worth considering other therapies, such as a nebulizer, for patients unable to regularly use their devices correctly.
The meta-analysis was limited by the sparse research available in general on MDI errors in the U.S. adult population, so the data on error rates for each individual step may not be broadly generalizable. The studies also did not distinguish between rates among users with asthma vs. users with COPD. Further, too few data exist on associations between MDI errors and health outcomes to have a clear picture of the clinical implications of regularly making multiple errors in MDI use.
Dr. Navaie is employed by Advance Health Solutions, which received Sunovion Pharmaceuticals funding for the study.
SOURCE: Navaie M et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.705.
SAN ANTONIO – Two-thirds of U.S. adults with (MDIs), according to new research. About half of patients failed to inhale slowly and deeply to ensure they received the appropriate dose, and about 40% of patients failed to hold their breath for 5-10 seconds afterward so that the medication made its way to their lungs, the findings show.
“There’s a need to educate patients on proper inhalation technique to optimize the appropriate delivery of medication,” Maryam Navaie, DrPH, of Advance Health Solutions in New York told attendees at the annual meeting of the American College of Chest Physicians. She also urged practitioners to think more carefully about what devices to prescribe to patients based on their own personal attributes.
“Nebulizer devices may be a better consideration for patients who have difficulty performing the necessary steps required by handheld inhalers,” Dr. Navaie said.
She and fellow researchers conducted a systematic review to gain more insights into the errors and difficulties experienced by U.S. adults using MDIs for COPD or asthma. They combed through PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar databases for English language studies about MDI-related errors in U.S. adult COPD or asthma patients published between January 2003 and February 2017.
The researchers included only randomized controlled trials and cross-sectional and observational studies, and they excluded studies with combined error rates across multiple devices so they could better parse out the data. They also used baseline rates only in studies that involved an intervention to reduce errors.
The researchers defined the proportion of overall MDI errors as “the percentage of patients who made errors in equal to or greater than 20% of inhalation steps.” They computed pooled estimates and created forest plots for both overall errors and for errors according to each step in using an MDI.
The eight studies they identified involved 1,221 patients, with ages ranging from a mean 48 to 82 years, 53% of whom were female. Nearly two-thirds of the patients had COPD (63.6%) while 36.4% had asthma. Most of the devices studied were MDIs alone (68.8%), while 31.2% included a spacer.
The pooled weighted average revealed a 66.5% error rate, that is, two-thirds of all the patients were making at least two errors during the 10 steps involved in using their device. The researchers then used individual error rates data in five studies to calculate the overall error rate for each step in using MDIs. The most common error, made by 73.8% of people in those five studies, was failing to attach the inhaler to the spacer. In addition, 68.7% of patients were failing to exhale fully and away from the inhaler before inhaling, and 47.8% were inhaling too fast instead of inhaling deeply.
“So these [findings] actually give you [some specific] ideas of how we could help improve patients’ ability to use the device properly,” Dr. Navaie told attendees, adding that these data can inform patient education needs and interventions.
Based on the data from those five studies, the error rates for all 10 steps to using an MDI were as follows:
- Failed to shake inhaler before use (37.9%).
- Failed to attach inhaler to spacer (73.8%).
- Failed to exhale fully and away from inhaler before inhalation (68.7%).
- Failed to place mouthpiece between teeth and sealed lips (7.4%).
- Failed to actuate once during inhalation (24.4%).
- Inhalation too fast, not deep (47.8%).
- Failed to hold breath for 5-10 seconds (40.1%).
- Failed to remove the inhaler/spacer from mouth (11.3%).
- Failed to exhale after inhalation (33.2%).
- Failed to repeat steps for second puff (36.7%).
Dr. Navaie also noted the investigators were surprised to learn that physicians themselves sometimes make several of these errors in explaining to patients how to use their devices.
“I think for the reps and other people who go out and visit doctors, it’s important to think about making sure the clinicians are using the devices properly,” Dr. Navaie said. She pointed out the potential for patients to forget steps between visits.
“One of the things a lot of our clinicians and key opinion leaders told us during the course of this study is that you shouldn’t just educate the patient at the time you are scripting the device but repeatedly because patients forget,” she said. She recommended having patients demonstrate their use of the device at each visit. If patients continue to struggle, it may be worth considering other therapies, such as a nebulizer, for patients unable to regularly use their devices correctly.
