Asthma

Inhaler technique may not be the cause of chronic uncontrolled asthma in a population of low-income, inner-city adults with the condition, a study has found.

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“Incorrect inhaler technique cannot explain the poor disease control in our patient population,” wrote Patrick K. Gleeson, MD, of the University of Pennsylvania, Philadelphia, and coinvestigators. Their report is in the Journal of Allergy and Clinical Immunology: In Practice. “In individuals with poorly controlled asthma, other factors contributing to disease mortality must be considered.”

The 586 patients in the study were observed using their inhalers, and their technique was scored by way of a checklist developed for the study. Inhaler technique – widely regarded as a risk factor for poor disease control – was “better than expected,” the investigators reported, with 56% of patients using metered dose inhalers and 64% of those using dry powder inhalers not making any errors.

“The seeming disassociation between subjects’ asthma control and inhaler technique is counterintuitive, and may be explained by important baseline characteristics in our patients,” they wrote. For instance, participants had suboptimal living conditions in lower income Philadelphia neighborhoods. Almost a quarter – 23% – were current smokers, and almost half were Medicaid recipients. In addition, their mean body mass index was 35.1 kg/m².

The investigators hypothesized that patients with lower health literacy would have poorer technique but found instead that technique did not vary by reading comprehension or numeracy levels.

More than half of the adults in the study had uncontrolled asthma as defined by prednisone use, an emergency department visit, or a hospitalization for asthma in the past 12 months. A subset had moderate to severe disease per a physician’s diagnosis, forced expiratory volume in 1 second less than 80% predicted, and improvement with a bronchodilator. All patients, however, were considered to have uncontrolled asthma.

There is “uncertainty” in the field about how to measure inhaler technique, and the technique checklist used in the study “may have omitted potentially important errors,” the investigators noted. Still, “good technique predominated among our [population of vulnerable patients].”

The project was supported through awards from the National Institutes of Health/National Heart, Lung, and Blood Institute and the Patient-Centered Outcomes Research Institute.

Coinvestigator Andrea J. Apter, MD, reported that she consults for UpToDate and is an associate editor for the journal. Coinvestigator Knashawn H. Morales, ScD, reported owning stock in Altria Group, British American Tobacco, and Philip Morris International. The other authors reported having no conflicts of interest.
 

SOURCE: Gleeson PK. J Allergy Clin Immunol Pract. 2019 Jun 5. doi: 10.1016/j.jaip.2019.05.048.

Inhaler technique may not be the cause of chronic uncontrolled asthma in a population of low-income, inner-city adults with the condition, a study has found.

Medioimages/Photodisc/ThinkStock

“Incorrect inhaler technique cannot explain the poor disease control in our patient population,” wrote Patrick K. Gleeson, MD, of the University of Pennsylvania, Philadelphia, and coinvestigators. Their report is in the Journal of Allergy and Clinical Immunology: In Practice. “In individuals with poorly controlled asthma, other factors contributing to disease mortality must be considered.”

The 586 patients in the study were observed using their inhalers, and their technique was scored by way of a checklist developed for the study. Inhaler technique – widely regarded as a risk factor for poor disease control – was “better than expected,” the investigators reported, with 56% of patients using metered dose inhalers and 64% of those using dry powder inhalers not making any errors.

“The seeming disassociation between subjects’ asthma control and inhaler technique is counterintuitive, and may be explained by important baseline characteristics in our patients,” they wrote. For instance, participants had suboptimal living conditions in lower income Philadelphia neighborhoods. Almost a quarter – 23% – were current smokers, and almost half were Medicaid recipients. In addition, their mean body mass index was 35.1 kg/m².

The investigators hypothesized that patients with lower health literacy would have poorer technique but found instead that technique did not vary by reading comprehension or numeracy levels.

More than half of the adults in the study had uncontrolled asthma as defined by prednisone use, an emergency department visit, or a hospitalization for asthma in the past 12 months. A subset had moderate to severe disease per a physician’s diagnosis, forced expiratory volume in 1 second less than 80% predicted, and improvement with a bronchodilator. All patients, however, were considered to have uncontrolled asthma.

There is “uncertainty” in the field about how to measure inhaler technique, and the technique checklist used in the study “may have omitted potentially important errors,” the investigators noted. Still, “good technique predominated among our [population of vulnerable patients].”

The project was supported through awards from the National Institutes of Health/National Heart, Lung, and Blood Institute and the Patient-Centered Outcomes Research Institute.

Coinvestigator Andrea J. Apter, MD, reported that she consults for UpToDate and is an associate editor for the journal. Coinvestigator Knashawn H. Morales, ScD, reported owning stock in Altria Group, British American Tobacco, and Philip Morris International. The other authors reported having no conflicts of interest.
 

SOURCE: Gleeson PK. J Allergy Clin Immunol Pract. 2019 Jun 5. doi: 10.1016/j.jaip.2019.05.048.

Inhaler technique may not be the cause of chronic uncontrolled asthma in a population of low-income, inner-city adults with the condition, a study has found.

Medioimages/Photodisc/ThinkStock

“Incorrect inhaler technique cannot explain the poor disease control in our patient population,” wrote Patrick K. Gleeson, MD, of the University of Pennsylvania, Philadelphia, and coinvestigators. Their report is in the Journal of Allergy and Clinical Immunology: In Practice. “In individuals with poorly controlled asthma, other factors contributing to disease mortality must be considered.”

The 586 patients in the study were observed using their inhalers, and their technique was scored by way of a checklist developed for the study. Inhaler technique – widely regarded as a risk factor for poor disease control – was “better than expected,” the investigators reported, with 56% of patients using metered dose inhalers and 64% of those using dry powder inhalers not making any errors.

