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FDA approves Nucala’s new at-home formulations
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.
The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.
The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.
Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.
Lack of inhaler at school a major barrier to asthma care
BALTIMORE – frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.
“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”
One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.
Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”
To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.
The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).
The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.
The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).
Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.
The researchers did not note use of external funding or author disclosures.
BALTIMORE – frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.
“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”
One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.
Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”
To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.
The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).
The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.
The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).
Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.
The researchers did not note use of external funding or author disclosures.
BALTIMORE – frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.
“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”
One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.
Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”
To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.
The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).
The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.
The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).
Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.
The researchers did not note use of external funding or author disclosures.
REPORTING FROM PAS 2019
Peanut desensitization comes at cost of anaphylaxis
based on a meta-analysis from more than 1,000 patients published in the Lancet.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).
Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).
In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).
Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.
The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.
The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.
However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.
The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.
Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.
SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.
“The key criticism of this systematic review is inherent in its method because studies with different designs were grouped together,” Graham Roberts, MD, and Elizabeth Angier, MD, wrote in an accompanying editorial. In addition, the studies chosen did not account for the development of long-term peanut tolerance after the therapy was discontinued.
Also, the researchers did not factor in the variation in patterns of anaphylactic events, with patients in the treatment groups having events at home in conjunction with daily peanut doses, while the control patients would have had events mainly away from home.
“Unfortunately, the trials have not provided information about which participants benefited most from the intervention,” they wrote.
“Trading treatment-related side effects at home for allergic reactions to accidental exposures out of the house [i.e., in social situations] might beneficial for some patients,” they added. However, more research is needed to determine which patients would benefit from different treatment options at home and outside the home. The less effective but safer option of epicutaneous immunotherapy might be preferred by some patients. And early introduction of peanut products during infancy may prevent many cases of peanut allergy.
Dr. Roberts and Dr. Angier are at the University of Southampton (England). Both are members of the European Academy of Allergy and Clinical Immunology Allergen Immunotherapy Guidelines Group, which has recently published guidelines on immunotherapy. They wrote an editorial to accompany the article by Chu et al (Lancet. 2019 June 1;393:2180-1). They had no financial conflicts to disclose.
“The key criticism of this systematic review is inherent in its method because studies with different designs were grouped together,” Graham Roberts, MD, and Elizabeth Angier, MD, wrote in an accompanying editorial. In addition, the studies chosen did not account for the development of long-term peanut tolerance after the therapy was discontinued.
Also, the researchers did not factor in the variation in patterns of anaphylactic events, with patients in the treatment groups having events at home in conjunction with daily peanut doses, while the control patients would have had events mainly away from home.
“Unfortunately, the trials have not provided information about which participants benefited most from the intervention,” they wrote.
“Trading treatment-related side effects at home for allergic reactions to accidental exposures out of the house [i.e., in social situations] might beneficial for some patients,” they added. However, more research is needed to determine which patients would benefit from different treatment options at home and outside the home. The less effective but safer option of epicutaneous immunotherapy might be preferred by some patients. And early introduction of peanut products during infancy may prevent many cases of peanut allergy.
Dr. Roberts and Dr. Angier are at the University of Southampton (England). Both are members of the European Academy of Allergy and Clinical Immunology Allergen Immunotherapy Guidelines Group, which has recently published guidelines on immunotherapy. They wrote an editorial to accompany the article by Chu et al (Lancet. 2019 June 1;393:2180-1). They had no financial conflicts to disclose.
“The key criticism of this systematic review is inherent in its method because studies with different designs were grouped together,” Graham Roberts, MD, and Elizabeth Angier, MD, wrote in an accompanying editorial. In addition, the studies chosen did not account for the development of long-term peanut tolerance after the therapy was discontinued.
Also, the researchers did not factor in the variation in patterns of anaphylactic events, with patients in the treatment groups having events at home in conjunction with daily peanut doses, while the control patients would have had events mainly away from home.
“Unfortunately, the trials have not provided information about which participants benefited most from the intervention,” they wrote.
“Trading treatment-related side effects at home for allergic reactions to accidental exposures out of the house [i.e., in social situations] might beneficial for some patients,” they added. However, more research is needed to determine which patients would benefit from different treatment options at home and outside the home. The less effective but safer option of epicutaneous immunotherapy might be preferred by some patients. And early introduction of peanut products during infancy may prevent many cases of peanut allergy.
