2016 AAAAI Annual Meeting

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]

LOS ANGELES – Fungi might play a far larger role in asthma and chronic sinusitis than previously thought, according to investigators at Baylor College of Medicine in Houston.

With the help of a special culturing technique to wash antifungal elements out of sputum samples, six or more fungal colony-forming units grew out of the sputum of 112 of 134 patients (83.5%) at the Houston Veterans Affairs Medical Center; about a third of the patients had asthma, a third had chronic sinusitis, and a third had both. Although Aspergillus and Candida species were common, more than 30 fungal species were identified. Only a handful of patients had positive results on IgE testing.

Of 62 patients treated with standard-dose voriconazole or terbinafine, sometimes for more than a year, 54 (87%) reported symptomatic benefit including 31 (50%) with decreased sputum production, 24 (39%) with improved breathing, 20 (32%) with less cough, and nine (14.5%) with less rescue inhaler use.

At Baylor, prescribing antifungals for patients with recalcitrant asthma and chronic sinusitis “has evolved into something we pretty much do all the time now regardless of sensitivity results. I’m pretty certain we are the only institution that does this,” said allergy and immunology fellow Dr. Evan Li.

“Fungi, we think, are important initiating factors in many cases of asthma. They set up chronic mucosal infection. Our [treatment] experience is extremely positive; it may be in the future that if you have significant asthma or sinusitis, you just go on an antifungal, but more research and clinical trials are needed,” said senior investigator Dr. David Corry, professor and chief of medical immunology, allergy, and rheumatology at Baylor.

“The standard culture techniques that have been used for 100 years are inadequate when it comes to culturing fungi from sputum, and why results almost invariably come back negative,” Dr. Corry said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The problem is that “almost everything in sputum” – eosinophils, macrophages, cytokines, and so on – “is designed to kill fungi.” Those elements have to be removed before plating. At Baylor, “we solubilize [sputum] with the reducing agent dithiothreitol, and vigorously stir the mixture to disperse the organisms and wash away the cellular elements and the other things.” The process leaves behind “a sandy material that’s basically fibrin clots mixed with a lot of fungal elements. You spread that on a plate, and it grows like wildfire,” he said.

“It’s easy to do, but time consuming. People are actually shipping their samples to us now from around the country, and we are happy to do those cultures,” Dr. Corry said. There’s no patent on the technique because “we want the community to use it. We want people to be helped,” he said.

Voriconazole seems to be the most effective option, and the team opts for it when possible, Dr. Corry noted. Terbinafine is the go-to drug for patients who can’t tolerate voriconazole. Fluconazole is sometimes added when monotherapy doesn’t seem to be doing the trick.

The work began as a search for household proteases. “One of our first discoveries was that” most are fungal. “The twist is that you are not inhaling the proteases, you are inhaling the fungus,” Dr. Corry said.

There have been both positive and negative results from the few prior investigations of antifungals for asthma. The team suspects that negative findings were a result of patients not being treated long enough, among other reasons.

The Baylor team is looking for funding for a prospective trial. The investigators hope to develop a protocol for diagnosis and treatment of fungal airway disease, but “there’s a lot of work that needs to get done,” Dr. Corry said.

The investigators had no relevant financial disclosures, and there was no outside funding for the work.

[email protected]

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

LOS ANGELES – A peanut protein–bearing skin patch known as the Viaskin Peanut gave a continued strong performance for treatment of peanut allergy in children during the second year of an international study of this novel form of epicutaneous immunotherapy.

The clinical response rate in 6- to 11-year-olds after 1 year of treatment with the 250-mcg dose of peanut protein in the medical device was 57% in the phase IIb, double-blind, 22-site, international VIPES trial, as reported last year.

©mates/Fotolia.com

After an additional year of treatment with the 250-mcg Viaskin Peanut in the open-label extension study known as OLFUS-VIPES, this rate climbed to 80%. Safety and tolerability of the device therapy remained excellent, Dr. Hugh A. Sampson said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

In adolescents and adults, however, the clinical response – while significantly better than placebo in VIPES – was less robust than in children, and it remained stable from year 1 to year 2. This is believed to be due to the greater plasticity of the immune system in children, observed Dr. Sampson, director of the Jaffe Food Allergy Institute at Kravis Children’s Hospital at Mount Sinai in New York and chief scientific officer at DBV Technologies, which is developing the Viaskin Peanut.

The ongoing phase III trial uses the 250-mcg dose of peanut protein – the highest of several doses studied in VIPES and OLFUS-VIPES – and is restricted to peanut-allergic children ages 4-11 years. Doses of peanut protein greater than 250 mcg will be explored in separate studies of adolescents and adults.

The clinical response rate in children on the 250-mcg Viaskin Peanut rose from 57% after 1 year to 80% – that is, 16 of 20 subjects – after 2 years. A clinical response in VIPES and OLFUS-VIPES was defined as nonreactivity to a dose of at least 1,000 mg of peanut protein – the equivalent of four peanuts – during a formal double-blind food challenge or at least a tenfold increase in the eliciting dose, compared to the original eliciting dose.

In VIPES, one-third of children on the 250-mcg device therapy for 1 year could tolerate at least 1,000 mg of peanut protein; after an additional year of open-label therapy, 60% of children were able to do so.

Among 6- to 11-year-olds, the median cumulative reactive dose of peanut protein was 44 mg at baseline, 444 mg after 12 months of using the 250-mcg Viaskin Peanut, and 1,444 mg at 2 years.

The children’s immunologic response to the Viaskin Peanut was impressive: A 40% reduction from baseline in peanut IgE at 2 years, along with a ninefold increase in protective peanut-specific IgG4.