“The seeming disassociation between subjects’ asthma control and inhaler technique is counterintuitive, and may be explained by important baseline characteristics in our patients,” they wrote. For instance, participants had suboptimal living conditions in lower income Philadelphia neighborhoods. Almost a quarter – 23% – were current smokers, and almost half were Medicaid recipients. In addition, their mean body mass index was 35.1 kg/m².

The investigators hypothesized that patients with lower health literacy would have poorer technique but found instead that technique did not vary by reading comprehension or numeracy levels.

More than half of the adults in the study had uncontrolled asthma as defined by prednisone use, an emergency department visit, or a hospitalization for asthma in the past 12 months. A subset had moderate to severe disease per a physician’s diagnosis, forced expiratory volume in 1 second less than 80% predicted, and improvement with a bronchodilator. All patients, however, were considered to have uncontrolled asthma.

There is “uncertainty” in the field about how to measure inhaler technique, and the technique checklist used in the study “may have omitted potentially important errors,” the investigators noted. Still, “good technique predominated among our [population of vulnerable patients].”

The project was supported through awards from the National Institutes of Health/National Heart, Lung, and Blood Institute and the Patient-Centered Outcomes Research Institute.

Coinvestigator Andrea J. Apter, MD, reported that she consults for UpToDate and is an associate editor for the journal. Coinvestigator Knashawn H. Morales, ScD, reported owning stock in Altria Group, British American Tobacco, and Philip Morris International. The other authors reported having no conflicts of interest.
 

SOURCE: Gleeson PK. J Allergy Clin Immunol Pract. 2019 Jun 5. doi: 10.1016/j.jaip.2019.05.048.

A needs- and barriers-based intervention that addressed psychosocial, physical, cognitive, and environmental barriers to self-management of asthma for older adults was successful in improving asthma outcomes and management, a recent trial has shown.

Medioimages/Photodisc/ThinkStock

“This study demonstrates the value of patient centeredness and care coaching in supporting older adults with asthma and for ongoing efforts to engage patients in care delivery design and personalization,” Alex D. Federman, MD, of the division of general internal medicine at Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote in their study, which was published in JAMA Internal Medicine. “It also highlights the challenges of engaging vulnerable populations in self-management support, including modest retention rates and reduced impact over time despite repeated encounters designed to sustain its effects.”

The researchers said older adults often have difficulty with self-management tasks like inhaler technique and use of inhaled corticosteroids, which can be caused by various psychosocial, physical, cognitive, or environmental barriers. However, an attempt at creating self-management tools around specific problems, rather than generalized training, has not been traditionally attempted, they noted.

For the SAMBA trial, Dr. Federman and colleagues enrolled 391 patients who were randomized to receive a home-based intervention, clinic-based intervention, or usual care, where an asthma care coach would identify the barriers to asthma control, train the patient in areas of improvement, and provide reinforcement when necessary. Patients were at least age 60 years (15.1% men) with uncontrolled asthma in New York City and were enrolled between February 2014 and December 2017. Researchers used the Mini Asthma Quality of Life Questionnaire, Asthma Control Test, metered dose inhaler technique, Medication Adherence Rating Scale, and visits to the emergency room to assess outcomes between interventions and usual care, and between home and clinic care. The data was analyzed using the ‘difference in differences’ statistical technique to compare the change differential between the groups.

They found significantly better asthma control scores between the intervention group and the control groups at 3 months (difference-in-differences, 1.2; 95% confidence interval, 0.2-2.2; P = .02), 6 months (D-in-Ds, 1.0; 95% CI, 0.0-2.1; P = .049), and 12 months (D-inDs, 0.6; 95% CI, −0.5 to 1.8; P = .28). Quality of life was significantly improved in the intervention group, compared with control patients (overall effect, chi-squared = 10.5; with 4 degrees of freedom; P = .01), as was adherence to medication (overall effect, chi-squared = 9.5, with 4 degrees of freedom; P = .049), and inhaler technique as measured by correctly completed steps at 12 months (75% vs. 58%). Visits to the emergency room were also lower in the intervention group, compared with the control group (6.2% vs. 12.7%; adjusted odds ratio, 0.8; 95% CI, 0.6-0.99; both P = .03). The researchers noted there were no significant differences between home care and clinic care.

Potential limitations in the study included a lower-than-planned statistical power, 70% retention in the intervention arms, low generalizability of the findings, and lack of blinding on the part of research assistants as well as some improvement in asthma control and outcomes in the control group.

This study was funded in part by the Patient-Centered Outcomes Research Institute. Coauthors Nandini Shroff reported grants from the Patient-Centered Outcomes Research Institute; Michael S. Wolf reported grants from Eli Lilly; and Juan P. Wisnivesky reported personal fees from Sanofi, Quintiles, and Banook, and grants from Sanofi and Quorum. The other authors reported no relevant conflicts of interest.

SOURCE: Federman AD et al. JAMA Intern Med. 2019; doi: 10.1001/jamainternmed.2019.1201.

A needs- and barriers-based intervention that addressed psychosocial, physical, cognitive, and environmental barriers to self-management of asthma for older adults was successful in improving asthma outcomes and management, a recent trial has shown.

Medioimages/Photodisc/ThinkStock

“This study demonstrates the value of patient centeredness and care coaching in supporting older adults with asthma and for ongoing efforts to engage patients in care delivery design and personalization,” Alex D. Federman, MD, of the division of general internal medicine at Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote in their study, which was published in JAMA Internal Medicine. “It also highlights the challenges of engaging vulnerable populations in self-management support, including modest retention rates and reduced impact over time despite repeated encounters designed to sustain its effects.”