Dr. Roberts and Dr. Angier are at the University of Southampton (England). Both are members of the European Academy of Allergy and Clinical Immunology Allergen Immunotherapy Guidelines Group, which has recently published guidelines on immunotherapy. They wrote an editorial to accompany the article by Chu et al (Lancet. 2019 June 1;393:2180-1). They had no financial conflicts to disclose.
based on a meta-analysis from more than 1,000 patients published in the Lancet.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).
Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).
In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).
Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.
The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.
The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.
However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.
The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.
Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.
SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.
based on a meta-analysis from more than 1,000 patients published in the Lancet.
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).
Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).
In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).
Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.
The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.
The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.
However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.
The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.
Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.
SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.
FROM THE LANCET
Children’s anxiety during asthma exacerbations linked to better outcomes
BALTIMORE – according to new research.
“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”
He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.
“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.
Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.
The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.
The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.
The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV1]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).
The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).
Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.
Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).
One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV1 measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).
The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.
For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV1 levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.
Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.
Although caregivers’ reports of children feeling panic-fear were linked to better FEV1 outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.
“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.
The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.
BALTIMORE – according to new research.
“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”
He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.
“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.
Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.
The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.
The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.
The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV1]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).
The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).
Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.
Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).
One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV1 measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).
The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.
For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV1 levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.
Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.
Although caregivers’ reports of children feeling panic-fear were linked to better FEV1 outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.
“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.
The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.
BALTIMORE – according to new research.
“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”
He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.
“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.
Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.
The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.
The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.
The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV1]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).
The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).
Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.
Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).
One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV1 measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).
The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.
For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV1 levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.
Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.
Although caregivers’ reports of children feeling panic-fear were linked to better FEV1 outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.
“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.
The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.
REPORTING FROM PAS 2019
Stock inhalers at school effectively meet students’ rescue medication needs
DALLAS – Allowing public and private schools to store multiuse stock albuterol inhalers for students with asthma is a legally and medically feasible way to provide students with rescue medication without their need to leave school, according to a recent study.
“Stakeholder coalitions can facilitate the large-scale adoption of stock inhaler programs in schools,” concluded Ashley A. Lowe, MSPH, a senior research specialist and PhD candidate at the University of Arizona, Tucson, and colleagues in a poster at the American Thoracic Society’s international conference.“These programs improve access to rescue medication while returning students back to their classroom.”
The Arizona legislature passed H.B. 2208, “Stock Inhalers for Schools” in March 2017 to allow schools to store and administer albuterol sulfate while indemnifying trained staff against liability when they allowed students to use the inhaler in good faith. A stock inhaler can used by different students because of its disposable valved-holding chambers.
“Such laws allow schools to overcome the legal obstacles that make it difficult for them to ensure such medication is readily available to all children experiencing respiratory distress,” the authors wrote. They assessed the use and outcomes of schools’ storage of stock inhalers during the 2017-2018 school year in Pima County, Arizona.
Of the 213 public, 90 charter, and 61 private/parochial schools in Pima County, 246 (67%) total schools participated, including nearly all of the public schools (93%), nearly half the private/parochial schools (49%), and 17% of the charter schools. A total of 134,251 students had access to a stock inhaler at school.
Each participating school received a kit containing a 60-dose albuterol sulfate inhaler, 10 valved-holding chambers, a signed standing medical order, a standardized emergency protocol for albuterol use, access to an online training curriculum and template resources, along with technical support.
Each time a school used the stock inhaler, they documented whether an asthma diagnosis was known or not, total puffs administered and where the student went next – returned to class, sent home with caregiver, 911 call without transport, or 911 call with EMS transport.
Based on data analyzed from 240 schools, the stock inhalers were used 1,032 times at 152 schools during the study period, predominantly at public schools (97%) and by students with a known asthma diagnosis (82%). In 12.2% of cases, the student did not have a known asthma diagnosis, and 5.8% of the time, asthma diagnosis status was unknown. The students received a mean 2.7 puffs at each use.
Ethnicity and race data of those students who used the inhalers was not complete. Most of the students for whom ethnicity data were available (n = 343) and who used the inhaler were Hispanic/Latino (69.8%) independent of race. Based only on the 437 students for whom data on race were available, students using the inhaler included 41% white, 11.7% black, 3.1% Native American/Alaskan Native, 1% Asian and 0.6% Native Hawaiian/Pacific Islander.