The skin patch consists of a dried allergen – in this case, peanut protein – which is made electrostatically adherent to a membrane on a Band-Aid–like chamber. A set of patches is placed on noneczematous skin on a child’s back and on the inner upper arm of older patients. Moisture emitted from the skin gradually causes the protein allergen to solubilize and get absorbed into the outer layer of the skin. It is then picked up by antigen-presenting Langerhans cells and transported to regional lymph nodes for deactivation. The patches are changed daily.

“It appears that we need to look at the skin as a tolerogenic organ when it’s uninflamed,” Dr. Sampson observed.

Compliance with treatment was in excess of 96% in both VIPES and OLFUS-VIPES. There have been no serious treatment-related adverse events and no need for the use of epinephrine. Side effects have been limited to occasional mild to moderate application site reactions easily managed with antihistamines and/or topical steroids, according to Dr. Sampson.

The double-blind VIPES study included 207 subjects with documented peanut allergy. OLFUS-VIPES, which will continue for 1 additional year of open-label therapy, includes 171 of the original 207, including 97 children, 49 adolescents, and 25 adults up to age 55 years.

“We’ll see if there’s continued improvement in children through the third year or it levels off, but based upon the immunologic parameters I think it’s having continued effect,” the pediatric allergist said.

[email protected]

LOS ANGELES – Once-daily tiotropium bromide inhalation spray as long-term, add-on maintenance therapy in patients with poorly controlled symptomatic asthma is similarly effective in both allergic and nonallergic asthma, according to Dr. Donald P. Tashkin.

In a series of analyses presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and his coinvestigators showed that tiotropium bromide inhalation spray (Spiriva Respimat) given as add-on maintenance therapy resulted in significantly improved lung function, enhanced asthma symptom control, and fewer asthma exacerbations. The important new finding in these post hoc analyses was that the medication was similarly effective across the full range of baseline serum IgE and blood eosinophil levels, said Dr. Tashkin, director of the pulmonary function laboratories at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

Last fall, the Food and Drug Administration approved an expanded indication for tiotropium bromide inhalation spray as long-term, add-on maintenance therapy of asthma in patients aged 12 and up who remain symptomatic despite taking other maintenance therapies. The once-daily medication had already been approved in the fall of 2014 for maintenance therapy of chronic obstructive pulmonary disease. Spiriva Respimat delivers a once-daily 2.5-mcg dose of tiotropium bromide via two 1.25-mcg puffs in a slow-moving, propellant-free mist designed to get the drug into the distal lungs independent of a patient’s skill in using a conventional metered-dose inhaler.

Dr. Tashkin and his coinvestigators presented a series of post hoc analyses combining data on 3,012 participants in the two prospective PrimoTinA-asthma and two MezzoTinA-asthma clinical trials. These phase III, double-blind, placebo-controlled trials defined participants’ allergic phenotype on the basis of the conventional cut points of a serum IgE level above or below 430 mcg/mL or a blood eosinophil count above or below 600 cells/mcL.

“The question is, are these appropriate cut points? Can we be sure that somebody below those cut points doesn’t have atopy? To answer that question, we looked at the whole spectrum of eosinophils in the blood from 5/mcL to 2,000/mcL and serum IgE levels from 2 mcg/mL to 2,000 mcg/mL. We found that the efficacy was similar across the entire spectrum of these measures of allergy,” he said in an interview.

Thus, these new findings support the use of this novel maintenance therapy without any need for lab tests to determine whether an individual patient’s asthma is T helper 2–cell dominant or not, Dr. Tashkin added.

The PrimoTinA-asthma trials were 48-week studies of add-on Spiriva Respimat or placebo conducted in patients with symptomatic asthma despite treatment with an inhaled corticosteroid plus a long-acting beta-agonist. The MezzoTinA-asthma studies were 24 weeks long and focused on patients who remained symptomatic despite at least moderate-dose inhaled corticosteroid therapy. Key endpoints included improvement in asthma symptom control as measured by the seven-question Asthma Control Questionnaire, improved peak and trough forced expiratory volume in 1 second, and time to a first severe asthma exacerbation.

Dr. Tashkin reported serving as a paid speaker on behalf of Boehringer Ingelheim, which markets Spiriva Respimat and sponsored the studies.

LOS ANGELES – Once-daily tiotropium bromide inhalation spray as long-term, add-on maintenance therapy in patients with poorly controlled symptomatic asthma is similarly effective in both allergic and nonallergic asthma, according to Dr. Donald P. Tashkin.

In a series of analyses presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and his coinvestigators showed that tiotropium bromide inhalation spray (Spiriva Respimat) given as add-on maintenance therapy resulted in significantly improved lung function, enhanced asthma symptom control, and fewer asthma exacerbations. The important new finding in these post hoc analyses was that the medication was similarly effective across the full range of baseline serum IgE and blood eosinophil levels, said Dr. Tashkin, director of the pulmonary function laboratories at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

Last fall, the Food and Drug Administration approved an expanded indication for tiotropium bromide inhalation spray as long-term, add-on maintenance therapy of asthma in patients aged 12 and up who remain symptomatic despite taking other maintenance therapies. The once-daily medication had already been approved in the fall of 2014 for maintenance therapy of chronic obstructive pulmonary disease. Spiriva Respimat delivers a once-daily 2.5-mcg dose of tiotropium bromide via two 1.25-mcg puffs in a slow-moving, propellant-free mist designed to get the drug into the distal lungs independent of a patient’s skill in using a conventional metered-dose inhaler.

Dr. Tashkin and his coinvestigators presented a series of post hoc analyses combining data on 3,012 participants in the two prospective PrimoTinA-asthma and two MezzoTinA-asthma clinical trials. These phase III, double-blind, placebo-controlled trials defined participants’ allergic phenotype on the basis of the conventional cut points of a serum IgE level above or below 430 mcg/mL or a blood eosinophil count above or below 600 cells/mcL.