The researchers said older adults often have difficulty with self-management tasks like inhaler technique and use of inhaled corticosteroids, which can be caused by various psychosocial, physical, cognitive, or environmental barriers. However, an attempt at creating self-management tools around specific problems, rather than generalized training, has not been traditionally attempted, they noted.

For the SAMBA trial, Dr. Federman and colleagues enrolled 391 patients who were randomized to receive a home-based intervention, clinic-based intervention, or usual care, where an asthma care coach would identify the barriers to asthma control, train the patient in areas of improvement, and provide reinforcement when necessary. Patients were at least age 60 years (15.1% men) with uncontrolled asthma in New York City and were enrolled between February 2014 and December 2017. Researchers used the Mini Asthma Quality of Life Questionnaire, Asthma Control Test, metered dose inhaler technique, Medication Adherence Rating Scale, and visits to the emergency room to assess outcomes between interventions and usual care, and between home and clinic care. The data was analyzed using the ‘difference in differences’ statistical technique to compare the change differential between the groups.

They found significantly better asthma control scores between the intervention group and the control groups at 3 months (difference-in-differences, 1.2; 95% confidence interval, 0.2-2.2; P = .02), 6 months (D-in-Ds, 1.0; 95% CI, 0.0-2.1; P = .049), and 12 months (D-inDs, 0.6; 95% CI, −0.5 to 1.8; P = .28). Quality of life was significantly improved in the intervention group, compared with control patients (overall effect, chi-squared = 10.5; with 4 degrees of freedom; P = .01), as was adherence to medication (overall effect, chi-squared = 9.5, with 4 degrees of freedom; P = .049), and inhaler technique as measured by correctly completed steps at 12 months (75% vs. 58%). Visits to the emergency room were also lower in the intervention group, compared with the control group (6.2% vs. 12.7%; adjusted odds ratio, 0.8; 95% CI, 0.6-0.99; both P = .03). The researchers noted there were no significant differences between home care and clinic care.

Potential limitations in the study included a lower-than-planned statistical power, 70% retention in the intervention arms, low generalizability of the findings, and lack of blinding on the part of research assistants as well as some improvement in asthma control and outcomes in the control group.

This study was funded in part by the Patient-Centered Outcomes Research Institute. Coauthors Nandini Shroff reported grants from the Patient-Centered Outcomes Research Institute; Michael S. Wolf reported grants from Eli Lilly; and Juan P. Wisnivesky reported personal fees from Sanofi, Quintiles, and Banook, and grants from Sanofi and Quorum. The other authors reported no relevant conflicts of interest.

SOURCE: Federman AD et al. JAMA Intern Med. 2019; doi: 10.1001/jamainternmed.2019.1201.

A needs- and barriers-based intervention that addressed psychosocial, physical, cognitive, and environmental barriers to self-management of asthma for older adults was successful in improving asthma outcomes and management, a recent trial has shown.

Medioimages/Photodisc/ThinkStock

“This study demonstrates the value of patient centeredness and care coaching in supporting older adults with asthma and for ongoing efforts to engage patients in care delivery design and personalization,” Alex D. Federman, MD, of the division of general internal medicine at Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote in their study, which was published in JAMA Internal Medicine. “It also highlights the challenges of engaging vulnerable populations in self-management support, including modest retention rates and reduced impact over time despite repeated encounters designed to sustain its effects.”

The researchers said older adults often have difficulty with self-management tasks like inhaler technique and use of inhaled corticosteroids, which can be caused by various psychosocial, physical, cognitive, or environmental barriers. However, an attempt at creating self-management tools around specific problems, rather than generalized training, has not been traditionally attempted, they noted.

For the SAMBA trial, Dr. Federman and colleagues enrolled 391 patients who were randomized to receive a home-based intervention, clinic-based intervention, or usual care, where an asthma care coach would identify the barriers to asthma control, train the patient in areas of improvement, and provide reinforcement when necessary. Patients were at least age 60 years (15.1% men) with uncontrolled asthma in New York City and were enrolled between February 2014 and December 2017. Researchers used the Mini Asthma Quality of Life Questionnaire, Asthma Control Test, metered dose inhaler technique, Medication Adherence Rating Scale, and visits to the emergency room to assess outcomes between interventions and usual care, and between home and clinic care. The data was analyzed using the ‘difference in differences’ statistical technique to compare the change differential between the groups.

They found significantly better asthma control scores between the intervention group and the control groups at 3 months (difference-in-differences, 1.2; 95% confidence interval, 0.2-2.2; P = .02), 6 months (D-in-Ds, 1.0; 95% CI, 0.0-2.1; P = .049), and 12 months (D-inDs, 0.6; 95% CI, −0.5 to 1.8; P = .28). Quality of life was significantly improved in the intervention group, compared with control patients (overall effect, chi-squared = 10.5; with 4 degrees of freedom; P = .01), as was adherence to medication (overall effect, chi-squared = 9.5, with 4 degrees of freedom; P = .049), and inhaler technique as measured by correctly completed steps at 12 months (75% vs. 58%). Visits to the emergency room were also lower in the intervention group, compared with the control group (6.2% vs. 12.7%; adjusted odds ratio, 0.8; 95% CI, 0.6-0.99; both P = .03). The researchers noted there were no significant differences between home care and clinic care.

Potential limitations in the study included a lower-than-planned statistical power, 70% retention in the intervention arms, low generalizability of the findings, and lack of blinding on the part of research assistants as well as some improvement in asthma control and outcomes in the control group.

