Asthma

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.

moodboard/ThinkStock

“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.

moodboard/ThinkStock

“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.

moodboard/ThinkStock

“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 – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, 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 – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, 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 – Children with cystic fibrosis or asthma report sleep interruptions 1 or 2 nights a week caused by their symptoms, 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 – A molecule that boosts innate viral immunity may protect elderly people with asthma from the root cause of most exacerbations – viral respiratory tract infections.

Michele G. Sullivan/MDedge News

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.

msullivan@mdedge.com

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.

Michele G. Sullivan/MDedge News

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.

msullivan@mdedge.com

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.

Michele G. Sullivan/MDedge News

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.

msullivan@mdedge.com

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.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, 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.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, 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.

Patients with mild asthma who rely solely on short-acting beta2-agonists (SABAs) to control their asthma symptoms remain at increased risk of exacerbations, 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.

NEW ORLEANS – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease 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 – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease 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 – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease 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 – 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 obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, 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.

koakes@mdedge.com

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 obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, 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.

koakes@mdedge.com

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 obesity-related, adult-onset asthma is a separate disease entity from allergic asthma, which usually begins in childhood, 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.

koakes@mdedge.com

SOURCE: Burak MF et al. ENDO 2019, Session OR01-1.

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Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

Even the best physicians make mistakes.

Each of us can recall a patient for whom our initial diagnosis was incorrect, or conversely, where we uncovered the correct diagnosis. My memorable mistake was missing an obvious case of hypothyroidism, and my happier encounter was correcting an incorrect diagnosis of asthma when the patient actually had primary pulmonary fibrosis. These patients came to mind as I read this month’s cover story, “COPD and asthma: Diagnostic accuracy requires spirometry.”

In a previous editorial, “When our biases derail the diagnosis,”¹ I discussed types of cognitive bias that can lead us to the wrong conclusion. Today, I want to address diagnostic errors in medicine as a patient safety issue.

Listening closely to the patient's and family's concerns can lead in a direction other than my initial impression.

The patient safety movement gained traction in 1999 with the publication of the Institute of Medicine (IOM, now National Academy of Medicine) report, To Err is Human: Building a Safer Health System. That report focused on health care system issues and had little to offer regarding improving diagnoses. It was not until 2015, with the publication of the IOM report Improving Diagnosis in Health Care, that serious national attention was directed to accurate diagnosis. It is worth reading the summary of this report, which includes 8 goals and is available at nas.edu/improvingdiagnosis.

The recommendations most pertinent to family physicians are to: 1) facilitate more effective teamwork among health care professionals, patients, and families, 2) teach health care professionals about the diagnostic process, 3) ensure that technology supports proper diagnosis, 4) establish a work culture that supports diagnostic processes, and 5) identify diagnostic errors and learn from them.

Teamwork. The first recommendation is intriguing because the focus on teamwork includes patients and their families. I have found that listening closely to the patient’s and family’s concerns can lead me in a direction other than my initial impression—especially when they are insistent about a particular diagnosis.

Technology. Despite all of their “warts,” electronic health records are gradually incorporating clinical decision support tools that really do help steer us in the right direction. I have found that electronic point-of-care references can be very helpful in establishing an accurate diagnosis in the exam room—and can help convince patients that my diagnosis is correct when they read it for themselves!

Continue to: Finally, discussing our mistakes...

Finally, discussing our mistakes openly with our colleagues helps us—and them—to avoid that mistake in the future. Let’s be sure to keep that dialogue open. And let’s continue to refine our diagnostic skills so that we can continue to keep our patients safe.

SAN FRANCISCO – Less than 4% of people who undergo drug-allergy testing are positive and need to avoid the drug in the future, but many patients who undergo drug-allergy testing and have a negative result cling to their allergic status and struggle with letting go.

Mitchel L. Zoler/MDedge News

New findings suggest that preexisting anxiety or depression plays a role in some people who refuse to believe a negative drug-allergy result, which suggests that these people may need a more tailored intervention to drug-allergy testing and its aftermath, including some type of behavioral intervention.