“The question is, are these appropriate cut points? Can we be sure that somebody below those cut points doesn’t have atopy? To answer that question, we looked at the whole spectrum of eosinophils in the blood from 5/mcL to 2,000/mcL and serum IgE levels from 2 mcg/mL to 2,000 mcg/mL. We found that the efficacy was similar across the entire spectrum of these measures of allergy,” he said in an interview.

Thus, these new findings support the use of this novel maintenance therapy without any need for lab tests to determine whether an individual patient’s asthma is T helper 2–cell dominant or not, Dr. Tashkin added.

The PrimoTinA-asthma trials were 48-week studies of add-on Spiriva Respimat or placebo conducted in patients with symptomatic asthma despite treatment with an inhaled corticosteroid plus a long-acting beta-agonist. The MezzoTinA-asthma studies were 24 weeks long and focused on patients who remained symptomatic despite at least moderate-dose inhaled corticosteroid therapy. Key endpoints included improvement in asthma symptom control as measured by the seven-question Asthma Control Questionnaire, improved peak and trough forced expiratory volume in 1 second, and time to a first severe asthma exacerbation.

Dr. Tashkin reported serving as a paid speaker on behalf of Boehringer Ingelheim, which markets Spiriva Respimat and sponsored the studies.

LOS ANGELES – Once-daily tiotropium bromide inhalation spray as long-term, add-on maintenance therapy in patients with poorly controlled symptomatic asthma is similarly effective in both allergic and nonallergic asthma, according to Dr. Donald P. Tashkin.

In a series of analyses presented at the annual meeting of the American Academy of Allergy, Asthma, and Immunology, he and his coinvestigators showed that tiotropium bromide inhalation spray (Spiriva Respimat) given as add-on maintenance therapy resulted in significantly improved lung function, enhanced asthma symptom control, and fewer asthma exacerbations. The important new finding in these post hoc analyses was that the medication was similarly effective across the full range of baseline serum IgE and blood eosinophil levels, said Dr. Tashkin, director of the pulmonary function laboratories at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

Last fall, the Food and Drug Administration approved an expanded indication for tiotropium bromide inhalation spray as long-term, add-on maintenance therapy of asthma in patients aged 12 and up who remain symptomatic despite taking other maintenance therapies. The once-daily medication had already been approved in the fall of 2014 for maintenance therapy of chronic obstructive pulmonary disease. Spiriva Respimat delivers a once-daily 2.5-mcg dose of tiotropium bromide via two 1.25-mcg puffs in a slow-moving, propellant-free mist designed to get the drug into the distal lungs independent of a patient’s skill in using a conventional metered-dose inhaler.

Dr. Tashkin and his coinvestigators presented a series of post hoc analyses combining data on 3,012 participants in the two prospective PrimoTinA-asthma and two MezzoTinA-asthma clinical trials. These phase III, double-blind, placebo-controlled trials defined participants’ allergic phenotype on the basis of the conventional cut points of a serum IgE level above or below 430 mcg/mL or a blood eosinophil count above or below 600 cells/mcL.

“The question is, are these appropriate cut points? Can we be sure that somebody below those cut points doesn’t have atopy? To answer that question, we looked at the whole spectrum of eosinophils in the blood from 5/mcL to 2,000/mcL and serum IgE levels from 2 mcg/mL to 2,000 mcg/mL. We found that the efficacy was similar across the entire spectrum of these measures of allergy,” he said in an interview.

Thus, these new findings support the use of this novel maintenance therapy without any need for lab tests to determine whether an individual patient’s asthma is T helper 2–cell dominant or not, Dr. Tashkin added.

The PrimoTinA-asthma trials were 48-week studies of add-on Spiriva Respimat or placebo conducted in patients with symptomatic asthma despite treatment with an inhaled corticosteroid plus a long-acting beta-agonist. The MezzoTinA-asthma studies were 24 weeks long and focused on patients who remained symptomatic despite at least moderate-dose inhaled corticosteroid therapy. Key endpoints included improvement in asthma symptom control as measured by the seven-question Asthma Control Questionnaire, improved peak and trough forced expiratory volume in 1 second, and time to a first severe asthma exacerbation.

Dr. Tashkin reported serving as a paid speaker on behalf of Boehringer Ingelheim, which markets Spiriva Respimat and sponsored the studies.

LOS ANGELES – For patients with severe atopic dermatitis and their families and treating physicians, there is big news: finally, there is light at the end of the tunnel, Dr. Lisa A. Beck declared in a plenary lecture at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Better drugs are on the way. The new agents in the developmental pipeline target specific immunologic pathways that appear to be central to atopic dermatitis. Moreover, exciting recent evidence indicates it’s possible to noninvasively identify children at high risk for atopic dermatitis and intervene preventively to reduce the likelihood of actually developing the disease, according to Dr. Beck, professor of dermatology and medicine at the University of Rochester (N.Y.).

Bruce Jancin/Frontline Medical News

“Many pharmaceutical companies have now turned their attention to atopic dermatitis and aren’t just focusing on asthma anymore. The biggest pipeline appears to involve drugs that might target the Th2 [T helper 2 cells] pathway, either by trying to eliminate alarmins such as TSLP [thymic stromal lymphopoietin], or reverse the effects of the Th2 cytokines interleukin-4 and -13, either alone or together, or prevent the recruitment of activated T cells,” she said.

Dr. Beck presented an update on three such promising investigational approaches on the horizon: the IL-4 and IL-13 inhibitor dupilumab; oral and topical Janus associated kinase (JAK) inhibitors; and anti-IgE therapies.

Dupilumab: This fully human monoclonal antibody that blocks IL-4 and IL-13 is also being developed as a treatment for eosinophilic asthma. Dr. Beck was first author of a report on a series of four phase II randomized trials of dupilumab for moderate to severe atopic dermatitis in adults. The publication caused a stir, with dupilumab-treated patients showing marked and rapid improvement to a degree previously unseen in the treatment of this disease (N Engl J Med. 2014;371[2]:130-9).