The meta-analysis was limited by the sparse research available in general on MDI errors in the U.S. adult population, so the data on error rates for each individual step may not be broadly generalizable. The studies also did not distinguish between rates among users with asthma vs. users with COPD. Further, too few data exist on associations between MDI errors and health outcomes to have a clear picture of the clinical implications of regularly making multiple errors in MDI use.
Dr. Navaie is employed by Advance Health Solutions, which received Sunovion Pharmaceuticals funding for the study.
SOURCE: Navaie M et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.705.
SAN ANTONIO – Two-thirds of U.S. adults with (MDIs), according to new research. About half of patients failed to inhale slowly and deeply to ensure they received the appropriate dose, and about 40% of patients failed to hold their breath for 5-10 seconds afterward so that the medication made its way to their lungs, the findings show.
“There’s a need to educate patients on proper inhalation technique to optimize the appropriate delivery of medication,” Maryam Navaie, DrPH, of Advance Health Solutions in New York told attendees at the annual meeting of the American College of Chest Physicians. She also urged practitioners to think more carefully about what devices to prescribe to patients based on their own personal attributes.
“Nebulizer devices may be a better consideration for patients who have difficulty performing the necessary steps required by handheld inhalers,” Dr. Navaie said.
She and fellow researchers conducted a systematic review to gain more insights into the errors and difficulties experienced by U.S. adults using MDIs for COPD or asthma. They combed through PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar databases for English language studies about MDI-related errors in U.S. adult COPD or asthma patients published between January 2003 and February 2017.
The researchers included only randomized controlled trials and cross-sectional and observational studies, and they excluded studies with combined error rates across multiple devices so they could better parse out the data. They also used baseline rates only in studies that involved an intervention to reduce errors.
The researchers defined the proportion of overall MDI errors as “the percentage of patients who made errors in equal to or greater than 20% of inhalation steps.” They computed pooled estimates and created forest plots for both overall errors and for errors according to each step in using an MDI.
The eight studies they identified involved 1,221 patients, with ages ranging from a mean 48 to 82 years, 53% of whom were female. Nearly two-thirds of the patients had COPD (63.6%) while 36.4% had asthma. Most of the devices studied were MDIs alone (68.8%), while 31.2% included a spacer.
The pooled weighted average revealed a 66.5% error rate, that is, two-thirds of all the patients were making at least two errors during the 10 steps involved in using their device. The researchers then used individual error rates data in five studies to calculate the overall error rate for each step in using MDIs. The most common error, made by 73.8% of people in those five studies, was failing to attach the inhaler to the spacer. In addition, 68.7% of patients were failing to exhale fully and away from the inhaler before inhaling, and 47.8% were inhaling too fast instead of inhaling deeply.
“So these [findings] actually give you [some specific] ideas of how we could help improve patients’ ability to use the device properly,” Dr. Navaie told attendees, adding that these data can inform patient education needs and interventions.
Based on the data from those five studies, the error rates for all 10 steps to using an MDI were as follows:
- Failed to shake inhaler before use (37.9%).
- Failed to attach inhaler to spacer (73.8%).
- Failed to exhale fully and away from inhaler before inhalation (68.7%).
- Failed to place mouthpiece between teeth and sealed lips (7.4%).
- Failed to actuate once during inhalation (24.4%).
- Inhalation too fast, not deep (47.8%).
- Failed to hold breath for 5-10 seconds (40.1%).
- Failed to remove the inhaler/spacer from mouth (11.3%).
- Failed to exhale after inhalation (33.2%).
- Failed to repeat steps for second puff (36.7%).
Dr. Navaie also noted the investigators were surprised to learn that physicians themselves sometimes make several of these errors in explaining to patients how to use their devices.
“I think for the reps and other people who go out and visit doctors, it’s important to think about making sure the clinicians are using the devices properly,” Dr. Navaie said. She pointed out the potential for patients to forget steps between visits.
“One of the things a lot of our clinicians and key opinion leaders told us during the course of this study is that you shouldn’t just educate the patient at the time you are scripting the device but repeatedly because patients forget,” she said. She recommended having patients demonstrate their use of the device at each visit. If patients continue to struggle, it may be worth considering other therapies, such as a nebulizer, for patients unable to regularly use their devices correctly.
The meta-analysis was limited by the sparse research available in general on MDI errors in the U.S. adult population, so the data on error rates for each individual step may not be broadly generalizable. The studies also did not distinguish between rates among users with asthma vs. users with COPD. Further, too few data exist on associations between MDI errors and health outcomes to have a clear picture of the clinical implications of regularly making multiple errors in MDI use.