This study was funded in part by the Patient-Centered Outcomes Research Institute. Coauthors Nandini Shroff reported grants from the Patient-Centered Outcomes Research Institute; Michael S. Wolf reported grants from Eli Lilly; and Juan P. Wisnivesky reported personal fees from Sanofi, Quintiles, and Banook, and grants from Sanofi and Quorum. The other authors reported no relevant conflicts of interest.

SOURCE: Federman AD et al. JAMA Intern Med. 2019; doi: 10.1001/jamainternmed.2019.1201.

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; [email protected].

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; [email protected].

The prevalence of allergic disease in the general population is quite high; 8.3% of adults and children have asthma and 11.4% of children have skin allergies.¹ Food allergies are present in 8% of children and 5% of adults,² and up to 10% of anaphylactic reactions in the United States are due to stinging insects.³

Allergy immunotherapy has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.

Moderate-to-severe food and environmental allergies can negatively affect multiple organ systems and significantly impact morbidity and mortality.⁴ Quality of life and the financial well-being of patients with allergic diseases, as well as that of their families, can also be significantly impacted by these conditions.^4,5 High prevalence and burden of disease mandate that family physicians (FPs) stay up-to-date on the full array of treatment options for allergic diseases. What follows are 6 common questions about allergy immunotherapy (AIT) and the evidence-based answers that will help you to identify and treat appropriate candidates, as well as educate them along the way.

IMAGE: © ALICIA BUELOW

Who is a candidate for AIT?

Patients with moderate-to-severe immunoglobulin (Ig)E-mediated allergies whose symptoms are not adequately controlled by medications and allergen trigger avoidance are candidates for AIT.^6-8 Skin prick/puncture testing provides the most reliable and cost-effective confirmation of allergies that are suspected, based on patient history and clinical assessment for allergic symptoms.⁹ Life-threatening reactions to skin prick/puncture testing are rare.⁹ While in vitro (laboratory) testing for IgE levels to specific antigens may be more convenient for patients and less invasive than skin prick/puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.⁹

What constitutes AIT?

AIT is a disease-modifying treatment that, along with allergen avoidance, can provide long-term remission of allergic disease in certain circumstances.^6,7 Consistent gradual exposure to an allergen helps to dampen the inflammatory reaction driven by T cells and B cells, producing clinical tolerance or desensitization that persists after the discontinuation of AIT.⁸ While subcutaneous immunotherapy (SCIT) is the most widely known type of AIT (ie, allergy shots), there are additional ways that AIT can be administered. These include sublingual immunotherapy (SLIT), venom immunotherapy (VIT), and oral immunotherapy (OIT). The selection of the route of administration depends on the exact nature and symptoms of the allergic condition being treated (TABLE^6,8-12).

AIT involves 2 phases

The first phase is the induction or buildup phase during which patients are given gradually increasing amounts of allergen to induce a protective immunologic response.⁶ After 8 to 28 weeks, the maintenance phase begins, during which continued, consistent allergen exposure is designed to prevent relapse of, and facilitate continued remission of, allergy symptoms.⁶ The maintenance phase of AIT can last 24 to 48 months.^6,10 Certain patients may qualify for an expedited AIT regimen called cluster or rush immunotherapy.⁶

While lab testing may be more convenient for patients and less invasive than skin prick/ puncture testing, it is also less sensitive and less reliable at quantifying the severity of sensitization.

Conventional schedules for AIT involve increasing the dose of allergen given at each visit (1-3 doses/wk), whereas rush dosing involves multiple, increasing doses given in a single extended visit to reach therapeutic desensitization faster.⁶ AIT has been shown to produce a 2.7- to 13.7-fold overall improvement in hypersensitivity reactions.¹⁰

Length of therapy must be individualized

Experts recommend that the length of treatment with AIT be customized for each patient based on the severity of pretreatment allergy symptoms, the benefit experienced with AIT, the inconvenience of AIT to the patient, and the anticipated impact of symptom relapse.^6,10 There are no physiologic symptoms or objective tests that predict which patients will remain in remission after discontinuing AIT; thus, a joint task force of allergy experts suggests that the decision to restart AIT in patients who have a relapse in allergic symptoms should be made based on the same factors used to determine the duration of the maintenance phase.⁶

Continue to: These allergans are appropriate for AIT

Allergens may be described in terms of mechanism and chronicity of exposure. While avoidance of offending allergens is recommended for those who are sensitized, avoidance is not always possible.^6,7,9,13 AIT has been studied as a therapeutic modality to prevent exposure-related symptoms associated with each of the following types of allergens.^6,7,9,11,14

Inhalant allergens circulate in disturbed and undisturbed air and may be seasonal (eg, pollen), perennial (eg, cat/dog allergens), and/or occupational.⁹ They can derive from the indoors (eg, cockroach, cat, dog, dust mite) or outdoors (eg, tree, grass, or weed pollen ),^6,7,9,11 and serve as triggers for many allergic diseases such as allergic rhinitis (AR), allergic rhinoconjunctivitis, allergic dermatitis, and asthma.^7,13

Food allergens. Sensitization to food allergens may produce a range of symptoms.^6,7 One person may experience nothing more than tingling of the lips when eating a peach, while another may experience throat tightness and anaphylaxis due to the aroma of shellfish cooking.

Occupational allergens. Exposure to occupational allergens varies depending on the setting. Those who work in health care or with animals can be exposed to allergens (eg, latex and animal proteins, respectively) that can cause skin or respiratory hypersensitivity reactions. Occupational allergens can also include chemicals; workers in agriculture or housekeeping may be particularly at risk.