“Underlying anxiety and depression may reduce the effectiveness of negative drug-allergy evaluation and functional delabeling,” Christine Rukasin, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. “In the future, tailored drug-allergy evaluation, behavioral interventions, targeted follow-up communication, and patient education appear necessary to improve the sustained effectiveness of a negative drug-allergy and functional delabeling,” said Dr. Rukasin, an allergy immunology physician at Vanderbilt University in Nashville, Tenn.

The results showed that some people who undergo drug allergy testing “have a high anxiety state and don’t feel comfortable regardless of their test result,” she said in an interview. “This is not where one size fits all. We usually perform a single, oral drug challenge and then pronounce the person free of allergy if the result was negative. We need to better anticipate how effective a drug evaluation will be for someone; will they believe the result?” Individual patients, especially those with diagnosed anxiety or depression, may need multiple challenge tests, both oral and skin, before they believe a negative result, and they may also need referral to a behavioral health specialist, she said.

Dr. Rukasin and her associates ran their study with 100 people who underwent assessment at the Vanderbilt drug-allergy clinic and completed a set of questionnaires. The range of suspected drug allergies included 40% with a suspected reaction to penicillin, 22% to a sulfa-containing drug, 17% to a cephalosporin, 8% to another antibiotic, 7% to an NSAID, and the remainder to other drugs. The 100 participants included 57 people without diagnosed anxiety or depression, 31 diagnosed with anxiety, and 33 diagnosed with depression; some patients had diagnoses for both anxiety and depression.

The questionnaire results from before and after drug-allergy testing showed an apparent association between anxiety, depression, and a decreased willingness to believe the results of a negative drug-allergy test. For example, when posed with the prospect of finding out they were not allergic to the tested drug, 24% of the people with anxiety and 20% of those with depression said that they still would not take the medication if it were prescribed to them, compared with 7% of those without anxiety or depression who gave this response.

Many patients who come to the drug-allergy clinic are scared and worried. “We want to dig deeper, to better help these patients,” Dr. Rukasin said. This is the first reported study to evaluate anxiety in the setting of drug-allergy testing. Further insight into ways to improve the effectiveness of drug-allergy testing hopefully will come from additional analysis of the findings.

Dr. Rukasin had no relevant financial disclosures.

mzoler@mdedge.com

SOURCE: Rukasin C et al. J Allergy Clin Immunol. 2019 Feb;143(2):AB428.

SAN FRANCISCO – Less than 4% of people who undergo drug-allergy testing are positive and need to avoid the drug in the future, but many patients who undergo drug-allergy testing and have a negative result cling to their allergic status and struggle with letting go.

Mitchel L. Zoler/MDedge News

New findings suggest that preexisting anxiety or depression plays a role in some people who refuse to believe a negative drug-allergy result, which suggests that these people may need a more tailored intervention to drug-allergy testing and its aftermath, including some type of behavioral intervention.

“Underlying anxiety and depression may reduce the effectiveness of negative drug-allergy evaluation and functional delabeling,” Christine Rukasin, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. “In the future, tailored drug-allergy evaluation, behavioral interventions, targeted follow-up communication, and patient education appear necessary to improve the sustained effectiveness of a negative drug-allergy and functional delabeling,” said Dr. Rukasin, an allergy immunology physician at Vanderbilt University in Nashville, Tenn.

The results showed that some people who undergo drug allergy testing “have a high anxiety state and don’t feel comfortable regardless of their test result,” she said in an interview. “This is not where one size fits all. We usually perform a single, oral drug challenge and then pronounce the person free of allergy if the result was negative. We need to better anticipate how effective a drug evaluation will be for someone; will they believe the result?” Individual patients, especially those with diagnosed anxiety or depression, may need multiple challenge tests, both oral and skin, before they believe a negative result, and they may also need referral to a behavioral health specialist, she said.