Among the 915 uses of the inhaler for which subsequent student location was available, the majority of students (84%) returned to their classroom after using the inhaler. Only five were transported to a medical facility via EMS following a 911 call, and 911 was called for one student who did not receive EMS transport.
According to the Allergy & Asthma Network, the following states have school stock albuterol laws: Arizona, Colorado, Georgia, Illinois, Missouri, New Hampshire, New Mexico, Oklahoma, Ohio, Texas, Utah, and West Virginia.*
The research was funded by Banner–University Medical Center Tucson, Thayer Medical Corporation, and the Asthma & Airway Disease Research Center. The authors had no disclosures.
SOURCE: Lowe AA et al. ATS 2019, Abstract A4070.
* This article was updated on July 15, 2019.
DALLAS – Allowing public and private schools to store multiuse stock albuterol inhalers for students with asthma is a legally and medically feasible way to provide students with rescue medication without their need to leave school, according to a recent study.
“Stakeholder coalitions can facilitate the large-scale adoption of stock inhaler programs in schools,” concluded Ashley A. Lowe, MSPH, a senior research specialist and PhD candidate at the University of Arizona, Tucson, and colleagues in a poster at the American Thoracic Society’s international conference.“These programs improve access to rescue medication while returning students back to their classroom.”
The Arizona legislature passed H.B. 2208, “Stock Inhalers for Schools” in March 2017 to allow schools to store and administer albuterol sulfate while indemnifying trained staff against liability when they allowed students to use the inhaler in good faith. A stock inhaler can used by different students because of its disposable valved-holding chambers.
“Such laws allow schools to overcome the legal obstacles that make it difficult for them to ensure such medication is readily available to all children experiencing respiratory distress,” the authors wrote. They assessed the use and outcomes of schools’ storage of stock inhalers during the 2017-2018 school year in Pima County, Arizona.
Of the 213 public, 90 charter, and 61 private/parochial schools in Pima County, 246 (67%) total schools participated, including nearly all of the public schools (93%), nearly half the private/parochial schools (49%), and 17% of the charter schools. A total of 134,251 students had access to a stock inhaler at school.
Each participating school received a kit containing a 60-dose albuterol sulfate inhaler, 10 valved-holding chambers, a signed standing medical order, a standardized emergency protocol for albuterol use, access to an online training curriculum and template resources, along with technical support.
Each time a school used the stock inhaler, they documented whether an asthma diagnosis was known or not, total puffs administered and where the student went next – returned to class, sent home with caregiver, 911 call without transport, or 911 call with EMS transport.
Based on data analyzed from 240 schools, the stock inhalers were used 1,032 times at 152 schools during the study period, predominantly at public schools (97%) and by students with a known asthma diagnosis (82%). In 12.2% of cases, the student did not have a known asthma diagnosis, and 5.8% of the time, asthma diagnosis status was unknown. The students received a mean 2.7 puffs at each use.
Ethnicity and race data of those students who used the inhalers was not complete. Most of the students for whom ethnicity data were available (n = 343) and who used the inhaler were Hispanic/Latino (69.8%) independent of race. Based only on the 437 students for whom data on race were available, students using the inhaler included 41% white, 11.7% black, 3.1% Native American/Alaskan Native, 1% Asian and 0.6% Native Hawaiian/Pacific Islander.
Among the 915 uses of the inhaler for which subsequent student location was available, the majority of students (84%) returned to their classroom after using the inhaler. Only five were transported to a medical facility via EMS following a 911 call, and 911 was called for one student who did not receive EMS transport.
According to the Allergy & Asthma Network, the following states have school stock albuterol laws: Arizona, Colorado, Georgia, Illinois, Missouri, New Hampshire, New Mexico, Oklahoma, Ohio, Texas, Utah, and West Virginia.*
The research was funded by Banner–University Medical Center Tucson, Thayer Medical Corporation, and the Asthma & Airway Disease Research Center. The authors had no disclosures.
SOURCE: Lowe AA et al. ATS 2019, Abstract A4070.
* This article was updated on July 15, 2019.
DALLAS – Allowing public and private schools to store multiuse stock albuterol inhalers for students with asthma is a legally and medically feasible way to provide students with rescue medication without their need to leave school, according to a recent study.