Insect allergens. Envenomation by stinging insects of the order Hymenoptera (bees, yellow jackets, hornets, wasps, fire ants) most commonly causes a pruritic, painful local reaction, but patients sensitized to Hymenoptera venom experience systemic allergic reactions that range from mild to life-threatening.^3,6,7

Continue to: When should you use AIT?

Allergic rhinitis (AR). AR can be triggered by exposure to indoor or outdoor inhalant allergens. Research has shown AIT to be an effective treatment for AR and the conjunctivitis caused by inhaled environmental allergens.^15-17 AIT results in improved symptom control and decreased use of rescue medication (standardized mean difference [SMD] -0.32; 95% confidence interval [CI], -0.23 to -0.33, favoring AIT intervention) in patients with seasonal or perennial AR.^15-17

SCIT effectiveness has been demonstrated in sensitized patients who have symptoms associated with pollen, animal allergens, dust mites, and mold/fungi,^15,16 and SCIT may be effective for the treatment of symptoms associated with cockroach exposure.¹¹ SLIT is approved by the US Food and Drug Administration (FDA) for the treatment of several pollen allergens with efficacy rates similar to those of SCIT and with no significant difference in adverse events (AEs).^8,15,16 Direct comparison studies of SCIT and SLIT preparations for treating grass allergy, while of low quality, showed comparable reductions in allergic rhinoconjunctival symptoms.¹⁵

Asthma. AIT (SCIT and SLIT) has been shown to be effective and safe in patients with mild-to-moderate asthma associated with inhalant allergens. Asthma should be controlled prior to initiation of AIT.^6,8,10 Well-known allergic triggers for asthma exacerbation include indoor inhaled allergens (eg, house dust mite, animal dander, cockroach), outdoor inhalant allergens (plants, pollen), and occupational inhaled allergens (silkworm, weevil).^11,13

In one meta-analysis of 796 patients with asthma from 19 different randomized controlled trials, SCIT significantly decreased asthma-related symptom scores (SMD = -0.94; 95% CI, -1.58 to -0.29; P = .004), as well as asthma medication scores (SMD = -1.06; 95% CI, -1.70 to -0.42; P = .001).¹⁸ While AIT has not been shown to improve lung function, meta-analyses have shown that adults with asthma treated with AIT experience fewer/less severe exacerbations and use less rescue medication when compared with those taking placebo.^19,20 Furthermore, studies have shown that SCIT and SLIT reduce asthma symptoms and asthma medication use compared with placebo or usual care in the pediatric population.²⁰

Adults with asthma treated with allergy immunotherapy use less rescue medication when compared to those taking placebo.

As helpful as AIT can be for some patients with mild-to-moderate asthma, patients with severe asthma experience more severe adverse reactions with AIT.²¹ Therefore, most experts recommend against administering AIT to patients with severe asthma.^6,8,21

Continue to: Stinging insects

Stinging insects. VIT is used for patients with hypersensitivity to the venom from insects of the order Hymenoptera (see previous list of insects).^3,11,22 A meta-analysis concluded, based on limited evidence from low-quality studies, that VIT has the potential to substantially reduce the incidence of severe allergic reactions in patients with Hymenoptera sensitivity with 72% of patients benefitting from VIT (number needed to treat [NNT] = 1.4).²² VIT reduces the risk of a systemic reaction, as well as the size and duration of large local reactions (LLRs).^6,22 Immunotherapy for stinging insects also has been shown to improve disease-specific quality of life (risk difference = 1.41 strongly favoring VIT).^6,22

Insect allergens. Research has shown AIT to be an effective therapy for many allergens even though the potency and effectiveness for some allergens are not standardized or regulated.^6,7,11,14 For example, AIT is available for some inhaled insect allergens; however, because the extracts are not standardized, AIT produces inconsistent outcomes.^11,14 As another example, certain occupations lead to exposure to inhaled insect allergens such as silkworm and weevils. AIT is not indicated for either because available silkworm extracts are used only for allergy testing.¹¹ There are no extracts to test for or treat weevil allergy.¹¹

Food. IgE-mediated food allergy can result in oral allergy syndrome, angioedema, urticaria, and/or anaphylaxis.^2,7,8 There is some evidence that AIT raises the threshold of reactivity in children with IgE-mediated food allergies.^6,7,23-25 But the studies available for meta-analyses (some of which involved OIT) were deemed to be of low quality due to a high risk of bias and a small number of participants.^24,25 AIT for food allergies is associated with a substantially increased incidence of moderate adverse reactions, including upper respiratory, gastrointestinal, and skin symptoms, with a probability of 46% during the buildup phase and a number needed to harm (NNH) of 2.1 (95% CI, 1.8-2.5; P < .0001).^6,25 Therefore, experts consider AIT in any form for food hypersensitivity to be investigational.^6,10

Allergen immunotherapy for allergic rhinitis has proven to be effective at improving quality of life and symptom control and decreasing comorbid disease and use of rescue medication.

But preliminary data from a recent phase 3 trial of OIT for peanut allergy involving 499 children and teens are promising; 67.2% tolerated the food challenge of ≥ 600 mg of peanut protein at the completion of peanut OIT without dose-limiting symptoms (difference = 63.2 percentage points; 95% CI, 53-73.3; P < .001).²⁶ More than twice as many participants in the placebo group vs the treatment group experienced AEs that were moderate (59% vs 25%, respectively) or severe (11% vs 5%, respectively).

There are ongoing trials of SCIT, SLIT, and OIT using modified food allergens to make participants less allergic while maintaining immunogenicity.^2,27 Additional trials include adjunctive treatments like probiotics to create safer, more effective options for children with food allergies.^2,27 Keep in mind that children with food allergies often have concomitant allergies (eg, inhalant allergies) that can benefit from AIT.

Continue to: Other clinical practice strategies include...