Dr. Rukasin and her associates ran their study with 100 people who underwent assessment at the Vanderbilt drug-allergy clinic and completed a set of questionnaires. The range of suspected drug allergies included 40% with a suspected reaction to penicillin, 22% to a sulfa-containing drug, 17% to a cephalosporin, 8% to another antibiotic, 7% to an NSAID, and the remainder to other drugs. The 100 participants included 57 people without diagnosed anxiety or depression, 31 diagnosed with anxiety, and 33 diagnosed with depression; some patients had diagnoses for both anxiety and depression.

The questionnaire results from before and after drug-allergy testing showed an apparent association between anxiety, depression, and a decreased willingness to believe the results of a negative drug-allergy test. For example, when posed with the prospect of finding out they were not allergic to the tested drug, 24% of the people with anxiety and 20% of those with depression said that they still would not take the medication if it were prescribed to them, compared with 7% of those without anxiety or depression who gave this response.

Many patients who come to the drug-allergy clinic are scared and worried. “We want to dig deeper, to better help these patients,” Dr. Rukasin said. This is the first reported study to evaluate anxiety in the setting of drug-allergy testing. Further insight into ways to improve the effectiveness of drug-allergy testing hopefully will come from additional analysis of the findings.

Dr. Rukasin had no relevant financial disclosures.

mzoler@mdedge.com

SOURCE: Rukasin C et al. J Allergy Clin Immunol. 2019 Feb;143(2):AB428.

SAN FRANCISCO – Less than 4% of people who undergo drug-allergy testing are positive and need to avoid the drug in the future, but many patients who undergo drug-allergy testing and have a negative result cling to their allergic status and struggle with letting go.

Mitchel L. Zoler/MDedge News

New findings suggest that preexisting anxiety or depression plays a role in some people who refuse to believe a negative drug-allergy result, which suggests that these people may need a more tailored intervention to drug-allergy testing and its aftermath, including some type of behavioral intervention.

“Underlying anxiety and depression may reduce the effectiveness of negative drug-allergy evaluation and functional delabeling,” Christine Rukasin, MD, said while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. “In the future, tailored drug-allergy evaluation, behavioral interventions, targeted follow-up communication, and patient education appear necessary to improve the sustained effectiveness of a negative drug-allergy and functional delabeling,” said Dr. Rukasin, an allergy immunology physician at Vanderbilt University in Nashville, Tenn.

The results showed that some people who undergo drug allergy testing “have a high anxiety state and don’t feel comfortable regardless of their test result,” she said in an interview. “This is not where one size fits all. We usually perform a single, oral drug challenge and then pronounce the person free of allergy if the result was negative. We need to better anticipate how effective a drug evaluation will be for someone; will they believe the result?” Individual patients, especially those with diagnosed anxiety or depression, may need multiple challenge tests, both oral and skin, before they believe a negative result, and they may also need referral to a behavioral health specialist, she said.

Dr. Rukasin and her associates ran their study with 100 people who underwent assessment at the Vanderbilt drug-allergy clinic and completed a set of questionnaires. The range of suspected drug allergies included 40% with a suspected reaction to penicillin, 22% to a sulfa-containing drug, 17% to a cephalosporin, 8% to another antibiotic, 7% to an NSAID, and the remainder to other drugs. The 100 participants included 57 people without diagnosed anxiety or depression, 31 diagnosed with anxiety, and 33 diagnosed with depression; some patients had diagnoses for both anxiety and depression.

The questionnaire results from before and after drug-allergy testing showed an apparent association between anxiety, depression, and a decreased willingness to believe the results of a negative drug-allergy test. For example, when posed with the prospect of finding out they were not allergic to the tested drug, 24% of the people with anxiety and 20% of those with depression said that they still would not take the medication if it were prescribed to them, compared with 7% of those without anxiety or depression who gave this response.

Many patients who come to the drug-allergy clinic are scared and worried. “We want to dig deeper, to better help these patients,” Dr. Rukasin said. This is the first reported study to evaluate anxiety in the setting of drug-allergy testing. Further insight into ways to improve the effectiveness of drug-allergy testing hopefully will come from additional analysis of the findings.

Dr. Rukasin had no relevant financial disclosures.

mzoler@mdedge.com

SOURCE: Rukasin C et al. J Allergy Clin Immunol. 2019 Feb;143(2):AB428.