“Stakeholder coalitions can facilitate the large-scale adoption of stock inhaler programs in schools,” concluded Ashley A. Lowe, MSPH, a senior research specialist and PhD candidate at the University of Arizona, Tucson, and colleagues in a poster at the American Thoracic Society’s international conference.“These programs improve access to rescue medication while returning students back to their classroom.”
The Arizona legislature passed H.B. 2208, “Stock Inhalers for Schools” in March 2017 to allow schools to store and administer albuterol sulfate while indemnifying trained staff against liability when they allowed students to use the inhaler in good faith. A stock inhaler can used by different students because of its disposable valved-holding chambers.
“Such laws allow schools to overcome the legal obstacles that make it difficult for them to ensure such medication is readily available to all children experiencing respiratory distress,” the authors wrote. They assessed the use and outcomes of schools’ storage of stock inhalers during the 2017-2018 school year in Pima County, Arizona.
Of the 213 public, 90 charter, and 61 private/parochial schools in Pima County, 246 (67%) total schools participated, including nearly all of the public schools (93%), nearly half the private/parochial schools (49%), and 17% of the charter schools. A total of 134,251 students had access to a stock inhaler at school.
Each participating school received a kit containing a 60-dose albuterol sulfate inhaler, 10 valved-holding chambers, a signed standing medical order, a standardized emergency protocol for albuterol use, access to an online training curriculum and template resources, along with technical support.
Each time a school used the stock inhaler, they documented whether an asthma diagnosis was known or not, total puffs administered and where the student went next – returned to class, sent home with caregiver, 911 call without transport, or 911 call with EMS transport.
Based on data analyzed from 240 schools, the stock inhalers were used 1,032 times at 152 schools during the study period, predominantly at public schools (97%) and by students with a known asthma diagnosis (82%). In 12.2% of cases, the student did not have a known asthma diagnosis, and 5.8% of the time, asthma diagnosis status was unknown. The students received a mean 2.7 puffs at each use.
Ethnicity and race data of those students who used the inhalers was not complete. Most of the students for whom ethnicity data were available (n = 343) and who used the inhaler were Hispanic/Latino (69.8%) independent of race. Based only on the 437 students for whom data on race were available, students using the inhaler included 41% white, 11.7% black, 3.1% Native American/Alaskan Native, 1% Asian and 0.6% Native Hawaiian/Pacific Islander.
Among the 915 uses of the inhaler for which subsequent student location was available, the majority of students (84%) returned to their classroom after using the inhaler. Only five were transported to a medical facility via EMS following a 911 call, and 911 was called for one student who did not receive EMS transport.
According to the Allergy & Asthma Network, the following states have school stock albuterol laws: Arizona, Colorado, Georgia, Illinois, Missouri, New Hampshire, New Mexico, Oklahoma, Ohio, Texas, Utah, and West Virginia.*
The research was funded by Banner–University Medical Center Tucson, Thayer Medical Corporation, and the Asthma & Airway Disease Research Center. The authors had no disclosures.
SOURCE: Lowe AA et al. ATS 2019, Abstract A4070.
* This article was updated on July 15, 2019.
REPORTING FROM ATS 2019
Pediatric lung disease plus nighttime screen time impact sleep quality
DALLAS – but nighttime use of technology may contribute more to sleep problems, according to a new study.
“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.
Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.
Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.
Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.
The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.
Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.
The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.
The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.
SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.
DALLAS – but nighttime use of technology may contribute more to sleep problems, according to a new study.
“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.
Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.
Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.
Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.
The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.
Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.
The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.
The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.
SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.
DALLAS – but nighttime use of technology may contribute more to sleep problems, according to a new study.
“Routinely addressing sleep concerns, sleep hygiene, and mental health is important in the care of pediatric patients with chronic illness,” concluded Lauren Greenawald, DO, and colleagues at the Alfred I. duPont Hospital for Children in Wilmington, Del. The researchers presented their findings on sleep quality and mental health of children with asthma or cystic fibrosis (CF) at the American Thoracic Society’s international conference.
Dr. Greenawald’s team screened 31 children (aged 7-17 years) with CF and 34 children with asthma for anxiety, depression, and ADHD. The researchers also assessed the children’s sleep hygiene, sleep quality, and physical and emotional symptoms. Instruments included the validated Pediatric Daytime Sleepiness Scale (PDSS), Pediatric Quality of Life Inventory, and Patient-Reported Outcomes Measurement Information System Pediatric Anxiety Survey, plus an investigator-designed survey about sleep habits.