Other clinical practice strategies include the introduction of extensively heated (baked) milk and egg products, which benefit the majority of milk- and egg-allergic children.^2,28 An American Academy of Allergy, Asthma and Immunology (AAAAI)-sponsored Task Force and the European Academy of Allergy and Clinical Immunology (EAACI) support exclusive breastfeeding for the first 4 to 6 months of life to decrease the risk of developing food allergies.^6,7

Atopic dermatitis (AD). AD is an IgE-mediated skin disease that affects children and adults. AD is associated with asthma, AR, and food allergy.¹³ Early studies showed that AIT reduced topical corticosteroid use and improved the SCORAD (SCORing Atopic Dermatitis; see www.scorad.corti.li/) score.¹⁰ However, Cochrane reviews of studies involving children and adults with AD undergoing AIT via SCIT, SLIT, or OIT routes found that AIT was not effective in treating AD when accounting for the quality and heterogeneity of the studies.^12,29 In addition, there were no significant differences in SCORAD scores.^10,12

Contact allergens. Contact allergens, including plant resins (eg, poison ivy) and metals (eg, nickel) cause local dermatitis through a cell-mediated, delayed hypersensitivity response. AIT is not indicated for contact dermatitis.^6,9

Why use AIT?

First, AIT has been shown to modify disease. Second, because of its disease-modifying properties, AIT may provide cost savings over standard drug treatment in patients with asthma and AR.^17,20,30 In fact, individual studies have demonstrated ≥ 80% cost savings of AIT over standard drug regimens, although meta-analyses have been unable to demonstrate the same.^30,31

In addition, initial studies suggested that AIT might help to prevent the development of new allergen sensitizations.³² One meta-analysis found that AIT decreased the short-term risk of developing asthma in children with AR; however, subsequent studies showed that AIT did not have efficacy in preventing new allergic disease.^31,33

Continue to: How do you administer AIT?

FPs may be asked to administer AIT to their patients. Patients will typically have weekly office visits during the induction phase of AIT and should have appointments every 6 to 12 months during the maintenance phase.^6,8

While allergy immunotherapy has not been shown to improve lung function in patients with asthma, studies have shown that patients experience fewer exacerbations.

Collaboration with an allergy specialist is wise for dosing schedules and possibly for information regarding adverse reactions during administration. It is essential that AIT be administered by clinicians who are knowledgeable about the signs and symptoms of minor allergic reactions (eg, pruritus, mild erythema, and swelling at the administration site) and severe ones (eg, angioedema, shock, anaphylaxis), as well as who have immediate access to emergency medications and resuscitation, should it be needed.^6-8,34

Most (86%) adverse reactions will occur within 30 minutes of administration of AIT; hence, the recommendation is to observe patients for 30 minutes following AIT administration.^6,7,34 Continual training and “mock” severe reaction responses are beneficial for staff administering AIT to ensure appropriate equipment is available and that appropriate procedures are followed. Late-phase reactions can occur and usually present within 6 to 12 hours of administration; thus, it is essential for patients to be educated on the signs and symptoms of adverse reactions and on symptomatic and emergent treatment.^9,34

Experts consider allergy immunotherapy in any form for food hypersensitivity to be investigational.

Rush immunotherapy regimens for inhalant allergens are associated with increased AEs; therefore, pretreatment with antihistamines, leukotriene antagonists, the monoclonal antibody omalizumab, corticosteroids, or combinations of these agents is often used.^6,34 In contrast to inhaled allergens, rush VIT has not been associated with an increased risk of adverse reactions in meta-analyses.^6,22,34 Most experts recommend that AIT be discontinued if anaphylaxis occurs.^8,34

Is AIT safe?

AIT is a proven safe and effective disease-modifying treatment option.^6-8,31,35 Even when AIT is initiated within the season of increased allergen exposure, meta-analyses reveal no increase in adverse events in patients undergoing AIT.³⁵ Given the lack of high-quality evidence confirming the safety of AIT in the following specific situations, both the AAAAI and EAACI have concluded that these conditions/situations are absolute contraindications for AIT due to the risk of severe reactions by activation of underlying disease^8,21,36:

• severe asthma;
• acquired immune deficiency syndrome (AIDS); and
• initiation of AIT during pregnancy.

Continue to: Patients with a history of transplantation...

Patients with a history of transplantation, cancer in remission, human immunodeficiency virus (HIV) without AIDS, and cardiovascular disease have been safely treated with AIT with a < 1.5% incidence of serious adverse events.^6,21,36 It is possible to give patients taking beta-blockers and/or angiotensin converting enzyme inhibitors (ACEIs) AIT with appropriate consideration. Both classes of drugs can interfere with emergency treatment, so one should consider substitution with an agent from another class if possible during AIT.^6,8,20,34 Patients taking ACEIs receiving VIT had substantially increased adverse reactions compared with other forms of AIT; thus, individual risks and benefits must be weighed carefully before initiating VIT.^6,34

Looking ahead

Studies evaluating the indications for AIT in oral allergy syndrome, food allergy, latex allergy, AD, and venom allergy are ongoing.^2,7,10,26 Although the incidence of severe adverse allergy reactions during AIT is rare, there are investigations of using various immune-modifying agents to improve the safety and efficacy of AIT.³⁷ Application of allergen preparation using skin patches, intralymphatic injections, and chemically modified allergens to make them less immunologically reactive are being researched to further improve safety profiles and make AIT less time consuming.³⁸ In Europe and the United States, there is a call for more rigid studies using standardized SLIT preparations. This will allow for an increased number of AIT studies with decreased heterogeneity.