In the 12-week study, for example, 85% of dupilumab-treated patients achieved at least a 50% improvement in the Eczema Area and Severity Index (EASI) score, compared with 35% of placebo-treated controls, with a significant between-group difference seen in the first week. Maximum improvement – a 75%-80% reduction in EASI scores – was noted at 6-8 weeks. Forty percent of dupilumab-treated patients achieved clear or near-clear skin by investigator’s global assessment, compared with just 7% of controls.

Itching decreased markedly beginning in the first week, too. The investigational agent’s side effect profile was similar to placebo. Phase III clinical trials in atopic dermatitis are ongoing.

A study by other investigators found that dupilumab resulted in rapid improvement in the molecular signature of atopic dermatitis in skin biopsy specimens (J Allergy Clin Immunol. 2014 Dec;134[6]:1293-300). The observed changes in gene expression suggest that dupilumab might have a beneficial effect on the dysfunctional skin barrier that is a hallmark of atopic dermatitis. Further studies are now being planned to take a closer look at that possibility.

JAK inhibitors: “We’re all really excited about this approach because dogs, too, get allergic dermatitis, and in 2013 a JAK 1 and 3 inhibitor [oclacitinib, Apoquel] was approved as a veterinary medicine therapy. It has resulted in dramatic improvement in itch within 1 week of administration, as well as significant improvement in the dermatitis,” Dr. Beck said.

Three JAK inhibitors are now in phase II clinical trials for atopic dermatitis in humans: the JAK 1 and 3 inhibitor tofacitinib (Xeljanz), both as a topical ointment and the familiar oral formulation; baricitinib, an oral JAK 1 and 2 inhibitor; and an agent known for now as PF-04965842, which is an oral inhibitor specifically of JAK 1.

“JAK inhibitors have been quite effective in treating a number of other inflammatory conditions, as well as cancers. I think they will have a role in the treatment of atopic dermatitis. The biggest concerns will be the off-target effects,” she predicted.

Anti-IgE agents: Omalizumab (Xolair), a humanized monoclonal antibody that binds to IgE, has gotten mixed reviews as an investigational treatment for atopic dermatitis. The best study to date, a randomized, single-center, placebo-controlled, double-blind, 16-week clinical trial, found that omalizumab depleted IgE but didn’t improve the clinical course of atopic dermatitis (J Dtsch Dermatol Ges. 2010 Dec;8[12]:990-8). Nonetheless, a phase II trial of omalizumab is ongoing. Plus, ligelizumab, an anti-IgE monoclonal antibody with a higher affinity for IgE than omalizumab, is also in a phase II trial for adult atopic dermatitis.

“Anti-IgE therapy, I think, is still not dead in atopic dermatitis. I look forward to seeing whether omalizumab will work in unique subsets of patients, or whether a more potent anti-IgE molecule will be more beneficial,” Dr. Beck commented.

As exciting as the prospects are for these investigational agents, there also have been several recent important advances in the prevention of atopic dermatitis, she continued. Investigators led by Dr. Alan D. Irvine of Trinity College, Dublin, noninvasively measured transepidermal water loss in early infancy in more than 1,900 Irish 2-day-old infants and found that those in the 75th percentile for this early marker of skin barrier dysfunction were at 3.1-fold increased risk for diagnosis of atopic dermatitis by age 2 years (J Allergy Clin Immunol. 2016 Apr;137[4]:1111-6). This new-found ability to identify at-risk infants will be extremely helpful in designing atopic dermatitis prevention studies, according to Dr. Beck.

The other advance in prevention was provided via a randomized trial by Dr. Eric L. Simpson of Oregon Health and Science University, Portland, and his coinvestigators. They randomized a group of infants at high risk for atopic dermatitis to daily application of any of five OTC skin moisturizers or a no-moisturizer control group from 2 weeks through 6 months of age. The study hypothesis was that the moisturizers would help reverse the skin barrier abnormalities that play a key role in atopic dermatitis. The hypothesis was borne out by the finding that there was at least a 50% reduction in physician-diagnosed atopic dermatitis by age 6 months in the daily moisturizer group (J Allergy Clin Immunol. 2014 Oct;134[4]:818-23).

Dr. Beck concluded by describing a likely near-term atopic dermatitis prevention and management scenario: High-risk infants will be identified on the basis of noninvasive assessment of epithelial features, such as transepidermal water loss or the presence of high levels of thymic stromal lymphopoietin on the skin surface. Encouragement of daily moisturizing for these high-risk infants will prevent some of them from going on to develop eczema.

For those who do get eczema, dilute bleach baths will help in restoring normal skin barrier function, as was confirmed in an in-press study by Dr. Beck and her coinvestigators, who found that 46% of a group of adults with atopic dermatitis experienced at least a 50% improvement in EASI scores, a big improvement in itch, and reduced transepidermal water loss after 12 weeks of the bleach baths. As other investigators have reported, the bleach baths were very well tolerated and safe.

Dr. Beck reported serving as a consultant to eight pharmaceutical companies with an interest in developing new treatments for atopic dermatitis.

[email protected]

LOS ANGELES – For patients with severe atopic dermatitis and their families and treating physicians, there is big news: finally, there is light at the end of the tunnel, Dr. Lisa A. Beck declared in a plenary lecture at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Better drugs are on the way. The new agents in the developmental pipeline target specific immunologic pathways that appear to be central to atopic dermatitis. Moreover, exciting recent evidence indicates it’s possible to noninvasively identify children at high risk for atopic dermatitis and intervene preventively to reduce the likelihood of actually developing the disease, according to Dr. Beck, professor of dermatology and medicine at the University of Rochester (N.Y.).