Just over half the children with CF (52%) and 14% of children with asthma had mental health diagnoses (P less than .01). The same proportion of patients with CF (52%) and nearly a third of patients with asthma (30%) reported they often or always felt they needed more sleep based on the PDSS. Further, 42% of children with CF and 55% of children with asthma said their symptoms kept them awake 1-2 nights a week. Only 6% of asthma patients and no CF patients said their symptoms keep them awake often, 3-4 nights a week. Just over a third of children with CF (36%) and 46% of those with asthma thought they would sleep better if they didn’t have a medical condition.
Yet, for the vast majority of children, the sleeping problems did not appear to result from worry about their illness: 85% of those with CF and nearly all of those with asthma (97%) did not have trouble sleeping as a result of anxiety about their medical condition.
The researchers identified nighttime use of technology that may affect the children’s sleep in ways similar to that of the general population. Many of the participants – 68% of those with CF and 47% of those with asthma – reported texting or using social media or other technology an hour before going to bed. In addition, 55% of those with CF and 25% of those with asthma said they use their phone after the lights are out at least 5 nights a week. One in five of those with CF (20%) said they go to bed later than they planned at least 5 days a week because of social media or texting, though only 6% of those with asthma said the same.
Despite the children’s reports of inadequate sleep, very few – 3.2% of children with CF and 5.9% of children with asthma – reported feeling low daytime energy.
The use of child self-reporting in the presence of family members is a study limitation, including potentially introducing social desirability bias.
The research was funded by the Nemours Summer Undergraduate Research Program. The authors reported no disclosures.
SOURCE: Greenawald L et al. ATS 2019, Abstract A2788.
REPORTING FROM ATS 2019
mTORC1 inhibitor protects elderly asthmatics from viral respiratory tract infections
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
DALLAS – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.
Dubbed RTB101, the oral medication is a selective, potent inhibitor of target of rapamycin complex 1 (TORC1). In phase 2b data presented at the American Thoracic Society’s international conference, RTB101 decreased by 52% the number of elderly subjects with severe, lab-confirmed respiratory tract infections (RTI) symptoms.
But the molecule was even more effective in patients with asthma aged 65 years and older, Joan Mannick, MD, said in an interview during the meeting. In this group, it reduced by 69% the percentage of subjects who developed RTIs and reduced the rate of infection by about 79%, compared with placebo.
“The core cause of asthma exacerbations in these patients is viral respiratory tract infection,” said Dr. Mannick, chief medical officer of resTORbio, the Boston company developing RTB101. “About 80% of the viruses detected in these infections are rhinoviruses, and there are 170 rhinovirus serotypes. We have never been able to develop a vaccine against rhinovirus, and we have no treatment other than to treat the inflammation caused by the infection.”
Centers for Disease Control and Prevention mortality records confirm the impact of viral respiratory infections on older people who experience asthma exacerbations: 6 of 10,000 will die, compared with less than 2 per 10,000 for all other age groups. Decreasing the number of these infections in older people with asthma would prevent morbidity and mortality and save considerable health care dollars.
“One of the reasons that asthmatics have such difficulty when they get respiratory infections is that they seem to have deficient antiviral immunity in the airways,” Dr. Mannick said. She pointed to a 2008 study of bronchial epithelial cells from both patients with asthma and healthy controls. When inoculated with rhinovirus, the cells from asthmatic airways were unable to mount a healthy immune response and were particularly deficient in producing interferon-beta.
By inhibiting mammalian TORC1 (mTORC1), RBT101 also inhibits sterol regulatory element binding transcription factor 2, a pathway that influences cholesterol synthesis. Cells perceive cholesterol synthesis attenuation as a threat, Dr. Mannick said, and react by up-regulating a number of immune response genes – including some specifically antiviral genes that up-regulate interferon-alpha and -beta production and immune cytokine signaling pathways.
RTB101 is not a particularly new molecule; Novartis originally investigated it as an anticancer agent. “It failed, because it was too selective for mTORC1,” Dr. Mannick said. After Novartis dropped the molecule, resTORbio, a Novartis spin-off, began to investigate it as an immunotherapy for RTIs, particularly in patients with asthma.
reSTORbio’s phase 2 studies on RTB101 comprised 264 healthy subjects aged 65 years and older, who received placebo or 10 mg RTB101 daily for 6 weeks, during cold and flu season. They were followed for a year, confirming the antiviral gene up-regulation. Treatment was also associated with a 42% reduction in the rate of respiratory tract infections.