CORRESPONDENCE
Dellyse Bright, MD, Carolinas Medical Center Family Medicine Residency Program, Atrium Health, 2001 Vail Avenue, Suite 400B, Charlotte, NC 28207; [email protected].

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved two new formulations for the anti–interleukin-5 biologic mepolizumab (Nucala) for treatment of certain severe or rare forms of asthma, according to a press release from the drug’s developer. The biologic will now be available as an autoinjector and as a prefilled safety syringe.

The 100-mg subcutaneous mepolizumab injection is indicated as an add-on treatment for patients 12 years and older with severe eosinophilic asthma, and the three-dose 100-mg subcutaneous injections are indicated for the rare eosinophilic granulomatosis and polyangiitis, with the biologic administered every 4 weeks in either context. The release emphasizes that mepolizumab is not approved for acute bronchospasm or status asthmaticus. Health care professionals should first determine whether self-assisted administration or administration provided by a caregiver is appropriate, and then they should provide patients and/or caregivers with proper training in how to do so.

The approval is based on two open-label, single-arm, phase 3a studies that demonstrated successful administration was possible with these options among patients with severe eosinophilic asthma, at rates of 89%-95% in one study and 100% in the other. These results were followed by those of an open-label, parallel group, single-dose study that confirmed the pharmacokinetic and pharmacodynamic profiles of these new means of administration were comparable with those currently approved.

Mepolizumab is not indicated for those with a history of hypersensitivity to either mepolizumab or to the formulation’s excipients, such as anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, or rash. Any reductions of inhaled corticosteroids after initiation of mepolizumab should be gradual and under the supervision of a health care professional. Some infections by herpes zoster have been observed. The most common adverse reactions (occurring in 3% or more of patients and more often than with placebo) during the first 24 weeks of treatment were headache (19%), injection site reaction (8%), back pain (5%), fatigue (5%), influenza (3%), urinary tract infection (3%), abdominal pain upper (3%), pruritus (3%), eczema (3%), and muscle spasm (3%). Full prescribing information can be found on the FDA website.

[email protected]

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

BALTIMORE – The biggest barrier to asthma care in public schools is students not having an albuterol inhaler with them, frequently because the parent did not provide an inhaler or did not provide a written order for one, according to new research. Only seven U.S. states have laws allowing schools to stock albuterol for students.

pelvidge/thinkstockphotos.com

“Most students only have access to this lifesaving medication when they bring a personal inhaler,” Alexandra M. Sims, MD, of Children’s National Hospital in Washington and colleagues wrote in their abstract at the annual meeting of Pediatric Academic Societies. “Interventions that address medication availability may be an important step in removing obstacles to asthma care in school.”

One such option is a stock inhaler available for any students to use. National guidelines from the Centers for Disease Control and Prevention recommend that students with asthma have access to inhaled albuterol at school, yet most states do not have legislation related to albuterol stocking in schools, according to the Asthma and Allergy Foundation of America.

Not having access to rescue inhaler medication at school contributes to lost class time and referrals to the emergency department, the authors note in their background information. Yet, “in most U.S. jurisdictions, including the school district we examined, students need both a personal albuterol inhaler and a physician order to receive medication at school.”

To determine what barriers exist regarding students’ asthma care in schools, the authors sent 166 school nurses in an urban school district an anonymous survey during the 2015-2016 school year. The survey asked about 21 factors that could delay or prevent students from returning to class and asked nurses’ agreement or disagreement with 25 additional statements.

The 130 respondents made up a 78% response rate. The institutions represented by the nurses included 44% elementary schools, 9% middle schools, 16% high schools, and 32% other (such as those who may serve multiple schools).

The majority of respondents (72%) agreed that asthma is one of the biggest health problems students face, particularly among middle and high school students (P less than .05). Most (74%) also said an albuterol inhaler at school could reduce the likelihood of students with asthma needing to leave school early.

The largest barrier to students returning to class was parents not providing an albuterol inhaler and/or a written order for an inhaler despite a request from the nurse, according to 69% of the respondents (P less than .05). In high schools in particular, another barrier was students simply not bringing their inhaler to school even though they usually carry one (P less than .01).

Only 15% of nurses saw disease severity as a significant barrier, and 17% cited the staff not adequately recognizing a student’s symptoms.

The researchers did not note use of external funding or author disclosures.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

Oral immunotherapy reduced sensitivity to peanuts in allergic individuals, but at the cost of increased risk of anaphylaxis and other reactions, based on a meta-analysis from more than 1,000 patients published in the Lancet.

copyright mates/Fotolia.com

In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, Derek K. Chu, MD, of McMaster University, Hamilton, Ont., and colleagues reviewed 12 trials conducted between 2011 and 2018 with a total of 1,041 patients (median age, 9 years).

Overall, the risk of anaphylaxis was significantly higher among children who received oral immunotherapy, compared with no therapy (risk ratio, 3.12) as was anaphylaxis frequency (incidence rate ratio, 2.72) and use of epinephrine (RR, 2.21).

In addition, oral immunotherapy increased serious adverse events, compared with no therapy (RR, 1.92). Nonanaphylactic reactions also went up among oral immunotherapy patients, with increased risk for vomiting (RR, 1.79), angioedema (RR, 2.25), upper respiratory tract reactions (RR, 1.36), and lower respiratory tract infections (RR, 1.55).

Quality of life scores were not significantly different between patients who did and did not receive oral immunotherapy, the researchers noted.

The oral immunotherapy consisted of defatted, lightly roasted peanut flour in 10 studies, and a combination of peanut paste, peanut extract, or ground and defatted peanut in the other studies.