SAN FRANCISCO – Clinicians safely used epicutaneous immunotherapy to resolve eosinophilic esophagitis in children and teens secondary to milk consumption in a placebo-controlled, pilot study that included 20 patients.

Mitchel L. Zoler/MDedge News

Following the randomized phase of the study, all 19 patients who continued to participate began an 11-month open-label phase of epicutaneous immunotherapy to milk. At the end of this open-label phase, nine patients (47%) followed in this phase showed a substantial cut in their eosinophilic esophagitis (EoE) response to milk, with fewer than 15 eosinophils in a high-powered field, said Jonathan M. Spergel, MD, chief of the allergy section and Stuart E. Starr Chair of Pediatrics at the Children’s Hospital of Philadelphia, while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. An immunologic response of this sort would likely correlate with substantial clinical benefit.

“I’m happy with a 47% response,” Dr. Spergel said, adding that the responding patients “tolerate milk without symptoms, and there is really no risk” from this form of immunotherapy, which produced no serious adverse effects and caused 1 of 15 patients to stop treatment because of a treatment-related effect during the randomized phase. The most common adverse reaction was gastrointestinal symptoms, but these were just marginally more common among patients on active treatment than in control patients.

In contrast, oral immunotherapy with milk has been ineffective in children with an EoE milk reaction, and results from subcutaneous or sublingual immunotherapy for this form of milk allergy haven’t been reported, he said. The most common, current approaches to managing EoE from milk in children are either milk avoidance or treatment to reduce inflammation.

The epicutaneous approach “uses substantially lower dosing [micrograms vs. milligrams], avoids oral allergen ingestion, and may have a more advantageous adverse event profile and better adherence than other therapies,” according to a recent report that tested epicutaneous immunotherapy for peanut allergy in a phase 3 trial with 356 children (JAMA. 2019 Feb 22. doi: 10.1001/jama.2019.1113). The Viaskin Milk system tested in the current milk study involves placing a disc coated with 500 mcg of lyophilized milk protein on the skin for a gradually increasing number of hours daily until the disc is worn continuously, with daily changes of the disk. On the skin, the protein on the disk interacts with epidermal Langerhans cells to trigger desensitization.

The Milk Patch for Eosinophilic Esophagitis (SMILEE) study enrolled 20 patients at Children’s Hospital aged 4-17 years old and had milk-induced EoE, and randomized 15 to receive active epicutaneous immunotherapy to milk and 5 to receive placebo treatment. The protocol called for 9 month of epicutaneous immunotherapy without any milk exposure, followed by 2 months of continued treatment coupled with at least 240 mL of milk consumption daily. At the end of 2 months the researchers performed an esophageal biopsy on each patient to determine eosinophil density in the tissue. The study’s primary endpoint was the number of eosinophils in a high-powered field.

During the randomized phase, 8 of the 15 patients assigned to active treatment and 3 of 5 patients assigned to the placebo arm had violations of the treatment protocol, the diet protocol, or both. A per protocol analysis that focused on the seven actively treated and two placebo patients who adhered to the protocol showed a mean eosinophil count of 26 cells in patients on active treatment and 95 cells among the controls, a statistically significant difference. However, for the intention-to-treat analysis, which included all 20 enrolled patients, the primary endpoint showed no significant difference in eosinophil counts between the two study arms.

Although Dr. Spergel said that he was not aware of the developing company’s plans for further study of epicutaneous milk immunotherapy, from a scientific standpoint the next step should be a phase 2 or phase 2/3 trial for safety and efficacy. EoE was historically considered a rare disease, but a 2015 review of the condition called it “one of the most common conditions diagnosed during the assessment of feeding problems in children” (New Engl J Med. 2015 Oct 22;373[17]:1640-8).

The study was funded by DBV Technologies, which is developing the epicutaneous immunotherapy system. Dr. Spergel has been a consultant to and has received research funding from DBV Technologies.

mzoler@mdedge.com

SOURCE: Spergel JM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB430.