Conversations with the Food and Drug Administration and payers collected, Dr. Mannick said. “They said that where this drug could really make a difference was if it could decrease these infections in high-risk elderly, who are expensive to treat. So, we targeted people 65 years and older with asthma, chronic obstructive pulmonary disease, and smokers, and people who are 85 years or older.”
The phase 2b trial comprised 652 of these elderly high-risk subjects randomized to the following treatment arms: RTB101 5 mg once daily (n = 61), RTB101 10 mg once daily (n = 176), RTB101 10 mg b.i.d. (n = 120), RTB101 10 mg plus everolimus 0.1 mg daily (n = 115), or matching placebo (n = 180) over 16 weeks, during the entire cold and flu season. The primary endpoint was laboratory-confirmed RTIs in all groups.
The RTB101 10-mg, once-daily group had the best results with a 30.6% reduction in the percentage of patients with lab-confirmed RTIs, compared with placebo, and a 52% reduction in the percentage with severe symptoms.
A subgroup analysis found even more benefit to those with asthma. Among these patients, RTB101 effected a 58.2% decrease in patients with RTIs, and a 66.4% decrease in the rate of infections, compared with placebo.
RTB101 was most effective against rhinoviruses, but it also prevented RTIs associated with influenza A and coronavirus OC43. It also decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
There were no safety signals, Dr. Mannick noted. Adverse events were similar in both placebo and active groups, and none were deemed related to the study drug. About 5% of each group discontinued the drug because an adverse event.
Plans for a phase 3 trial are underway. A phase 3, placebo-controlled study in the Southern Hemisphere is now ongoing, during the winter cold and flu season. The Northern Hemisphere phase 3 will commence fall and winter of 2019.
Whether RBT101 can help younger people with asthma is an open question. Elderly patients not only have the asthma-related immune deficiency, but also the general age-related immune issues. Younger patients, however, still express the same asthma-related impairment of bronchial immunity.
“We would like to investigate this in younger people and in children, but that will have to wait until our other phase 3 studies are complete,” Dr. Mannick said.
The trial was sponsored by resTORbio.
SOURCE: Mannick J et al. ATS 2019, Abstract A2623.
CORRECTION 5/24/2019 The article was corrected to state a decreased the incidence of RTIs caused by respiratory syncytial virus, parainfluenza 4, influenza B, metapneumovirus, or other coronavirus serotypes.
REPORTING FROM ATS 2019
Eosinophil levels affect glucocorticoid response in mild, persistent asthma
according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
Gary W. K. Wong, MD, commented in an editorial accompanying the two studies, “Approximately 1 year ago, the SYGMA 1 and SYGMA 2 trials, involving patients with mild persistent asthma, suggested that as-needed use of a budesonide–formoterol combination was as effective as budesonide maintenance therapy in the prevention of exacerbations, with the added benefit of decreased overall glucocorticoid exposure; however, it remained unknown if this strategy was appropriate for patients with mild intermittent asthma and among patients lacking eosinophilic inflammation. The two reported studies attempt to address these knowledge gaps.”
He noted that both trials showed that “patients with mild asthma whose only asthma treatment was a SABA [short-acting beta2-agonists] as needed for relief of asthma symptoms were at considerable risk for exacerbations. Replacement of as-needed SABA treatment with as-needed budesonide/formoterol or inhaled glucocorticoid maintenance therapy could reduce such risk by approximately 50%. When considering maintenance therapy for persistent asthma, one must be aware that not all types of airway inflammation respond equally well to inhaled glucocorticoid therapy.”
Gary W.K. Wong, MD, is a professor in the department of pediatrics at Prince of Wales Hospital, Chinese University of Hong Kong. He made his remarks in an editorial in the New England Journal of Medicine (2019 May 19. doi: 10.1056/NEJMe1905354). Dr. Wong disclosed that he has no relevant financial conflicts of interest.
according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
according to investigators.
Two recent studies presented at the American Thoracic Society’s international conference demonstrated the benefits of glucocorticoid therapy among patients with mild persistent or intermittent asthma while highlighting differential responses to steroids among patients with high versus low levels of eosinophils in sputum. Both studies were simultaneously published in the New England Journal of Medicine.