The oral immunotherapy did induce desensitization to peanuts in support of earlier studies including the subcutaneous immunotherapy trial, but “this outcome does not translate into achieving the clinical and patient-desired aim of less allergic reactions and anaphylaxis,” Dr. Chu and associates wrote.

However, “rather than take the view that these data denounce current research in oral immunotherapy as not successful, we instead suggest that this research has reached an important milestone in mechanistic but not clinical efficacy. From a clinical or biological perspective, the apparently paradoxical desensitization versus longitudinal clinical findings show the lability and unreliability of allergen thresholds identified during oral food challenges because patients often unpredictably reacted to previously tolerated doses outside of clinic,” they emphasized.

The findings were limited by several factors including the small sample size, compared with similar studies for asthma or cardiovascular conditions, and by incomplete or inconsistent data reporting, the researchers noted. However, the results are the most comprehensive to date, and support the need for food allergy treatments with better safety profiles, using peanut allergy immunotherapy as a model for other food allergies.

Dr. Chu and two other authors reported being investigators on a federally funded ongoing peanut oral immunotherapy trial. Two authors reported receiving a variety of grants from organizations such as the National Institutes of Health; the American Academy of Allergy, Asthma, & Immunology; or pharmaceutical companies.

SOURCE: Chu DK et al. Lancet. 2019 June 1;393:2222-32.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

BALTIMORE – Experiencing panic-fear during asthma exacerbations predicted several beneficial outcomes in Mexican and Puerto Rican children with asthma, according to new research.

Tara Haelle/MDedge News

“When kids are anxious specifically during their asthma attacks, that can be a good thing because it means that they’re more vigilant,” lead author Jonathan M. Feldman, PhD, of the Albert Einstein College of Medicine’s Children’s Hospital at Montefiore and of Yeshiva University in the New York said in an interview. “They may be more likely to react during the early stages of an attack, and they may be more likely to be using self-management strategies at home and using their controller medications on a daily basis.”

He said pediatric providers can ask their patients with asthma how they feel during asthma attacks, such as whether they ever feel scared or worried.

“If a kid says no, not at all, then I would be concerned as a provider because they may not be paying attention to their asthma symptoms and they may not be taking it seriously,” Dr. Feldman said.

Past research has suggested that “illness-specific panic-fear” – the amount of anxiety someone experiences during asthma exacerbations – helps adults develop adaptive asthma management strategies, so Dr. Feldman and his colleagues examined the phenomenon as a potential protective factor in children. They shared their findings at the annual meeting of the Pediatric Academic Societies.

The research focused on Puerto Rican (n = 79) and Mexican (n = 188) children because of the substantial disparity in asthma prevalence and control between these two different Latino populations. Puerto Rican children have the highest asthma prevalence and morbidity among American children, whereas Mexican children have the lowest rates.

The 267 participants, aged 5-12 years, included 110 children from two inner-city hospitals in the New York and 157 children from two school-based health clinics and a Breathmobile in Phoenix. Nearly all the Arizona children were Mexican, and most (71%) of the Bronx children were Puerto Rican.

The authors collected the following measures at baseline and at 3, 6, 9, and 12 months follow-up: spirometry (forced expiratory volume in 1 second [FEV₁]), Childhood Asthma Control Test (CACT) for children 5-11 years old, the Asthma Control Test (ACT) for 12-year-olds, adherence to inhaled corticosteroids (ICS), and acute health care utilizations (clinic sick visits, ED visits, and hospitalizations).

The authors also queried patients on four illness-specific panic-fear measures from the Childhood Asthma Symptoms Checklist: how often they felt frightened, panicky, afraid of being alone, and afraid of dying during an asthma attack (Likert 1-5 scale).

Mexican children reported higher levels of illness-specific panic-fear at the start of the study. They also tended to have lower severity of asthma, better asthma control, and better adherence to ICS, compared with Puerto Rican children.

Also at baseline, the Mexican children’s caregivers tended to be younger, poorer, and more likely to be married and to speak Spanish. The Puerto Rican caregivers, on the other hand, had a higher educational level, including 61% high school graduates, and had more depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D).

One-year data revealed several links between baseline reports of panic-fear and better outcomes. Mexican children who reported experiencing panic-fear at baseline were more likely to have higher FEV₁ measures at 1 year of follow-up than were those who didn’t experience panic-fear (P = .02). Similarly, Puerto Rican children initially reporting panic-fear had better asthma control at 1 year, compared with those who didn’t report panic-fear (P = .007).

The researchers reported their effect sizes in terms of predicted variance in a model that accounted for the child’s age, sex, asthma duration, asthma severity, social support, acculturation, health care provider relationship, and number of family members with asthma. The model also factored in the caregiver’s age, sex, marital status, poverty level, education, and depressive symptoms.

For example, in their model, experiencing panic-fear accounted for 67% of the variance in FEV₁ levels in Mexican children and 53% of the variance in asthma control in Puerto Rican children.

Less acute health care utilization also was associated with children’s baseline levels of illness-specific panic-fear. In the model, 12% of the variance in acute health care utilization among Mexican children (P = .03) and 41% of the variance among Puerto Rican children (P = .02) was explained by child-reported panic-fear. No association was seen with medication adherence.

Although caregivers’ reports of children feeling panic-fear were linked to better FEV₁ outcomes in Mexican children (P = .02), the association was only slightly significant in Puerto Rican children (P = .05). Caregiver reports of children’s panic-fear were not associated with asthma control, acute health care utilization, or medication adherence.

“Providers should be aware that anxiety focused on asthma may be beneficial and facilitate adaptive asthma management strategies,” the authors concluded.

The research was funded by the National Institutes of Health. The authors reported no relevant financial disclosures.

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.