Bruce Jancin/Frontline Medical News

“Many pharmaceutical companies have now turned their attention to atopic dermatitis and aren’t just focusing on asthma anymore. The biggest pipeline appears to involve drugs that might target the Th2 [T helper 2 cells] pathway, either by trying to eliminate alarmins such as TSLP [thymic stromal lymphopoietin], or reverse the effects of the Th2 cytokines interleukin-4 and -13, either alone or together, or prevent the recruitment of activated T cells,” she said.

Dr. Beck presented an update on three such promising investigational approaches on the horizon: the IL-4 and IL-13 inhibitor dupilumab; oral and topical Janus associated kinase (JAK) inhibitors; and anti-IgE therapies.

Dupilumab: This fully human monoclonal antibody that blocks IL-4 and IL-13 is also being developed as a treatment for eosinophilic asthma. Dr. Beck was first author of a report on a series of four phase II randomized trials of dupilumab for moderate to severe atopic dermatitis in adults. The publication caused a stir, with dupilumab-treated patients showing marked and rapid improvement to a degree previously unseen in the treatment of this disease (N Engl J Med. 2014;371[2]:130-9).

In the 12-week study, for example, 85% of dupilumab-treated patients achieved at least a 50% improvement in the Eczema Area and Severity Index (EASI) score, compared with 35% of placebo-treated controls, with a significant between-group difference seen in the first week. Maximum improvement – a 75%-80% reduction in EASI scores – was noted at 6-8 weeks. Forty percent of dupilumab-treated patients achieved clear or near-clear skin by investigator’s global assessment, compared with just 7% of controls.

Itching decreased markedly beginning in the first week, too. The investigational agent’s side effect profile was similar to placebo. Phase III clinical trials in atopic dermatitis are ongoing.

A study by other investigators found that dupilumab resulted in rapid improvement in the molecular signature of atopic dermatitis in skin biopsy specimens (J Allergy Clin Immunol. 2014 Dec;134[6]:1293-300). The observed changes in gene expression suggest that dupilumab might have a beneficial effect on the dysfunctional skin barrier that is a hallmark of atopic dermatitis. Further studies are now being planned to take a closer look at that possibility.

JAK inhibitors: “We’re all really excited about this approach because dogs, too, get allergic dermatitis, and in 2013 a JAK 1 and 3 inhibitor [oclacitinib, Apoquel] was approved as a veterinary medicine therapy. It has resulted in dramatic improvement in itch within 1 week of administration, as well as significant improvement in the dermatitis,” Dr. Beck said.

Three JAK inhibitors are now in phase II clinical trials for atopic dermatitis in humans: the JAK 1 and 3 inhibitor tofacitinib (Xeljanz), both as a topical ointment and the familiar oral formulation; baricitinib, an oral JAK 1 and 2 inhibitor; and an agent known for now as PF-04965842, which is an oral inhibitor specifically of JAK 1.

“JAK inhibitors have been quite effective in treating a number of other inflammatory conditions, as well as cancers. I think they will have a role in the treatment of atopic dermatitis. The biggest concerns will be the off-target effects,” she predicted.

Anti-IgE agents: Omalizumab (Xolair), a humanized monoclonal antibody that binds to IgE, has gotten mixed reviews as an investigational treatment for atopic dermatitis. The best study to date, a randomized, single-center, placebo-controlled, double-blind, 16-week clinical trial, found that omalizumab depleted IgE but didn’t improve the clinical course of atopic dermatitis (J Dtsch Dermatol Ges. 2010 Dec;8[12]:990-8). Nonetheless, a phase II trial of omalizumab is ongoing. Plus, ligelizumab, an anti-IgE monoclonal antibody with a higher affinity for IgE than omalizumab, is also in a phase II trial for adult atopic dermatitis.

“Anti-IgE therapy, I think, is still not dead in atopic dermatitis. I look forward to seeing whether omalizumab will work in unique subsets of patients, or whether a more potent anti-IgE molecule will be more beneficial,” Dr. Beck commented.

As exciting as the prospects are for these investigational agents, there also have been several recent important advances in the prevention of atopic dermatitis, she continued. Investigators led by Dr. Alan D. Irvine of Trinity College, Dublin, noninvasively measured transepidermal water loss in early infancy in more than 1,900 Irish 2-day-old infants and found that those in the 75th percentile for this early marker of skin barrier dysfunction were at 3.1-fold increased risk for diagnosis of atopic dermatitis by age 2 years (J Allergy Clin Immunol. 2016 Apr;137[4]:1111-6). This new-found ability to identify at-risk infants will be extremely helpful in designing atopic dermatitis prevention studies, according to Dr. Beck.

The other advance in prevention was provided via a randomized trial by Dr. Eric L. Simpson of Oregon Health and Science University, Portland, and his coinvestigators. They randomized a group of infants at high risk for atopic dermatitis to daily application of any of five OTC skin moisturizers or a no-moisturizer control group from 2 weeks through 6 months of age. The study hypothesis was that the moisturizers would help reverse the skin barrier abnormalities that play a key role in atopic dermatitis. The hypothesis was borne out by the finding that there was at least a 50% reduction in physician-diagnosed atopic dermatitis by age 6 months in the daily moisturizer group (J Allergy Clin Immunol. 2014 Oct;134[4]:818-23).

Dr. Beck concluded by describing a likely near-term atopic dermatitis prevention and management scenario: High-risk infants will be identified on the basis of noninvasive assessment of epithelial features, such as transepidermal water loss or the presence of high levels of thymic stromal lymphopoietin on the skin surface. Encouragement of daily moisturizing for these high-risk infants will prevent some of them from going on to develop eczema.

For those who do get eczema, dilute bleach baths will help in restoring normal skin barrier function, as was confirmed in an in-press study by Dr. Beck and her coinvestigators, who found that 46% of a group of adults with atopic dermatitis experienced at least a 50% improvement in EASI scores, a big improvement in itch, and reduced transepidermal water loss after 12 weeks of the bleach baths. As other investigators have reported, the bleach baths were very well tolerated and safe.