The first study, SIENA, led by Stephen C. Lazarus, MD of the University of California, San Francisco, and colleagues, involved 295 patients with mild, persistent asthma. Patients were classified as having either a high or low level of eosinophils in sputum, with a low level defined by two sputum samples consisting of less than 2% eosinophils. After a single-blind placebo run-in period of 6 weeks, patients were randomized to receive either mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist [LAMA]), or placebo for 12 weeks each, with subsequent crossover through the two remaining treatments. The primary outcome was the response to each active agent, compared with placebo among low-eosinophil patients who had a differential response to a trial agent.
Out of 295 patients, 221 (75%) had low eosinophils and 74 (25%) had high eosinophils. In the low-eosinophil subgroup, 59% of patients had a differential response to a trial agent; among these, 57% responded better to mometasone, compared with 43% who responded better to placebo, and 60% responded better to tiotropium, compared with 40% who responded better to placebo.
Turning to secondary analyses, among patients with high eosinophil levels who had a differential response, 74% responded better to mometasone, compared with 26% who responded better to placebo, and 57% responded better to tiotropium, compared with 43% who responded better to placebo.
In an additional exploratory analysis, adults with low eosinophil levels had better responses to tiotropium than placebo (62% vs 38%).
The researchers stated that a key finding of the study is that three-quarters of the mild, persistent asthma population had low eosinophil levels, far fewer than expected and that the difference in their response to mometasone compared to tiotropium was not significant.
“Our results raise the question of whether treatment guidelines should be reevaluated for patients with mild, persistent asthma for whom evidence of type 2 inflammation is lacking,” the investigators wrote. “The need for a change in treatment strategy is further highlighted by a growing body of literature suggesting that mild, persistent asthma can be managed safely without the daily use of inhaled glucocorticoids and by data showing that patients with a low eosinophil level may not have a favorable response to inhaled glucocorticoids” (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917).
The second study, Novel START, conducted by lead author Richard Beasley, DSc, of the Medical Research Institute of New Zealand, Wellington, and colleagues, compared the efficacy of two inhaled glucocorticoid regimens and albuterol alone for patients with mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Initial randomization involved 675 patients, of whom 668 were included in the final analysis. Patients were randomized into three groups: albuterol as needed (100 mcg, two inhalations as needed for asthma symptoms), budesonide maintenance (200 mcg, one inhalation twice daily with as-needed albuterol), or budesonide/formoterol (budesonide 200 mcg and formoterol 6 mcg, one inhalation as needed). Along with annualized exacerbation rate, several secondary outcomes assessed symptoms, respiratory function, and number of severe exacerbations.
Data analysis showed that patients in the budesonide groups had similar rates of annualized exacerbation, both of which were significantly better than the exacerbation rate in the albuterol-only group; the absolute rate of exacerbations per patient per year was 0.175, 0.195, and 0.400 for budesonide maintenance, budesonide/formoterol, and albuterol only, respectively. Similarly, the median fraction of exhaled nitric oxide (FENO) was lower in the budesonide groups than in the albuterol-only group. Patients in the budesonide/formoterol group had a 56% lower relative risk of severe pulmonary exacerbation than patients in the budesonide maintenance group and a 60% lower relative risk than the albuterol group. However, maintenance budesonide provided better symptom relief than budesonide/formoterol, “which suggests that for the patient for whom asthma symptoms rather than exacerbations are the most bothersome, maintenance treatment has value,” the investigators wrote (New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963).
“The findings of our trial are consistent with evidence regarding the treatment of moderate and severe asthma – that maintenance and reliever therapy” with inhaled glucocorticoid/formoterol “results in a lower risk of severe exacerbations than maintenance therapy with an inhaled glucocorticoid–[long-acting beta agonist] and as-needed SABA,” the investigators concluded.
SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
SOURCES: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
FROM ATS 2019
Key clinical point: Inhaled glucocorticoid/formoterol therapy for mild persistent or intermittent asthma is effective, but responses to steroids differ among patients with high versus low levels of eosinophils in sputum.
Major finding: Among patients with low eosinophils levels of, 57% responded better to mometasone versus 43% who responded better to placebo. Among those with high eosinophil levels, 74% responded better to mometasone versus 26% who responded better to placebo.
Study details: The SIENA study included 295 patients with mild, persistent asthma and eosinophils measured in sputum samples, and the Novel START study included 688 patients with the mild persistent or intermittent asthma, measured by annualized exacerbation rate.