Dr. Navaie is employed by Advance Health Solutions, which received Sunovion Pharmaceuticals funding for the study.
SOURCE: Navaie M et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.705.
REPORTING FROM CHEST 2018
Key clinical point: 67% of US adult patients with COPD or asthma report making errors in using metered-dose inhalers.
Major finding: 69% of patients do not exhale fully and away from the inhaler before inhalation; 50% do not inhale slowly and deeply.
Study details: Meta-analysis of eight studies involving 1,221 U.S. adult patients with COPD or asthma who use metered-dose inhalers.
Disclosures: Dr. Navaie is employed by Advance Health Solutions, which received Sunovion Pharmaceuticals funding for the study.
Source: Navaie M et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.705.
Dupilumab offers extra benefits to asthmatic teens
SAN ANTONIO – For adolescents with asthma, treatment with the biologic agent dupilumab provided benefits that were at least comparable with what was seen in adults, results from a retrospective analysis of a randomized, phase 3 study suggest.
Adolescents had reduced asthma exacerbations in line with what was seen in adults and had improvements in lung function that were at a greater magnitude than adults, according to study coauthor Neil M.H. Graham, MD, of Regeneron Pharmaceuticals, Tarrytown, N.Y.
“We think, overall, it’s a very good treatment response from this drug in this high-risk population, and it is generally well tolerated, as we’ve seen in other studies,” Dr. Graham said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Dr. Graham presented results of an analysis of the 1,902-patient, phase 3 Liberty Asthma QUEST trial, published in May 2018 in the New England Journal of Medicine.
Top-line results of QUEST showed that treatment with dupilumab, a fully human anti–IL-4Ra monoclonal antibody, resulted in significantly lower rates of severe asthma exacerbation, along with improved lung function, in patients aged 12 years and older with moderate to severe asthma.
Now, this retrospective analysis shows that, in adolescents, improvements from baseline to week 12 in forced expiratory volume in 1 second (FEV1) were significant and at a greater magnitude than in adults, according to Dr. Graham and his coinvestigators.
The improvement over 12 weeks in FEV1 for adolescents was 0.36 L and 0.27 L, respectively, for the 200- and 300-mg doses of dupilumab (P less than .05 vs. placebo for both), Dr. Graham and his coinvestigators reported. In adults, the improvement was 0.12 L.
The annualized exacerbation rate dropped by 46.4% for those adolescents who received 200 mg dupilumab, though there was no treatment effect versus placebo for dupilumab 300 mg; the investigators said the lack of effect in this retrospective analysis could have been caused by imbalances in prior event rates or the small sample size.
A total of 107 out of 1,902 patients in QUEST were adolescents, and of those, 68 were randomly assigned to dupilumab, according to the report. Injection site reaction was the most common adverse event in adolescents in both dosing groups.
Dr. Graham reported disclosures related to his employment with Regeneron. Study coauthors reported disclosures related to Regeneron, AstraZeneca, Sanofi, Teva Pharmaceutical, GlaxoSmithKline, Boehringer Ingelheim, Merck, Genentech, and others.
SOURCE: Graham NMH et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.022.
SAN ANTONIO – For adolescents with asthma, treatment with the biologic agent dupilumab provided benefits that were at least comparable with what was seen in adults, results from a retrospective analysis of a randomized, phase 3 study suggest.
Adolescents had reduced asthma exacerbations in line with what was seen in adults and had improvements in lung function that were at a greater magnitude than adults, according to study coauthor Neil M.H. Graham, MD, of Regeneron Pharmaceuticals, Tarrytown, N.Y.
“We think, overall, it’s a very good treatment response from this drug in this high-risk population, and it is generally well tolerated, as we’ve seen in other studies,” Dr. Graham said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Dr. Graham presented results of an analysis of the 1,902-patient, phase 3 Liberty Asthma QUEST trial, published in May 2018 in the New England Journal of Medicine.
Top-line results of QUEST showed that treatment with dupilumab, a fully human anti–IL-4Ra monoclonal antibody, resulted in significantly lower rates of severe asthma exacerbation, along with improved lung function, in patients aged 12 years and older with moderate to severe asthma.
Now, this retrospective analysis shows that, in adolescents, improvements from baseline to week 12 in forced expiratory volume in 1 second (FEV1) were significant and at a greater magnitude than in adults, according to Dr. Graham and his coinvestigators.