Dr. Beck reported serving as a consultant to eight pharmaceutical companies with an interest in developing new treatments for atopic dermatitis.

[email protected]

LOS ANGELES – For patients with severe atopic dermatitis and their families and treating physicians, there is big news: finally, there is light at the end of the tunnel, Dr. Lisa A. Beck declared in a plenary lecture at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Better drugs are on the way. The new agents in the developmental pipeline target specific immunologic pathways that appear to be central to atopic dermatitis. Moreover, exciting recent evidence indicates it’s possible to noninvasively identify children at high risk for atopic dermatitis and intervene preventively to reduce the likelihood of actually developing the disease, according to Dr. Beck, professor of dermatology and medicine at the University of Rochester (N.Y.).

Bruce Jancin/Frontline Medical News

“Many pharmaceutical companies have now turned their attention to atopic dermatitis and aren’t just focusing on asthma anymore. The biggest pipeline appears to involve drugs that might target the Th2 [T helper 2 cells] pathway, either by trying to eliminate alarmins such as TSLP [thymic stromal lymphopoietin], or reverse the effects of the Th2 cytokines interleukin-4 and -13, either alone or together, or prevent the recruitment of activated T cells,” she said.

Dr. Beck presented an update on three such promising investigational approaches on the horizon: the IL-4 and IL-13 inhibitor dupilumab; oral and topical Janus associated kinase (JAK) inhibitors; and anti-IgE therapies.

Dupilumab: This fully human monoclonal antibody that blocks IL-4 and IL-13 is also being developed as a treatment for eosinophilic asthma. Dr. Beck was first author of a report on a series of four phase II randomized trials of dupilumab for moderate to severe atopic dermatitis in adults. The publication caused a stir, with dupilumab-treated patients showing marked and rapid improvement to a degree previously unseen in the treatment of this disease (N Engl J Med. 2014;371[2]:130-9).

In the 12-week study, for example, 85% of dupilumab-treated patients achieved at least a 50% improvement in the Eczema Area and Severity Index (EASI) score, compared with 35% of placebo-treated controls, with a significant between-group difference seen in the first week. Maximum improvement – a 75%-80% reduction in EASI scores – was noted at 6-8 weeks. Forty percent of dupilumab-treated patients achieved clear or near-clear skin by investigator’s global assessment, compared with just 7% of controls.

Itching decreased markedly beginning in the first week, too. The investigational agent’s side effect profile was similar to placebo. Phase III clinical trials in atopic dermatitis are ongoing.

A study by other investigators found that dupilumab resulted in rapid improvement in the molecular signature of atopic dermatitis in skin biopsy specimens (J Allergy Clin Immunol. 2014 Dec;134[6]:1293-300). The observed changes in gene expression suggest that dupilumab might have a beneficial effect on the dysfunctional skin barrier that is a hallmark of atopic dermatitis. Further studies are now being planned to take a closer look at that possibility.

JAK inhibitors: “We’re all really excited about this approach because dogs, too, get allergic dermatitis, and in 2013 a JAK 1 and 3 inhibitor [oclacitinib, Apoquel] was approved as a veterinary medicine therapy. It has resulted in dramatic improvement in itch within 1 week of administration, as well as significant improvement in the dermatitis,” Dr. Beck said.

Three JAK inhibitors are now in phase II clinical trials for atopic dermatitis in humans: the JAK 1 and 3 inhibitor tofacitinib (Xeljanz), both as a topical ointment and the familiar oral formulation; baricitinib, an oral JAK 1 and 2 inhibitor; and an agent known for now as PF-04965842, which is an oral inhibitor specifically of JAK 1.

“JAK inhibitors have been quite effective in treating a number of other inflammatory conditions, as well as cancers. I think they will have a role in the treatment of atopic dermatitis. The biggest concerns will be the off-target effects,” she predicted.

Anti-IgE agents: Omalizumab (Xolair), a humanized monoclonal antibody that binds to IgE, has gotten mixed reviews as an investigational treatment for atopic dermatitis. The best study to date, a randomized, single-center, placebo-controlled, double-blind, 16-week clinical trial, found that omalizumab depleted IgE but didn’t improve the clinical course of atopic dermatitis (J Dtsch Dermatol Ges. 2010 Dec;8[12]:990-8). Nonetheless, a phase II trial of omalizumab is ongoing. Plus, ligelizumab, an anti-IgE monoclonal antibody with a higher affinity for IgE than omalizumab, is also in a phase II trial for adult atopic dermatitis.

“Anti-IgE therapy, I think, is still not dead in atopic dermatitis. I look forward to seeing whether omalizumab will work in unique subsets of patients, or whether a more potent anti-IgE molecule will be more beneficial,” Dr. Beck commented.

As exciting as the prospects are for these investigational agents, there also have been several recent important advances in the prevention of atopic dermatitis, she continued. Investigators led by Dr. Alan D. Irvine of Trinity College, Dublin, noninvasively measured transepidermal water loss in early infancy in more than 1,900 Irish 2-day-old infants and found that those in the 75th percentile for this early marker of skin barrier dysfunction were at 3.1-fold increased risk for diagnosis of atopic dermatitis by age 2 years (J Allergy Clin Immunol. 2016 Apr;137[4]:1111-6). This new-found ability to identify at-risk infants will be extremely helpful in designing atopic dermatitis prevention studies, according to Dr. Beck.

The other advance in prevention was provided via a randomized trial by Dr. Eric L. Simpson of Oregon Health and Science University, Portland, and his coinvestigators. They randomized a group of infants at high risk for atopic dermatitis to daily application of any of five OTC skin moisturizers or a no-moisturizer control group from 2 weeks through 6 months of age. The study hypothesis was that the moisturizers would help reverse the skin barrier abnormalities that play a key role in atopic dermatitis. The hypothesis was borne out by the finding that there was at least a 50% reduction in physician-diagnosed atopic dermatitis by age 6 months in the daily moisturizer group (J Allergy Clin Immunol. 2014 Oct;134[4]:818-23).