SAN FRANCISCO – Clinicians safely used epicutaneous immunotherapy to resolve eosinophilic esophagitis in children and teens secondary to milk consumption in a placebo-controlled, pilot study that included 20 patients.

Mitchel L. Zoler/MDedge News

Following the randomized phase of the study, all 19 patients who continued to participate began an 11-month open-label phase of epicutaneous immunotherapy to milk. At the end of this open-label phase, nine patients (47%) followed in this phase showed a substantial cut in their eosinophilic esophagitis (EoE) response to milk, with fewer than 15 eosinophils in a high-powered field, said Jonathan M. Spergel, MD, chief of the allergy section and Stuart E. Starr Chair of Pediatrics at the Children’s Hospital of Philadelphia, while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. An immunologic response of this sort would likely correlate with substantial clinical benefit.

“I’m happy with a 47% response,” Dr. Spergel said, adding that the responding patients “tolerate milk without symptoms, and there is really no risk” from this form of immunotherapy, which produced no serious adverse effects and caused 1 of 15 patients to stop treatment because of a treatment-related effect during the randomized phase. The most common adverse reaction was gastrointestinal symptoms, but these were just marginally more common among patients on active treatment than in control patients.

In contrast, oral immunotherapy with milk has been ineffective in children with an EoE milk reaction, and results from subcutaneous or sublingual immunotherapy for this form of milk allergy haven’t been reported, he said. The most common, current approaches to managing EoE from milk in children are either milk avoidance or treatment to reduce inflammation.

The epicutaneous approach “uses substantially lower dosing [micrograms vs. milligrams], avoids oral allergen ingestion, and may have a more advantageous adverse event profile and better adherence than other therapies,” according to a recent report that tested epicutaneous immunotherapy for peanut allergy in a phase 3 trial with 356 children (JAMA. 2019 Feb 22. doi: 10.1001/jama.2019.1113). The Viaskin Milk system tested in the current milk study involves placing a disc coated with 500 mcg of lyophilized milk protein on the skin for a gradually increasing number of hours daily until the disc is worn continuously, with daily changes of the disk. On the skin, the protein on the disk interacts with epidermal Langerhans cells to trigger desensitization.

The Milk Patch for Eosinophilic Esophagitis (SMILEE) study enrolled 20 patients at Children’s Hospital aged 4-17 years old and had milk-induced EoE, and randomized 15 to receive active epicutaneous immunotherapy to milk and 5 to receive placebo treatment. The protocol called for 9 month of epicutaneous immunotherapy without any milk exposure, followed by 2 months of continued treatment coupled with at least 240 mL of milk consumption daily. At the end of 2 months the researchers performed an esophageal biopsy on each patient to determine eosinophil density in the tissue. The study’s primary endpoint was the number of eosinophils in a high-powered field.

During the randomized phase, 8 of the 15 patients assigned to active treatment and 3 of 5 patients assigned to the placebo arm had violations of the treatment protocol, the diet protocol, or both. A per protocol analysis that focused on the seven actively treated and two placebo patients who adhered to the protocol showed a mean eosinophil count of 26 cells in patients on active treatment and 95 cells among the controls, a statistically significant difference. However, for the intention-to-treat analysis, which included all 20 enrolled patients, the primary endpoint showed no significant difference in eosinophil counts between the two study arms.

Although Dr. Spergel said that he was not aware of the developing company’s plans for further study of epicutaneous milk immunotherapy, from a scientific standpoint the next step should be a phase 2 or phase 2/3 trial for safety and efficacy. EoE was historically considered a rare disease, but a 2015 review of the condition called it “one of the most common conditions diagnosed during the assessment of feeding problems in children” (New Engl J Med. 2015 Oct 22;373[17]:1640-8).

The study was funded by DBV Technologies, which is developing the epicutaneous immunotherapy system. Dr. Spergel has been a consultant to and has received research funding from DBV Technologies.

mzoler@mdedge.com

SOURCE: Spergel JM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB430.