The improvement over 12 weeks in FEV1 for adolescents was 0.36 L and 0.27 L, respectively, for the 200- and 300-mg doses of dupilumab (P less than .05 vs. placebo for both), Dr. Graham and his coinvestigators reported. In adults, the improvement was 0.12 L.
The annualized exacerbation rate dropped by 46.4% for those adolescents who received 200 mg dupilumab, though there was no treatment effect versus placebo for dupilumab 300 mg; the investigators said the lack of effect in this retrospective analysis could have been caused by imbalances in prior event rates or the small sample size.
A total of 107 out of 1,902 patients in QUEST were adolescents, and of those, 68 were randomly assigned to dupilumab, according to the report. Injection site reaction was the most common adverse event in adolescents in both dosing groups.
Dr. Graham reported disclosures related to his employment with Regeneron. Study coauthors reported disclosures related to Regeneron, AstraZeneca, Sanofi, Teva Pharmaceutical, GlaxoSmithKline, Boehringer Ingelheim, Merck, Genentech, and others.
SOURCE: Graham NMH et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.022.
SAN ANTONIO – For adolescents with asthma, treatment with the biologic agent dupilumab provided benefits that were at least comparable with what was seen in adults, results from a retrospective analysis of a randomized, phase 3 study suggest.
Adolescents had reduced asthma exacerbations in line with what was seen in adults and had improvements in lung function that were at a greater magnitude than adults, according to study coauthor Neil M.H. Graham, MD, of Regeneron Pharmaceuticals, Tarrytown, N.Y.
“We think, overall, it’s a very good treatment response from this drug in this high-risk population, and it is generally well tolerated, as we’ve seen in other studies,” Dr. Graham said in a podium presentation at the annual meeting of the American College of Chest Physicians.
Dr. Graham presented results of an analysis of the 1,902-patient, phase 3 Liberty Asthma QUEST trial, published in May 2018 in the New England Journal of Medicine.
Top-line results of QUEST showed that treatment with dupilumab, a fully human anti–IL-4Ra monoclonal antibody, resulted in significantly lower rates of severe asthma exacerbation, along with improved lung function, in patients aged 12 years and older with moderate to severe asthma.
Now, this retrospective analysis shows that, in adolescents, improvements from baseline to week 12 in forced expiratory volume in 1 second (FEV1) were significant and at a greater magnitude than in adults, according to Dr. Graham and his coinvestigators.
The improvement over 12 weeks in FEV1 for adolescents was 0.36 L and 0.27 L, respectively, for the 200- and 300-mg doses of dupilumab (P less than .05 vs. placebo for both), Dr. Graham and his coinvestigators reported. In adults, the improvement was 0.12 L.
The annualized exacerbation rate dropped by 46.4% for those adolescents who received 200 mg dupilumab, though there was no treatment effect versus placebo for dupilumab 300 mg; the investigators said the lack of effect in this retrospective analysis could have been caused by imbalances in prior event rates or the small sample size.
A total of 107 out of 1,902 patients in QUEST were adolescents, and of those, 68 were randomly assigned to dupilumab, according to the report. Injection site reaction was the most common adverse event in adolescents in both dosing groups.
Dr. Graham reported disclosures related to his employment with Regeneron. Study coauthors reported disclosures related to Regeneron, AstraZeneca, Sanofi, Teva Pharmaceutical, GlaxoSmithKline, Boehringer Ingelheim, Merck, Genentech, and others.
SOURCE: Graham NMH et al. CHEST. 2018 Oct. doi: 10.1016/j.chest.2018.08.022.
REPORTING FROM CHEST 2018
Key clinical point: Dupilumab’s benefits in adolescents with moderate to severe asthma are at least comparable with what has been reported in adults.
Major finding: The improvement over 12 weeks in forced expiratory volume in 1 second for adolescents was 0.36 L and 0.27 L, respectively, for the 200- and 300-mg doses of dupilumab versus 0.12 L for adults.
Study details: A retrospective analysis of 1,902 patients (including 107 adolescents) in Liberty Asthma QUEST, a recently reported randomized, phase 3 trial.
Disclosures: Several study coauthors reported employment with Regeneron. Dr. Graham reported disclosures related to his employment with Regeneron. Other reported disclosures were related to AstraZeneca, Sanofi, Teva Pharmaceutical, GlaxoSmithKline, Boehringer Ingelheim, Merck, and Genentech, among other entities.
Source: Graham NMH et al. CHEST. 2018 Oct. doi: 10.1016/j/chest.2018.08.002.