Dr. Beck concluded by describing a likely near-term atopic dermatitis prevention and management scenario: High-risk infants will be identified on the basis of noninvasive assessment of epithelial features, such as transepidermal water loss or the presence of high levels of thymic stromal lymphopoietin on the skin surface. Encouragement of daily moisturizing for these high-risk infants will prevent some of them from going on to develop eczema.

For those who do get eczema, dilute bleach baths will help in restoring normal skin barrier function, as was confirmed in an in-press study by Dr. Beck and her coinvestigators, who found that 46% of a group of adults with atopic dermatitis experienced at least a 50% improvement in EASI scores, a big improvement in itch, and reduced transepidermal water loss after 12 weeks of the bleach baths. As other investigators have reported, the bleach baths were very well tolerated and safe.

Dr. Beck reported serving as a consultant to eight pharmaceutical companies with an interest in developing new treatments for atopic dermatitis.

[email protected]

LOS ANGELES – A new Cochrane systematic review and meta-analysis has concluded there is no consistent evidence that specific allergen immunotherapy is beneficial in patients with atopic dermatitis, Dr. Herman H. Tam reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“We know that for specific allergen immunotherapy, there have been really good results in allergic rhinitis and venom allergy. For atopic dermatitis, however, dating back almost 40 years, we found there have only been 12 randomized trials using standardized allergen extracts. The quality of evidence was low, and the study findings have been inconsistent,” Dr. Tam, first author of the Cochrane review, said in an interview.

Bruce Jancin/Frontline Medical News

The dozen trials included a total of 733 children and adults in nine countries. Because of insufficient follow-up in most of the studies, coupled with the use of a variety of endpoints, the analysis concluded that “specific allergen immunotherapy cannot be recommended for atopic eczema at present” (Cochrane Database Syst Rev. 2016 Feb 12;2:CD008774).

“We found no consistent evidence that specific allergen immunotherapy provides a treatment benefit for people with allergic eczema, compared with placebo or no treatment. The message of this review is that we need more large randomized trials with better controls, modern high-quality allergen extracts that have proven themselves in other allergic diseases, and patient-centered outcome measures,” according to Dr. Tam, who participated in the Cochrane review while at Imperial College London and is now a pediatric resident at the University of Manitoba, Winnipeg.

He reported having no relevant financial conflicts.

[email protected]

LOS ANGELES – A new Cochrane systematic review and meta-analysis has concluded there is no consistent evidence that specific allergen immunotherapy is beneficial in patients with atopic dermatitis, Dr. Herman H. Tam reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“We know that for specific allergen immunotherapy, there have been really good results in allergic rhinitis and venom allergy. For atopic dermatitis, however, dating back almost 40 years, we found there have only been 12 randomized trials using standardized allergen extracts. The quality of evidence was low, and the study findings have been inconsistent,” Dr. Tam, first author of the Cochrane review, said in an interview.

Bruce Jancin/Frontline Medical News

The dozen trials included a total of 733 children and adults in nine countries. Because of insufficient follow-up in most of the studies, coupled with the use of a variety of endpoints, the analysis concluded that “specific allergen immunotherapy cannot be recommended for atopic eczema at present” (Cochrane Database Syst Rev. 2016 Feb 12;2:CD008774).

“We found no consistent evidence that specific allergen immunotherapy provides a treatment benefit for people with allergic eczema, compared with placebo or no treatment. The message of this review is that we need more large randomized trials with better controls, modern high-quality allergen extracts that have proven themselves in other allergic diseases, and patient-centered outcome measures,” according to Dr. Tam, who participated in the Cochrane review while at Imperial College London and is now a pediatric resident at the University of Manitoba, Winnipeg.

He reported having no relevant financial conflicts.

[email protected]

LOS ANGELES – A new Cochrane systematic review and meta-analysis has concluded there is no consistent evidence that specific allergen immunotherapy is beneficial in patients with atopic dermatitis, Dr. Herman H. Tam reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“We know that for specific allergen immunotherapy, there have been really good results in allergic rhinitis and venom allergy. For atopic dermatitis, however, dating back almost 40 years, we found there have only been 12 randomized trials using standardized allergen extracts. The quality of evidence was low, and the study findings have been inconsistent,” Dr. Tam, first author of the Cochrane review, said in an interview.

Bruce Jancin/Frontline Medical News

The dozen trials included a total of 733 children and adults in nine countries. Because of insufficient follow-up in most of the studies, coupled with the use of a variety of endpoints, the analysis concluded that “specific allergen immunotherapy cannot be recommended for atopic eczema at present” (Cochrane Database Syst Rev. 2016 Feb 12;2:CD008774).

“We found no consistent evidence that specific allergen immunotherapy provides a treatment benefit for people with allergic eczema, compared with placebo or no treatment. The message of this review is that we need more large randomized trials with better controls, modern high-quality allergen extracts that have proven themselves in other allergic diseases, and patient-centered outcome measures,” according to Dr. Tam, who participated in the Cochrane review while at Imperial College London and is now a pediatric resident at the University of Manitoba, Winnipeg.

He reported having no relevant financial conflicts.

[email protected]

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

[email protected]

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

[email protected]

LOS ANGELES – Children who pass oral food challenges to baked egg and milk with wheat flour are at risk for reacting to baked goods made with nonwheat flours, according to a review of more than 200 pediatric food challenges at National Jewish Health in Denver.

The children were already known to be sensitive to egg and milk, and some were being challenged to see if exposure therapy was helping. Unbeknown to the pediatric food allergy team, a kitchen worker at National Jewish had started making muffins with rice flour, thinking it would be safer.