Disclosures: SIENA was funded by National Heart, Lung, and Blood Institute, with medications provided by Boehringer Ingelheim, Merck, and Teva; the investigators reported relationships with Sanofi, Vectura, Circassia, DBV Technologies, and others. Novel START was funded by AstraZeneca and the Health Research Council of New Zealand; the investigators reported relationships with GlaxoSmithKline, Genentech, Theravance Biopharma, and others.
Sources: Beasley et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1901963; Lazarus et al. New Engl J Med. 2019 May 19. doi: 10.1056/NEJMoa1814917.
Noninfected children of HIV-positive mothers have high rates of obesity
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
NEW ORLEANS – than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.
Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.
In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.
For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).
These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.
Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).
REPORTING FROM ENDO 2019
In obesity-related asthma, a new hormonal target
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
NEW ORLEANS – A hormone that is oversecreted in obesity may provide a pathway from adipose to lung tissue in individuals with both obesity and asthma, according to new research presented at the annual meeting of the Endocrine Society.
“Obesity-related asthma is a really understudied and new phenomenon. It’s a unique complication of obesity,” said Furkan Burak, MD, in a video interview after an obesity-focused press conference.
“In addition to being a standalone disease, obesity mostly comes as a package. And that’s the problem,” said Dr. Burak, pointing to obesity-related asthma’s clustering with diseases such as diabetes and atherosclerosis.
Asthma affects 10% of the world population, and it’s becoming increasingly understood that said Dr. Burak, an endocrinology fellow at Brigham and Women’s Hospital, Boston.
“There are two types of asthma related to obesity,” he said. Classic allergic asthma can get worse with obesity; however, asthma can sometimes occur de novo in adults, particularly women, with obesity. “What is important is … that they are less responsive to classic treatments,” such as steroids and beta-agonists. “And the problem is not small: Of asthmatics, 40% are obese. It’s a therapeutic problem, and we are not able to treat them well.”
The fatty acid binding protein 4, aP2, a hormone that is released by adipose tissue, travels to distant organs and regulates metabolic responses. Levels of aP2 are known to be increased in obesity, particularly in individuals with asthma, said Dr. Burak.
Citing work done at Brigham and Women’s Hospital and at Boston’s Harvard Medical School, as well as elsewhere, Dr. Burak and his collaborators noted in the abstract accompanying the presentation that “increased serum aP2 levels strongly correlate with poor metabolic, inflammatory, and cardiovascular outcomes in multiple independent human studies.”
Dr. Burak said he and his colleagues are trying to sort out “how a fat-tissue–borne hormone could potentially cause a problem in the lung.”
A big clue came with the discovery that patients with asthma and obesity have elevated levels of aP2 within their airways when bronchoalveolar lavage is performed, suggesting that the hormone may be the pathological mediator linking obesity to asthma – “a direct link between the fat tissue and the lung,” he said.
Serum aP2 levels were available from the Nurse’s Health Study, so Dr. Burak and his colleagues looked at those levels in randomly selected study participants. “We found that aP2 levels were elevated 25.6% – significantly – in asthmatics, compared with nonasthmatics, but only in obese and overweight [participants, and] not in lean” participants, he said.
Dr. Burak and his colleagues compared 525 individuals with body mass indices of less than 25 kg/m2, of whom 15 had asthma, with 385 individuals with body mass indices of more than 25, of whom 15 of whom had asthma.
Collecting bronchoalveolar lavage fluid from individuals with asthma showed a mean increase of 23% in aP2 levels in patients with obesity compared with lean individuals.
These data taken together show both systemic and local elevations of aP2 in human obesity. “That could contribute to the airway hyperreactivity and to the asthma pathogenesis,” which would confirm findings from animal studies, said Dr. Burak.
Further investigation will focus on individuals who are haploinsufficient for aP2. The group already is known to have lower risk for dyslipidemia, diabetes, and cardiovascular disease, but Dr. Burak and his collaborators also will determine whether asthma incidence is also lower.
The eventual goal is to attack aP2 as a therapeutic target. “Can we inhibit and target aP2 therapeutically in the context of obesity to treat obesity-related asthma? We have a big hope for that.”
Dr. Burak and his colleagues reported no disclosures or financial conflicts of interest.
SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.
REPORTING FROM ENDO 2019