SAN FRANCISCO – Clinicians safely used epicutaneous immunotherapy to resolve eosinophilic esophagitis in children and teens secondary to milk consumption in a placebo-controlled, pilot study that included 20 patients.

Mitchel L. Zoler/MDedge News

Following the randomized phase of the study, all 19 patients who continued to participate began an 11-month open-label phase of epicutaneous immunotherapy to milk. At the end of this open-label phase, nine patients (47%) followed in this phase showed a substantial cut in their eosinophilic esophagitis (EoE) response to milk, with fewer than 15 eosinophils in a high-powered field, said Jonathan M. Spergel, MD, chief of the allergy section and Stuart E. Starr Chair of Pediatrics at the Children’s Hospital of Philadelphia, while presenting a poster at the annual meeting of the American Academy of Allergy, Asthma, and Immunology. An immunologic response of this sort would likely correlate with substantial clinical benefit.

“I’m happy with a 47% response,” Dr. Spergel said, adding that the responding patients “tolerate milk without symptoms, and there is really no risk” from this form of immunotherapy, which produced no serious adverse effects and caused 1 of 15 patients to stop treatment because of a treatment-related effect during the randomized phase. The most common adverse reaction was gastrointestinal symptoms, but these were just marginally more common among patients on active treatment than in control patients.

In contrast, oral immunotherapy with milk has been ineffective in children with an EoE milk reaction, and results from subcutaneous or sublingual immunotherapy for this form of milk allergy haven’t been reported, he said. The most common, current approaches to managing EoE from milk in children are either milk avoidance or treatment to reduce inflammation.

The epicutaneous approach “uses substantially lower dosing [micrograms vs. milligrams], avoids oral allergen ingestion, and may have a more advantageous adverse event profile and better adherence than other therapies,” according to a recent report that tested epicutaneous immunotherapy for peanut allergy in a phase 3 trial with 356 children (JAMA. 2019 Feb 22. doi: 10.1001/jama.2019.1113). The Viaskin Milk system tested in the current milk study involves placing a disc coated with 500 mcg of lyophilized milk protein on the skin for a gradually increasing number of hours daily until the disc is worn continuously, with daily changes of the disk. On the skin, the protein on the disk interacts with epidermal Langerhans cells to trigger desensitization.

The Milk Patch for Eosinophilic Esophagitis (SMILEE) study enrolled 20 patients at Children’s Hospital aged 4-17 years old and had milk-induced EoE, and randomized 15 to receive active epicutaneous immunotherapy to milk and 5 to receive placebo treatment. The protocol called for 9 month of epicutaneous immunotherapy without any milk exposure, followed by 2 months of continued treatment coupled with at least 240 mL of milk consumption daily. At the end of 2 months the researchers performed an esophageal biopsy on each patient to determine eosinophil density in the tissue. The study’s primary endpoint was the number of eosinophils in a high-powered field.

During the randomized phase, 8 of the 15 patients assigned to active treatment and 3 of 5 patients assigned to the placebo arm had violations of the treatment protocol, the diet protocol, or both. A per protocol analysis that focused on the seven actively treated and two placebo patients who adhered to the protocol showed a mean eosinophil count of 26 cells in patients on active treatment and 95 cells among the controls, a statistically significant difference. However, for the intention-to-treat analysis, which included all 20 enrolled patients, the primary endpoint showed no significant difference in eosinophil counts between the two study arms.

Although Dr. Spergel said that he was not aware of the developing company’s plans for further study of epicutaneous milk immunotherapy, from a scientific standpoint the next step should be a phase 2 or phase 2/3 trial for safety and efficacy. EoE was historically considered a rare disease, but a 2015 review of the condition called it “one of the most common conditions diagnosed during the assessment of feeding problems in children” (New Engl J Med. 2015 Oct 22;373[17]:1640-8).

The study was funded by DBV Technologies, which is developing the epicutaneous immunotherapy system. Dr. Spergel has been a consultant to and has received research funding from DBV Technologies.

mzoler@mdedge.com

SOURCE: Spergel JM et al. J Allergy Clin Immunol. 2019 Feb;143[2]:AB430.