During the month of muffins with rice flour, the failure rate for baked egg challenge muffins rose from 28% (33/120) to 58% (11/19) with rice flour. Failure to baked milk muffins rose from 14% (9/66) to 36% (5/14) (J Allergy Clin Immunol. 2016 Feb. doi: 10.1016/j.jaci.2015.12.579).

Adjusting for age, gender, and atopic dermatitis, children were more than five times more likely to fail baked eggs without wheat (odds ratio, 5.4; P = .002), and more than four times more likely to fail baked milk (OR, 4.06; P = .05).

Given that the phenomenon hasn’t been reported before, “This was very surprising to us,” said study investigator Dr. Bruce Lanser, director of the pediatric food allergy program at National Jewish. “You have to warn parents that if children pass a baked challenge with wheat, they have to continue to eat their baked milk and egg with wheat. Gluten-free products are not going to have the same effect.

“If somebody is avoiding wheat because it causes a bit of redness and itchiness, you have to clear that wheat allergy” before moving to baked egg and milk, Dr. Lanser added.

There’s also concern that “kids will go home after passing a wheat muffin challenge, eat something that’s gluten-free, and have a reaction,” he noted. Wheat-free baked goods might also not build tolerance as well, although that’s not clear from the study, Dr. Lanser said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

Wheat seems to have something unique that alters the allergic properties of egg and milk proteins to help children outgrow their sensitivities. “Rice doesn’t have the same effect,” he observed, and it’s not known if any other grains do. Dr. Lanser said he is interested in looking into rye, barley, oats, and other alternatives.

The mean age of the children in the study was 6 years, and most children had multiple food allergies. Sensitization was confirmed by skin tests and specific IgE.

Meanwhile, there’s a new rule in the National Jewish kitchen: Unless a child has true celiac disease, “always make [challenge] muffins with wheat,” Dr. Lanser said.

There was no industry funding for the work, and the investigators had no disclosures.

[email protected]

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

[email protected]

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

[email protected]

LOS ANGELES – Evidence is building for the hypothesis that impairments in the skin’s microbiome promote Staphylococcus aureus colonization and drive atopic dermatitis, Dr. Donald Y.M. Leung said at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

The link between the bacteria and atopic dermatitis has long been discussed, but its role in pathogenesis still needs definition, he said.

“We’ve never been able to look at the total bacterial composition of the skin, but now with next-generation sequencing it’s finally possible to look at all the phylla and species. Other investigators have shown that during flares of atopic dermatitis there’s a reduction in bacterial diversity and an increase in staph, with S. aureus being particularly abundant. Then, post-flare, you see see a drop in S. aureus; this clearly suggests (it’s) important,” according to Dr. Leung, head of the division of pediatric allergy and immunology at National Jewish Health in Denver and professor of pediatrics at the University of Colorado.

Staphylococcus aureus is known to secrete virulence factors including cytotoxins, superantigens, lipases, and proteases that activate inflammatory cells and can cause significant skin barrier dysfunction.

The discovery that filaggrin mutations result in structural abnormalities in the skin barrier and are associated with sharply increased rates of atopic dermatitis and peanut allergy have strengthened the association, but filaggrin can’t be the whole story. Mutations in filaggrin are largely confined to individuals of Northern European ancestry; African Americans don’t have filaggrin mutations.

Yet atopic dermatitis is a global phenomenon. Further, a skin barrier defect is not enough to cause atopic dermatitis, Dr. Leung said. But such a defect, whether caused by a filaggrin mutation or something else, allows S. aureus to attach to and colonize the skin. Staph overgrowth or infection then activates an inflammatory cell cascade involving natural killer T cells, mast cells, cytokines, and Langerhans cells. That’s why the most effective treatments for atopic dermatitis address both the need to rebuild the skin barrier as well as the counterproductive immune response, he added.

Elsewhere at the AAAAI meeting, Dr. Andrea L. Jones, of National Jewish Health, presented an analysis of 718 children and adolescents with atopic dermatitis, all of whom had been cultured for S. aureus, in that institution’s database. Methicillin-resistant S. aureus (MRSA) was found in 19%; 57% were positive for methicillin-sensitive S. aureus (MSSA) and 23% lacked S. aureus. Of note, the prevalence of peanut allergy was highest at 78% in the group with MRSA; the prevalence was 39% in those with MSSA and 4% in those without S. aureus.

The prevalence of allergies to wheat, egg, milk, or soybeans in the youths with atopic dermatitis was unrelated to MRSA colonization.

“Our hypothesis – although we need to do a prospective study – is that staph colonization may lead to barrier dysfunction and thus allow environmental allergens to invade through the skin. Interestingly enough, people who weren’t colonized by staph had a very low level of sensitization to peanut,” said Dr. Leung, who was the senior investigator in the study.

Dr. Leung was a coauthor on another study that points to a potential new avenue of treatment in atopic dermatitis. Presented by investigators at the University of California, San Diego, at a recent meeting of the Society for Investigative Dermatology, the study showed that atopic dermatitis is marked by a defect in the commensal skin bacteria which normally keep S. aureus in check.

In that study, the amount of S. aureus growing on a defined area of lesional skin of atopic dermatitis patients was nearly 10-fold greater than that on nonlesional skin and the skin of controls without atopic dermatitis.

Commensal bacteria on lesional skin may possess markedly reduced antimicrobial activity. The NIH-sponsored Atopic Dermatitis Research Network plans to conduct clinical trials to see if transplanting beneficial commensal bacteria will reduce staph colonization in atopic dermatitis patients and thereby result in therapeutic benefit, Dr. Leung noted.

He reported serving on scientific advisory boards for more than half a dozen pharmaceutical companies and receiving numerous research grants from the NIH.

[email protected]